Distinct neurophysiological profiles in irritable bowel syndrome.

The objective of this study was to determine whether cortical evoked potentials (CEPs) can define neurophysiological patterns in irritable bowel syndrome (IBS). In this prospective study of consecutive patients attending secondary and tertiary centers, patients with Rome II-defined IBS underwent rectal sensory and pain threshold (RST and RPT, respectively) testing with electrical stimulation on three separate visits. CEPs were collated for 75% pain thresholds, and anxiety [Spielberger State-Trait Anxiety Inventory (SSTAI)] questionnaires were completed. Subjects were 33 IBS patients (27 female, mean age 40.1 yr) and 21 healthy controls (14 female, mean age 31.4 yr). At visit 3, RPT was significantly lower [mean (95% CI)] in IBS patients than in control subjects: 58.2 mA (48.0-68.5) vs. 79.5 mA (69.3-89.6) (P < 0.01). No significant differences were observed in CEP latencies and amplitudes between visits 1, 2, and 3 within each group, except P2 latency for controls (P = 0.04) and N2 latency (P = 0.04) and N2 amplitude (P = 0.02) for IBS patients. Group comparisons showed significant differences in 3-day mean RPT, CEP amplitudes, and CEP latencies between IBS patients and controls. RPT <50 mA and P1 latency >106 ms were identified four IBS subgroups: 24% were hypersensitive, 12% were hypervigilant, 15% were hyposensitive, and 49% exhibited normal P1 latency and pain threshold. CEPs are reliable and reproducible measures of early sensory processing. Identification of four IBS neurophysiological patterns highlights its heterogeneous nature. These findings mark the first step toward personalized medicine in IBS, whereby therapy may be directed at the underlying physiological process.

GSK2586184, a JAK1 selective inhibitor, in two patients with ulcerative colitis.

Tofacitinib, a non-selective Janus kinase (JAK) inhibitor, is effective in inducing clinical and endoscopic remission in patients with active ulcerative colitis (UC). Tofacitinib inhibits cytokine signalling through blockade of JAK1, JAK2, JAK3 and tyrosine kinase 2 (TYK2). Adverse events including neutropenia and anaemia resulting from JAK2 inhibition have been observed in actively treated patients. By selectively targeting JAK1, such adverse events could be expected to be avoided. This open label study was designed to enrol 15 patients with UC, however the trial was discontinued after two inclusions due to safety concerns with the agent in a parallel trial for systemic lupus erythematosus. GSK2586184 was administered in two patients with moderate-to-severe UC. The JAK1 selective inhibitor GSK2586184 was well tolerated and induced clinical and endoscopic response in two patients with moderate-to-severe UC. In addition, treatment with GSK2586184 decreased histology scores and faecal calprotectin levels at early withdrawal.