Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma-Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation.

BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

Portal hypertension in patients with hepatocellular carcinoma and immunotherapy: prognostic relevance of CT-morphologic estimates.

BACKGROUND: Clinically significant portal hypertension (CSPH) has been identified as an important prognostic factor in patients with hepatocellular carcinoma (HCC) undergoing curative treatment. This study aimed to assess PH estimates as prognostic factors in patients with HCC treated with immunotherapy. METHODS: All patients with HCC treated with an immunotherapeutic agent in first or subsequent lines at our tertiary care center between 2016 and 2021 were included (n = 50). CSPH was diagnosed using the established PH score for non-invasive PH estimation in pre-treatment CT data (cut-off ≥ 4). Influence of PH on overall survival (OS) and progression-free survival (PFS) was assessed in uni- and multivariable analyses. RESULTS: Based on the PH score, 26 patients (52.0%) were considered to have CSPH. After treatment initiation, patients with CSPH had a significantly impaired median OS (4.1 vs 33.3 months, p < 0.001) and a significantly impaired median PFS (2.7 vs 5.3 months, p = 0.02). In multivariable Cox regression, CSPH remained significantly associated with survival (HR 2.9, p = 0.015) when adjusted for established risk factors. CONCLUSIONS: Non-invasive assessment of CSPH using routine CT data yielded an independent prognostic factor in patients with HCC and immunotherapy. Therefore, it might function as an additional imaging biomarker to detect high-risk patients with poor survival and possibly for treatment decision making.

Guiding Attention via a Cognitive Aid During a Simulated In-Hospital Cardiac Arrest Scenario: A Salience Effort Expectancy Value Model Analysis.

OBJECTIVE: To investigate the effect of a cognitive aid on the visual attention distribution of the operator using the Salience Effort Expectancy Value (SEEV) model. BACKGROUND: Cognitive aids aim to support an operator during the execution of a task. The effect of cognitive aids on performance is frequently evaluated but whether a cognitive aid improved, for example, attention distribution has not been considered. METHOD: We built the Expectancy Value (EV) model version which can be considered to indicate optimal attention distribution for a given event. We analyzed the eye tracking data of emergency physicians while using a cognitive aid application versus no application during a simulated in-hospital cardiac arrest scenario. RESULTS: The EV model could fit the attention distribution in such a simulated emergency situation. Partially supporting our hypothesis, the cognitive aid application group showed a significantly better EV model fit than the no application group in the first phases of the event, but a worse fit in the last phase. CONCLUSION: We demonstrated that a cognitive aid affected attention distribution and that the SEEV model provides the means of capturing these effects. We suggest that the aid supported and improved visual attention distribution in the stressful first phases of a cardiopulmonary resuscitation but may have focused attention on objects that are relevant for lower priority goals in the last phase. APPLICATION: The SEEV model can provide insights into expected and unexpected effects of cognitive aids on visual attention distribution and may help to design better artifacts.

Left atrial strain correlates with severity of cardiac involvement in Anderson-Fabry disease.

