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Objective:  Alveolar echinococcosis (AE) is a rare disease in Austria, Switzerland and Germany (DACh) caused by an infection with the parasite Echinococcus multilocularis. The aim of the study was to describe differences in the detection and reporting systems of alveolar echinococcosis in Austria, Switzerland and Germany and to describe epidemiological trends., Methodology:  As part of an epidemiological update on 6 th September 2019 in Ulm, Germany, experts and representatives discussed differences in the reporting and recording systems as well as the current epidemiological situation., Results:  Since 2004, Austria has had an obligation to report suspected cases, diseases and deaths of alveolar echinococcosis by name in accordance with §1 Para. 1 of the Epidemiegesetz 1950 (EpidemieG) and the Ordinance on Notifiable Communicable Diseases. According to §7 Para. 3 of the German Infection Protection Act (IfSG), Germany has also been subject to a reporting obligation since 2001, but not by name. In addition, national registers are available in both countries, which can be used to answer scientific questions. In Switzerland, there is no obligation to report human alveolar echinococcosis since 1997. Efforts are currently being made to implement a national register for alveolar echinococcosis in Switzerland. Despite different reporting and recording systems, a similar epidemiological trend can be observed for DACh., Conclusions:  In Austria, Switzerland and Germany there is a slightly increasing trend of human cases with alveolar echinococcosis. The direct comparability is limited due to different reporting obligations. The structures often do not allow a joint answering of scientific questions concerning diagnostics, treatment and care., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)

Background: The Doppler sonography technique known as "superb microvascular imaging" (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation., Methods: We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations., Results: Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260)., Conclusion: We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes., (© 2021. The Author(s).)

Background: When Echinococcus multilocularis infects humans as a false intermediate host, alveolar echinococcosis (AE) usually manifests primarily intrahepatically and is initially asymptomatic. If the disease remains undiagnosed and untreated, progressive growth occurs, reminiscent of malignant tumours. The only curative therapy is complete resection, which is limited to localised stages, and palliative drug therapy is used otherwise. Consequently, early diagnosis and reliable detection of AE lesions are important. For this reason, abdominal ultrasonography, as the most common primary imaging for AE, relies on classification systems., Aim: To investigate how hepatic AE lesion sonomorphology changes over time in the Echinococcosis Multilocularis Ulm Classification (EMUC)-ultrasound (US) classification., Methods: Based on data from Germany's national echinococcosis database, we evaluated clinical and US imaging data for 59 patients according to the AE case definition in our preliminary retrospective longitudinal study. There had to be at least two liver sonographies ≥ 6 mo apart, ≥ 1 hepatic AE lesion, and complete documentation in all US examinations. The minimum interval between two separately evaluated US examinations was 4 wk. The AE reference lesion was the largest hepatic AE lesion at the time of the first US examination. To classify the sonomorphologic pattern, we used EMUC-US. In addition to classifying the findings of the original US examiner, all reference lesions at each examination time point were assigned EMUC-US patterns in a blinded fashion by two investigators experienced in US diagnosis. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, United Stated). P values < 0.05 were considered statistically significant., Results: The preliminary study included 59 patients, 38 (64.5%) women and 21 (35.6%) men. The mean age at initial diagnosis was 59.9 ± 16.9 years. At the time of initial ultrasonography, a hailstorm pattern was present in 42.4% (25/59) of cases, a hemangioma-like pattern in 16.9% (10/59), a pseudocystic pattern in 15.3% (9/59), and a metastasis-like pattern in 25.4% (15/59). For the hailstorm pattern, the average lesion size was 67.4 ± 26.3 mm. The average lesion size was 113.7 ± 40.8 mm with the pseudocystic pattern and 83.5 ± 27.3 mm with the hemangioma-like pattern. An average lesion size of 21.7 ± 11.0 mm was determined for the metastasis-like pattern. Although the sonomorphologic pattern remained unchanged in 84.7% (50/59) of AE reference lesions, 15.3% (9/59) showed a change over time. A change in pattern was seen exclusively for AE lesions initially classified as hemangioma-like or pseudocystic. A total of 70% (7/10) of AE lesions initially classified as hemangioma-like showed a relevant change in pattern over time, and 85.7% (6/7) of these were secondarily classified as having a hailstorm pattern, with the remainder (1/7; 14.3%) classified as having a pseudocystic pattern. A total of 22.2% (2/9) of AE lesions initially classified as pseudocystic showed a relevant change in pattern over time and were classified as having a hailstorm pattern. For AE lesions initially classified as having a hailstorm or metastatic pattern, no pattern change was evident. All patients with pattern change were on continuous drug therapy with albendazole., Conclusion: The sonomorphology of hepatic AE lesions may change over time. The hemangioma-like and pseudocystic patterns are affected., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background:  We aimed to determine the prevalence and incidence of gallbladder stones in a random population-based collective in Germany., Methods:  We determined the prevalence and incidence rates of gallbladder stones in a random population sample of 1909 individuals from the Echinococcus-multilocularis in Leutkirch (EMIL) study in 2002 and 380 individuals in a follow-up analysis in the year 2013. The sonographic analysis was performed with a Philipps HDI 5000 (2002) and IU 22 (2013) (Netherlands) transducer 1-5 MHz. Statistical analysis was performed using SAS Version 9.4., Results:  The prevalence of gallbladder stones was 3.8 % (69/1909) in 2002 and 10.8 % (41/380) in 2013. In 2013, the gallbladder stone prevalence was 15.1 % (26/172) in women, compared to 7.2 % (15/208) in men. No gallbladder stones were found in participants in the 18-30 or 31-40 age groups. The average annual incidence was 1.03 % in the 41-50 age group, 0.79 % in the 51-65 age group, and 0.63 % in the > 65 age group. The annual incidence was higher among women (1.04 %) than men (0.53 %). The age-associated annual incidence rates for women and men were 1.93 % and 0.5 % in the 41-50 age group, 0.8 % and 0.78 % in the 51-65 age group, and 1.06 % and 0.30 % in the > 65 age group., Conclusion:  For the investigated German collective from 2002 to 2013, the average annual incidence of gallbladder stones was 0.75 %, with a higher incidence rate among women. These results are consistent with data from comparable international studies., Competing Interests: The Ethics Committee of the Baden-Württemberg Medical Association approved the EMIL-I study in 2002 and the EMIL-II study in 2013 (Application numbers 133/02 and 244/13, respectively). The participating patients gave their written consent., (Thieme. All rights reserved.)

Background: The main endemic areas of alveolar echinococcosis (AE) are in central Europe and western China. The infiltration of intrahepatic vascular and bile ducts as well as extrahepatic disease can lead to complications and may increase morbidity in AE., Purpose: To evaluate the vascular/biliary involvement of hepatic alveolar echinococcosis (HAE) and distant extrahepatic disease at each of four locations in Germany, France, and China., Material and Methods: Contrast-enhanced abdominal magnetic resonance imaging (MRI) scans of patients with HAE, 200 in total, were evaluated by five examiners. AE liver lesions were classified according to Kodama's classification. Furthermore, distant extrahepatic manifestations were documented with additionally performed imaging modalities. Vascular/biliary involvement of hepatic manifestations as well as the presence of extrahepatic manifestations were correlated with the respective Kodama type of the liver lesion., Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe (12/100 vs. 3/100; Fisher's exact test: P =0.0286). A significant relationship exists between presence of distant extrahepatic disease manifestation and size of the AE liver lesion (132.53 ± 48.65 vs. 92.49 ± 50.06; P  = 0.0030). Vascular/biliary involvement is significantly more frequent in China than in Europe (86/100 vs. 65/100; χ 2  = 11.92; P  = 0.0006). Vascular/biliary involvement depends on lesion size (111.10 ± 47.44 vs. 47.36 ± 24.36; P <0.0001). Different types of AE liver lesions are associated with differences in vascular/biliary involvement and extrahepatic manifestations., Conclusion: Vascular/biliary involvement and presence of distant extrahepatic manifestations depend on size of the HAE lesions and are more frequently detected in China. Different MRI morphological patterns influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations.

