RPS 2001 - Shining a spotlight on HCC and liver transplant

Author Block: Y. Xu, J. Liu, J. Zhou; Lanzhou City/CN
Purpose: Post-hepatectomy liver failure (PHLF) is a severe postoperative complication with a high incidence and mortality rate, particularly in patients with narrow-margin (NM). This study aims to predict PHLF in NM-hepatocellular carcinoma (HCC) using iodine map histogram analysis of non-tumorous hepatic parenchyma.
Methods or Background: A retrospective analysis was conducted on the clinical and imaging data of 107 patients with NM-HCC who underwent hepatectomy, divided into those with PHLF (n=45) and without PHLF (n=62). Histogram parameters of non-tumorous hepatic parenchyma were calculated from iodine map derived from the portal venous phase of spectral CT, including Min, Max, Mean, SD, Skewness, Kurtosis, Entropy, and percentiles (V10-V95), along with the future liver remnant volume (FLV) and standardized future residual liver volume ratio (SFLV%). Logistic regression analyse was used to identify independent predictors of PHLF, and a comprehensive model was developed. The performance of the new comprehensive model was assessed using ROC curve analysis and was compared with ALBI and MELD scores.
Results or Findings: Significant intergroup differences were observed in the iodine map histogram analysis of non-tumorous hepatic parenchyma for Skewness, Kurtosis, V50, V75, V90, V95, FLV, and SFLV% (P < 0.01 to P = 0.04). Multivariate logistic regression analysis revealed that V95, Kurtosis, and SFLV% were independent risk factors for predicting PHLF. The comprehensive model (ModelALL), developed by combining these independent risk factors, exhibited the highest predictive efficacy for PHLF, with an AUC of 0.77 (0.67-0.87), outperforming both the ALBI and MELD scores, which had AUCs of 0.70 (0.58-0.81) and 0.62 (0.49-0.74), respectively.
Conclusion: The model which combines the iodine map histogram parameters of non-tumorous hepatic parenchyma (V95 and Kurtosis) with SFLV%, aids in the preoperative prediction of PHLF in NM-HCC patients and outperforms conventional scoring systems.
Limitations: Not applicable
Funding for this study: This study has received funding by grants of Natural Science Foundation of China (82260361, 82371914), Lanzhou University Second Hospital Second Hospital “Cuiying Technology Innovation Plan” (CY2022-QN-A10), Lanzhou University Second Hospital "Cuiying Postgraduate Instructor Cultivation Program Project (CYDSPY202003) and Outstanding Young Talents and Backbone Talents Project of Gansu Provincial Health Industry Research Program (GSWSQN2023-04).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The present study was approved by our hospital ethics committee (No. 2022A-112) and performed according to the ethical guidelines of the 1975 Declaration of Helsinki.

Author Block: M. Mattone, F. Quintarelli, A. Napoli, C. Catalano; Rome/IT
Purpose: To evaluate the per-patient diagnostic performance of an abbreviated magnetic resonance protocol for hepatocellular carcinoma (HCC) surveillance in cirrhotic liver.
Methods or Background: Retrospective study including cirrhotic patients with HCC who are candidates for liver transplant enrolled in a surveillance program based on the use of MRI with hepatobiliary contrast agent. Two different sets of images for each patient are provided to two radiologists, who interpret the images independently, to simulate an abbreviated protocol. Interobserver variability was assessed using Cohen's kappa coefficient. A reference standard based on histologic examination or radiologic criteria (LIRADS at least equal to 4) was used to determine the diagnostic accuracy of each set of images.
Results or Findings: A total of 200 patients who underwent MRI for HCC surveillance were included in this study. One set of images consisted of the complete protocol (Set1) and one set of images consisted of T2WI with fat saturation, DWI and hepatobiliary sequences (Set2).The sensitivity, specificity, and accuracy of Set of readers 1 and 2 were 91.5%/90.5%, 88.6.4%/87.6% and 87.5%/85.0%, respectively. The sensitivities of the sets were not significantly different. Inter-reader agreement was substantial. Ascites, previous surgical and interventional radiology treatments, and small tumor size are associated with lower sensitivity.
Conclusion: An abbreviated MRI protocol including T2WI with fat saturation, DWI and hepatobiliary sequences is highly sensitive and can be a valid method for HCC surveillance in cirrhotic liver in patients candidates to liver transplant.
Limitations: Low number of readers
Funding for this study: No founds were used
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Not applicable