OBJECTIVES: Cardiac involvement in Anderson-Fabry disease (AFD) results in myocardial lipid depositions. An early diagnosis can maximize therapeutic benefit. Thus, this study aims to investigate the potential of cardiac MRI (CMR) based parameters of left atrial (LA) function and strain to detect early stages of AFD. METHODS: Patients (n = 58, age 40 (29-51) years, 31 female) with genetically proven AFD had undergone CMR including left ventricular (LV) volumetry, mass index (LVMi), T1, and late gadolinium enhancement, complemented by LA and LV strain measurements and atrial emptying fractions. Patients were stratified into three disease phases and compared to age and sex-matched healthy controls (HC, n = 58, age 41 [26-56] years, 31 female). RESULTS: A total of 19 early-, 20 intermediate-, and 19 advanced-phase patients were included. LV and LA reservoir strain was significantly impaired in all AFD phases, including early disease (both p < 0.001). In contrast, LA volumetry, T1, and LVMi showed no significant differences between the early phase and HC (p > 0.05). In the intermediate phase, LVMi and T1 demonstrated significant differences. In advanced phase, all parameters except active emptying fractions differed significantly from HC. ROC curve analyses of early disease phases revealed superior diagnostic confidence for the LA reservoir strain (AUC 0.88, sensitivity 89%, specificity 75%) over the LV strain (AUC 0.82). CONCLUSIONS: LA reservoir strain showed impairment in early AFD and significantly correlated with disease severity. The novel approach performed better in identifying early disease than the established approach using LVMi and T1. Further studies are needed to evaluate whether these results justify earlier initiation of therapy and help minimize cardiac complications. KEY POINTS: • Parameters of left atrial function and deformation showed impairments in the early stages of Anderson-Fabry disease and correlated significantly with the severity of Anderson-Fabry disease. • Left atrial reservoir strain performed superior to ventricular strain in detecting early myocardial involvement in Anderson-Fabry disease and improved diagnostic accuracies of approaches already using ventricular strain. • Further studies are needed to evaluate whether earlier initiation of enzyme replacement therapy based on these results can help minimize cardiac complications from Anderson-Fabry disease.

Radiomics-Based Prediction of Future Portal Vein Tumor Infiltration in Patients with HCC-A Proof-of-Concept Study.

Portal vein infiltration (PVI) is a typical complication of HCC. Once diagnosed, it leads to classification as BCLC C with an enormous impact on patient management, as systemic therapies are henceforth recommended. Our aim was to investigate whether radiomics analysis using imaging at initial diagnosis can predict the occurrence of PVI in the course of disease. Between 2008 and 2018, we retrospectively identified 44 patients with HCC and an in-house, multiphase CT scan at initial diagnosis who presented without CT-detectable PVI but developed it in the course of disease. Accounting for size and number of lesions, growth type, arterial enhancement pattern, Child-Pugh stage, AFP levels, and subsequent therapy, we matched 44 patients with HCC who did not develop PVI to those developing PVI in the course of disease (follow-up ended December 2021). After segmentation of the tumor at initial diagnosis and texture analysis, we used LASSO regression to find radiomics features suitable for PVI detection in this matched set. Using an 80:20 split between training and holdout validation dataset, 17 radiomics features remained in the fitted model. Applying the model to the holdout validation dataset, sensitivity to detect occurrence of PVI was 0.78 and specificity was 0.78. Radiomics feature extraction had the ability to detect aggressive HCC morphology likely to result in future PVI. An additional radiomics evaluation at initial diagnosis might be a useful tool to identify patients with HCC at risk for PVI during follow-up benefiting from a closer surveillance.

The prognostic role of early tumor shrinkage in patients with hepatocellular carcinoma undergoing immunotherapy.

BACKGROUND: Early tumor shrinkage (ETS) has been identified as a promising imaging biomarker for patients undergoing immunotherapy for several cancer entities. This study aimed to validate the potential of ETS as an imaging biomarker for patients undergoing immunotherapy for hepatocellular carcinoma (HCC). METHODS: We screened all patients with HCC that received immunotherapy as the first or subsequent line of treatment at our tertiary care center between 2016 and 2021. ETS was defined as the reduction in the sum of the sizes of target lesions, between the initial imaging and the first follow-up. The ETS was compared to the radiologic response, according to the modified response evaluation criteria in solid tumors (mRECIST). Furthermore, we evaluated the influence of ETS on overall survival (OS), progression-free survival (PFS), and the alpha-fetoprotein (AFP) response. RESULTS: The final analysis included 39 patients with available cross-sectional imaging acquired at the initiation of immunotherapy (baseline) and after 8-14 weeks. The median ETS was 5.4%. ETS was significantly correlated with the response according to mRECIST and with the AFP response. Patients with an ETS ≥10% had significantly longer survival times after the first follow-up, compared to patients with < 10% ETS (15.1 months vs. 4.0 months, p = 0.008). Additionally, patients with both an ETS ≥10% and disease control, according to mRECIST, also had significantly prolonged PFS times after the initial follow-up (23.6 months vs. 2.4 months, p < 0.001). CONCLUSION: ETS was strongly associated with survival outcomes in patients with HCC undergoing immunotherapy. Thus, ETS is a readily assessable imaging biomarker that showed potential for facilitating a timely identification of patients with HCC that might benefit from immunotherapy.