Background: Few systematic comparative studies of the different methods of physical elastography of the spleen are currently available., Aim: To compare point shear wave and two-dimensional elastography of the spleen considering the anatomical location (upper, hilar, and lower pole)., Methods: As part of a prospective clinical study, healthy volunteers were examined for splenic elasticity using four different ultrasound devices between May 2015 and April 2017. The devices used for point shear wave elastography were from Siemens (S 3000) and Philips (Epiq 7), and those used for two-dimensional shear wave elastography were from GE (Logiq E9) and Toshiba (Aplio 500). In addition, two different software versions (5.0 and 6.0) were evaluated for the Toshiba ultrasound device (Aplio 500). The study consisted of three arms: A, B, and C., Results: In study arm A, 200 subjects were evaluated (78 males and 122 females, mean age 27.9 ± 8.1 years). In study arm B, 113 subjects were evaluated (38 men and 75 women, mean age 26.0 ± 6.3 years). In study arm C, 44 subjects were enrolled. A significant correlation of the shear wave velocities at the upper third of the spleen ( r = 0.33088, P < 0.0001) was demonstrated only for the Philips Epiq 7 device compared to the Siemens Acuson S 3000. In comparisons of the other ultrasound devices (GE, Siemens, Toshiba), no comparable results could be obtained for any anatomical position of the spleen. The influencing factors age, gender, and body mass index did not show a clear correlation with the measured shear wave velocities., Conclusion: The absolute values of the shear wave elastography measurements of the spleen and the two different elastography methods are not comparable between different manufacturers or models., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Members of the pentatricopeptide repeat (PPR) protein family act as specificity factors in C-to-U RNA editing. The expansion of the PPR superfamily in plants provides the sequence variation required for design of consensus-based RNA-binding proteins. We used this approach to design a synthetic RNA editing factor to target one of the sites in the Arabidopsis chloroplast transcriptome recognised by the natural editing factor CHLOROPLAST BIOGENESIS 19 (CLB19). We show that our synthetic editing factor specifically recognises the target sequence in in vitro binding assays. The designed factor is equally specific for the target rpoA site when expressed in chloroplasts and in the bacterium E. coli. This study serves as a successful pilot into the design and application of programmable RNA editing factors based on plant PPR proteins.

Objectives:  This study aimed to compare spleen sizes in a hospital and a population sample using ultrasound and define normal values and factors influencing spleen size., Methods:  Both samples' spleen sizes (n = 1520) were measured using ultrasound under the same conditions. Blood counts and other laboratory parameters were determined under the same conditions in both samples., Results:  In the hospital sample (n = 760), the mean spleen size was 114.7 mm, and in the population sample (n = 760), it was 99.1 mm. In both, spleen size in men was significantly higher than in women (p < 0.0001) and influenced by body height, weight, and BMI (body mass index) (p < 0.0001). In the hospital sample, there was a correlation with higher values for ALT (p = 0.0160), AST (p = 0.0394), AP (p = 0.0482), and ferritin (p = 0.0008) and lower values for HDL (p = 0.0091) and thrombocytes (p < 0.0001). In the multivariate analysis, higher values for AP (p = 0.0059) and lower values for hemoglobin (p = 0.0014) and thrombocytes (p = 0.0001) were found. Stratified for sex (men, women), spleen size increased with higher values for ALT (p = 0.0116, p = 0.0113), AST (p = 0.0014, p = 0.0113), and AP (p = 0.0001, p = 0.0012), and with lower values of hemoglobin (p = 0.0057, p = 0.0016), thrombocytes (p < 0.0001, p = 0.0003), and albumin (p = 0.0029, p = 0.0432). In women, there was a discordant correlation with red blood cells (p = 0.0005) and a concordant correlation with GGT (p = 0.0241), and in men discordant correlations with cholesterol (p = 0.0010) and HDL (p = 0.0404)., Conclusions:  The already proven impact of anthropometric data on spleen size was confirmed. The role of laboratory values should be further analyzed., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Introduction: Determining the normal values for acoustic radiation force impulse (ARFI) shear wave elastography of the thoracolumbar fascia (TLF) and define possible factors of influence., Methods: We measured the shear wave velocity (SWV) in m/s and the diameter (anterior-posterior) in mm of the TLF bilateral in 267 healthy participants with the Acuson S3000™ (Siemens) using the virtual touch image quantification mode (VTIQ). The parameters were tested for correlations with the anthropometric data of the participants, between different age groups and the genders, as well as information obtained from the history, such as smoking and sporting activities., Results: We determined a mean SWV of 3.28 ± 0.55 m/s for the left thoracolumbar fascia and 3.44 ± 0.55 m/s for the right. The diameter on the right was 2.7 ± 0.8 mm. On the left, it was 2.7 ± 0.9 mm. Neither body mass index (BMI) nor gender had a significant effect on either of the measured parameters (p > 0.05). The same goes for regular medication, sporting activity or the consumption of alcohol (p > 0.05). The results concerning the effect of smoking and age were inconclusive as they only had a significant influence to either the right or the left side of the TLF but not on the other side., Conclusions: We collected the normal value for ARFI shear wave elastography of the TLF in 267 healthy participants. Furthermore, neither gender, BMI, sports activity nor the consumption of alcohol affected the elasticity or the diameter of the thoracolumbar fascia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background:  Ultrasound as a non-ionizing imaging procedure is one of the most important diagnostic procedures in everyday clinical practice. The technology is widely used. Due to constant technical innovations, sonographic procedures, such as contrast-enhanced ultrasound (CEUS), sonoelastography, new microvascular Doppler modalities and, as an example of interventional procedures, sonographically controlled microwave ablation (MWA), are becoming increasingly important in diagnostic imaging and interventional medicine alongside CT and MRI. However, this also requires greater expertise, specialization and qualification on the part of users., Method:  This review article provides information about the range of technical innovations in ultrasound in recent years and describes the underlying technology, the clinical applications, and their diagnostic value. These are presented in the context of the current literature, explaining their advantages and disadvantages and their clinical value., Results and Conclusion:  Contrast-enhanced ultrasound (CEUS), microvascular Doppler modalities, fusion imaging and elastography complement B-scan ultrasound and conventional Doppler procedures for various problems. Microwave ablation (MWA) has a firm place as an ablative procedure for local tumor therapy in different organ systems and can be performed under ultrasound guidance. Thanks to new developments, the possibilities of ultrasound are now greater than ever. Knowledge of the technology, indications, and possible applications of newer procedures is essential for adequate patient care., Key Points:   · Contrast-enhanced ultrasound (CEUS) allows an increase in sensitivity and specificity in the assessment of parenchymal lesions.. · CEUS allows the microperfusion to be visualized and quantified. For larger vessels, CEUS is an important instrument in diagnosing endoleak after stenting.. · Microvascular Doppler techniques with clutter suppression algorithms allow a more accurate representation of the smallest vessels than regular color or power Doppler.. · Elastography of the liver in diffuse hepatopathies is a noninvasive diagnostic tool to exclude higher grade fibrosis/cirrhosis.. · Microwave ablation (MWA) also offers sonographically controlled ablation of tumors.., Citation Format: · Kloth C, Kratzer W, Schmidberger J et al. Ultrasound 2020 - Diagnostics & Therapy: On the Way to Multimodal Ultrasound: Contrast-Enhanced Ultrasound (CEUS), Microvascular Doppler Techniques, Fusion Imaging, Sonoelastography, Interventional Sonography . Fortschr Röntgenstr 2021; 193: 23 - 32., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Symptoms caused by chronic pancreatitis (CP) are common but often elusive hampering therapeutic decisions. Though correlations of morphologic findings in imaging and clinical appearance remain vague. We aimed in investigating whether a distinct combination of clinical parameters can better define the extent of pancreatic insufficiency and disease burden., Methods: Data from 350 CP patients were evaluated retrospectively from a single center data base following predefined criteria: (i) confirmed CP, (ii) endoscopic ultrasound (EUS) plus (iii) fecal elastase-1 testing, (iv) age ≥18 years, and (v) Cambridge Score ≥1 on EUS evaluation., Results: In total, 182 patients (137 male, 45 female) fulfilled criteria. Median age was 52 years (range 19-88 years). Etiology distributed as follows: idiopathic 50%, alcohol 42.3%, autoimmune 7.7%. Totally, 56.6% of patients suffered from chronic pain that was significantly associated with male sex and younger age. Stool elastase-1 activity discriminated exocrine pancreatic function in Cambridge IV significantly better than in lower stages. Similarly, the endocrine function was significantly more reduced in Cambridge IV CP. Multinominal regression analysis revealed (i) presence of diabetes, (ii) presence of complications, and (iii) extent of Cambridge score as main determinants for exocrine impairment., Conclusion: A high disease burden is linked to extensive morphological alterations in EUS, while pain is more frequent in younger and male patients. The etiology of CP predicts the course of disease in terms of complications., (© 2020 S. Karger AG, Basel.)

