Background The effects that therapies for inflammatory bowel disease (IBD) have on immune responses to SARS-CoV-2 vaccination are not yet fully known. Therefore, we sought to determine whether COVID-19 vaccineinduced antibody responses were altered in patients with IBD on commonly used immunosuppressive drugs. Methods In this multicentre, prospective, case-control study (VIP), we recruited adults with IBD treated with one of six different immunosuppressive treatment regimens (thiopurines, infliximab, a thiopurine plus infliximab, ustekinumab, vedolizumab, or tofacitinib) and healthy control participants from nine centres in the UK. Eligible participants were aged 18 years or older and had received two doses of COVID-19 vaccines (either ChAdOx1 nCoV-19 [Oxford-AstraZeneca], BNT162b2 [Pfizer-BioNTech], or mRNA1273 [Moderna]) 6-12 weeks apart (according to scheduling adopted in the UK). We measured antibody responses 53-92 days after a second vaccine dose using the Roche Elecsys Anti-SARS-CoV-2 spike electrochemiluminescence immunoassay. The primary outcome was anti-SARS-CoV-2 spike protein antibody concentrations in participants without previous SARS-CoV-2 infection, adjusted by age and vaccine type, and was analysed by use of multivariable linear regression models. This study is registered in the ISRCTN Registry, ISRCTN13495664, and is ongoing. Findings Between May 31 and Nov 24, 2021, we recruited 483 participants, including patients with IBD being treated with thiopurines (n=78), infliximab (n=63), a thiopurine plus infliximab (n=72), ustekinumab (n=57), vedolizumab (n=62), or tofacitinib (n=30), and 121 healthy controls. We included 370 participants without evidence of previous infection in our primary analysis. Geometric mean anti-SARS-CoV-2 spike protein antibody concentrations were significantly lower in patients treated with infliximab (156•8 U/mL [geometric SD 5•7]; p<0•0001), infliximab plus thiopurine (111•1 U/mL [5•7]; p<0•0001), or tofacitinib (429•5 U/mL [3•1]; p=0•0012) compared with controls (1578•3 U/mL [3•7]). There were no significant differences in antibody concentrations between patients treated with thiopurine monotherapy (1019•8 U/mL [4•3]; p=0•74), ustekinumab (582•4 U/mL [4•6]; p=0•11), or vedolizumab (954•0 U/mL [4•1]; p=0•50) and healthy controls. In multivariable modelling, lower anti-SARS-CoV-2 spike protein antibody concentrations were independently associated with infliximab (geometric mean ratio 0•12, 95% CI 0•08-0•17; p<0•0001) and tofacitinib (0•43, 0•23-0•81; p=0•0095), but not with ustekinumab (0•69, 0•41-1•19; p=0•18), thiopurines (0•89, 0•64-1•24; p=0•50), or vedolizumab (1•16, 0•74-1•83; p=0•51). mRNA vaccines (3•68, 2•80-4•84; p<0•0001; vs adenovirus vector vaccines) were independently associated with higher antibody concentrations and older age per decade (0•79, 0•72-0•87; p<0•0001) with lower antibody concentrations. Interpretation For patients with IBD, the immunogenicity of COVID-19 vaccines varies according to immunosuppressive drug exposure, and is attenuated in recipie...

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BackgroundEndoscopy is performed for direct inspection of the mucosa and acquisition of biopsies in dogs with inflammatory bowel disease (IBD).AimTo evaluate the interobserver agreement in the endoscopic assessment of duodenal mucosa in dogs with IBD.MethodsThirty‐five archived endoscopic images of grossly normal (n = 6) and inflamed (n = 29) duodenal mucosa were displayed to 3 expert and 5 trainee endoscopists. Each image was assessed independently by endoscopists for mucosal abnormalities using established indices (of hyperemia, granularity, friability, lymphatic dilatation, and erosions) or interpreted as normal mucosa (trial 1). A repeated trial (trial 2) was performed with the same images presented in random order 1 month later, and accompanied by a visual template.ResultsThere was slight interobserver agreement in initial mucosal assessment for expert and trainee endoscopists in trial 1 (kappa ≤ 0.02, P > .05). Interobserver agreement improved in trial 2 for both expert and trainee endoscopists (kappa = 0.2, P > .05) for experts and (P < .05) for trainees. There was a significant (P < .01) improvement in trainee endoscopy scores of lesions from trial 1 to trial 2. Regression analysis showed a significant (P < .01) difference between expert versus trainee endoscopy scores in trial 1. Repeat lesion assessment aided by use of a visual template (trial 2) improved the overall scores of trainee endoscopists to near that of expert endoscopists (P = .06).Conclusions and Clinical ImportanceInterobserver agreement of IBD mucosal appearance from endoscopic findings benefitted from operator experience.

Pseudobulbar affect is a disorder resulting from neurologic damage manifesting as sudden, stereotyped affective outbursts that are not reflective of internal emotion. A literature review was completed to examine the current understanding of the epidemiology, characterization, diagnosis, pathophysiology, and treatment of pseudobulbar affect. This review revealed that it is common in neurodegenerative disorders but is poorly recognized, placing significant impacts on patients and their families. The disorder appears to result from a disruption of the cortico-limbicsubcortical-thalamic-pontocerebellar network involved in emotional expression and regulation with resulting disruptions of neurotransmitter systems. Effective treatment is available with agents such as selective serotonin reuptake inhibitors and dextromethorphan combined with quinidine, but further well-designed comparative studies are needed. Advances in technology such as neuroimaging may enhance knowledge about the pathophysiology of this disorder, and help guide future interventions.