Citations

Abstract Background Irritable bowel syndrome (IBS) is a complex condition with multiple factors contributing to its aetiology and pathophysiology. Aetiologically these include genetics, life‐time events and environment, and physiologically, changes in motility, central processing, visceral sensitivity, immunity, epithelial permeability and gastrointestinal microflora. Such complexity means there is currently no specific reliable biomarker for IBS, and thus IBS continues to be diagnosed and classified according to symptom based criteria, the Rome Criteria. Carefully phenotyping and characterisation of a ‘large’ pool of IBS patients across Europe and even the world however, might help identify sub‐populations with accuracy and consistency. This will not only aid future research but improve tailoring of treatment and health care of IBS patients. Purpose The aim of this position paper is to discuss the requirements necessary to standardize the process of selecting and phenotyping IBS patients and how to organise the collection and storage of patient information/samples in such a large multi‐centre pan European/global study. We include information on general demographics, gastrointestinal symptom assessment, psychological factors, quality of life, physiological evaluation, genetic/epigenetic and microbiota analysis, biopsy/blood sampling, together with discussion on the organisational, ethical and language issues associated with implementing such a study. The proposed approach and documents selected to be used in such a study was the result of a thoughtful and thorough four‐year dialogue amongst experts associated with the European COST action BM1106 GENIEUR ( www.GENIEUR.eu ).

Background: Thyroid-stimulating hormone (TSH)–secreting pituitary adenomas are a rare cause of secondary hyperthyroidism. Anesthetic management of these patients has not been formally described in the literature. Materials and Methods: Patients who underwent resection of a TSH-secreting pituitary adenoma during 1987 to 2012 at a single institution were identified. Preoperative thyroid hormone state, anesthetic management, and outcome were recorded. Hemodynamic associations with intraoperative events were compared between those who were hyperthyroid and euthyroid at the time of surgery. Results: Of 2268 patients having transsphenoidal resection of a pituitary tumor, 19 (0.84%) had resection of a TSH-secreting adenoma. At the time of surgery, 6 (32%) were hyperthyroid, 11 (58%) were euthyroid, and 2 (10%) were hypothyroid based on serum thyroxine concentration. General anesthesia was maintained with a potent inhaled anesthetic in all patients, and included nitrous oxide in 18 of 19 (95%). Seventeen (90%) had an arterial catheter placed for surgery. Only 1 patient (5%) required an intraoperative blood transfusion. There were no significant differences in heart rate or blood pressure at induction of anesthesia, upon intranasal injection of local anesthetic containing epinephrine, or upon emergence from anesthesia, between patients who were chemically hyperthyroid or euthyroid. Twelve of 19 (63%) had tumor extension beyond the sella turcica. Common complications were nausea and vomiting (42%), diabetes insipidus (32%), and temporary or permanent hypopituitarism (42%). Conclusions: Patients having resection of TSH-secreting pituitary adenomas can present in any thyroid state. An awareness of risks and potential complications in patients with TSH-secreting adenomas can help tailor perioperative care.

AbstractAimThe Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch–anal anastomosis. The model incorporates four predictive variables: completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohn's disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients who had RPC.MethodValidation was performed in a multicentre cohort of 747 consecutive patients who had an RPC between 1990 and 2015 in three tertiary‐care facilities, using a Kaplan–Meier survival analysis and Cox regression analysis. The performance of the model was expressed using the Harrell concordance error rate. The primary outcome measure was pouch survival with maintenance of anal function.ResultsDuring the study period, 45 (6.0%) patients experienced failure at a median interval of 31 months (interquartile range 9–82 months) from the original RPC. Multivariable analysis showed handsewn anastomosis to be the only significant independent predictor. The Harrell concordance error rate was 0.42, indicating poor performance. Anastomotic leakage and Crohn's disease of the pouch were strong postoperative predictors for pouch failure and showed a significant difference in pouch survival after 10 years (P < 0.001).ConclusionThe poor performance of the Cleveland Clinic prognostic model makes it unsuitable for daily clinical practice. Handsewn anastomosis was associated with pouch failure in our cohort with relatively few events. A prediction model for anastomotic leakage or Crohn's disease of the pouch may be a better solution since these variables are strongly associated with pouch failure.

Brain-derived neurotrophic factor (BDNF), a neurotrophin produced by airway smooth muscle (ASM), enhances inflammation effects on airway contractility, supporting the idea that locally produced growth factors influence airway diseases such as asthma. We endeavored to dissect intrinsic mechanisms regulating endogenous, as well as inflammation (TNF-α)-induced BDNF secretion in ASM of nonasthmatic vs. asthmatic humans. We focused on specific Ca2+ regulation- and inflammation-related signaling cascades and quantified BDNF secretion. We find that TNF-α enhances BDNF release by ASM cells, via several mechanisms relevant to asthma, including transient receptor potential channels TRPC3 and TRPC6 (but not TRPC1), ERK 1/2, PI3K, PLC, and PKC cascades, Rho kinase, and transcription factors cAMP response element binding protein and nuclear factor of activated T cells. Basal BDNF expression and secretion are elevated in asthmatic ASM and increase further with TNF-α exposure, involving many of these regulatory mechanisms. We conclude that airway BDNF secretion is regulated at multiple levels, providing a basis for autocrine effects of BDNF under conditions of inflammation and disease, with potential downstream influences on contractility and remodeling.

BACKGROUNDPatients with FMS like tyrosine kinase 3 (FLT3)‐mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT).METHODSData from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes.RESULTSIn total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild‐type (WT) group (38% [95% confidence interval (CI), 30%‐45%] vs 28% [95% CI, 24%‐33%]; P = .04; relative risk, 1.60 [95% CI, 1.15‐2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia‐free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3‐year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%‐57%; WT group: 55%, 95% CI, 50%‐60%; P = .20).CONCLUSIONSThe current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long‐term survivors. Cancer 2016;122:3005‐3014. © 2016 American Cancer Society.

SAGE-Journals-Accessible-Video-Player 10.1089/vid.2016.0030.M1 sj-vid-1-vid-10.1089_vid.2016.0030