Baseline Splenic Volume Outweighs Immuno-Modulated Size Changes with Regard to Survival Outcome in Patients with Hepatocellular Carcinoma under Immunotherapy.

Background: An association between immunotherapy and an increase in splenic volume (SV) has been described for various types of cancer. SV is also highly predictive of overall survival (OS) in patients with hepatocellular carcinoma (HCC). We evaluated SV and its changes with regard to their prognostic influence in patients with HCC undergoing immunotherapy. Methods: All patients with HCC who received immunotherapy in first or subsequent lines at our tertiary care center between 2016 and 2021 were screened for eligibility. SV was assessed at baseline and follow-up using an AI-based tool for spleen segmentation. Patients were dichotomized into high and low SV based on the median value. Results: Fifty patients were included in the analysis. The median SV prior to treatment was 532 mL. The median OS of patients with high and low SV was 5.1 months and 18.1 months, respectively (p = 0.01). An increase in SV between treatment initiation and the first follow-up was observed in 28/37 (75.7%) patients with follow-up imaging available. This increase in itself was not prognostic for median OS (7.0 vs. 8.5 months, p = 0.73). However, patients with high absolute SV at the first follow-up continued to have impaired survival (4.0 months vs. 30.7 months, p = 0.004). Conclusion: High SV prior to and during treatment was a significant prognostic factor for impaired outcome. Although a large proportion of patients showed an SV increase after the initiation of immunotherapy, this additional immuno-modulated SV change was negligible compared to long-standing changes in the splanchnic circulation in patients with HCC.

Fully automated AI-based splenic segmentation for predicting survival and estimating the risk of hepatic decompensation in TACE patients with HCC.

OBJECTIVES: Splenic volume (SV) was proposed as a relevant prognostic factor for patients with hepatocellular carcinoma (HCC). We trained a deep-learning algorithm to fully automatically assess SV based on computed tomography (CT) scans. Then, we investigated SV as a prognostic factor for patients with HCC undergoing transarterial chemoembolization (TACE). METHODS: This retrospective study included 327 treatment-naïve patients with HCC undergoing initial TACE at our tertiary care center between 2010 and 2020. A convolutional neural network was trained and validated on the first 100 consecutive cases for spleen segmentation. Then, we used the algorithm to evaluate SV in all 327 patients. Subsequently, we evaluated correlations between SV and survival as well as the risk of hepatic decompensation during TACE. RESULTS: The algorithm showed Sørensen Dice Scores of 0.96 during both training and validation. In the remaining 227 patients assessed with the algorithm, spleen segmentation was visually approved in 223 patients (98.2%) and failed in four patients (1.8%), which required manual re-assessments. Mean SV was 551 ml. Survival was significantly lower in patients with high SV (10.9 months), compared to low SV (22.0 months, p = 0.001). In contrast, overall survival was not significantly predicted by axial and craniocaudal spleen diameter. Furthermore, patients with a hepatic decompensation after TACE had significantly higher SV (p < 0.001). CONCLUSION: Automated SV assessments showed superior survival predictions in patients with HCC undergoing TACE compared to two-dimensional spleen size estimates and identified patients at risk of hepatic decompensation. Thus, SV could serve as an automatically available, currently underappreciated imaging biomarker. KEY POINTS: • Splenic volume is a relevant prognostic factor for prediction of survival in patients with HCC undergoing TACE, and should be preferred over two-dimensional surrogates for splenic size. • Besides overall survival, progression-free survival and hepatic decompensation were significantly associated with splenic volume, making splenic volume a currently underappreciated prognostic factor prior to TACE. • Splenic volume can be fully automatically assessed using deep-learning methods; thus, it is a promising imaging biomarker easily integrable into daily radiological routine.