Background: Alveolar (AE) and cystic echinococcosis (CE) in humans are caused by the metacestode of the tapeworms Echinococcus multilocularis and Echinococcus granulosus sensu lato (s.l.). Immunohistochemistry with the monoclonal antibodies (mAb) Em2G11, specific for AE, and the mAb EmG3, specific for AE and CE, is an important pillar of the histological diagnosis of these two infections. Our aim was to further evaluate mAb EmG3 in a diagnostic setting and to analyze in detail the localization, distribution, and impact of small particles of Echinococcus multilocularis (spems) and small particles of Echinococcus granulosus s.l. (spegs) on lymph nodes., Methodology/principal Findings: We evaluated the mAb EmG3 in a cohort of formalin-fixed, paraffin embedded (FFPE) specimens of AE (n = 360) and CE (n = 178). These samples originated from 156 AE-patients and 77 CE-patients. mAb EmG3 showed a specific staining of the metacestode stadium of E. multilocularis and E. granulosus s.l. and had a higher sensitivity for spems than mAb Em2G11. Furthermore, we detected spegs in the surrounding host tissue and in almost all tested lymph nodes (39/41) of infected patients. 38/47 lymph nodes of AE showed a positive reaction for spems with mAb EmG3, whereas 29/47 tested positive when stained with mAb Em2G11. Spegs were detected in the germinal centers, co-located with CD23-positive follicular dendritic cells, and were present in the sinuses. Likewise, lymph nodes with spems and spegs in AE and CE were significantly enlarged in size in comparison to the control group., Conclusions/significance: mAb EmG3 is specific for AE and CE and is a valuable tool in the histological diagnosis of echinococcosis. Based on the observed staining patterns, we hypothesize that the interaction between parasite and host is not restricted to the main lesion since spegs are detected in lymph nodes. Moreover, in AE the number of spems-affected lymph nodes is higher than previously assumed. The enlargement of lymph nodes with spems and spegs points to an immunological interaction with the small immunogenic particles (spems and spegs) of Echinococcus spp., Competing Interests: The authors have declared that no competing interests exist.

Alveolar echinococcosis (AE) is a rare zoonotic disease caused by the larval stage of Echinococcus multilocularis. Despite its low world-wide prevalence, this disease shows differences in the regional distribution of cases. In the present cohort study, we analyse the distribution of AE according to environmental and geographical factors in Germany. We identified the place of residence of 591 cases of AE from the national database for AE, and georeferenced these localities in the Universal Transverse Mercator coordinate system. Data on elevation, air temperature, precipitation height and land cover were mapped out and correlated with the distribution of cases of disease during the period 1992-2018. Moran's I statistic was used for spatial autocorrelation. Differences in frequency distribution between elevation, air temperature, precipitation height and landscape feature classes were analysed with the Kruskal-Wallis test. With the multiple linear regression analysis, we determined the influences and interactions of geographical and climatic factors on the number of AE cases. The results showed a heterogeneous distribution of AE cases with a higher concentration in southern Germany than in the rest of Germany (I = 0.225517, Z = 35.8182 and p < 0.001). There was a statistically significant difference in frequency distribution between precipitation height, air temperature, elevation and landscape feature classes and AE cases in Germany (p < 0.0001). In regions with higher elevations (505-672 m), moderate average air temperatures (6.0-7.9°C) and higher precipitation rates (701-1000 mm) most AE cases were recorded. It seems, that regions with higher precipitation rates, higher elevations and moderate average air temperatures have a higher infection burden and infection conditions. It is therefore extremely important to generate greater awareness of the disease in these regions, with the aim of recognising potential cases of AE as early as possible and introducing the appropriate therapeutic measures., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The main endemic areas of alveolar echinococcosis (AE) are in Central Europe and Western China. Both the infiltration of intrahepatic vascular and bile duct structures as well as extrahepatic disease can lead to further complications and may increase morbidity in patients with AE., Aim: To evaluate vascular/biliary involvement in hepatic AE and its distant extrahepatic disease manifestations in an international collective was the aim., Methods: Consecutively, five experienced examiners evaluated contrast-enhanced abdominal computed tomography (CT) scans for 200 patients with hepatic AE of each of four locations ( n = 50) in Germany, France and China. Therefore, we retrospectively included the 50 most recent abdominal contrast-enhanced CT examinations at each center, performed because of hepatic AE from September 21, 2007 to March 21, 2018. AE liver lesions were classified according to the echinococcosis multilocularis Ulm classification for CT (EMUC-CT). Distant extrahepatic manifestations were documented either by whole body positron emission tomography-CT or with the addition of thoracic CT and cranial magnetic resonance imaging. Vascular/biliary involvement of the hepatic disease as well as the presence of distant extrahepatic manifestations were correlated with the EMUC-CT types of liver lesion. Statistical analysis was performed using SAS Version 9.4 (SAS Institute Inc., Cary, NC, United States)., Results: Distant extrahepatic AE manifestations were significantly more frequent in China than in Europe ( P = 0.0091). A significant relationship was found between the presence of distant extrahepatic disease and AE liver lesion size ( P = 0.0075). Vascular/biliary structures were involved by the liver lesions significantly more frequently in China than in Europe ( P < 0.0001), and vascular/biliary involvement depended on lesion size. Different morphological types of AE liver lesions led to varying frequencies of vascular/biliary involvement and were associated with different frequencies of distant extrahepatic manifestations: Vascular/biliary involvement as a function of lesions primary morphology ranged from 5.88% of type IV liver lesions to 100% among type III lesions. Type IV differed significantly in these associations from types I, II, and III ( P < 0.0001). With respect to extrahepatic disease, the primary morphology types IV and V of liver lesions were not associated with any case of distant extrahepatic disease. In contrast, distant extrahepatic manifestations in types I-III were found to varying degrees, with a maximum of 22% for type III., Conclusion: Different CT morphological patterns of hepatic AE lesions influence vascular/biliary involvement and the occurrence of distant extrahepatic manifestations. There are intercontinental differences regarding the characteristics of AE manifestation., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Alveolar echinococcosis (AE) is caused by the intermediate stage of Echinococcus multilocularis . We aimed to correlate computed tomography (CT) data with histology to identify distinct characteristics for different lesion types. We classified 45 samples into five types with the Echinococcus multilocularis Ulm Classification for Computed Tomography (EMUC-CT). The various CT lesions exhibited significantly different histological parameters, which led us to propose a progression model. The initial lesion fit the CT type IV classification, which comprises a single necrotic area with the central located laminated layer, a larger distance between laminated layer and border zone, a small fibrotic peripheral zone, and few small particles of Echinococcus multilocularis (spems). Lesions could progress through CT types I, II, and III, characterized by shorter distances between laminated layer and border zone, more spems inside and surrounding the lesion, and a pronounced fibrotic rim (mostly in type III). Alternatively, lesions could converge to a highly calcified, regressive state (type V). Our results suggest that the CT types mark sequential stages of the infection, which progress over time. These distinct histological patterns advance the understanding of interactions between AE and human host; moreover, they might become prognostically and therapeutically relevant.

