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Background Individuals hospitalized with severe ulcerative colitis represent a complex group of patients. Variation exists in the quality of care of admitted patients with inflammatory bowel disease. We hypothesized that implementation of a standardized admission order set could result in improved adherence to current best practice guidelines (Toronto Consensus Statements) for the management of this patient population. Methods A retrospective cohort study of patients admitted with severe ulcerative colitis to a Montreal tertiary center was conducted. Two cohorts were defined based on pre- and post-implementation of a standardized order set. Adherence to 11 quality indicators was assessed before and after implementation of the intervention. These included: Clostridioides difficile and stool cultures testing, ordering an abdominal X-ray and CRP, organizing a flexible sigmoidoscopy, documenting latent tuberculosis, initiating thromboprophylaxis, use of intravenous steroids, prescribing infliximab if refractory to steroids, limiting narcotics, and surgical consultation if refractory to medical therapy. Results Adherence to 6 of the 11 quality indicators was improved in the post-intervention cohort. Significant increases were noted in adherence to C difficile testing (75.5% versus 91.9%, P < 0.05), CRP testing (71.4% versus 94.6%, P < 0.01), testing for latent tuberculosis (38.1% versus 84.6%, P < 0.01), thromboprophylaxis (28.6% versus 94.6%, P < 0.01), adequate corticosteroids prescription (72.9% versus 94.6%, P < 0.01), and limitation of narcotics prescribed (68.8% versus 38.9%, P < 0.01). Conclusions Implementation of a standardized order set, focused on pre-defined quality indicators for hospitalized patients with severe UC, was associated with meaningful improvements to most quality indicators defined by the Toronto Consensus Statements.

Background/Aims In patients receiving ustekinumab (UST) for treatment of Crohn’s disease, there is no proven strategy to enhance or re-capture response. We assessed the utility of UST intravenous (IV) reinduction (~6 mg/kg) to achieve clinical, biochemical and endoscopic response or remission, in patients with partial or loss of response to UST maintenance therapy. Methods A multicentre, retrospective cohort study was performed. Adults who received an IV reinduction dose of UST for either partial response or secondary loss of response to UST were assessed. The primary outcome was clinical remission off corticosteroids (Harvey Bradshaw Index Results Sixty-five patients (median age 38 years, 54.7% women) underwent IV UST reinduction between January 2017 and April 2019. Most patients (88.3%) were already on escalated maintenance dosing of UST 90 mg subcutaneous every 4 weeks. Clinical outcomes were assessed at a median of 14 weeks (IQR: 12–19) post-reinduction. The primary outcome of clinical remission off corticosteroids with biochemical and/or endoscopic response was achieved in 31.0% (n = 18). Pre-reinduction UST concentrations were ≥1 μg/mL in 88.6% (mean 3.2 ± 2.0 μg/mL). No serious adverse events were reported. Conclusions UST IV reinduction can be effective in patients with Crohn’s disease with partial or loss of response to UST maintenance therapy. Further studies evaluating this strategy are warranted.

Mechanosensing is essential for several physiological functions including touch and pain sensations, osmoregulation, and controlling the myogenic tone of resistance arteries. Understanding how mechanosensitive ion channels (MSCs) are gated can provide important information regarding these processes. We have previously demonstrated that during pathological conditions such as polycystic kidney disease, polycystin 2 (TRPP2) inhibits the activity of potassium-selective MSCs through a filamin A-mediated cytoskeletal effect, and renders tubular epithelial cells susceptible to apoptosis. However, the nature of this cytoskeletal inhibition remains poorly understood. In this study we use a combination of electrophysiology, structured illumination microscopy, and fluorescence recovery after photobleaching (FRAP) to examine the dynamic nature of the TRPP2-mediated cytoskeletal inhibition of the potassium-selective MSC TREK1. Our data indicate that this inhibition of MSC activity occurs through an accelerated cytoskeletal inhibition, and ultimately decreases the open probability of the TREK1 channel. These results shed light on a novel mode of regulation of MSCs gating, which may be at play in several physiological functions.

SUMMARY Neuropathic pain is a chronic debilitating disease that results from nerve damage, persists long after the injury has subsided, and is characterized by spontaneous pain and mechanical hypersensitivity. Although loss of inhibitory tone in the dorsal horn of the spinal cord is a major contributor to neuropathic pain, the molecular and cellular mechanisms underlying this disinhibition are unclear. Here, we combined pharmacogenetic activation and selective ablation approaches in mice to define the contribution of spinal cord parvalbumin (PV)-expressing inhibitory interneurons in naive and neuropathic pain conditions. Ablating PV neurons in naive mice produce neuropathic pain-like mechanical allodynia via disinhibition of PKCγ excitatory interneurons. Conversely, activating PV neurons in nerve-injured mice alleviates mechanical hypersensitivity. These findings indicate that PV interneurons are modality-specific filters that gate mechanical but not thermal inputs to the dorsal horn and that increasing PV inter-neuron activity can ameliorate the mechanical hypersensitivity that develops following nerve injury., In Brief Improved therapy for neuropathic pain requires a better understanding of the spinal cord neuronal networks that process peripheral sensory inputs in health and disease. Petitjean et al. find that a subset of inhibitory interneurons, containing the marker parvalbumin (PV), prevent touch inputs from activating pain circuits. After nerve injury, a decrease is seen in the number of these synapses, and light touch can elicit pain.