Tumor Burden in Patients With Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Head-to-Head Comparison of Current Scoring Systems.

Objectives: Recently, several scoring systems for prognosis prediction based on tumor burden have been promoted for patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). This multicenter study aimed to perform the first head-to-head comparison of three scoring systems. Methods: We retrospectively enrolled 849 treatment-naïve patients with HCC undergoing TACE at six tertiary care centers between 2010 and 2020. The tumor burden score (TBS), the Six-and-Twelve score (SAT), and the Seven-Eleven criteria (SEC) were calculated based on the maximum lesion size and the number of tumor nodes. All scores were compared in univariate and multivariate regression analyses, adjusted for established risk factors. Results: The median overall survival (OS) times were 33.0, 18.3, and 12.8 months for patients with low, medium, and high TBS, respectively (p<0.001). The median OS times were 30.0, 16.9, and 10.2 months for patients with low, medium, and high SAT, respectively (p<0.001). The median OS times were 27.0, 16.7, and 10.5 for patients with low, medium, and high SEC, respectively (p<0.001). In a multivariate analysis, only the SAT remained an independent prognostic factor. The C-Indexes were 0.54 for the TBS, 0.59 for the SAT, and 0.58 for the SEC. Conclusion: In a direct head-to-head comparison, the SAT was superior to the TBS and SEC in survival stratification and predictive ability. Therefore, the SAT can be considered when estimating the tumor burden. However, all three scores showed only moderate predictive power. Therefore, tumor burden should only be one component among many in treatment decision making.

Quantitative washout in patients with hepatocellular carcinoma undergoing TACE: an imaging biomarker for predicting prognosis?

BACKGROUND: The delayed percentage attenuation ratio (DPAR) was recently identified as a novel predictor of an early complete response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). In this study, we aimed to validate the role of DPAR as a predictive biomarker for short-, mid-, and long-term outcomes after TACE. METHODS: We retrospectively reviewed laboratory and imaging data for 103 treatment-naïve patients undergoing initial TACE treatment at our tertiary care center between January 2016 and November 2020. DPAR and other washin and washout indices were quantified in the triphasic computed tomography performed before the initial TACE. The correlation of DPAR and radiologic response was investigated. Furthermore, the influence of DPAR on the 6-, 12-, 18-, and 24-month survival rates and the median overall survival (OS) was compared to other established washout indices and estimates of tumor burden and remnant liver function. RESULTS: The DPAR was significantly of the target lesions (TLs) with objective response to TACE after the initial TACE session was significantly higher compared to patients with stable disease (SD) or progressive disease (PD) (125 (IQR 118-134) vs 110 (IQR 103-116), p < 0.001). Furthermore, the DPAR was significantly higher in patients who survived the first 6 months after TACE (122 vs. 115, p = 0.04). In addition, the number of patients with a DPAR > 120 was significantly higher in this group (n = 38 vs. n = 8; p = 0.03). However, no significant differences were observed in the 12-, 18-, and 24-month survival rates after the initial TACE. Regarding the median OS, no significant difference was observed for patients with a high DPAR compared to those with a low DPAR (18.7 months vs. 12.7 months, p = 0.260). CONCLUSIONS: Our results confirm DPAR as the most relevant washout index for predicting the short-term outcome of patients with HCC undergoing TACE. However, DPAR and the other washout indices were not predictive of mid- and long-term outcomes.