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.

The main endemic areas for alveolar echinococcosis (AE) are in Central Europe and Western China, and in >98% of cases, AE manifests in the liver. The aim of this work was to compare European and Chinese patient groups for number, size, and computed tomography (CT) appearance of hepatic AE lesions. A total of 200 CT scans of patients with hepatic AE were evaluated by four blinded, experienced radiologists from two European (Besancon, Ulm) and two Chinese centres (Xining, Urumqi). In addition to noting the number, size, and localisation of the lesions, the radiologists evaluated morphological appearance using the Echinococcus multilocularis Ulm Classification - CT scheme. Chinese patients were younger than European patients (36.8 ± 13.2 vs. 63.5 ± 17.7; p  < 0.0001) and had significantly larger lesions (120.4 ± 50.8 vs. 70.9 ± 39.8; p < 0.0001). The morphological appearance of the lesions on CT differed significantly between the two groups ( p  < 0.05), as did the number of lesions (2.6 ± 3.9 in European centres versus 3.8 ± 5.0 in Chinese centres; p  = 0.0062). Patient age and AE-related morphological manifestations differ between Europe and China, but the reasons for the differences are unknown., Competing Interests: All the authors declare that there is no conflict of interest., (© 2020 Published by Elsevier Inc. on behalf of International Association of Food and Waterborne Parasitology.)

Purpose:  Comparison of vascularization of schwannomas, benign peripheral nerve sheath tumors, using color-coded Doppler sonography (CCDS) and the Toshiba monochrome Superb Microvascular Imaging (mSMI) (Minato, Tokyo, Japan) technique., Methods:  In a retrospective single-center analysis, 16 patients were identified with histologically confirmed schwannomas. Between March and June 2018, all of them underwent ultrasonography using mSMI and CCDS before surgery. Schwannoma vascularization was quantitatively measured using ImageJ, an open platform for scientific image analysis. As the diagnostic gold standard, magnetic resonance imaging was mandatory., Results:  The mSMI and CCDS vascularization showed a moderate agreement between the techniques (κ = 0.5556; p  = 0.0066). The quantitative visual assessment of the vascularization revealed no difference (25.3 ± 8.2 vs. 18.2 ± 3.8; p  = 0.0532). Significant differences were found for the quantitative assessment of CCDS with ImageJ (26.8 ± 8.8 vs. 19.3 ± 2.8; p  = 0.0368). However, in a subanalysis of highly vascularized schwannomas, mSMI revealed significant differences to slightly vascularized schwannomas (32.0 ± 8.2 vs. 21.3 ± 6.1; p  = 0.0065) but not between moderately and slightly vascularized types ( p  = not significant)., Conclusion:  The mSMI mode is qualitatively superior to conventional CCDS; however, quantitative analysis of the vascularization of schwannomas revealed no significant quantitative advantage for mSMI. Nevertheless, the mean ImageJ values showed a positive trend toward a better representation of the vascularization degree of schwannomas with mSMI., Competing Interests: None declared., (Georg Thieme Verlag KG Stuttgart · New York.)

Apolipoprotein C3 is a lipid-binding protein with a pivotal role in triglyceride metabolism and inflammation. This 11-year follow-up study aimed to evaluate apolipoprotein C3 levels and other parameters as markers of hepatic steatosis, in a random, population-based cohort in southern Germany. In 2013, we selected and re-examined 406 study participants (193 women, 213 men; average age 58.1±11.3 years) from the original "Echinococcus multilocularis and other internal diseases in Leutkirch I" (EMIL I) cohort studied in 2002. All participants received upper abdominal sonography to grade potential hepatic steatosis, and blood tests to determine apolipoprotein C3 levels and other laboratory parameters. Body mass index, waist-to-hip ratio, and anthropometric measures were documented. The follow-up study conducted in 2013 included a partial correlation analysis. We found an association between hepatic steatosis and elevated apolipoprotein C3 levels (p<0.0001). Study participants with a novel diagnosis of hepatic steatosis had the highest apolipoprotein C3 serum levels (p=0.0002). Hepatic steatosis was associated with low levels of high density lipoprotein cholesterol (p=0.0374), high levels of total cholesterol (p=0.0117), increased homeostasis model assessment of insulin resistance (p=0.0002), elevated alanine transaminase (p<0.0001), elevated aspartate transaminase (p=0.0003), and elevated C-reactive protein (p=0.0446). Apolipoprotein C3 serum levels were associated with the presence, disease grade, and new development of hepatic steatosis likewise to biomarkers of the metabolic syndrome., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Owing to technical development of specific fluorophore filters, the neurosurgical application of sodium fluorescein (SF) has regained value in brain tumor surgery. The aim of this study was to determine the usefulness of SF during nerve biopsies., Methods: This single-center study included 5 cases of nerve biopsies performed under microscope-based fluorescence with SF performed between March 2016 and February 2017. SF was applied intravenously (1 mg/kg body weight). After microsurgical dissection of the involved nerve segment, fluorescence-guided fascicular biopsy was performed. Selection of target fascicles was at the surgeon's discretion and took into account nerve stimulation for preservation of motor function and fluorescence intensity. Correlation to histopathologic examination was examined. Video analysis of intraoperative images comparing target fascicles with intense fluorescent response to adjacent fascicles of the same nerve segment was performed using ImageJ., Results: All patients had motor or sensory deficits. Magnetic resonance imaging findings were similar, depicting long segments of gadolinium enhancement (minimum 11.7 cm). Each biopsy sample was positive resulting in diverse histopathologic results. Digital image analysis revealed a statistically significant difference of the complementary color green (P = 0.0473)., Conclusions: Magnetic resonance imaging is the gold standard in diagnostic work-up of peripheral nerve disorders. Longitudinal nerve thickening with positive contrast enhancement is an unspecific magnetic resonance imaging finding. Various pathologies, such as tumors and inflammatory lesions, may cause this morphologic phenomenon. Nerve biopsies may be needed for diagnostic work-up. Intraoperative SF may help to depict the most affected fascicles and identify target fascicles for biopsy and increase diagnostic certainty of nerve biopsies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Human alveolar echinococcosis (AE) is a potentially lethal zoonosis caused by the cestode Echinococcus multilocularis. The aim of this systematic review is to establish a comprehensive global AE literature overview taking into account the epidemiologically relevant AE research of the twenty-first century., Methods: We systematically searched the global literature published from 2001 through 2018 via MEDLINE, EMBASE, the Russian databases eLIBRARY.RU, CyberLeninka, the Chinese databases CNKI, VIP, Journals., Research: ac.ir (Farsi language-based), Jordan E-Library (Arab language-based) and supplementary Google Scholar, in accordance with the PRISMA guidelines. QGIS software was used for the mapping of the affected countries., Results: We have listed 154 relevant publications in the final literature synopsis in consideration of our quality assessment. Including non-autochthonous cases, human AE was reported in 36 countries within the northern hemisphere from 2001 to 2018. The first publication of AE in Tajikistan, Pakistan, South Korea, Belgium, the Netherlands, Slovakia, Hungary, Lithuania, Latvia, Slovenia and Morocco occurred in this century; further first cases in Taiwan, Thailand, and Denmark were considered to be non-autochthonous by the authors. The highest total case numbers (n ≥ 100 in a single article) were reported in France, Germany, Switzerland, Poland, and Lithuania, including China and Kyrgyzstan with by far the highest prevalence figures., Conclusions: Our paper emphasises the increasing spread of reported cases and the rise in its numbers in the literature of the twenty-first century, especially in western, northern and eastern Europe, as well as in central Asia. Epidemiological studies on human infections are lacking in many parts of the world.