Author Block: D. Tore¹, C. Guarnaccia¹, A. Depaoli², C. Gaetani¹, M. Anna Pia¹, M. Visciano¹, M. Dini¹, F. Tandoi³, P. Fonio¹; ¹Turin/IT, ²Ivrea/IT, ³Bari/IT
Purpose: To evaluate the impact of CT-defined sarcopenia on survival in patients undergoing orthotropic liver transplant (OLT).
Methods or Background: Monocentric retrospective study. 440 patients (70 females, 370 males) who underwent OLT at our Institution within 01.01.2014 and 31.12.2019 with an abdomen CT scan acquired within six month before surgery were selected.
Skeletal muscles segmentations at the level of L3 and L4 were performed using open source software 3D Slicer using thresholds (-29 to 150 HU); psoas muscle area (PMA), skeletal muscle area (SMA), psoas muscle index (PMI) and skeletal muscle index (SMI) were calculated at both levels.
Optimal cut-offs to dichotomize between sarcopenic and non-sarcopenic patients divided in females and males were calculated using Youden's J statistic and ROC curves. Survival analysis was performed using Kaplan-Meyer's curves.
Results or Findings: Male patients classified as sarcopenic according to SMI criterion at L3 level presented an increased risk of mortality compared to non-sarcopenic with an hazard ratio of 1.63 (p=0.03). Male patients classified as sarcopenic according to SMA criterion at L3 level presented an increased risk of mortality compared to non-sarcopenic with an hazard ratio of 1.87 (p=0.008).
In the female group none of the sarcopenia definitions tested highlighted an increased risk of mortality with p values always >0.05.
Conclusion: PMI and SMA CT-defined sarcopenia at L3 level represented a negative prognostic factor for male patients survival after OLT. The use of such definitions of sarcopenia may identify more fragile subjects in this setting and improve care and, possibly outcomes, for such patients.
The absence of statistically significant differences between sarcopenic and non-sarcopenic female subjects may be due to the relatively limited sample size for such group of patients.
Limitations: Monocentric retrospective study.
Funding for this study: No funds were received for this work.
Has your study been approved by an ethics committee? Not applicable
Ethics committee - additional information: Not applicable, retrospective study

Author Block: X. Zhong; Guangzhou/CN
Purpose: To establish a Hepatic Functional Reserve (HFR) score based on liver stiffness (LS) and liver volume, and to explore its feasibility in evaluating preoperative hepatic reserve and predicting postoperative remnant hepatic function in hepatocellular carcinoma (HCC). Additionally, the study aimed to determine a safe future liver remnant (FLR) volume threshold to prevent post-hepatectomy liver failure (PHLF).
Methods or Background: The study included 345 HCC patients, with 265 in the training group and 80 in the test group. Preoperative LS was measured using two-dimensional shear-wave elastography. Total liver volume (TLV), tumor volume (TuV), and FLR were simulated using the IQQA system. The median LS of patients without significant fibrosis (7.6kPa) and standard liver volume (SLV) were used as normal references for liver quality and quantity. The preoperative HFR score (HFR-PRE) was calculated as 7.6/LS×(TLV-TuV)/SLV, and its correlation with liver function indicators was assessed. The postoperative HFR score (HFR-POST) was calculated as 7.6/LS×FLR/SLV, and its effectiveness in predicting PHLF was evaluated. The optimal FLR threshold was determined using the maximum Youden index.
Results or Findings: HFR-PRE showed significant correlation with preoperative liver function indicators such as Child-Pugh, MELD, ALBI scores, and ICG-R15 (all p<0.05). The AUC for HFR-POST in predicting PHLF was 0.864 in the training group and 0.857 in the test group. HFR-POST outperformed ALBI, MELD, and ICG-R15 scores (all p<0.05) in predicting PHLF. The minimum FLR/SLV threshold was 5/76*LS to prevent PHLF, with a sensitivity of 81.5% and specificity of 77.3%.
Conclusion: The HFR score effectively evaluates preoperative liver function and predicts PHLF in HCC patients. It also helps determine a safe residual liver volume to reduce the risk of PHLF.
Limitations: LS measurement acquired from one liver segment might not represent the quality of the whole liver.
Funding for this study: None
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study protocol received approval from the Institutional Review Board of The First Affiliated Hospital of Sun Yat-sen University (IRB approval number: [2019]046).

