Safety of endoscopic retrograde cholangiopancreatography in pregnancy: Fluoroscopy time and fetal exposure,does it matter?

AIM: To estimate the fetal radiation exposure using thermoluminescent dosimeters (TLD’s) in pregnant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and assess its relevance. METHODS: Data on thirty-five therapeutic ERCPs conducted in pregnant patients from 2001 to 2009 were retrieved from a prospective database. Techniques to minimize fluoroscopy time were implemented and the fluoroscopy times captured. TLD’s were placed on the mother to estimate the fetal radiation exposure and the results were compared to the maximum allowed dose of radiation to the fetus [0.005 gray (Gy)]. Obstetrics consultations were obtained and the fetus was monitored before and after the ERCP. Fluoroscopy wasperformed at 75 kVp. ERCP was performed with the patients supine by dedicated biliary endoscopists performing more than 500 cases a year. RESULTS: A total of 35 pregnant patients underwent ERCP and biliary sphincterotomy (14 in first trimester, 11 in second trimester, and 10 in third trimester). Mean maternal age was 25 years (range 16-37 years) and mean gestational age was 18.9 wk (range 4-35 wk). Mean fluoroscopy time was 0.15 min (range 0-1 min). For 23 women, the estimated fetal radiation exposure was almost negligible (< 0.0001 Gy) while for 8 women, it was within the 0.0001-0.0002 Gy range. Three women had an estimated fetal radiation exposure between 0.0002 and 0.0005 Gy and 1 woman had an estimated fetal radiation exposure greater than 0.0005 Gy. Complications included 2 post-sphincterotomy bleeds, 2 post-ERCP pancreatitis, and 1 fatal acute respiratory distress syndrome. One patient developed cholecystitis 2 d after ERCP. CONCLUSION: ERCP with modified techniques is safe during pregnancy, and estimating the fetal radiation exposure from the fluoroscopy time or measuring it via TLD’s is unnecessary.     

C57Bl/6 mice are protected from respiratory syncytial virus (RSV) challenge and IL-5 associated pulmonary eosinophilic infiltrates following intranasal immunization with Protollin-eRSV vaccine

The protective efficacy of an intranasal (IN) Protollin-eRSV vaccine has recently been demonstrated in the RSV-susceptible BALB/c mouse model. Here, we report the safety, immunogenicity and efficacy of Protollin-eRSV vaccine in the relatively resistant C57Bl/6 mouse model. C57Bl/6 mice immunized IN with either two or three doses of Protollin-eRSV produced significant systemic and mucosal RSV-specific antibodies. Mice immunized with the Protollin vaccine displayed polarized Th1 responses with augmented IFNgamma/IL-5 ratios in RSV-restimulated lung and spleen cell preparations compared with animals that received antigen alone. The Protollin-eRSV immunized C57Bl/6 mice were fully protected against challenge without eosinophilic pulmonary pathology observed in the animals immunized with the formalin-inactivated RSV vaccine. This new model will permit us to dissect the respective roles of the TLR2 and TLR4 ligands contained in the vaccine using TLR knock-out animals established on the C57Bl/6 background.     

Risk factors for late-onset ventilator-associated pneumonia in trauma patients receiving selective digestive decontamination

Objective To determine the independent risk factors for late-onset ventilator-associated pneumonia (VAP) in trauma patients receiving selective digestive decontamination (SDD).Design A 4-year, prospective cohort study of trauma patients meeting the following criteria: injury severity score >15, and duration of mechanical ventilation >5 days. Predictors of late-onset VAP occurrence were assessed by logistic regression analysis.Population All patients received SDD consisting of polymixin E, gentamicin, and amphotericin B applied in nostrils, mouth, and gut with a 3-day course of parenteral cefazolin. VAP was suspected on clinical and radiological signs, and confirmed by the presence of at least one microorganism at a concentration of at least 10⁴ CFU/ml on the broncho-alveolar lavage.Measurement Independent risk factors for late-onset VAP.Results A late-onset VAP was diagnosed in 90 (56%) out of 159 patients. Predicting factors for late-onset VAP were: use of non-depolarizing muscle relaxant agents for intubation [3.4 (CI 1.08–10.73)], duration of intubation [1.06 (CI 1.01–1.17)], length of intensive care unit (ICU) stay [1.05 (CI 1.02–1.09)], and prior tracheal colonization [1.03 (CI 1.02–1.21)]. Exposure to prior antimicrobial treatment, except SDD, conferred protection [0.3 (0.12–0.74)].Conclusion This study confirms the role of duration of intubation, length of ICU stay, and prior tracheal colonization in the development of late-onset VAP. The results also highlight the importance of the initial management on the development of late-onset VAP. The type of neuromuscular blocking agents to intubate trauma patients should be evaluated in future studies.     