Prevalence and clinical significance of clinically evident portal hypertension in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BACKGROUND: Clinically evident portal hypertension (CEPH) was previously identified as a prognostic factor for patients with hepatocellular carcinoma (HCC). However, little is known about the prognostic influence of CEPH on the long-term outcome of patients with HCC undergoing transarterial chemoembolization (TACE), particularly in Western populations. OBJECTIVES: This study investigated the prevalence and prognostic influence of CEPH in a Western population of patients with HCC undergoing TACE. METHODS: This retrospective study included 349 treatment-naïve patients that received initial TACE treatment at our tertiary care center between January 2010 and November 2020. CEPH was defined as a combination of ascites, esophageal/gastric varices, splenomegaly and a low platelet count. We assessed the influence of CEPH and its defining factors on median overall survival (OS) in HCC patients. We compared the effects of CEPH to those of well-known prognostic factors. RESULTS: Of the 349 patients included, 304 (87.1%) patients had liver cirrhosis. CEPH was present in 241 (69.1%) patients. The median OS times were 10.6 months for patients with CEPH and 17.1 months for patients without CEPH (log rank p = 0.036). Median OS without a present surrogate was 17.1 months, while patients with one respectively more than two present CEPH surrogates had a median OS of 10.8 and 9.4 months (log rank p = 0.053). In multivariate analysis, CEPH was no significant risk factor for OS (p = 0.190). Of the CEPH-defining factors, only ascites reached significance in a univariate analysis. CONCLUSION: CEPH was present in more than two thirds of the patients with HCC undergoing TACE in our cohort of Western patients. Patients with CEPH had a significantly impaired survival in univariate analysis. However, no significance was reached in multivariate analysis. Thus, when TACE treatment is deemed oncologically reasonable, patients should not be excluded from TACE treatment due to the presence of surrogates of portal hypertension alone.

Commercial AI solutions in detecting COVID-19 pneumonia in chest CT: not yet ready for clinical implementation?

OBJECTIVES: In response to the COVID-19 pandemic, many researchers have developed artificial intelligence (AI) tools to differentiate COVID-19 pneumonia from other conditions in chest CT. However, in many cases, performance has not been clinically validated. The aim of this study was to evaluate the performance of commercial AI solutions in differentiating COVID-19 pneumonia from other lung conditions. METHODS: Four commercial AI solutions were evaluated on a dual-center clinical dataset consisting of 500 CT studies; COVID-19 pneumonia was microbiologically proven in 50 of these. Sensitivity, specificity, positive and negative predictive values, and AUC were calculated. In a subgroup analysis, the performance of the AI solutions in differentiating COVID-19 pneumonia from other conditions was evaluated in CT studies with ground-glass opacities (GGOs). RESULTS: Sensitivity and specificity ranges were 62-96% and 31-80%, respectively. Negative and positive predictive values ranged between 82-99% and 19-25%, respectively. AUC was in the range 0.54-0.79. In CT studies with GGO, sensitivity remained unchanged. However, specificity was lower, and ranged between 15 and 53%. AUC for studies with GGO was in the range 0.54-0.69. CONCLUSIONS: This study highlights the variable specificity and low positive predictive value of AI solutions in diagnosing COVID-19 pneumonia in chest CT. However, one solution yielded acceptable values for sensitivity. Thus, with further improvement, commercial AI solutions currently under development have the potential to be integrated as alert tools in clinical routine workflow. Randomized trials are needed to assess the true benefits and also potential harms of the use of AI in image analysis. KEY POINTS: • Commercial AI solutions achieved a sensitivity and specificity ranging from 62 to 96% and from 31 to 80%, respectively, in identifying patients suspicious for COVID-19 in a clinical dataset. • Sensitivity remained within the same range, while specificity was even lower in subgroup analysis of CT studies with ground-glass opacities, and interrater agreement between the commercial AI solutions was minimal to nonexistent. • Thus, commercial AI solutions have the potential to be integrated as alert tools for the detection of patients with lung changes suspicious for COVID-19 pneumonia in a clinical routine workflow, if further improvement is made.

Immunonutritive Scoring for Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization: Evaluation of the CALLY Index.

