As a non-invasive and readily available diagnostic tool, ultrasound is one of the most important imaging techniques in medicine. Ultrasound is usually trained during residency preferable according to German Society of Ultrasound in Medicine (DEGUM) standards. Our curriculum calls for undergraduate training in ultrasound of medical students in their 4th year of undergraduate education. An explorative pilot study evaluated the acceptance of this teaching method, and compared it to other practical activities in medical education at Muenster University. 240 medical students in their 4th year of undergraduate medical education participated in the training and completed a pre- and post-questionnaire for self-assessment of technical knowledge, self-assurance of the procedure, and motivation in performing ultrasound using a Likert scale. Moreover, students were asked about their interest in pursuing a career in internal medicine. To compare this training to other educational activities a standardized online evaluation tool was used. A direct observation of procedural skills assessment (DOPS) for the first time applied on ultrasound aimed to independently assess the success of our teaching method. There was a significant increase in technical knowledge and self-assurance (p < 0.001) of the students’ self-assessments. The clinical relevance and self-motivation of the teaching were evaluated positively. The students’ DOPS results demonstrated proficiency in the understanding of anatomic structures shown in ultrasonographic images, including terminology, machine settings, and transducer frequencies. Training ultrasound according to certified DEGUM standards was successful and should be offered in undergraduate medical education. The evaluation of the course affirmed the necessity, quality and clinical relevance of the course with a top ranking score of hands-on training courses within the educational activities of the Medical Faculty of Muenster.

Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment tool in decompensated liver cirrhosis that has been shown to prolong transplant-free survival. Hepatic encephalopathy (HE) is a frequent complication of decompensated cirrhosis, eventually induced and/or aggravated by TIPS, that remains a clinical challenge especially in these patients. Therefore, patient selection for TIPS requires careful assessment of risk factors for HE. TIPS procedural parameters regarding stent size and invasive portosystemic pressure gradient measurements thereby have an important role. Endovascular shunt modification, in combination with a conservative medical approach, often results in a significant reduction of symptoms. This review summarizes HE molecular mechanisms and pathophysiology as well as diagnostic and therapeutic approaches targeting shunt-induced HE.

Purpose: To evaluate predictive parameters for the development of Hepatic Encephalopathy (HE) after Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement and for success of shunt modification in the management of shunt-induced HE. Methods: A retrospective analysis of all patients with TIPS (n = 344) has been performed since 2011 in our university liver center. n = 45 patients with HE after TIPS were compared to n = 48 patients without HE after TIPS (case-control-matching). Of n = 45 patients with TIPS-induced HE, n = 20 patients received a reduction stent (n = 18) or TIPS occlusion (n = 2) and were differentiated into responders (improvement by at least one HE grade according to the West Haven classification) and non-responders (no improvement). Results: Older patient age, increased serum creatinine and elevated International Normalized Ratio (INR) immediately after TIPS placement were independent predictors for the development of HE. In 11/20 patients (responders, 55%) undergoing shunt modification, the HE grade was improved compared with nine non-responders (45%), with no relevant recurrence of refractory ascites or variceal bleeding. A high HE grade after TIPS insertion was the only positive predictor of treatment response (p = 0.019). A total of 10/11 responders (91%) survived the 6 months follow-up after modification but only 6/9 non-responders (67%) survived. Discussion: Older patient age as well as an increased serum creatinine and INR after TIPS are potential predictors for the development of HE. TIPS reduction for the treatment of TIPS-induced HE is safe, with particular benefit for patients with pronounced HE.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Background: Aminopeptidase N (CD13) is present on tumor vasculature cells and some tumor cells. Truncated tissue factor (tTF) with a C-terminal NGR-peptide (tTF-NGR) binds to CD13 and causes tumor vascular thrombosis with infarction. Methods: We treated 17 patients with advanced cancer beyond standard therapies in a phase I study with tTF-NGR (1-h infusion, central venous access, 5 consecutive days, and rest periods of 2 weeks). The study allowed intraindividual dose escalations between cycles and established Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity (DLT) by verification cohorts. Results: MTD was 3 mg/m² tTF-NGR/day × 5, q day 22. DLT was an isolated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae. Three thromboembolic events (grade 2), tTF-NGR-related besides other relevant risk factors, were reversible upon anticoagulation. Imaging by contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) showed major tumor-specific reduction of blood flow in all measurable lesions as proof of principle for the mode of action of tTF-NGR. There were no responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), although some lesions showed intratumoral hemorrhage and necrosis after tTF-NGR application. Pharmacokinetic analysis showed a t_{1/2(terminal)} of 8 to 9 h without accumulation in daily administrations. Conclusion: tTF-NGR is safely applicable with this regimen. Imaging showed selective reduction of tumor blood flow and intratumoral hemorrhage and necrosis.