Non-invasive assessment of steatohepatitis indicates increased risk of coronary artery disease.

INTRODUCTION: Fatty liver diseases (FLD), especially defined as metabolic dysfunction-associated FLD (MAFLD), is of growing importance for patients and health-care providers. Extrahepatic comorbidities, predominantly coronary artery disease (CAD), contribute to excess morbidity and mortality in FLD. Although the association of FLD and CAD is well known, underlying pathophysiological links are not fully understood. Non-invasive means of liver diagnostic enable a fast and thorough characterization of FLD. We therefore assessed the severity of FLD in a cohort of patients at risk of CAD. METHODS: Patients scheduled for coronary angiography were characterized by anthropometry, serum-based indices of liver fibrosis (NFS, FIB4), abdominal ultrasound and vibration controlled transient elastography (VCTE) including controlled attenuation parameter (CAP) and the Fibroscan-AST (FAST) score. Patients were stratified according to indication of therapeutic coronary intervention. RESULTS: 120 patients were recruited, MAFLD was found in 41%, while advanced fibrosis or cirrhosis were present in only 5%. Coronary vascular intervention was indicated in 42% (n = 50). Severity of steatosis assessed by CAP and risk of fibrosis defined by elevated liver stiffness (VCTE>8 kPa) and fibrosis indices were associated with the need for coronary intervention. FAST score, a marker of fibrotic steatohepatitis, was elevated in the intervention group (0.22 vs. 0.12, p<0.001). Multivariate regression analysis revealed FAST score as strongest predictor of CAD (OR 2.3 95%, CI 1.40-2.96). DISCUSSION: MAFLD is a frequent comorbidity in patients at CAD risk, but advanced liver disease has a low prevalence in patients undergoing elective coronary angiography. Therefore, a routine VCTE-based screening for FLD cannot be recommended in cardiac patients. The association of indicators of steatohepatitis with advanced CAD points to inflammatory processes as a conjoint mechanism of both diseases.

Risk of chronic pancreatitis in carriers of the c.180C>T (p.Gly60=) CTRC variant: case-control studies and meta-analysis.

Chymotrypsin C (CTRC) is a digestive serine protease produced by the pancreas that regulates intrapancreatic trypsin activity and provides a defensive mechanism against chronic pancreatitis (CP). CTRC exerts its protective effect by promoting degradation of trypsinogen, the precursor to trypsin. Loss-of-function missense and microdeletion variants of CTRC are found in around 4% of CP cases and increase disease risk by approximately 3-7-fold. In addition, a commonly occurring synonymous CTRC variant c.180C>T (p.Gly60=) was reported to increase CP risk in various cohorts but a global analysis of its impact has been lacking. Here, we analyzed the frequency and effect size of variant c.180C>T in Hungarian and pan-European cohorts, and performed meta-analysis of the new and published genetic association data. When allele frequency was considered, meta-analysis revealed an overall frequency of 14.2% in patients and 8.7% in controls (allelic odds ratio (OR) 2.18, 95% confidence interval (CI) 1.72-2.75). When genotypes were examined, c.180TT homozygosity was observed in 3.9% of CP patients and in 1.2% of controls, and c.180CT heterozygosity was present in 22.9% of CP patients and in 15.5% of controls. Relative to the c.180CC genotype, the genotypic OR values were 5.29 (95% CI 2.63-10.64), and 1.94 (95% CI 1.57-2.38), respectively, indicating stronger CP risk in homozygous carriers. Finally, we obtained preliminary evidence that the variant is associated with reduced CTRC mRNA levels in the pancreas. Taken together, the results indicate that CTRC variant c.180C>T is a clinically relevant risk factor, and should be considered when genetic etiology of CP is investigated.

Enhanced surface second harmonic generation in nanolaminates.

Second-harmonic generation (SHG) is a second-order nonlinear optical process that is not allowed in media with inversion symmetry. However, due to the broken symmetry at the surface, surface SHG still occurs, but is generally weak. We experimentally investigate the surface SHG in periodic stacks of alternating, subwavelength dielectric layers, which have a large number of surfaces, thus enhancing surface SHG considerably. To this end, multilayer stacks of SiO2/TiO2 were grown by Plasma Enhanced Atomic Layer Deposition (PEALD) on fused silica substrates. With this technique, individual layers of a thickness of less than 2 nm can be fabricated. We experimentally show that under large angles of incidence (> 20 degrees) there is substantial SHG, well beyond the level, which can be observed from simple interfaces. We perform this experiment for samples with different periods and thicknesses of SiO2/TiO2 and our results are in agreement with theoretical calculations.

