Inflammasome Activation in Pulmonary Arterial Hypertension.

Inflammasomes are multi-protein complexes that sense both infectious and sterile inflammatory stimuli, launching a cascade of responses to propagate danger signaling throughout an affected tissue. Recent studies have implicated inflammasome activation in a variety of pulmonary diseases, including pulmonary arterial hypertension (PAH). Indeed, the end-products of inflammasome activation, including interleukin (IL)-1ß, IL-18, and lytic cell death ("pyroptosis") are all key biomarkers of PAH, and are potentially therapeutic targets for human disease. This review summarizes current knowledge of inflammasome activation in immune and vascular cells of the lung, with a focus on the role of these pathways in the pathogenesis of PAH. Special emphasis is placed on areas of potential drug development focused on inhibition of inflammasomes and their downstream effectors.

Management Strategies for Abdominal Bloating and Distension.

Bloating and distension are among the most common gastrointestinal complaints reported by patients with functional gut disorders and by the general population. These 2 complaints are also among the most prevalent of the severe symptoms reported by patients with irritable bowel syndrome. Nonetheless, only a limited number of published studies have specifically addressed bloating; it is infrequently studied as a primary endpoint, and what little systematic information exists has often been garnered from the assessment of secondary endpoints or the dissection of composite endpoints. This lack of data, and our consequent limited understanding of the pathophysiology of bloating, had hampered the quest for effective and targeted therapies until recently. Advances in the knowledge of underlying mechanisms, particularly with regard to the roles of diet, poorly absorbed fermentable carbohydrates, dysbiosis of the gut bacteria, alterations in visceral hypersensitivity, and abnormal viscerosomatic reflexes, have enabled the development of improved treatment options. The most significant recent advance has been a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, which significantly reduces patients' symptoms and improves quality of life. Given the prevalence of bloating and its perceived severity, it is clear that further studies regarding the pathogenesis and treatment of this problem are needed.

Cytomegalovirus disease, haemophagocytic syndrome, immunosuppression in patients with IBD: 'a cocktail best avoided, not stirred'.

We report two cases of cytomegalovirus (CMV) viraemia resulting in severe pneumonitis and associated haemophagocytic syndrome manifesting in patients with inflammatory bowel disease, on stable doses of azathioprine in clinical remission. In both cases, azathioprine was withdrawn at time of hospital presentation and after delays in diagnosis; intravenous ganciclovir was then administered, with resultant rapid improvement of haematological and clinical parameters. Following recovery, immunomodulators were not recommenced given patient aversion and the theoretical risk of CMV reactivation, albeit the evidence for this approach is limited. CMV-related haemophagocytic syndrome and organ dysfunction, in the context of immunomodulator therapy in IBD are rare but life-threatening, and thus requires further investigation and discussion.