The novel CRP-albumin-lymphocyte (CALLY) index is an improved immunonutritive scoring system, based on serum C-reactive protein (CRP), serum albumin, and the lymphocyte count. It has shown promise as a prognostic index for patients with hepatocellular carcinoma (HCC) undergoing resections. This study evaluated the prognostic ability of the CALLY index for patients with HCC undergoing transarterial chemoembolization (TACE). We retrospectively identified 280 treatment-naïve patients with HCC that underwent an initial TACE at our institution, between 2010 and 2020. We compared the CALLY index to established risk factors in univariate and multivariate regression analyses for associations with median overall survival (OS). A low CALLY score was associated with low median OS (low vs. high CALLY: 9.0 vs. 24.0 months, p < 0.001). In the multivariate analysis, the CALLY index remained an independent prognostic predictor (p = 0.008). Furthermore, all factors of the CALLY index reached significance in univariate and in-depth multivariate analyses. However, the concordance index (C-index) of the CALLY index (0.60) was similar to the C-indices of established immunonutritive and inflammation scoring systems (range: 0.54 to 0.63). In conclusion, the CALLY index showed promise as a stratification tool for patients with HCC undergoing TACE. Notably, the CALLY index was not superior to other immunonutritive and inflammation scoring systems in predicting the median OS. Thus, future studies should re-evaluate the mathematical calculation of the index, particularly the contributions of individual parameters.

Online teaching in radiology as a pilot model for modernizing medical education: results of an international study in cooperation with the ESR.

BACKGROUND: Due to the outbreak of the coronavirus disease 2019 (COVID-19), it proved necessary to rapidly change medical education from on-site to online teaching. Thus, medical educators were forced to rethink the purpose of teaching and the best form of transmission of knowledge. In cooperation with the European Society of Radiology (ESR), we investigated the attitudes of radiologists in Europe and North America toward innovative online teaching concepts. METHODS: In total, 224 radiologists from 31 different countries participated in our cross-sectional, web-based survey study. On a 7-point Likert scale, participants had to answer 27 questions about the online teaching situation before/during the pandemic, technical and social aspects of online teaching and the future role of online teaching in radiology. RESULTS: An overwhelming majority stated that radiology is particularly well-suited for online teaching (91%), that online teaching should play a more prominent role after the pandemic (73%) and that lecturers should be familiar with online teaching techniques (89%). Difficulties include a higher workload in preparing online courses (59%), issues with motivating students to follow online courses (56%) and the risk of social isolation (71%). Before the pandemic, only 12% of teaching was provided online; for the future, our participants deemed a proportion of approximately 50% online teaching appropriate. CONCLUSION: Our participants are open-minded about online teaching in radiology. As the best way of transferring knowledge in medical education is still unclear, online teaching offers potential for innovation in radiology education. To support online teaching development, a structured, framework-based "online curriculum" should be established.

Structured reporting of CT scans of patients with trauma leads to faster, more detailed diagnoses: An experimental study.

PURPOSE: This study aimed to determine whether structured reports (SRs) reduce reporting time and/or increase the level of detail for trauma CT scans compared to free-text reports (FTRs). METHOD: Eight radiology residents used SRs and FTRs to describe 14 whole-body CT scans of patients with polytrauma in a simulated emergency room setting. Each resident created both a brief report and a detailed report for each case using one of the two formats. We measured the time to complete the detailed reports and established a scoring system to objectively measure report completeness and the level of detail. Scoring sheets divided the CT findings into main and secondary criteria. Finally, the radiological residents completed a questionnaire on their opinions of the SRs and FTRs. RESULTS: The detailed SRs were completed significantly faster than the detailed FTRs (mean 19 min vs. 25 min; p < 0.001). The maximum allowance of 25 min was used for 25% of SRs and 59% of FTRs. For brief reports, the SRs contained more secondary criteria than the FTRs (p = 0.001), but no significant differences were detected in main criteria. Study participants rated their own SRs as significantly more time-efficient, concise, and clearly structured compared to the FTRs. However, SRs and FTRs were rated similarly for quality, accuracy, and completeness. CONCLUSION: We found that SRs for whole-body trauma CT add clinical value compared to FTRs because SRs reduce reporting time and increase the level of detail for trauma CT scans.

