Abstract
Background
Tofacitinib is a partially selective Janus kinase inhibitor approved for the treatment of refractory moderate to severe ulcerative colitis UC. We sought to define the ...effectiveness and adverse effects of tofacitinib in a real-world cohort.
Methods
We conducted a retrospective observational cohort study of 134 patients with UC 64% male; median age 37 years range 16–81; 83% of patients had previously received at least one biologic treated with tofacitinib from October 2018 to October 2019 in four UK centres. Disease activity was assessed using the Simple Clinical Colitis Activity Index SCCAI or partial Mayo score PMS, depending on study site. Response and remission were defined as a reduction in SCCAI or PMS of ≥3and SCCAI ≤2 or a PMS ≤1, respectively.
Results
Overall, 74% (88/119; 95 confidence interval CI 65–81% patients responded to tofacitinib at Week 8 and steroid-free remission was observed in 44% 47/108; 95% CI 3453% patients at Week 26. Primary non-response was independently associated with younger age p = 0.014 and higher C-reactive protein CRP levels at baseline p = 0.004. Only 23% 3/13 of patients who continued tofacitinib in the setting of primary non-response were in steroid-free remission at Week 26. Prior biologic exposure did not influence response or remission rates. Dose escalation, however, recaptured response in approximately half of patients who had lost response. Dyslipidaemia was observed in 20% 27/134; 95% CI 1428% of patients, but adverse events necessitating drug withdrawal were uncommon and no venous thromboembolic events occurred.
Conclusions
In this multicentre real-world cohort, tofacitinib was well tolerated and clinically effective in a treatment-refractory UC population.
The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and ...asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER.
All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal GI endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI).
A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m
) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %.
Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.
Aim
Rectal neuroendocrine tumours (NETs) are the most common type of gastrointestinal NET. European Neuroendocrine Tumour Society guidelines suggest that rectal NETs measuring ≤10 mm are indolent ...with low risk of spread. In practice, many patients with lesions ≤1 cm do not undergo complete tumour staging. However, the size of the lesion may not be the only risk factor for nodal involvement/metastases. The aim of this study was to determine if MRI ± nuclear medicine imaging alters tumour stage in patients with rectal NETs ≤10 mm.
Methods
Patients referred to a tertiary NET centre between 2005 and 2020 who met the inclusion criteria of a rectal NET ≤10 mm, full cross‐sectional imaging, primarily an MRI scan and, if abnormal findings were identified, a subsequent 68Ga‐DOTATATE positron emission tomography scan were included. All patients were followed up at our institution.
Results
In all, 32 patients with rectal NETs 10 mm or less were included in the study: 16 women; median age 58 years (range 33–71); 47% (n = 15) were referred from bowel cancer screening procedures. The median size of the lesions was 5 mm (range 2–10 mm). 81% (n = 26) were World Health Organization Grade 1 tumours with Ki67 <3%. Radiological staging confirmed nodal involvement in 25% (8/32); two cases had distant metastatic disease. Lymphovascular invasion was present in 3% (1/32) of patients but none demonstrated peri‐neural invasion.
Conclusion
This study demonstrates that small rectal NETs can develop nodal metastases; therefore it is important to stage these tumours accurately with MRI at baseline and, if there are concerns regarding potential lymph node metastases, to consider 68Ga‐DOTATATE positron emission tomography imaging.
Full text
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
(Poly)phenols (PPs) may have a therapeutic benefit in gastrointestinal (GI) disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD). The aim of this review is to ...summarise the evidence-base in this regard. Observational evidence does not give a clear indication that PP intake has a preventative role for IBD or IBS, while interventional studies suggest these compounds may confer symptomatic and health-related quality of life improvements in known patients. There are inconsistent results for effects on markers of inflammation, but there are promising reports of endoscopic improvement. Work on the effects of PPs on intestinal permeability and oxidative stress is limited and therefore conclusions cannot be formed. Future work on the use of PPs in IBD and IBS will strengthen the understanding of clinical and mechanistic effects.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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