The aim of this study was to investigate any association between the adipose tissue-derived protein, visfatin, and non-alcoholic fatty liver disease (NAFLD) and its potential long-term impact on hepatic steatosis. A cross-sectional study including 2429 randomly selected subjects was performed in 2002. Later, 403 subjects were re-evaluated in 2013. Serum visfatin concentrations were determined by sandwich enzyme-linked immunosorbent assay. Phenotyping included abdominal ultrasonography, anthropometric data, and laboratory investigations. No association was found between circulating visfatin levels and the presence of NAFLD at baseline (2002: p=0.0967) or during follow-up (2013: p=0.1312). However, a significant increase in visfatin levels in relation to the level of steatosis was seen during follow-up (p<0.0001). During the more than 10-year follow-up, the metabolic status of the study subjects worsened, with a significant increase in body mass index (BMI) (p<0.0001), waist-to-hip ratio (p<0.0001), triglycerides (TG) (p<0.0001), low-density lipoprotein (p=0.0305), homeostasis model assessment (p<0.0001), and presence of diabetes (p<0.0001). This change was accompanied by an increase in serum visfatin levels, which showed a weak correlation with BMI (p<0.0001, r=0.27586) and presence of diabetes (p<0.0043, r=0.14188). A statistically significant correlation between leucocyte numbers and serum visfatin concentration (p<0.0001, r=0.25615) was found. We found no association between visfatin levels and the presence or absence of NAFLD or the degree of hepatic fatty infiltration at baseline. There was a strong correlation between serum visfatin concentrations and the number of leucocytes, which may suggest a proinflammatory role for visfatin., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim:  To compare ARFI-based elastography procedures of the GE LOGIQ E9, Philips EPIQ7, and Toshiba Aplio 500 (versions 5.0 and 6.0) ultrasound scanners with the Siemens Acuson S3000 reference scanner in subjects with healthy livers, taking various impact factors into account., Materials and Methods:  The study consisted of two subsequent study parts. Study 1 (n = 205) evaluated the 2D-SWE techniques of GE and Toshiba 5.0 and the pSWE technique of the Philips scanner against the reference scanner Siemens. Study 2 (n = 113) evaluated Toshiba 6.0 against Siemens in a different cohort. Out of 433 study participants in both studies, 318 (M:F = 122:196) met the inclusion criteria. Elastography measurements were performed in the right lobe of the liver at depths of 3, 5 and 7 cm. At each depth, five measurements were acquired with the Siemens and Philips scanners and one measurement each with the GE and Toshiba machines., Results:  The Philips (r = 0.58, p < 0.0001) and the GE (r = 0.63, p < 0.0001) scanners showed the strongest correlation of shear wave velocities between Siemens and comparator scanners, at a depth of 5 cm. We found the strongest relationship with Toshiba (software version 6.0) at a depth of 3 cm (r = 0.57, p < 0.0001). Toshiba software version 5.0 did not give satisfactory results. The factors of sex and BMI showed scanner-specific differences in the values measured (p < 0.05). The age of the subjects did not seem to have any effect., Conclusion:  With the exception of Toshiba software version 5.0, all of the scanners we tested can be recommended without reservation for comparative ultrasound elastography of the healthy liver at measurement depths of 3 cm up to 5 cm., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Alveolar echinococcosis (AE) is a rare zoonosis caused by the parasite Echinococcus multilocularis . Nothing is known about the health-related quality of life (HRQoL) in patients with AE receiving different types of therapy. Therefore, the aim of the study was to compare HRQoL in patients with AE in Germany depending on their therapeutic regimen namely conservative drug treatment with long-term benzimidazoles versus surgical therapy by resection of the parasitic liver lesions. The 36-Item Short Form Health Survey (SF-36) questionnaire, including other echinococcosis-related questions, was used to measure HRQoL. The SF-36 scales were evaluated according to the algorithms provided by the authors. The statistical analysis was performed with SAS version 9.2. The significance level was set at α = 0.05, p  < 0.05 corresponds to statistical significance. The investigated group consisted of conservatively drug treated ( n  = 30) and patients with curative surgery ( n  = 25) with confirmed AE. The study was performed at an infectious disease outpatient department from April 2018 to October 2018. The conservatively drug treated patient group consisted of 15 men (50.0%) and 15 women (50.0%) with an average age of 55.7 ± 16.7 years (Median: 59). The surgery group consisted of nine men (36.0%) and 16 women (64.3%) with an average age of 53.3 ± 31.9 years (Median: 54). The physical quality of life of the conservatively drug treated patients did not show any significant differences to the surgical treated group (45.2 ± 11.4 vs. 47.6 ± 9.9; p  = 0.4079). There was also no significant difference regarding the mental quality of life between the conservatively drug treated patients, and those treated with curative surgery (45.5 ± 10.6 vs. 47.3 ± 10.8; 0.5206). Nevertheless, there was a slight advantage in the physical and mental scores of the patients treated with surgery. Furthermore, for 13 of the 25 surgically treated patients, some aspects of the HRQoL improved significantly after surgery. The evaluation showed no statistically significant differences in HRQoL in patients with AE dependent on the applied treatment strategy (conservative drug versus curative surgical therapy)., Competing Interests: None., (© 2019 The Authors.)

Background: The intravenous application of sodium fluorescein (SF) for brain tumor surgery goes back to the late 1940s. The development of specific fluorophore filters significantly reduced the required dosage of SF and therefore diminished possible side effects. This study investigates the application of SF in benign peripheral nerve sheath tumors (PNSTs), concentrating on its feasibility during microsurgical removal., Methods: The single-center study includes 10 consecutive schwannoma cases operated on between September 2016 and March 2017. Inclusion criteria were defined as age ≥18 years, preoperative magnetic resonance imaging with suspicion of schwannoma, and final histopathologic confirmation of schwannoma. Exclusion criteria were a history of intolerance to SF and renal insufficiency. The microsurgical part of each surgery was video recorded, and the collected material was retrospectively analyzed. Red, green, and blue values of various regions of interest set on tumor and normal nerve of each patient were evaluated using ImageJ, an open platform for scientific image analysis., Results: Digital video analysis confirmed the intraoperative impression of increased fluorescence of the tumor in contrast with normal nerve tissue. Because the color yellow is predominantly a mixture of red and green, values of these colors were significantly increased in schwannomas compared with normal nerve tissue (P = 0.0003 and P = 0.0023, respectively)., Conclusions: SF reveals increased fluorescence in schwannomas compared with normal nerve tissue. Intraoperative differentiation of tumor and normal nerve tissue becomes possible using a low dose of SF (0.5-1 mg/kg). No side effects occurred. Secure microsurgical preparation is feasible during application of the YELLOW 560 nm filter., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: For patients with cystic fibrosis, the imaging of the pancreas is of crucial importance for the early detection of pancreatic carcinoma. Comparative studies between Magnetic Resonance Imaging (MRI) and sonographic pancreas sonography are not yet available. The aim of the study was to compare MRI, sonography and point-shearwave elastography (pSWE). A total of 19 patients were included (10 male, 9 female; age 29.7 ± 14.3 years) in the study. Ultrasonography with pSWE and contrast enhanced MRI with MRCP were performed., Results: Significant differences between measurements of pancreatic body were registered in MRI with 1.4 ± 0.6 cm vs 1.0 ± 0.4 cm in ultrasound (p = 0.049), however not for pancreatic head and tail. In 10/19 patients (52.6%) pancreatic parenchyma did not show in MRI because of complete lipomatous transformation, but could be detected in ultrasound. pSWE-values showed no significant differences between the full and partial fatty transformation in pancreatic head (p = 0.968), body (p = 0.657) and tail (p = 0.840). pSWE-values did not correlate with measured signal intensity in T1w flash (p = 0.930, r = 0.025) and T2w HASTE sequences (p = 0.152, r = - 0.375). In patients with CF ultrasound is superior to MRI for displaying full fibro-fatty parenchymal transformation, pancreatic duct. Ultrasound elastography did not provide additional clinical relevant information.

