Cardiotrophin-1 activates the Jak/STAT, PI3K/Akt, p38 and p42/44 MAPK pathways in cardiac fibroblasts. Use of pharmacologic inhibitors reveals that each of these pathways play a role in CT-1 induced protein synthesis.

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BACKGROUND: Although the body of evidence supporting nonoperative management for rectal cancer has been accumulating, there has been little systematic investigation to explore how physicians and patients value the tradeoffs between oncologic and functional outcomes after abdominal perineal resection and nonoperative management. OBJECTIVE: The purpose of this study was to elicit patient and physician preferences for nonoperative management relative to abdominal perineal resection in the setting of low rectal cancer. DESIGN: We conducted a standardized interviews of patients and a cross-sectional survey of physicians. SETTINGS: Patients from 1 tertiary care center and physicians from across Canada were included. PATIENTS: The study involved 50 patients who were previously treated for rectal cancer and 363 physicians who treat rectal cancer. INTERVENTIONS: Interventions included standardized interviews using the threshold technique with patients and surveys mailed to physicians. MAIN OUTCOMES MEASURES: We measured absolute increase risk in local regrowth and absolute decrease in overall survival that patients and physicians would accept with nonoperative management relative to abdominal perineal resection. RESULTS: Patients were willing to accept a 20% absolute increase for local regrowth (ie, from 0% to 20%) and a 20% absolute decrease in overall survival (ie, from 80% to 60%) with nonoperative management relative to abdominal perineal resection, whereas physicians were willing to accept a 5% absolute increase for local regrowth (ie, from 0% to 5%) and a 5% absolute decrease in overall survival (ie, from 80% to 75%) with nonoperative management relative to abdominal perineal resection. LIMITATIONS: Data were subject to response bias and generalizable to only a select group of patients with low rectal cancer. CONCLUSIONS: Offering nonoperative management as an option to patients, even if oncologic outcomes are not equivalent, may be more consistent with the values of patients in this setting. See Video Abstract at http://links.lww.com/DCR/A688.

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Irritable bowel syndrome (IBS) affects a significant proportion of the North American population; however, the etiology and pathophysiology of this disease remain poorly understood, and treatment is focused on symptom management. Over the years, research has revealed that the bacterial flora in the human gut interact with the bowel in a complex and dynamic relationship and may be responsible for the induction and progression of some of the pathophysiologic aspects of IBS. Probiotics are nonpathogenic bacteria that benefit the host, and the roles they can play in the bacterio-gut relationship provide hope of a safe treatment that would allow for modulation of IBS disease states. Probiotic treatment for IBS has undergone significant exploration, yet the exact therapeutic effects and doses of these beneficial bacteria remain unclear due to the conflicting nature of available evidence. This review discusses the evidence from randomized controlled trials on probiotic treatment of IBS and presents the current understanding of the mechanisms of action of probiotics as they apply to IBS and provides a plausible explanation for the variability in evidence documented by the various trials under review.

Granulomatosis with polyangiitis (GPA) is one of the most common forms of systemic vasculitis, which usually involves the upper and lower respiratory tract, but it may affect also multiple organs. The aim of the study was an echocardiographic evaluation of cardiac involvement in GPA patients during remission. Eighty eight patients with GPA were evaluated in the study. The control group consisted of 40 age and sex-matched patients without a previous history of cardiovascular disease. We found that there were no differences between GPA and control groups regarding left atrial enlargement and interventricular septal hypertrophy. In one GPA patient, all heart chambers were enlarged. Left ventricle systolic function was decreased (LVEF ≤ 50%) in eight patients with GPA, and left ventricle wall motion abnormalities were observed in 12 patients. Left ventricle relaxation dysfunction, mitral valve and tricuspid valve regurgitation were observed with the same frequency in both GPA and control groups. Aortic regurgitation was the single abnormality that occurred significantly more often in the GPA group than in controls (28% vs. 7.5%; p = 0.03). Pericardial effusion was observed in three GPA patients and in none from the control group. We conclude that the most common echocardiographic manifestation in GPA patients in remission was aortic valve regurgitation. However, cardiac involvement in such patients is rather rare and in the majority of cases clinically insignificant.

The majority of patients diagnosed with Crohn's disease eventually require surgical intervention. Unfortunately, postsurgical remission tends to be short lived; a significant number of patients experience clinical relapse and many require additional operations. The pathogenesis of this postoperative recurrence is poorly understood and, currently, there are no reliable tools to predict when and in whom the disease will recur. Furthermore, the postoperative prophylaxis profiles of available Crohn's disease therapeutic agents such as 5-aminosalicylates, immunomodulators, steroids and probiotics have been disappointing. Recently, the combination of antibiotics and azathioprine in selected high-risk patients has demonstrated some potential for benefit. The goal of the present article is to provide a coherent summary of previous and new research to guide clinicians in managing the challenging and complex problem of postoperative Crohn's disease recurrence.