About 30% of patients with Cystic Fibrosis (CF) develop CF-associated liver disease (CFLD). Recent studies have shown that transient elastography (TE), as a method to quantify liver stiffness, allows non-invasive diagnosis of CFLD in adults and children with CF. Within this study we aimed to prospectively identify patients at risk for development of CFLD by longitudinal analysis of liver stiffness and fibrosis scores in a 5-year follow-up. 36 pediatric and 16 adult patients with initial liver stiffness below the cut-off value indicative of CFLD (6.3 kPa) were examined by transient elastography for 4-5 years. TE, APRI-, and FIB-4-scores were assessed and compared by Kruskal-Wallis test and receiver operating characteristic (ROC)-analysis. Frequencies were compared by Chi 2 -test. Among the 36 patients participating in this study, a subgroup of 9 patients developed liver stiffness >6.3 kPa after 4-5 years with an increase of ΔTE >0.38 kPa/a (the group with increasing liver stiffness was labelled TE inc ). APRI-and FIB-4 scores confirmed the rationale for grouping. The frequency of CFLD assessed by conventional diagnosis was significantly higher in TE inc -group compared to the control group (TE norm ). None of the adult CF patients matched criteria for TE incgroup. For the first time it was shown that the non-invasive longitudinal assessment of TE allows identification of patients with progression of CFLD in a subgroup of juvenile but not in adult CF patients. Comparing TE to conventional fibrosis-scores underlined the strength of the continuous assessment of liver stiffness for the exact diagnosis of progressive CFLD. The newly described cut-off for pathologic increase of liver stiffness, ΔTE cutoff = 0.38kPa/a, might enable to detect developing CFLD using consequent follow up TE measurements before reaching the level of stiffness indicating established CFLD. Nevertheless, the limited size of the analyzed cohort should encourage a prospective, multi-center, long term follow up study to confirm the suggested cut-off for the rise in liver stiffness.PLOS ONE | https://doi.org/10.1371/journal.pone

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Sixty-two patients with metastatic soft tissue sarcomas of various histological types were treated with Cyvadic. No chemotherapy had been given previously. Complete remission (CR) was obtained in 10% and complete plus partial remission (PR) in 20% of the patients. Mean duration of CR was 25 months, that of PR 2.5 months. Median survival time of responders was 28 months, that of nonresponders 14 months. Chemotherapy with a combination of ifosfamide plus cisplatin given to patients with primary or secondary resistance to Cyvadic led to CR + PR in 50% of the patients.

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