Background: The aim of our study was to investigate the prevalence and natural long-term progression of gallbladder polyps in a random sample of the general population., Methods: Four hundred and thirteen subjects (190 women, 223 men; aged 29-75 years) were studied first in 2002 and again eleven years later in 2013. All subjects were interviewed using a standardised questionnaire, anthropometric data were recorded, and an abdominal ultrasound scan was carried out., Results: The prevalence of gallbladder polyps was 6.1% (115/1880) in the 2002 study and 12.1% (50/413) in the 2013 follow-up study. After eleven years, 36 subjects (8.7%, 36/413) had developed new polyps, thirteen subjects (48.1%, 13/27) no longer had gallbladder polyps, and 14 subjects (51.9%, 14/27) still had polyps. The number of polyps had increased in six of these subjects (43%, 6/14), decreased in a further six (43%, 6/14), and remained unchanged in two (14%, 2/14). The mean polyp size was 4.7 mm (± 2.2 mm, range 2-20 mm) in 2002 and 4.0 mm (± 1.9 mm, range 0.5-11 mm) at follow-up. A decrease in polyp size was noted in seven (50%) of the 14 subjects, an increase in size in five subjects (35.7%), and no change in two subjects (14.3%). The shape of the polyps had changed from pedunculated to sessile in two subjects (14.3%, 2/14) and from sessile to pedunculated in one subject (7.1%, 1/14)., Conclusions: In long-term follow-up, the prevalence of gallbladder polyps increased, with new lesions developing in 8.7% of the population. Polyps persisted in 51.9% of the subjects who had them in the original study and disappeared in the other 48.1%.

Purpose: The Alveolar echinococcosis (AE) is a rare zoonosis caused by the parasite Echinococcus multilocularis. To date, nothing is known about the health-related quality of life (HRQoL) in patients with AE. The aim of the study was to evaluate the HRQoL in patients with AE in comparison of the healthy population., Methods: We used the 36-Item Short Form Health Survey (SF-36) questionnaire to evaluate the HRQoL. The SF-36 scales have a range of 0-100 (0 represents the worst and 100 the most favourable state of health). SAS Version 9.2 was used for the statistical analysis of AE-cases (n = 30) and the healthy control group (n = 35)., Results: The analysis showed that the HRQoL in people with AE is reduced in comparison with the control population. The study group consisted of 15 (50.0%) men and 15 (50.0%) women; the control group of 16 (45.7%) men and 19 (54.3%) women. The mean age was 55.73 ± 16.65 years, while that of the control group was 54.57 ± 15.34 years. The physical quality of life in patients with AE (45.21 ± 11.42) was not significantly less than that of the control group (50.54 ± 10.52); p = 0.0568. Nevertheless, AE-patients show lower SF-36 scores for the physical quality of life. For the mental quality of life, patients with AE had a significantly lower score (45.46 ± 10.57) than the control group (51.57 ± 9.04); p = 0.0154., Conclusions: The HRQoL in people with AE is reduced in comparison with a control population. Assessment of the physical and mental quality of life in patients with AE may help to evaluate the patient outcome.

Background: The aims of this study were to establish shear wave elastography of the pancreas by comparing measurements in patients with type 1 diabetes (T1D) and healthy volunteers and to consider whether this method could contribute to the screening or prevention of T1D., Methods: This pilot study included 15 patients with T1D (10 men, 5 women) and 15 healthy volunteers (10 men, 5 women) as controls. Measurements were performed with a Siemens Acuson S3000 (Siemens Healthcare, Erlangen, Germany) using a 6C1 convex transducer and the Virtual Touch™ tissue quantification (VTQ) method., Results: The mean shear wave velocity of the head of the pancreas was 1.0 ± 0.2 m/s (median: 1.1 m/s) for the study group and likewise 1.0 ± 0.2 m/s (median: 0.9 m/s) for the control group. Velocities of 1.2 ± 0.2 m/s (median: 1.2 m/s) were measured in the body of the pancreas in both groups. There was a significant difference between the values obtained in the tail of the pancreas: patients 1.1 ± 0.1 m/s (median: 1.0 m/s) versus controls 0.9 ± 0.1 m/s (median: 0.8 m/s) (p = 0.0474). The mean value in the whole pancreas of the study group was not significantly above that of the control group: 1.1 ± 0.1 m/s (median: 1.0 m/s) versus 1.0 ± 0.1 m/s (median: 1.0 m/s) (p = 0.2453)., Conclusions: Sonoelastography of the pancreas revealed no overall difference between patients with T1D and healthy volunteers. Patients with T1D showed higher values only in the tail segment. Future studies need to determine whether specific regional differences can be found in a larger study population.

Purpose:  The diagnosis of an inguinal hernia is usually made clinically. Precise imaging appears to be necessary when the clinical examination is inconclusive. The aim of this study was to determine the diagnostic value of ultrasonography for inguinal hernias and whether it influences the decision for or against surgery., Materials and Methods:  This study was a single-center retrospective study carried out from January 2012 to December 2016. All 326 patients had undergone ultrasound scanning of the groin as part of the diagnostic workup. Besides surgical findings being the gold standard, follow-up data and alternative ultrasound diagnoses were considered as references, allowing us to assess the accuracy of negative ultrasound findings as well., Results:  The findings on ultrasonography were positive in 248 patients and negative in 78 patients. In addition to 201 operated patients, we were able to validate a further 40 patients by means of a questionnaire and the alternative ultrasound diagnoses. The correlation with all three references resulted in a sensitivity of 97 %, a specificity of 77 %, a positive predictive value of 95 %, and a negative predictive value of 87 %., Conclusion:  Ultrasonography is an accurate method for evaluating inguinal hernias. High sensitivity makes it particularly suitable for ruling out an inguinal hernia when the findings are negative. An ultrasound scan carried out in addition to clinical examination can therefore help to determine the right indication for surgical intervention., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: Manifestations of cystic fibrosis in the pancreas are gaining in clinical importance as patients live longer. Conventional ultrasonography and point shear wave elastography (pSWE) imaging are non-invasive and readily available diagnostic methods that are easy to perform. The aim of this study was to perform conventional ultrasonography and obtain pSWE values in the pancreases of patients with cystic fibrosis and to compare the findings with those of healthy controls., Methods: 27 patients with cystic fibrosis (13 women/14 men; mean age 27.7 ± 13.7 years; range 9-58 years) and 60 healthy control subjects (30 women/30 men; mean age 30.3 ± 10.0 years; range 22-55 years) underwent examinations of the pancreas with conventional ultrasound and pSWE imaging., Results: Patients with cystic fibrosis have an echogenic pancreatic parenchyma. We found cystic lesions of the pancreas in six patients. pSWE imaging of the pancreatic parenchyma gave significantly lower shear wave velocities in patients with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p < 0.001)., Conclusions: Using pSWE imaging in vivo, we have shown that the pancreas is considerably softer in patients with cystic fibrosis than in a healthy control population.

Purpose: Alveolar echinococcosis (AE) is a life-threatening helminthic disease. In humans, AE mostly affects the liver; the regional hepatic lymph nodes may be involved, indicating dissemination of AE from the liver. To achieve complete removal of the disease, enlarged hepatic lymph nodes may be resected during surgical treatment. We evaluated the frequency of affected lymph nodes by conventional microscopic and immunohistochemical analyses including detection of small particles of Echinococcus multilocularis (spem). Furthermore, we analyzed the association of resection of enlarged and affected lymph nodes with long-term outcome after surgical therapy of patients who underwent surgery with curative intent., Materials and Methods: We identified 43 patients who underwent hepatic surgery with curative intent with lymph node resection for AE. We analyzed the cohort for the manifestation of the parasite in the resected lymph nodes by conventional histology and by immunohistochemistry and compared these data with the further course of AE., Results: Microscopically infected lymph nodes (laminar layer visible) were found in 7 out of these 43 patients (16%). In more than three quarters (25/32) of all specimens investigated, lymph nodes showed spems when stained with antibody against Em2G11, a monoclonal antibody specific for the Em2 antigen of the Echinococcus multilocularis metacestode. Most frequently, lymph nodes were resected due to enlargement. The median size of microscopically affected lymph nodes was 2 cm (range, 1.2 to 2.5 cm), the median size of immunohistochemically and non-affected lymph nodes was 1.3 cm each (range, "small" to 2.3 or 2.5 cm, respectively). Median follow-up was 8 years for all patients, 5 years for patients with lymph node resection, and 4 years for patients with infested lymph nodes. Overall, recurrent disease was seen in ten patients (10/109; 9%) after a median period of 1.5 years (range, 4 months to 4 years). None of the seven patients with conventionally microscopically affected lymph nodes suffered from recurrent disease. One patient with negative resected nodes and one patient with spems showed recurrent disease after 4 and 35 months, respectively., Conclusions: Lymph node involvement in AE is frequent, particularly when evaluated by immunohistochemical examination of lymph nodes with the monoclonal antibody Em2G11. Affected lymph nodes tend to be larger in size. Lymph node involvement is not associated with recurrent disease and therefore warrants further analysis of the biological significance of lymph node involvement.

