Late allocation of organs for transplant impairs post-liver transplantation (LT) survival. Cardiac dysfunction, especially diastolic and autonomic dysfunction, is frequent and plays an important role in the prognosis of patients with cirrhosis. However, the role of myocardial contractility is unexplored, and its prognostic value is controversially discussed. This study analyses the role of myocardial contractility assessed by speckle tracking echocardiography in LT allocation. In total, 168 patients with cirrhosis (training cohort, 111; validation cohort [VC], 57) awaiting LT in 2 centers were included in this retrospective study. Also, 51 patients from the training and all patients from the VC were transplanted, 36 patients of the training and 38 of the VC were alive at the end of follow-up, and 21 nontransplanted patients died. Contractility of the left ventricle (LV) increased with severity of the Child-Pugh score. Interestingly, higher LV contractility in the training cohort patients, especially in those with Child-Pugh C, was an independent predictor of reduced transplant-free survival. In male patients, the effects on survival of increased left and right ventricular myocardial contractility were more pronounced. Notably, competing risk analysis demonstrated that increased contractility is associated with earlier LT, which could be confirmed in the VC. Importantly, LV myocardial contractility had no impact on survival of patients not receiving LT or on post-LT survival. In conclusion, this study demonstrates for the first time that increased myocardial contractility in decompensated patients identifies patients who require LT earlier, but without increased post-LT mortality.Liver Transplantation 24 15-25 2018 AASLD.

Purpose Long non-coding RNAs (lncRNA) are involved in oncogenesis and tumor progression in various tumor entities. At present, little is known about the role in tumor biology of the lncRNA Fer-1 like family member 4 (Fer1L4) in clear-cell renal-cell carcinoma (ccRCC). The aim of this study is to evaluate the expression of Fer1L4 in patients with ccRCC, its association with clinicopathological parameters, and value as prognostic biomarker. Material and methods The expression of Fer1L4 was analyzed in the TCGA ccRCC cohort (n = 603; ccRCC n = 522, normal n = 81) and subsequently validated by quantitative real-time PCR in an independent cohort (n = 103, ccRCC n = 69, normal n = 34). Expression profiles were statistically correlated with clinicopathological and survival data. Results Fer1L4 lncRNA is overexpressed in ccRCC compared to adjacent normal tissues. Increased expression significantly correlates with tumor aggressiveness: high expression levels of Fer1L4 RNA were found in higher grade, higher stage, and metastatic tumors. Furthermore, Fer1L4 overexpression is an independent prognostic factor for overall, cancer-specific, and progression-free survival of patients with ccRCC. Conclusion Fer1L4 expression significantly correlates with aspects of tumor aggressiveness. Based on this impact on tumor progression and its influence as an independent prognostic factor, Fer1L4 appears to exert properties as an oncogene in ccRCC. As a prognostic tissue biomarker, further functional investigations are warranted to investigate Fer1L4 as a potential therapeutic target.

Abbreviations & Acronyms ccRCC = clear cell renal cell carcinoma CI = confidence interval CSS = cancer-specific survival Fer1L4 = Fer-1-like family member 4 HR = hazard ratio IHC = immunohistochemistry NA = not applicable OS = overall survival OTOF = otoferlin PCR = polymerase chain reaction PFS = progression-free survival qPCR = quantitative polymerase chain reaction qRT-PCR = quantitative real-time polymerase chain reaction RCC = renal cell carcinoma TCGA = The Cancer Genome Atlas TMA = tissue microarrays