How COVID-19 kick-started online learning in medical education-The DigiMed study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students' attitudes to online learning to provide a broad scientific basis to guide future development of medical education. METHODS: Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-point Likert scale, participants rated the online learning situation during the pandemic at their medical schools, technical and social aspects, and the current and future role of online learning in medical education. RESULTS: The majority of medical schools managed the rapid switch to online learning (78%) and most students were satisfied with the quantity (67%) and quality (62%) of the courses. Online learning provided greater flexibility (84%) and led to unchanged or even higher attendance of courses (70%). Possible downsides included motivational problems (42%), insufficient possibilities for interaction with fellow students (67%) and thus the risk of social isolation (64%). The vast majority felt comfortable using the software solutions (80%). Most were convinced that medical education lags behind current capabilities regarding online learning (78%) and estimated the proportion of online learning before the pandemic at only 14%. In order to improve the current curriculum, they wish for a more balanced ratio with at least 40% of online teaching compared to on-site teaching. CONCLUSION: This study demonstrates the positive attitude of medical students towards online learning. Furthermore, it reveals a considerable discrepancy between what students demand and what the curriculum offers. Thus, the COVID-19 pandemic might be the long-awaited catalyst for a new "online era" in medical education.

Refining Prognosis in Chemoembolization for Hepatocellular Carcinoma: Immunonutrition and Liver Function.

A combination of albumin-bilirubin (ALBI) grading and the Prognostic Nutritional Index (PNI) was identified recently as a highly predictive tool for patients with hepatocellular carcinoma (HCC) undergoing tumor ablation. The present study evaluated this combination in patients undergoing transarterial chemoembolization (TACE). Between 2010 and 2020, 280 treatment-naïve patients were retrospectively identified. The influence of ALBI grade, PNI and the novel ALBI-PNI on the median overall survival (OS) was assessed. In the next step, the prognostic ability of the combined approach was compared to established scoring systems. Both ALBI grade 2-3 and a low PNI were highly predictive for median OS (ALBI grade 1-3: 39.0 vs. 16.3 vs. 5.4 months, p < 0.001; high vs. low PNI: 21.4 vs. 7.5, p < 0.001). The combination of both resulted in a median OS of 39.0, 20.1, 10.3, and 5.4 months (p < 0.001). With a Concordance Index (C-Index) of 0.69, ALBI-PNI outperformed each individual score (ALBI 0.65, PNI 0.64) and was also better than BCLC, HAP, mHAP-II, and the Six-and-Twelve score (C-Indices 0.66, 0.60, 0.59, and 0.55). Thus, the easy-to-calculate ALBI-PNI may be a promising stratification tool for patients with HCC undergoing TACE, reflecting both immunonutritive status and liver function.

Pneumatosis intestinalis and porto-mesenteric venous gas: a multicenter study.

BACKGROUND: Estimating the prognosis of patients with pneumatosis intestinalis (PI) and porto-mesenteric venous gas (PMVG) can be challenging. The purpose of this study was to refine prognostication to improve decision making in daily clinical routine. METHODS: A total of 290 patients with confirmed PI were included in the final analysis. The presence of PMVG and mortality (90d follow-up) were evaluated with regard to the influence of possible risk factors. Furthermore, a linear estimation model was devised combining significant parameters to calculate accuracies for predicting death in patients undergoing surgery by means of a defined operation point (ROC-analysis). RESULTS: Overall, 90d mortality was 55.2% (160/290). In patients with PI only, mortality was 46.5% (78/168) and increased significantly to 67.2% (82/122) in combination with PMVG (median survival: PI: 58d vs. PI and PMVG: 41d; p < 0.001). In the entire patient group, 53.5% (155/290) were treated surgically with a 90d mortality of 58.8% (91/155) in this latter group, while 90d mortality was 51.1% (69/135) in patients treated conservatively. In the patients who survived > 90d treated conservatively (24.9% of the entire collective; 72/290) PMVG/PI was defined as "benign"/reversible. PMVG, COPD, sepsis and a low platelet count were found to correlate with a worse prognosis helping to identify patients who might not profit from surgery, in this context our calculation model reaches accuracies of 97% specificity, 20% sensitivity, 90% PPV and 45% NPV. CONCLUSION: Although PI is associated with high morbidity and mortality, "benign causes" are common. However, in concomitant PMVG, mortality rates increase significantly. Our mathematical model could serve as a decision support tool to identify patients who are least likely to benefit from surgery, and to potentially reduce overtreatment in this subset of patients.