Background: To determine normal values for acoustic radiation force impulse (ARFI) shear wave elastography of the Achilles tendon., Methods: Using the VTIQ mode with the Acuson S3000™ (Siemens Healthcare, Erlangen, Germany), we measured the shear wave velocity (SWV) in m/s and the diameter in mm of both Achilles tendons in 182 healthy volunteers. The tendon was displayed in a sagittal view with a relaxed tendon. The parameters were tested for correlations with the anthropometric data of the subjects, between the genders and different age groups, as well as information obtained from the history, such as smoking and sporting activities., Results: Using a sagittal acoustic window, we determined a mean SWV of 9.09 ± 0.71 m/s for the left Achilles tendon and 9.17 ± 0.61 m/s for the right. There was a significant difference between the results for the right and left side (p < 0.05). The diameter on the left was 4.7 ± 0.9 mm. On the right, it was 4.8 ± 0.9 mm. Likewise there was a significant difference between the results for the diameter of the left and right side (p < 0.05). Neither gender, body mass index (BMI) nor age had a significant effect on either of the measured parameters (p > 0.05). The same goes for the consumption of tobacco and alcohol (p > 0.05)., Conclusions: Age, gender, BMI, smoking or the consumption of alcohol did not affect either the elasticity or the diameter of the Achilles tendon.

Purpose: Alveolar echinococcosis is a rare disease caused by the parasite Echinococcus multilocularis. The newly established national database should enable us to determine high-risk areas and evaluate the endemic levels., Methods: The national database was implemented using SQL Workbench. We used EpiInfo™ software to display the prevalence of disease. Moran's I geodata analysis according to cluster and high risk areas was performed with GeoDa™. SAS Version 9.2 was used for the statistical analysis of the cases (n = 523)., Results: The analysis showed a concentration of cases in Baden-Württemberg and Bavaria. Moran's I showed a heterogeneous case distribution throughout Germany (I = 0.208815, Z = 32.6175, p < 0.001). In the period from 1992 to 2016, the prevalence was 0.64/100,000 inhabitants in the whole of Germany, 2.18/100,000 inhabitants in Baden-Württemberg and 1.48/100,000 inhabitants in Bavaria. The analysis also revealed a difference between men and women, with a prevalence of 0.58/100,000 and 0.69/100,000, respectively. The analysis of spatial autocorrelation and possible risk areas showed that the southeast regions of Baden-Württemberg (I = 0.188514, Z = 11.3197, p < 0.001) and the southwest part of Bavaria (I = 0.176953, Z = 13.5144, p < 0.001) constitute the high risk areas., Conclusions: The prevalence of disease is noticeably high in the Swabian Jura, the Bavarian Alps and the Alpine foothills. Raising awareness and educating doctors in high risk areas may prevent new cases and assist in earlier diagnosis.

Objective: Search for meaningful laboratory and anthropometric parameters in lean non-alcoholic fatty liver disease (lean NAFLD) in the general population. Out of 2445 subjects in a random population sample, we compared those who had a body mass index (BMI) < 25 and a fatty liver [lean NAFLD (LN), n = 5] with obese subjects who had a BMI > 30 but no fatty liver [non-NAFLD (NN), n = 27] in a follow-up examination. Ultrasonic, anthropometric and laboratory parameters were collected., Results: There were significant differences (p < 0.05) between the LN and the NN groups with respect to serum ferritin (199.2 ± 72.1 LN vs 106.0 ± 89.6 NN), haemoglobin (14.9 ± 0.8 LN vs 13.5 ± 1.2 NN), haematocrit (0.438 ± 0.019 LN vs 0.407 ± 0.035 NN) and Mean corpuscular haemoglobin concentration (34 ± 0.6 LN vs 33.2 ± 0.8 NN). Significantly lower values of soluble transferrin receptor were measured in the LN group (2.8 ± 0.4 LN vs 3.8 ± 1.5 NN). In both groups, the measured HOMA-IR index (homeostatic model assessment of insulin resistance index) (2.3; normal range ≤ 1) was abnormal. Mean cholesterol (6.2 ± 1.4 LN and 5.6 ± 1.1 NN) and low-density lipoprotein levels (3.8 ± 1.0 LN 3.4 ± 0.9 NN) were above the upper limit of normal in both groups, as was the mean triglycerides level in the LN group (2.6 ± 2.0). In summary, there are differences in parameters of iron and fat metabolism between subjects with LN and overweight subjects without fatty liver infiltration.

Objective: The aim of the study was to examine the quantitative tissue properties of the Achilles tendon and plantar fascia using a handheld, non-invasive MyotonPRO device, in order to generate normal values and examine the biomechanical relationship of both structures., Design: Prospective study of a large, healthy sample population., Participants: The study sample included 207 healthy subjects (87 males and 120 females) for the Achilles tendon and 176 healthy subjects (73 males and 103 females) for the plantar fascia. For the correlations of the tissue parameters of the Achilles tendon and plantar fascia an intersection of both groups was formed which included 150 healthy subjects (65 males and 85 females)., Interventions: All participants were measured in a prone position. Consecutive measurements of the Achilles tendon and plantar fascia were performed by MyotonPRO device at defined sites., Results: For the left and right Achilles tendons and plantar fasciae all five MyotonPRO parameters (Frequency [Hz], Decrement, Stiffness [N/m], Creep and Relaxation Time [ms]) were calculated of healthy males and females. The correlation of the tissue parameters of the Achilles tendon and plantar fascia showed a significant positive correlation of all parameters on the left as well as on the right side., Conclusions: The MyotonPRO is a feasible device for easy measurement of passive tissue properties of the Achilles tendon and plantar fascia in a clinical setting. The generated normal values of the Achilles tendon and plantar fascia are important for detecting abnormalities in patients with Achilles tendinopathy or plantar fasciitis in the future. Biomechanically, both structures are positively correlated. This may provide new aspects in the diagnostics and therapy of plantar fasciitis and Achilles tendinopathy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: This study uses virtual touch imaging quantification (VTIQ) technology for the first time to conduct measurements of the trapezius and erector spinae muscles in a large study population. The significance of various influencing factors, such as age and sex, are also examined., Method: The study population comprised 278 subjects. The Siemens Acuson S3000 and VTIQ technology were used for measurements of the trapezius and erector spinae muscles (Siemens Healthcare, Erlangen, Germany)., Results: The following mean values ± standard deviation were calculated: left trapezius: males 2.89 ± 0.38 m/s, females 2.71 ± 0.37 m/s; right trapezius: males 2.84 ± 0.41 m/s, females 2.70 ± 0.38 m/s; left erector spinae: males 2.97 ± 0.50 m/s, females 2.81 ± 0.57 m/s; right erector spinae: males 3.00 ± 0.52 m/s, females 2.77 ± 0.59 m/s. A significant difference between male and female subjects was demonstrated both for the shear wave velocities of the trapezius and erector spinae as well as for the thickness of the trapezius muscle (p < 0.05). There was also a significant difference in muscle elasticity between subjects over 60 years of age and those under 60 (p < 0.05). Furthermore, the results indicate that regular physical activity has an effect on muscle elasticity., Conclusions: Our results demonstrate significantly different results between male and female subjects and between under- and over-sixty-year-old subjects. This means that sex-related and age-adapted considerations are obviously needed for further studies.