Pas de deux in groups of four--the biogenesis of KATP channels

The biogenesis of K(ATP) channels provides an interesting example of the assembly of structurally very different membrane protein subunits into a heterooligomeric complex. This review summarizes our current knowledge with respect to the protein domains driving heteromultimeric assembly in the endoplasmic reticulum, quality control, as well as the determinants and kinetics of subcellular sorting of the K(ATP) channel complex. The impact of disease-associated mutations on K(ATP) channel biogenesis is discussed.     

Contribution of the IL-17/IL-23 axis to the pathogenesis of inflammatory bowel disease

Inflammatory bowel diseases(IBDs) are chronic disorders of modern society, requiring management strategies aimed at prolonging an active life and establishing the exact etiology and pathogenesis.These idiopathic diseases have environmental, genetic,immunologic, inflammatory, and oxidative stress components. On the one hand, recent advances have shown that abnormal immune reactions against the microorganisms of the intestinal flora are responsible for the inflammation in genetically susceptible individuals. On the other hand, in addition to T helper cell-type(Th) 1 and Th2 immune responses,other subsets of T cells, namely regulatory T cells and Th17 maintained by IL-23 are likely to develop IBD. IL-23 acts on innate immune system members and also facilitates the expansion and maintenance of Th17 cells. The IL-17/IL-23 axis is relevant in IBD pathogenesis both in human and experimental studies. Novel biomarkers of IBD could be calprotectin,microRNAs, and serum proinflammatory cytokines.An efficient strategy for IBD therapy is represented by the combination of IL-17 A and IL-17 F in acute IL-17 A knockout TNBS-induced colitis, and also definite decrease of the inflammatory process in IL-17 F knockout, DSS-induced colitis have been observed.Studying the correlation between innate and adaptive immune systems, we hope to obtain a focused reviewin order to facilitate future approaches aimed at elucidating the immunological mechanisms that control gut inflammation.     

Mutational profiles of Brenner tumors show distinctive features uncoupling urothelial carcinomas and ovarian carcinoma with transitional cell histology

Brenner tumors (BT) are rare ovarian tumors encompassing benign, borderline, and malignant variants. While the histopathology of BTs and their clinical course is well described, little is known about the underlying genetic defects. We employed targeted next generation sequencing to analyze the mutational landscape in a cohort of 23 BT cases (17 benign, 2 borderline, and 4 malignant) and 3 ovarian carcinomas with transitional cell histology (TCC). Copy number variations (CNV) were validated by fluorescence in‐situ hybridization (FISH) and quantitative PCR‐based copy number assays. Additionally, we analyzed the TERT promotor region by conventional Sanger sequencing. We identified 25 different point mutations in 23 of the analyzed genes in BTs and 10 mutations in 8 genes in TCCs. About 57% percent of mutations occurred in genes involved in cell cycle control, DNA repair, and epigenetic regulation processes. All TCC cases harbored TP53 mutations whereas all BTs were negative and none of the mutations observed in BTs were present in TCCs. CNV analysis revealed recurrent MDM2 amplifications in 3 out of 4 of the malignant BT cases with one case harboring a concomitant amplification of CCND1. No mutations were observed in the TERT promoter region in BTs and TCCs, which is mutated in about 50%‐75% of urothelial carcinoma and in 16% of ovarian clear‐cell carcinomas. In conclusion, our study highlights distinct genetic features of BTs, and detection of the triplet phenotype MDM2 amplification/TP53 wt/TERT wt may aid diagnosis of malignant BT in difficult cases. Moreover, selected genetic lesions may be clinically exploitable in a metastatic setting.