Author Block: A. Garg, J. Chowdhary, P. K. Sukhani, S. P. Joshi; Jaipur/IN
Purpose: To evaluate the accuracy of semi-automated CT volumetry (CTV) in estimating liver volume in potential living donor liver transplant (LDLT) donors, compared to the gold standard of intraoperative graft weight measurement.

Aim:
1. Inform transplant surgeons and radiologists about the reliability of semi-automated CTV in LDLT donor evaluation.
2. Highlight the potential benefits of using CTV in preoperative planning, improved donor selection and reduced surgical complications.
3. Discuss the implications of accurate volume assessment on LDLT outcomes and patient safety.
Methods or Background: Background:

Living Donor Liver Transplantation (LDLT) is a life-saving procedure for patients with end-stage liver disease. Accurate liver volume assessment is crucial in LDLT to ensure sufficient graft volume for recipient survival, prevent small-for-size graft syndrome and reduce donor morbidity and mortality.

Methods:
This retrospective study included 70 potential LDLT donors who underwent:
Semi-automated CTV using AW VolumeShare 7 on 128 slice - GE Healthcare, Optima.

Inclusion Criteria:
Adult LDLT donors (>18 years)

Exclusion Criteria:
Previous liver surgery/disease
Variant vascular/biliary anatomy, not allowing safe resection
Results or Findings: Primary Outcome:
Strong correlation (r = 0.92, p < 0.001) Sensitivity: 93.2% (95% CI: 85.1-97.5) Specificity: 90.5% (95% CI: 81.2-95.8)
Mean difference between CTV and intraoperative graft weight: 25.6 ± 57.8 grams
Secondary Outcomes:
Bland-Altman analysis showed good agreement between CTV and intraoperative graft weight, with 95% limits of agreement (-89.2 to 140.4 grams)
CTV accurately predicted graft weight within 10% of actual weight in 85% of cases (n = 70)
Conclusion: Semi-automated CTV demonstrates high accuracy and reliability in estimating liver volume in LDLT donors.
CTV accurately predicts graft weight with good agreement with intraoperative measurements thus helping in preoperative evaluation and surgical planning for LDLT.
Limitations: Single-center experience, Operator dependence, Intraoperative graft weight measurement variability
Funding for this study: No external funding
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Approved by the Institutional Ethics Committee, Mahatma Gandhi Medical College and Hospital, India

Author Block: S. Zhou, Y-C. Wang; Nanjing/CN
Purpose: We aimed to evaluate the diagnostic performance of the MRI-based Nonradiation LR-TRA v2024 and the value of incorporating ancillary features (AFs) on improving diagnostic precision.
Methods or Background: This retrospective study included patients with HCC who underwent local-regional therapy (LRT) followed by curative treatments between January 2017 and December 2022. Each treated lesion was evaluated according to the LR-TRA v2024, LR-TRA v2017, and modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, with pathologic response serving as the reference. The sensitivity, specificity, and accuracy of different treatment response criteria were compared using the McNemar test.
Results or Findings: A total of 231 patients (198 males; median age, 56 years; IQR, 50-63 years) with 306 treated lesions (249 incomplete pathologic necrosis) were evaluated. LR-TRA v2024-Viable (without AFs) exhibited comparable sensitivity and accuracy than LR-TRA v2017-Viable and mRECIST (sensitivity: 81.1% [95%CI: 75.8, 85.8], 79.5% [95% CI: 74.0, 84.4], and 80.3% [95% CI: 74.8, 85.1]; accuracy: 80.1% [95% CI: 75.1, 84.4], 79.4% [95% CI: 74.4, 83.8] and 75.2% [95% CI: 69.9, 79.9], respectively) for predicting incomplete pathologic tumor necrosis. Both LR-TRA v2024 (without AFs)-Viable and v2017-Viable exhibited significantly higher specificity than mRECIST (both P ≤ .001). LR-TRA v2024 (with AFs)-Viable incorporating ancillary features exhibited the highest sensitivity (85.9% [95% CI: 81.0, 90.0]) and accuracy (83.7% [95% CI: 79.0, 87.6]) among different treatment response criteria, and showed a statistic difference compared to LR-TRA v2017-Viable (both P = .006), without sacrificing specificity (73.7% [95% CI: 60.3, 84.5]).
Conclusion: LR-TRA v2024 (without AFs) demonstrates good diagnostic performance and ease of use. AFs significantly enhance diagnostic sensitivity and accuracy through category adjustments, without sacrificing specificity. LR-TRA v2024 combined with AFs is strongly recommended for use in clinical practice.
Limitations: Selection bias；only based on MRI
Funding for this study: This study has received funding by four National Natural Science Foundation of China (NSFC, No. 82271978, 92359304, 82330060, 823B2040); Zhongda Hospital Affiliated to Southeast University, Jiangsu Province High-Level Hospital Pairing Assistance Construction Funds (No. zdyyxy09).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by our institutional review board, and the requirement for written informed consent was waived for the retrospective data [No. 2022ZDSYLL410-P01].