Liver Resection for Intrahepatic Cholangiocarcinoma-Single-Center Experience with 286 Patients Undergoing Surgical Exploration over a Thirteen Year Period.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) accounts for about 10% of primary liver cancer. Surgery is the only potentially curative treatment. We report on our current series of 229 consecutive hepatic resections for iCCA, which is one of the largest Western single-center series published so far. METHODS: Between January 2008 to December 2020, a total of 286 patients underwent 307 surgical explorations for intended liver resection of iCCA at our department. Data were analyzed with regard to (1) preoperative treatment of tumor, (2) operative details, (3) perioperative morbidity and mortality, (4) histopathology, (5) outcome measured by tumor recurrence, treatment of recurrence and survival and (6) prognostic factors for overall and disease-free survival. RESULTS: the resectability rate was 74.6% (229/307). In total, 202 primary liver resections, 21 repeated, 5 re-repeated, and 1 re-re-repeated liver resections were performed. In primary liver resections there were 77% (155/202) major hepatectomies. In 39/202 (20%) of patients additional hepatic wedge resections and in 87/202 (43%) patients additional 119 other surgical procedures were performed next to hepatectomy. Surgical radicality in first liver resections was 166 R0-, 33 R1- and 1 R2-resection. Following the first liver resection, the calculated 1-, 3- and 5-year-survival is 80%, 39%, and 22% with a median survival of 25.8 months. Until the completion of data acquisition, tumors recurred in 123/202 (60.9%) patients after a median of 7.5 months (range 1-87.2 months) after resection. A multivariate cox regression revealed tumor size (p < 0.001), T stage (p < 0.001) and N stage (p = 0.003) as independent predictors for overall survival. N stage (p = 0.040), preoperative therapy (p = 0.005), T stage (p = 0.004), tumor size (p = 0.002) and M stage (p = 0.001) were independent predictors for recurrence-free survival. CONCLUSIONS: For complete surgical removal, often extended liver resection in combination with complex vascular or biliary reconstruction is required. However, despite aggressive surgery, tumor recurrence is frequent and long-term oncological results are poor. This indicated that surgery alone is unlikely to make great strides in improving prognosis of patients with iCCA, instead clearly suggesting that liver resection should be incorporated in multimodal treatment concepts.

The Addition of Transarterial Chemoembolization to Palliative Chemotherapy Extends Survival in Intrahepatic Cholangiocarcinoma.

Incidence and mortality of intrahepatic cholangiocarcinoma (iCCA) have been increasing continuously. Recent studies suggest that the combination of palliative chemotherapy (pCTX) and transarterial chemoembolization (TACE) improves overall survival (OS). This study aimed to evaluate the outcome of patients treated with TACE and pCTX in unresectable iCCA at our tertiary care center. A group of 14 patients was treated with both pCTX and TACE. The non-randomized control group of 59 patients received pCTX alone. Patients received a median of two pCTX lines in both groups. Those treated with TACE underwent a median number of 3.5 sessions. Median OS from the time of unresectability was 26.2 months in the pCTX + TACE group versus 13.1 months in the pCTX group (p = 0.008). Controlling for albumin, bilirubin, ECOG (Eastern Cooperative Oncology Group) performance status, and UICC (Union for International Cancer Control) stage, the addition of TACE still conferred an OS benefit of 12.95 months (p = 0.014). A propensity score matching analysis yielded an OS benefit of 14 months from the time of unresectability for the pCTX + TACE group (p = 0.020). The addition of TACE to pCTX may provide an OS benefit for patients with unresectable iCCA. Thus, patients with liver-dominant iCCA undergoing standard-of-care pCTX should be considered for additional treatment with TACE.