Second harmonic generation under doubly resonant lattice plasmon excitation.

Second harmonic generation is enhanced at the surface lattice resonance in plasmonic nanoparticle arrays. We carried out a parametric investigation on two-dimensional lattices composed of gold nanobars where the centrosymmetry is broken at oblique incidence. We study the influence of the periodicity, the incidence angle and the direction of the linear input polarization on the second harmonic generation. Excitation of the surface lattice resonance either at the fundamental or second harmonic wavelength, achieved by varying the incidence angle, enhance the conversion efficiency. As a special case, we demonstrate that both the wavelengths can be simultaneously in resonance for a specific period of the lattice. In this double resonant case, maximum second harmonic power is achieved.

Endoscopic Bariatric Treatment with Duodenal-Jejunal Bypass Liner Improves Non-invasive Markers of Non-alcoholic Steatohepatitis.

PURPOSE: People with obesity often develop non-alcoholic fatty liver disease (NAFLD) and are at high risk of progression to non-alcoholic steatohepatitis (NASH). Few therapies are effective other than bariatric surgery. We therefore analyzed data from duodenal-jejunal bypass liner (DJBL) patients regarding steatosis, fibrosis, and NASH. METHODS: Consecutive DJBL patients with type 2 diabetes underwent standardized assessments up to device removal at 48 weeks. These included aspartate and alanine transaminase (AST, ALT), controlled attenuation parameter (CAP, for steatosis), and liver stiffness measurement (LSM, for fibrosis). The NAFLD fibrosis score (NFS), fibrosis-4 score (FIB4), and enhanced liver fibrosis (ELF) test were also used to assess fibrosis and the Fibroscan-AST (FAST) score to assess NASH. Mixed models were used and missing data were accounted for with multiple imputation. RESULTS: Thirty-two patients (18 female, mean age 55.1, mean BMI 40.2 kg/m2) were included. After 48 weeks, the change compared to baseline with 95% CI was a factor 0.74 (0.65 to 0.84) for AST, 0.63 (0.53 to 0.75) for ALT, and a difference of - 0.21 (- 0.28 to - 0.13) for FAST, all with p < 0.001. Fibrosis based on LSM, NFS, and ELF did not change whereas FIB4 exhibited slight improvement. Eight DJBL were explanted early due to device-related complications and eight complications led to hospitalization. CONCLUSIONS: One year of DJBL therapy is associated with relevant improvements in non-invasive markers of steatosis and NASH, but not fibrosis, and is accompanied by a substantial number of complications. Given the lack of alternatives, DJBL deserves further attention.

Quantum imaging with a photon counting camera.

Classical light sources emit a randomly-timed stream of individual photons, the spatial distribution of which can be detected with a camera to form an image. Quantum light sources, based on parametric down conversion, emit photons as correlated photon-pairs. The spatial correlations between the photons enables imaging systems where the preferential selection of photon-pairs allows for enhancements in the noise performance over what is possible using classical light sources. However, until now the technical challenge of measuring, and correlating both photons has led to system complexity. Here we show that a camera capable of resolving the number of individual photons in each pixel of the detector array can be used to record an image formed from these photon-pair events and hence achieve a greater contrast than possible using a classical light source. We achieve an enhancement in the ratio of two-photon events compared to one-photon events using spatially correlated SPDC light compared to uncorrelated illumination by a LED. These results indicate the potential advantages of using photon counting cameras in quantum imaging schemes and these advantages will further increase as the technology is developed. Operating in photon sparse regimes such systems have potential applications in low-light microscopy and covert imaging.

Enhancement of third harmonic generation induced by surface lattice resonances in plasmonic metasurfaces.

We investigate experimentally third harmonic generation (THG) from plasmonic metasurfaces consisting of two-dimensional rectangular lattices of centrosymmetric gold nanobars. By varying the incidence angle and the lattice period, we show how surface lattice resonances (SLRs) at the involved wavelengths are the major contributors in determining the magnitude of the nonlinear effects. A further boost on THG is observed when we excite together more than one SLR, either at the same or at different frequency. When such multiple resonances take place, interesting phenomena are observed, such as maximum THG enhancement for counter-propagating surface waves along the metasurface, and cascading effect emulating a third-order nonlinearity.

