Citations

4109 Background: Prognostic nomograms have been developed in various cancers, including ovarian, breast, and gastrointestinal; however, there is limited information on nomograms in MPC. The large, phase 3 MPACT study of nab-P + Gem vs Gem alone for the treatment of MPC provides a robust database for the development of a nomogram to predict OS using baseline patient variables. Methods: A multivariable Cox model was created from MPACT data using factors that were significantly predictive of OS in univariable analysis or considered clinically important (stepwise selection to remain in model). From the Cox model, a nomogram was derived that assigned points equal to the weighted sum of relative significance of each variable. The nomogram was internally validated using bootstrapping, a concordance index (c-index), and calibration plots. Results: Data from all 861 pts were used. Seven of the 34 considered variables were retained in the multivariable analysis (Table; all factors significant at the P < 0.01 level, except for analgesic use [ P = 0.07]). The resulting nomogram was able to distinguish low (n = 216), medium (n = 430), and high (n = 215) risk groups (c-index: 0.69; CI: 0.67-0.71) with median OS values of 12.9, 8.2, and 3.7 months, respectively. Calibration curves showed that the nomogram’s predicted probabilities were mostly consistent with observed probabilities for 6-, 9-, and 12-month OS. Conclusions: Treatment arm, Karnofsky performance status (KPS), neutrophil-to-lymphocyte ratio (NLR), albumin level, sum of longest tumor diameters (SLD), and presence of liver metastasis were the key predictors of OS. This nomogram, which will be presented in visual format in the final presentation, may help physicians and pts make informed treatment decisions. Clinical trial information: NCT00844649. [Table: see text]

The gene product affected in cystic fibrosis, the cystic fibrosis transmembrane conductance regulator (CFTR), is a chloride-selective ion channel that is regulated by cAMP-dependent protein kinase-mediated phosphorylation, ATP binding and ATP hydrolysis. Mutations in the CFTR gene may result in cystic fibrosis characterized by severe pathology (e.g. recurrent pulmonary infection, male infertility and pancreatic insufficiency) involving organs expressing the CFTR. Interestingly, in the kidney, where expression of the CFTR has been reported, impaired ion transport in patients suffering from cystic fibrosis could not be observed. To understand the role of the CFTR in chloride transport in the kidney, we attempted to identify an epithelial cell line that can serve as a model. We demonstrate that the CFTR is expressed constitutively in MadineŐDarby canine kidney (MDCK) type I cells, which are thought to have originated from the distal tubule of the dog nephron. We show expression at the mRNA level, using reverse transcriptase-PCR, and at the protein level, using Western blot analysis with three different monoclonal antibodies. Iodide efflux measurements indicate that CFTR expression confers a plasma membrane anion conductance that is responsive to stimulation by cAMP. The cAMP-stimulated iodide release is sensitive to glybenclamide, diphenylamine carboxylic acid and 5-nitro-2-(3-phenylpropylamino)benzoic acid, but not to 4,4ƀ-di-isothiocyanostilbene-2,2ƀ-disulphonic acid, an inhibitor profile characteristic of the CFTR chloride channel. Finally, the polarized localization of the CFTR to the apical plasma membrane was established by iodide efflux measurements and cell-surface biotinylation on MDCK I monolayers. Interestingly, MDCK type II cells, which are thought to have originated from the proximal tubule of the kidney, lack CFTR protein expression and cAMP-stimulated chloride conductance. In conclusion, we propose that MDCK type I and II cells can serve as convenient model systems to study the physiological role and differential expression of CFTR in the distal and proximal tubule respectively.

Abstract Background: The existence, etiology, diagnosis, and treatment of median arcuate ligament syndrome (MALS) have long been subjects of debate. To our knowledge, there have not been any studies assessing the effectiveness of surgical treatment in improving physical and psychological quality of life in pediatric patients. Subjects and Methods: This is an Institutional Review Board–approved prospective study including all patients undergoing surgical treatment of MALS between 2009 and 2012 at our institution. Demographic information, presenting symptoms, radiological imaging, procedure duration, hospital length of stay, and perioperative complications were gathered for analysis. Patients and their parents were asked to complete the Child Health Questionnaire, a physical and psychological health survey, both within 1 week prior to and at least 3 months following their surgery. Results: Six patients underwent laparoscopic release for MALS. The majority of patients were female ( n =5 [83.3%]), with an average age of 15.7±1.5 years. Presenting symptoms lasted on average 16.5±12.7 months prior to treatment. Average pre- and postsurgical ultrasound celiac artery peak velocities with inspiration were 332.0±34.1 cm/second and 224.3±31.2 cm/second, respectively, with a statistically significant decrease of 107.67 cm/second ( P =.03). The average follow-up period from time of surgery to time of quality of life survey completion was 13±11.3 months, with a range of 3–29 months. A significant improvement from pre- to postsurgical scores was observed in the physical functioning ( P =.03), mental health ( P =.03), and self-esteem categories ( P =.03) of the child assessment. Similarly, there was a significant postsurgical improvement in all categories pertaining to the parent's quality of life ( P =.03). Improvement was also seen in the parents' perception of their child's physical functioning ( P =.03), bodily pain/discomfort ( P =.03), mental health ( P =.03), and general health perceptions ( P =.03). No intraoperative or postoperative complications occurred. Conclusions: Our preliminary results demonstrate that laparoscopic median arcuate ligament release for MALS in the pediatric population is safe and effective and improves overall quality of life for the patients and their parents. In carefully selected patients, laparoscopic release for MALS without additional celiac artery reconstruction normalizes blood flow in the celiac artery and improves physical and psychosocial quality of life for the child and his or her parents.

Objectives To review the need for operative intervention and critical care services for motocross truncal injuries in children. Design cohort Retrospective review of patients identified via the hospital trauma registry. Setting Our Level 1 Pediatric Trauma Center serves five motocross tracks. These patients require frequent medical care for injuries. Participants All patients ≤17 years of age with truncal injuries sustained during motocross activities, between 2000 and 2011, were identified through the trauma registry. Primary and secondary outcome measures Operative intervention, intensive care unit (ICU) admission, length of stay, morbidity and demographics were reviewed. Results Motocross injured 162 children. Thirty (18.5%) were thoracic or abdominal injuries. Operative intervention was required in eight (27%) patients. Mean injury severity score (ISS) was 11.8. ICU admission was required in 50% and average hospital length of stay was 4.1 days. The most common injuries include pulmonary contusion, pneumothorax, spleen and liver lacerations. 13% of subjects suffered truncal injury from motocross on more than one occasion. Conclusions Paediatric motocross-related truncal injuries are significant. Surgical intervention is required in 27% of patients. The lower ISS incurred from motocross combined with high surgical and ICU admission rates suggests focal high-impact injuries to the chest and abdomen. Despite significant injury, 13% of motocross patients suffer recurrent injuries. Parents and children need injury prevention education.