Author Block: C. Van De Braak, F. Willemssen, F. Smits, R. De Man, A. Van Der Lugt, D. Bos, R. S. Dwarkasing; Rotterdam/NL
Purpose: Current guidelines recommend biannual US screening for patients with high risk of developing hepatocellular carcinoma (HCC). It was reported that the sensitivity of US for detecting early-stage HCC in these patients is merely 47%. Our aim is to validate a Short MRI Surveillance (SMS)-protocol in current surveillance patients and compare it to US in a prospective, multicentre study. Here, we present our first results on image quality.
Methods or Background: From November 2023, patients from the current HCC surveillance programme were invited to undergo paired US-MRI screening. The MRI was performed on 1.5/3.0-T systems using a dedicated 8-16 channel range body coil. The protocol consisted of T1W in-out phase, T2W with fat saturation and DWI. One radiologist evaluated the US- and MRI images, while a second and third radiologist solely evaluated the MRI images. US was reported according to the LIRADS-US surveillance classification. The current analyses were restricted to the first 50 study participants and revolve around descriptive analyses of the image quality and presence of lesions.
Results or Findings: The most common indication for the HCC surveillance programme was Hepatitis B (35/50, 70%), followed by cirrhosis (16/50, 32%). Image quality was rated as good in 64% of the US examinations and 94% of the MRI examinations. Based on US, a total of 16 lesions were found in eight patients, whilst on MRI this total was 109 lesions in 21 patients. Reported lesions were benign (e.g. cysts), except for one lesion that was noted on SMS, but undetected on US, which proved to be LIRADS-3 on subsequent contrast-enhanced MRI.
Conclusion: Our preliminary results show the potential of MRI for HCC surveillance, through better image quality and a higher detection rate of focal lesions.
Limitations: No limitations were identified.
Funding for this study: Funding was provided by a grant of the Dutch Cancer Society (grant number: 2021-2/13803).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: This study was approved by the institutional review board and written consent was obtained from all participants.