A study on the influence of ligand variation on formamidinate complexes of yttrium: new precursors for atomic layer deposition of yttrium oxide.

The synthesis and characterization of a series of closely related Y(III) compounds comprising the formamidinate ligands (RNCHNR) (R = alkyl) is reported, with the scope of using them as prospective precursors for atomic layer deposition (ALD) of yttrium oxide (Y2O3) thin films. The influence of the side chain variation on the thermal properties of the resulting complexes is studied and benchmarked by thermal analysis and vapor pressure measurements. Density functional theory (DFT) studies give theoretical insights into the reactivity of the compounds towards water, which was targeted as a co-reactant for the deposition of Y2O3via thermal ALD in the next step. Among the four complexes analyzed, tris(N,N'-di-tert-butyl-formamidinato)yttrium(III) [Y(tBu2-famd)3] 1 was found to possess enhanced thermal stability and was selected for Y2O3 ALD process development. A broad ALD window ranging from 200 °C to 325 °C was obtained, yielding films of high compositional quality. Furthermore, with a film density of (4.95 ± 0.05) g cm-1 close to the bulk value, polycrystalline fcc Y2O3 layers with a smooth topography resulted in promising dielectric properties when implemented in metal insulator semiconductor (MIS) capacitor structures.

QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.

Atomic layer deposition of dielectric Y2O3 thin films from a homoleptic yttrium formamidinate precursor and water.

We report the application of tris(N,N'-diisopropyl-formamidinato)yttrium(iii) [Y(DPfAMD)3] as a promising precursor in a water-assisted thermal atomic layer deposition (ALD) process for the fabrication of high quality Y2O3 thin films in a wide temperature range of 150 °C to 325 °C. This precursor exhibits distinct advantages such as improved chemical and thermal stability over the existing Y2O3 ALD precursors including the homoleptic and closely related yttrium tris-amidinate [Y(DPAMD)3] and tris-guanidinate [Y(DPDMG)3], leading to excellent thin film characteristics. Smooth, homogeneous, and polycrystalline (fcc) Y2O3 thin films were deposited at 300 °C with a growth rate of 1.36 Å per cycle. At this temperature, contamination levels of C and N were under the detectable limits of nuclear reaction analysis (NRA), while X-ray photoelectron spectroscopy (XPS) measurements confirmed the high purity and stoichiometry of the thin films. From the electrical characterization of metal-insulator-semiconductor (MIS) devices, a permittivity of 13.9 at 1 MHz could be obtained, while the electric breakdown field is in the range of 4.2 and 6.1 MV cm-1. Furthermore, an interface trap density of 1.25 × 1011 cm-2 and low leakage current density around 10-7 A cm-2 at 2 MV cm-1 are determined, which satisfies the requirements of gate oxides for complementary metal-oxide-semiconductor (CMOS) based applications.

Current NAFLD guidelines for risk stratification in diabetic patients have poor diagnostic discrimination.

Patients with type 2 diabetes (T2D) are at risk for non-alcoholic fatty liver disease (NAFLD) and associated complications. This study evaluated the performance of international (EASL-EASD-EASO) and national (DGVS) guidelines for NAFLD risk stratification. Patients with T2D prospectively underwent ultrasound, liver stiffness measurement (LSM) and serum-based fibrosis markers. Guideline-based risk classification and referral rates for different screening approaches were compared and the diagnostic properties of simplified algorithms, genetic markers and a new NASH surrogate (FAST score) were evaluated. NAFLD risk was present in 184 of 204 screened patients (age 64.2 ± 10.7 years; BMI 32.6 ± 7.6 kg/m2). EASL-EASD-EASO recommended specialist referral for 60-77% depending on the fibrosis score used, only 6% were classified as low risk. The DGVS algorithm required LSM for 76%; 25% were referred for specialised care. The sensitivities of the diagnostic pathways were 47-96%. A simplified referral strategy revealed a sensitivity/specificity of 46/88% for fibrosis risk. Application of the FAST score reduced the referral rate to 35%. This study (a) underlines the high prevalence of fibrosis risk in T2D, (b) demonstrates very high referral rates for in-depth hepatological work-up, and (c) indicates that simpler referral algorithms may produce comparably good results and could facilitate NAFLD screening.

Sequencing of the complex CTRB1-CTRB2 locus in chronic pancreatitis.