Background/Aim: Myoferlin (MYOF) has emerged as an oncogenic protein in various human cancer types. This study was conducted to investigate comprehensively the expression and functional properties of MYOF in clear-cell renal-cell carcinoma (ccRCC) with respect to its value as diagnostic biomarker and therapeutic target. Materials and Methods: mRNA and protein expression of MYOF were assessed by quantitative polymerase chain reaction and immunohistochemistry. siRNA-mediated knockdown of MYOF was performed in the RCC cell line ACHN followed by proliferation, migration and invasion assays. Results: MYOF mRNA and protein expression were significantly up-regulated in ccRCC. Higher mRNA levels were measured in advanced tumors. MYOF protein expression was increased in tumors with higher histological grades, and those with positive lymph node and surgical margin status. MYOF knockdown led to reduction of migration and invasion in ACHN cells, whereas expression of angiogenesis-associated genes tyrosine-protein kinase receptor-2 (TIE2), angiopoietin 2 (ANG2) and caveolin-1 (CAV1) was up-regulated following knockdown. Conclusion: MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.

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ZusammenfassungEs wird über den Fall eines 12-jährigen Jungen mit sportinduzierter, rezidivierender Makrohämaturie und linksseitigen Flankenschmerzen berichtet. Nach umfangreicher laborchemischer sowie bildgebender Diagnostik wird in Zusammenschau des charakteristischen klinischen Bildes die Diagnose Nussknackersyndrom gestellt. Unter konservativen Maßnahmen sowie Verzicht auf den auslösenden Sport kam es zu einer klinischen sowie bildmorphologisch bestätigten Maturation.

Background: F-box/SPRY domain-containing protein 1 (FBXO45) plays a crucial role in the regulation of apoptosis via the ubiquitylation and degradation of specific targets. Recent studies indicate the prognostic potential of FBXO45 in several cancers. However, its specific role in prostate carcinoma remains unclear. Methods: A systematic analysis of FBXO45 mRNA expression in PCA was performed using The Cancer Genome Atlas database and a publicly available Gene Expression Omnibus progression PCA cohort. Subsequently, FBXO45 protein expression was assessed via immunohistochemical analysis of a comprehensive tissue microarray cohort. The expression data were correlated with the clinicopathological parameters and biochemical-free survival. The immunohistochemical analyses were stratified according to the TMPRSS2–ERG rearrangement status. To assess the impact of FBXO45 knockdown on the tumour proliferation capacity of cells and metastatic potential, transfection with antisense-oligonucleotides was conducted within a cell culture model. Results: FBXO45 mRNA expression was associated with adverse clinicopathological parameters in the TCGA cohort and was enhanced throughout progression to distant metastasis. FBXO45 was associated with shortened biochemical-free survival, which was pronounced for the TMPRSS2–ERG-positive tumours. In vitro, FBXO45 knockdown led to a significant reduction in migration capacity in the PC3, DU145 and LNCaP cell cultures. Conclusions: Comprehensive expression analysis and functional data suggest FBXO45 as a prognostic biomarker in PCA.

In boys with posterior urethral valves (PUVs) the main treatment aim is to preserve long-term bladder and renal function. To determine the effectiveness of secondary vesicostomy in boys with PUVs, the medical records of 21 patients with PUV (2010–2019), divided into two groups (group I: valve ablation; group II: secondary vesicostomy), were reviewed regarding the course of serum creatinine, renal ultrasound, voiding cystourethrogram, urodynamics, postoperative complications, need of further surgery, and long-term solution. The median age of all patients at first follow-up was 11 (9–13) months and at last follow-up 64.5 (39.5–102.5) months. Despite a significant difference of the SWDR score (shape, wall, reflux, and diverticula) (p = 0.014), both groups showed no significant differences preoperatively. Postoperatively, serum creatinine (p = 0.024), grade of vesicoureteral reflux (p = 0.003), side of upper tract dilatation (p = 0.006), side of megaureter (p = 0.004), and SWDR score (p = 0.002) were significantly decreased in group II. Postoperative urodynamic measurements showed comparable results in both groups. Stoma complications were found in three (20%) patients (group II). Eight (53.3%) patients already received a closure of the vesicostomy. Seven out of eight (87.5%) patients were able to micturate spontaneously. Vesicostomy remains a reliable treatment option for boys with PUV to improve bladder function and avoid further damage to the urinary tract.