Author Block: F. Rizzetto, S. Tortora, E. Rondi, P. Carboni, M. M. B. Barabino, A. Vanzulli; Milan/IT
Purpose: Intraoperative ultrasound (IOUS) can identify signs of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) during surgery. We evaluated whether preoperative CT-derived radiomics can offer a less invasive alternative.
Methods or Background: All patients who underwent surgical resection with IOUS for histologically confirmed HCC lesions were retrospectively included. For those with available preoperative triphasic CT scans, HCC nodules were segmented across the arterial, venous, and delayed phases. Using PyRadiomics, radiomic features (RFs) were extracted from each segmentation. After dimensionality reduction, the selected RFs from each phase were used to train and validate various predictive models based on Support Vector Machine (SVM) algorithm, with histopathological confirmation of MVI as ground truth. The best performing model was tested on an independent dataset. Qualitative IOUS features were selected through multivariate regression and used to build a corresponding SVM model. Performance for detecting MVI was assessed using the area under the Receiver Operating Characteristic curve (AUC-ROC), with model comparisons made using the DeLong test.
Results or Findings: A total of 124 patients, each with a single HCC lesion, were selected, with preoperative CT scans acquired in nearly 30 different institutions. Of them, 86 patients were assigned to the training and validation dataset (80:20 split), while the remaining 38 served as independent test dataset. The most performing radiomic model included 10 RFs extracted from arterial phase. ROC analysis in the independent test yielded an AUC-ROC of 70% (95% confidence interval[CI]: 52-88%; p=0.030) for radiomic model and 70% (95%CI: 51-87%; p=0.020) for IOUS model, with no statistical difference (p=1.00).
Conclusion: Preoperative CT-derived radiomics demonstrated equivalent predictive performance to IOUS in assessing MVI in HCC, offering a non-invasive preoperative alternative for MVI risk stratification.
Limitations: Retrospective design is the main study limitation.
Funding for this study: No fundings were received for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Institutional Review Board approved the retrospective data collection in anonymous form

Author Block: Y. Shi, M. Li, Y. Pei, W. Li; Changsha/CN
Purpose: To evaluate the diagnostic performance of a CT-based radiomics model for predicting P53-mutated hepatocellular carcinoma (HCC).
Methods or Background: In this retrospective single-center study, patients with histopathologically confirmed HCC who underwent preoperative contrasted-enhanced CT examination and surgery between November 2017 and July 2022 were recruited. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using the gene sequencing. Radiological features were analyzed and clinical information were collected. Radscore was based on radiomics features extracted from the plain scan, arterial phase and portal vein phase images using the random forest method. Univariable and multivariable logistic regression analyses were used to identify variables that were significantly and independently associated with P53-mutated HCC, which were furtherly to develop a model. The model performance was evaluated with the area under the receiver operating characteristic curve (AUC), and the log-rank test was used to analyze recurrence-free survival (RFS).
Results or Findings: A total of 109 patients were enrolled, and assigned randomly (8:2) into training (87 patients) and validation sets (22 patients). The univariable analysis showed that the presence of enhancing capsule and intratumoral artery, and the radscore were significant risk factors for P53-mutated HCC. Further multivariable analysis identified that only the radscore was the independent predictor (odds ratio (OR), 3.05 [95% CI, 2.00–4.67], p<0.001) for P53-mutated HCC, and was used to develop the radiomics model. The model showed excellent performance in predicting P53-mutated HCC, with AUC of 0.899 (95% CI: 0.836-0.962) in the training set and 0.744 (95% CI: 0.523-0.964) in the validation set, Patients with predicted P53-mutated HCC has shorter RFS than those with predicted non-P53-mutated HCC (p=0.03).
Conclusion: A CT-based radiomics model could accurately predict P53-mutated HCC.
Limitations: A single-center retrospective study with a small sample.
Funding for this study: Funding: This work was supported by the National Natural Science Foundation of China (82071895, Wenzheng Li; 82271984, Wenzheng Li), the Natural Science Foundation of Hunan Province (2023JJ30903, Wenzheng Li; 2022JJ30950, Yigang Pei), the Natural Science Foundation for Youth of Hunan Province (2024JJ6665, Mengsi Li; 2023JJ40970, Wenguang Liu), the Youth Science Foundation of Xiangya Hospital (2023Q06, Mengsi Li) and Postdoctoral Fellowship Programof CPSF (GZC20242047, Mengsi Li).
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Institutional Review Board approval was abtained.