BACKGROUND: /Objectives: A recent Genome-wide Association Study (GWAS) in alcoholic chronic pancreatitis (ACP) identified a novel association with the CTRB1-CTRB2 (chymotrypsinogen B1, B2) locus, linked to a 16.6 kb inversion that was confirmed in non-alcoholic chronic pancreatitis (NACP). Moreover, recent findings on the function of CTRB1 and CTRB2 suggest a protective role in pancreatitis development. The aim of the present study was to investigate the CTRB1-CTRB2 locus for rare genetic variants associated with chronic pancreatitis (CP). METHODS: We analyzed 134 patients with ACP and 203 patients with NACP and compared them to up to 258 healthy controls. Genotyping was performed with polymerase chain reaction, followed by Sanger sequencing of all exons and the exon-intron-boundaries of CTRB1 and CTRB2. Finally, in silico analyses of the identified variants were conducted. RESULTS: None of the seven rare missense variants or the single 5'-UTR variant in CTRB1 and CTRB2 was associated with ACP or NACP. In silico analysis predicted that variant p. Trp5Leu in CTRB1 and variant c.-4C > T in CTRB2 might alter protein expression and variants p. Asp222His in CTRB1 and p. Ala247Thr in CTRB2 might affect protein function. However, all of these variants were also described in public databases. CONCLUSIONS: The present study did not reveal an association of rare variants in CTRB1 and CTRB2 with ACP or NACP. Although rare missense variants were almost exclusively found in patients, only four variants were predicted to affect protein expression or function. Thus, a major influence of rare variants in the CTRB1-CTRB2 locus on CP development is unlikely.

The quality of pain management in pancreatic cancer: A prospective multi-center study.

BACKGROUND/OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain management in PDAC is scarce. METHODS: This is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression. RESULTS: 139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23-9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05-6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09-9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05-0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05-0.89, p = 0.034) was associated with less undertreatment. CONCLUSIONS: The results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.

Serum levels of advanced glycation end products and their receptors sRAGE and Galectin-3 in chronic pancreatitis.

BACKGROUND: /Objectives: AGE and their receptors like RAGE and Galectin-3 can activate inflammatory pathways and have been associated with chronic inflammatory diseases. Several studies investigated the role of AGE, Galectin-3 and sRAGE in pancreatic diseases, whereas no comprehensive data for chronic pancreatitis (CP) are available. METHODS: Serum samples from CP patients without an active inflammatory process (85 ACP; 26 NACP patients) and 40 healthy controls were collected. Levels of AGE, sRAGE and Galectin-3 were measured by ELISA. To exclude potential influences of previously described RAGE SNPs on detected serum levels, we analyzed variants rs207128, rs207060, rs1800625, and rs1800624 by melting curve technique in 378 CP patients and 338 controls. RESULTS: AGE and Galectin-3 serum levels were significantly elevated in both ACP and NACP patients compared to controls (AGE: 56.61 ± 3.043 vs. 31.71 ± 2.308 ng/mL; p < 0.001; Galectin-3: 16.63 ± 0.6297 vs. 10.81 ± 0.4835 ng/mL; p < 0.001). In contrast, mean serum sRAGE levels were significantly reduced in CP patients compared to controls (sRAGE: 829.7 ± 37.10 vs. 1135 ± 55.74 ng/mL; p < 0.001). All results were consistent after correction for gender, age and diabetes mellitus. No genetic association with CP was found. CONCLUSIONS: Our extensive analysis demonstrated the importance of aging related pathways in the pathogenesis of CP. As the results were consistent in ACP and NACP, both entities most likely share common pathomechanisms. Most probably the involved pathways are a general hallmark of an inflammatory state in CP that is even present in symptom-free intervals.

Mean muscle attenuation correlates with severe acute pancreatitis unlike visceral adipose tissue and subcutaneous adipose tissue.

