We have used a stepwise approach consisting of initial interrogation, confirmation and fine mapping to analyze STAT3, IL1B and IFNGR1 as modifiers of cystic fibrosis disease building upon the data and sample collection of the European Cystic Fibrosis Twin and Sibling Study. We have observed direct correlation between the length of the intronic microsatellite STAT3Sat to STAT3 expression levels among F508del-CFTR homozygous patients (P¼0.0075), and an association of longer STAT3Sat-alleles with the presence of CFTR-mediated residual chloride secretion (P¼0.0031), measured as the manifestation of the CF basic defect in intestinal tissue. Both, family-based analysis by TDT and case-reference comparison identified consistently the same intragenic IL1B haplotype as a risk variant (P raw ¼0.055 for TDT, P raw o0.3 for case-reference comparison). Using haplotypeguided hierarchical fine mapping, we have identified two single nucleotide exchanges for which concordant and discordant sibling pairs differ at a 7 kb -spanning core haplotype in IFNGR1 (P raw ¼0.0113). Taken together, our findings imply that immunorelevant pathways and ion secretion, dominated by CFTR in intestinal and respiratory epithelium, merge at the level of the epithelial cell to integrate the signaling of cytokines due to innate and acquired immune defense.

Introduction: To analyze the primary stone free rate (pSFR) of flexible ureterorenoscopy (fURS) in the treatment of renal stones and to identify clinical predictors for the primary freedom from renal stones. Materials and Methods: Two hundred and seventy five patients, who underwent fURS for kidney stones were analyzed. Results: Index stone size was 6 mm. The stone was located in the lower calyx in 48%. Ureteral access sheath was used in 97%. Operation time was 35 min and primary stone clearance was 83%. pSFR increased from 74% in 2012 to 83% in 2013 and 90% in 2014 (p = 0.001). Preoperative stenting, index stone size, cumulative stone size, lithotripsy, ureteral access sheath and operation time were significantly correlated with the pSFR by univariate analysis. Multivariate regression analysis showed index stone size, cumulative stone size, ureteral access sheath and operation time as independent parameters for pSFR. Conclusions: fURS for kidney stones is safe with a high pSFR. Clinical parameters for pSFR are stone size, use of ureteral access sheath and operation time. In future, the effective use of fURS for the removal of kidney stones needs to be checked by prospective randomized trials.