Author Block: U. Eryürük, M. N. Tasdemir, E. Cakir, S. Aslan; Giresun/TR
Purpose: To investigate the efficacy of the residual relative enhancement index (RREI), derived from gadoxetic acid-enhanced MRI, in estimating liver function in patients with hepatocellular carcinoma (HCC), by validating with the albumin-bilirubin (ALBI) grade.
Methods or Background: We retrospectively analyzed 41 patients with HCC who underwent gadoxetic acid-enhanced MRI. Enhancement ratio (ER) was calculated using the formula ER=(SI_HBP20-SI_pre)/SI_pre, where SI_HBP20 represents the signal intensity in the hepatobiliary phase and SI_pre represents the pre-contrast signal intensity. RREI was calculated as RREI=residual liver volume (RLV)×ER. Receiver operating characteristic curve analysis was performed to determine optimal cut-off values of RLV, ER, and RREI for predicting ALBI grades. Spearman's rank correlation was used to evaluate correlations between RLV, ER, RREI, and ALBI scores. Intraclass correlation coefficient (ICC) was used to assess intra-reader reliability and inter-reader agreement for RLV, ER, and RREI measurements.
Results or Findings: ROC analysis showed that the optimal RREI cut-off for predicting ALBI grade 1 was 680-698, and for ALBI grade 3 was 537-496, for reader 1 and reader 2, respectively. RREI demonstrated good performance in predicting ALBI grade 1, with accuracy of 85.3%-95.1%, sensitivity of 89.4%-94.7%, and specificity of 81.8%-95.4%. In differentiating ALBI grade 3 from other grades, RREI showed excellent performance, with accuracy of 92.7%-97.6%, sensitivity of 90.6%-96.9%, and specificity of 100%. Strong correlations were observed between RREI and ALBI scores, with correlation coefficients of -0.852 and -0.839 for both readers. Intra-reader and inter-reader reliability was almost perfect, with ICC values of 0.975 and 0.937, respectively.
Conclusion: RREI exhibited a strong correlation with ALBI scores for assessing liver function in HCC patients and showed good accuracy in predicting ALBI grades, indicating its potential as a reliable radiological tool for evaluating liver function.
Limitations: This was a retrospective study.
Funding for this study: None.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: The study was approved by the local ethics commitee.

Author Block: J. Kittinger, T. Müllner-Bucsics, L. Hartl, L. Reider, F. Wolf, M. Trauner, M. Mandorfer, T. Reiberger, K. Lampichler; Vienna/AT
Purpose: Transjugular intrahepatic portosystemic shunt (TIPS) is used to treat complications of portal hypertension in patients with cirrhosis. Sarcopenia in cirrhosis has been linked to worse patient outcomes but may improve after TIPS. We aimed to evaluate the prevalence of sarcopenia in patients undergoing TIPS and its evolution after TIPS.
Methods or Background: Retrospective analysis of the Vienna TIPS cohort from 01/2004 to 03/2022. Transversal psoas muscle thickness (TPMT) was evaluated on cross-sectional abdominal imaging both (i) prior to TIPS (time interval < 3 months) and (ii) at follow-up time points (FU 1: 3-18 months; FU 2 > 18 months) – by two independent radiologists. Sarcopenia was defined by previously published height-corrected TPMT cut-offs at the level of L3 (men < 12mm/m; women < 8mm/m).
Results or Findings: 199 patients were included (mean age 55.7±11 years, 69.3% male; median MELD: 11 (9-18) ; history of variceal bleeding 33.2% and ascites 79.9%). FU imaging was available in 70 patients (FU 1) and 57 patients (FU 2), respectively. Interrater reliability of psoas muscle measurements was excellent (κ=0.985). Sarcopenia was highly prevalent in patients undergoing TIPS (42.7%, 85/199). 4/45 (8.9%) of non-sarcopenic patients at baseline developed sarcopenia after TIPS implantation at FU 1 and 5/35 (14.3%) at FU 2, respectively. Transplant-free survival (TFS) of patients without sarcopenia was favourable (median: 59 months, IQR: 15 months – ∞), while mortality was high among patients with sarcopenia at baseline (TFS: median 21, IQR 1.8 – 106 months; p < 0.001). Resolution of sarcopenia was linked to a significant survival benefit (HR 0.121; p<0.001; adjusted to age and MELD score).
Conclusion: Sarcopenia is prevalent in TIPS patients and linked to worse outcome.
Limitations: CT-based diagnosis of sarcopenia without functional testing.
Funding for this study: No funding was provided for this study.
Has your study been approved by an ethics committee? Yes
Ethics committee - additional information: Approval of local ethics committee (Medical University of Vienna) was obtained: EK 1760/2014, 14-264-VK, EK 1943/2017.