Background: Acute pancreatitis (AP) is a frequent disorder with considerable morbidity and mortality. Obesity has previously been reported to influence disease severity. Objective: The aim of this study was to investigate the association of adipose and muscle parameters with the severity grade of AP. Methods: In total 454 patients were recruited. The first contrast-enhanced computed tomography of each patient was reviewed for adipose and muscle tissue parameters at L3 level. Associations with disease severity were analysed through logistic regression analysis. The predictive capacity of the parameters was investigated using receiver operating characteristic (ROC) curves. Results: No distinct variation was found between the AP severity groups in either adipose tissue parameters (visceral adipose tissue and subcutaneous adipose tissue) or visceral muscle ratio. However, muscle mass and mean muscle attenuation differed significantly with p-values of 0.037 and 0.003 respectively. In multivariate analysis, low muscle attenuation was associated with severe AP with an odds ratio of 4.09 (95% confidence intervals: 1.61-10.36, p-value 0.003). No body parameter presented sufficient predictive capability in ROC-curve analysis. Conclusions: Our results demonstrate that a low muscle attenuation level is associated with an increased risk of severe AP. Future prospective studies will help identify the underlying mechanisms and characterise the influence of body composition parameters on AP.

Correction: Luminescent Nd2S3 thin films: a new chemical vapour deposition route towards rare-earth sulphides.

Correction for 'Luminescent Nd2S3 thin films: a new chemical vapour deposition route towards rare-earth sulphides' by Stefan Cwik et al., Dalton Trans., 2019, 48, 2926-2938.

Systemic inflammation contributes to impairment of quality of life in chronic pancreatitis.

Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1ß, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.

Endoscopic full-thickness transoral outlet reduction with semicircumferential endoscopic submucosal dissection.

BACKGROUND: Endoscopic full-thickness transoral outlet reduction (efTOR) is a therapeutic option to reduce a dilated gastrojejunal anastomosis (GJA) after Roux-en-Y gastric bypass (RYGB). Mucosal ablation with argon plasma coagulation (APC) is usually performed to achieve tissue adaptation. However, rupture of sutures before scarring can lead to recurrent dilatation of the GJA. Here, we describe efTOR with a semicircumferential endoscopic submucosal dissection (ESD-efTOR) as an alternative to APC-efTOR. METHODS: We enrolled 41 patients with comparable baseline characteristics (APC-efTOR 26; ESD-efTOR 15). The main objectives were reduction in the GJA diameter and in ruptured sutures. Technical success, complications, total weight loss (TWL), and percentage of total and excess weight loss (%TWL and %EWL) at 3 and 12 months, were assessed. RESULTS: ESD-efTOR resulted in significantly fewer ruptured sutures (20 % vs. 69 %; P = 0.004) and a greater reduction in the GJA (major 20 % vs. 0 %; minor 54 % vs. 37 %; no reduction 13 % vs. 58 %; P = 0.02) after 3 months. Technical efficacy, examination time, and rate of complications were comparable. CONCLUSIONS: ESD-efTOR resulted in a significantly greater reduction in the GJA diameter and a lower risk of ruptured sutures compared with APC-efTOR.

Author Correction: Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement.

In the original article, the affiliations were presented incorrectly. David Petroff is in fact the only author at affiliation 2. All other authors listed as being at affiliation 2 (Tina Weiße, Sebastian Beer, Franziska Gnatzy, Joachim Mössner, Michael Tröltzsch, Johannes Wiegand and Volker Keim) are in fact just at affiliation 1. These have now been corrected in the original article.

Predicting hepatic complications of allogeneic hematopoietic stem cell transplantation using liver stiffness measurement.

Allogeneic hematopoietic stem cell transplantation is the only curative option for a variety of diseases. Despite advances, it is associated with considerable morbidity and mortality, often involving liver complications. Liver disease can be characterized using ultrasound-based liver stiffness measurement. To assess its prognostic value, consecutive patients undergoing allogeneic hematopoietic stem cell transplantation were prospectively evaluated in a single-center study. Endpoints included liver event-free survival and all-cause mortality at 1 year. Competing risk and Cox-regression were used for analysis. We evaluated 106 patients (42 female, age 57) and observed 33 life-threatening events (14 died) including 16 liver complications at 100 days. At 1 year, 36 patients had died, 20 with disease relapse. The hazard ratios for liver-related complications at 100 days were 3.2 (95% CI: 1.8-14.6, p = 0.0022) and 4.4 (95% CI: 1.6-11.9, p = 0.0042) for elevated transient elastography (n = 11) and shear-wave velocity (n = 31), respectively. Results were analogous for all-cause mortality at 1 year. Prior stem cell therapy and elevated gamma glutamyltransferase were also associated with outcome. This demonstrates that elastography is a promising and viable tool for risk prediction and should be included in upcoming multi-center trials to establish new means of guiding treatment and prophylaxis.