Purpose  Contrast-enhanced ultrasound (CEUS) has been established for many years and has become an increasingly important cornerstone of the diagnostic imaging of various organ systems. However, this modality is rarely performed by radiologists and is primarily employed by other medical disciplines. The goal of this questionnaire study is to present the current value of CEUS in radiology and to encourage reevaluation of the method within this medical discipline. Materials and Methods  560 directors of radiology departments throughout Germany were contacted and given a 3-page questionnaire. The questionnaire included 37 questions on 5 different topics (general structures, CEUS and interdisciplinarity, CEUS in pediatric radiology, education/professional development, outlook) to assess the value of ultrasound (US) and in particular CEUS in radiology. Results  The response rate was 42.3 %. A statistical analysis of the answers was performed, including subgroup analysis. Overall, it could be shown that CEUS is performed in comparatively few radiology departments (26.6 %), while the current value of the modality is given an average to high range of importance even by radiologists. More than half of all participating radiologists (54.9 %) would like this method to be included in the requirements catalog for the specialist examination. Conclusion  The nationwide questionnaire to evaluate CEUS within radiology departments in Germany had a very high response rate, which reflects the assessment of this topic by radiologists. There is a substantial discrepancy between the currently low utilization of CEUS in radiology and the high ranking of CEUS by many radiologists. The analyses of the replies point out important aspects of professional policy regarding this topic within the radiology community. Key points   · The high response rate reflects the assessment of this topic by radiologists.. · The questionnaire study depicts the currently low use of CEUS in radiology.. · CEUS is given a high range of importance by radiologists.. Citation Format · Graeter T, Kratzer W, Seufferlein T et al. Evaluation of the Value of Contrast-Enhanced Ultrasound (CEUS) within Radiology Departments in Germany. Fortschr Röntgenstr 2017; 189: 748 - 759., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Alveolar echinococcosis (AE) is caused by the metacestode stage of Echinococcus multilocularis. The inflammatory response to this infection is influenced by the interaction of the parasite with the host. We aimed to analyze human liver lesions infected with Echinococcus multilocularis and the changes of the cellular infiltrates during albendazole (ABZ) treatment., Methodology/principal Findings: We analyzed liver tissue samples from 8 untreated patients, 5 patients treated with two daily doses of 400 mg ABZ for up to two months and 7 patients treated for more than two months with the same ABZ therapy. A broad panel of monoclonal antibodies was used to characterize the lesion by immunohistochemistry. A change in the cellular infiltrate was observed between the different chemotherapy times. During the initial phases of treatment an increase in CD15+ granulocytes and CD68+ histocytes as well as in small particles of Echinococcus multilocularis (spems) was observed in the tissue surrounding the metacestode. Furthermore, we observed an increase in CD4+ T cells, CD20+ B cells and CD38+ plasma cells during a longer duration of treatment., Conclusions/significance: ABZ treatment of AE leads to morphological changes characterized by an initial, predominantly acute, inflammatory response which is gradually replaced by a response of the adaptive immune system.

Purpose: A variety of elastographic techniques have been developed to facilitate the non-invasive assessment of tissue properties. The goal of the study was to examine the influence of gender, age, BMI, alcohol consumption, and smoking in healthy volunteers., Methods: Of the 263 participants who met all the study inclusion criteria, 234 had successful measurements. The examination was performed with the Siemens Acuson S3000 (Siemens Healthcare, Erlangen, Germany), using the 6C1 curved array transducer with the virtual touch tissue quantification (VTQ) method., Results: The values determined with the curved array in the head of the pancreas were 1.44 ± 0.39 m/s for women and 1.19 ± 0.29 m/s for men; in the body, the results were 1.49 ± 0.37 m/s for women and 1.26 ± 0.30  m/s for men; in the tail, the corresponding values were 1.29 ± 0.36 m/s for women and 1.05 ± 0.30 m/s for men. Comparison of gender showed that men have significantly lower mean values than women. There were significantly higher values in all parts of the organ with the increasing age of the participants (p < 0.0001). For BMI, there was a significant correlation with the values only when considering the BMI in continuous form. Alcohol consumption and smoking did not have any significant effects., Conclusions: ARFI-VTQ is qualified for use on pancreatic tissue. Further studies are required to examine the influence of other factors in larger populations.

Eukaryotes and prokaryotes possess fatty acid synthase (FAS) biosynthetic pathways that comprise iterative chain elongation, reduction, and dehydration reactions. The bacterial FASII pathway differs significantly from human FAS pathways and is a long-standing target for antibiotic development against Gram-negative bacteria due to differences from the human FAS, and several existing antibacterial agents are known to inhibit FASII enzymes. N-Acetylcysteamine (NAC) fatty acid thioesters have been used as mimics of the natural acyl carrier protein pathway intermediates to assay FASII enzymes, and we now report an assay of FabV from Pseudomonas aeruginosa using (E)-2-decenoyl-NAC. In addition, we have converted an existing UV absorbance assay for FabA, the bifunctional dehydration/epimerization enzyme and key target in the FASII pathway, into a high-throughput enzyme coupled fluorescence assay that has been employed to screen a library of diverse small molecules. With this approach, N-(4-chlorobenzyl)-3-(2-furyl)-1H-1,2,4-triazol-5-amine (N42FTA) was found to competitively inhibit (pIC50=5.7±0.2) the processing of 3-hydroxydecanoyl-NAC by P. aeruginosa FabA. N42FTA was shown to be potent in blocking crosslinking of Escherichia coli acyl carrier protein and FabA, a direct mimic of the biological process. The co-complex structure of N42FTA with P. aeruginosa FabA protein rationalises affinity and suggests future design opportunities. Employing NAC fatty acid mimics to develop further high-throughput assays for individual enzymes in the FASII pathway should aid in the discovery of new antimicrobials., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The expression and harvesting of proteins from insoluble inclusion bodies by solubilization and refolding is a technique commonly used in the production of recombinant proteins. Despite the importance of refolding, publications in the literature are essentially ad hoc reports consisting of a dazzling array of experimental protocols and a diverse collection of buffer cocktails. For the protein scientists, using this information to refold their protein of interest presents enormous challenges. Here, we describe some of the practical considerations in refolding and present several standard protocols. Further, we describe how refolding procedures can be designed and modified using the information in the REFOLD database (http://refold.med.monash.edu.au), a freely available, open repository for protocols describing the refolding and purification of recombinant proteins.

There is a pressing need for the archiving and curation of raw X-ray diffraction data. This information is critical for validation, methods development and improvement of archived structures. However, the relatively large size of these data sets has presented challenges for storage in a single worldwide repository such as the Protein Data Bank archive. This problem can be avoided by using a federated approach, where each institution utilizes its institutional repository for storage, with a discovery service overlaid. Institutional repositories are relatively stable and adequately funded, ensuring persistence. Here, a simple repository solution is described, utilizing Fedora open-source database software and data-annotation and deposition tools that can be deployed at any site cheaply and easily. Data sets and associated metadata from federated repositories are given a unique and persistent handle, providing a simple mechanism for search and retrieval via web interfaces. In addition to ensuring that valuable data is not lost, the provision of raw data has several uses for the crystallographic community. Most importantly, structure determination can only be truly repeated or verified when the raw data are available. Moreover, the availability of raw data is extremely useful for the development of improved methods of image analysis and data processing.

Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65 and GAD67). GAD67 is constitutively active and is responsible for basal GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is transiently activated in response to the demand for extra GABA in neurotransmission, and cycles between an active holo form and an inactive apo form. We have determined the crystal structures of N-terminal truncations of both GAD isoforms. The structure of GAD67 shows a tethered loop covering the active site, providing a catalytic environment that sustains GABA production. In contrast, the same catalytic loop is inherently mobile in GAD65. Kinetic studies suggest that mobility in the catalytic loop promotes a side reaction that results in cofactor release and GAD65 autoinactivation. These data reveal the molecular basis for regulation of GABA homeostasis.