Inhibitors of the Janus Kinases: A New Oral Treatment Option for Ulcerative Colitis.

BACKGROUND: The treatment of ulcerative colitis (UC) is based on conventional therapies (aminosalicylates, corticosteroids, and immunosuppressants) and when these are ineffective, biologic drugs. However, in a substantial portion of patients undergoing treatment with biologic agents there is primary or secondary loss of response. Thus, new therapeutic options are been actively explored; among these, there is interest in the Janus kinase (JAK) inhibitors, small molecules that can be administered orally. METHODS: We carried out an extensive literature search concerning the effects of JAK inhibitors for the treatment of patients with UC. RESULTS: Tofacitinib is the drug more extensively studied in this setting, and it was recently approved in Europe for the treatment of moderate to severe UC. The available data suggest that this drug can be effective in obtaining clinical and endoscopic remission in UC patients unresponsive to other treatments, even in those previously treated with biologic drugs. In addition, the drug was able to improve significantly the quality of life of these patients. There are still few data available for the treatment of UC with other JAK inhibitors. CONCLUSIONS: The JAK inhibitors, in particular tofacitinib, are a new class of orally administered drugs effective for the treatment of UC. However, more studies are needed to ascertain the safety of tofacitinib in the long term and whether other compounds of this class may be equally effective.

Pathogenesis of Diverticulosis and Diverticular Disease.

In this session different problems regarding the pathogenesis of diverticular disease were considered, including "Genetics", "Neuromuscular function abnormalities", "Patterns of mucosa inflammation", and "Impact of lifestyle". The patients affected by diverticular disease have clear genetic pattern, that might predispose to the occurrence of the disease as well as to its complications. Neuromuscular abnormalities may be recognized already at the stage of diverticulosis, and inflammation may explain symptoms occurrence in symptomatic uncomplicated diverticular disease (SUDD) or symptoms persistence after an episode of acute diverticulitis. Finally, lifestyle might also have an impact on symptoms' occurrence. Specifically smoking, but also obesity seem to play an important role, while the role of low-fiber diet and constipation is now under debate.

Mood disorders and non-celiac gluten sensitivity.

The association between gluten related disorders and psychiatric diseases has been firmly demonstrated. Non-celiac gluten sensitivity (NCGS) is a syndrome diagnosed in patients responsive to gluten-free diet after ruling out celiac disease and wheat allergy. The pathogenesis of neuro-psychiatric disorders in NCGS is unclear. An association between gluten and schizophrenia was described for the first time in 1950 by Bender et al. In the 1950's, Dicke noted that gluten-free diet improved mood in celiac patients. In 1970, Goldberg et al., in a study of 80 celiac patients, found that 34% of them showed minor affective disorders. Bipolar disorder patients show an increase of blood anti gliadin deamidated antibodies (IgG). The effect of diet and nutrition on autistic spectrum disorders has been investigated in the last two decades, particularly focusing on the symptoms of hyperactivity and attention. Toxoplasma gondii and other neurotropic pathogens as Influenzavirus and Coronavirus may be associated with mood disorders, probably secondary to an increased intestinal permeability. Abnormalities of host-microbiota interactions or of gut-microbiota composition have been associated with central nervous system disorders, such as autism, anxiety, depression and the integrity of intestinal microbiota may be considered a potential therapeutic goal to treat these conditions.