Real-life assessment of standardized contrast-enhanced ultrasound (CEUS) and CEUS algorithms (CEUS LI-RADS®/ESCULAP) in hepatic nodules in cirrhotic patients-a prospective multicenter study.

OBJECTIVES: Hepatocellular carcinoma (HCC) can be diagnosed non-invasively with contrast-enhanced ultrasound (CEUS) in cirrhosis if the characteristic pattern of arterial phase hyperenhancement followed by hypoenhancement is present. Recent studies suggest that diagnosis based on this "hyper-hypo" pattern needs further refinement. This study compares the diagnostic accuracies of standardized CEUS for HCC according to the current guideline definition and following the newly developed CEUS algorithms (CEUS LI-RADS®, ESCULAP) in a prospective multicenter real-life setting. METHODS: Cirrhotic patients with liver lesions on B-mode ultrasound were recruited prospectively from 04/2018 to 04/2019, and clinical and imaging data were collected. The CEUS standard included an additional examination point after 4-6 min in case of no washout after 3 min. The diagnostic accuracies of CEUS following the guidelines ("hyper-hypo" pattern), based on the examiner's subjective interpretation ("CEUS subjective"), and based on the CEUS algorithms ESCULAP and CEUS LI-RADS® were compared. RESULTS: In total, 470 cirrhotic patients were recruited in 43 centers. The final diagnosis was HCC in 378 cases (80.4%) according to the reference standard (histology 77.4%, MRI 16.4%, CT 6.2%). The "hyper-hypo" pattern yielded 74.3% sensitivity and 63% specificity. "CEUS subjective" showed a higher diagnostic accuracy (sensitivity, 91.5%; specificity, 67.4%; positive predictive value, 92%; negative predictive value, 66%). Sensitivity was higher for ESCULAP (95%) and "CEUS subjective" (91.5%) versus CEUS LI-RADS® (65.2%; p < 0.001). Specificity was highest for CEUS LI-RADS® (78.6%; p < 0.001). CONCLUSIONS: CEUS has an excellent diagnostic accuracy for the non-invasive diagnosis of HCC in cirrhosis. CEUS algorithms may be a helpful refinement of the "hyper-hypo" pattern defined by current HCC guidelines. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) has a high diagnostic accuracy for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. • The CEUS algorithm ESCULAP (Erlanger Synopsis for Contrast-enhanced Ultrasound for Liver lesion Assessment in Patients at risk) showed the highest sensitivity, whereas the CEUS LI-RADS® (Contrast-Enhanced UltraSound Liver Imaging Reporting and Data System) algorithm yielded the highest specificity. • A standardized CEUS examination procedure with an additional examination point in the late phase, after 4-6 min in lesions with no washout after 3 min, is vital.

Noninferiority trial investigating the efficacy of a nonantibiotic intramammary therapy in the treatment of mild-to-moderate clinical mastitis in dairy cows with longer lasting udder diseases.

A nonblinded, positively controlled, noninferiority trial was conducted to evaluate the efficacy of an alternative, nonantibiotic therapy with Masti Veyxym® to reduce ineffective antibiotic usage in the treatment of nonsevere clinical mastitis (CM) in cows with longer lasting udder diseases. The solely intramammary treatment with Masti Veyxym® (three applications, 12 hr apart) and the combined treatment with Masti Veyxym® and antibiotics as usual on the farm according to label of the respective product were compared with the reference treatment of solely antibiotic therapy. The matched field study was conducted on eight free-stall dairy farms located in Eastern Germany. Cases of mild-to-moderate CM in cows with longer lasting high somatic cell counts in preceding dairy herd improvement test days and with previous CM cases in current lactation were randomly allocated to one of the three treatment groups. A foremilk sample of the affected quarter was taken before treatment and again approximately 14 days and 21 days after the end of therapy for cyto-bacteriological examination. Primary outcomes were clinical cure (CC) and no CM recurrence within 60 days after the end of treatment (no R60). Bacteriological cure (BC) and quarter somatic cell count (QSCC) cure were chosen as secondary outcomes although low probabilities of BC and QSCC cure for selected cows were expected. The study resulted in the following findings: the pathogens mostly cultured from pretreatment samples were Streptococcus uberis, followed by Staphylococcus aureus and coagulase-negative staphylococci. There were no significant differences between the two test treatments in comparison with the reference treatment regarding all outcome variables. The sole therapy with Masti Veyxym® resulted in a numerically lower likelihood of BC without significant differences to the reference treatment. The combined therapy group showed a numerically higher nonrecurrence rate than the two other treatment groups and noninferiority compared to the reference treatment was proven. Having regard to the selection criteria of cows in this study, the findings indicated that sole treatment with Masti Veyxym® in nonsevere CM cases may constitute an alternative therapy to reduce antibiotics. However, noninferiority evaluations were mostly inconclusive. Further investigations with a larger sample size are required to confirm the results and to make a clear statement on noninferiority.