The natural history of COVID-19 in vaccinated inflammatory bowel disease patients.

AIM: Assess the characteristics of break through COVID-19 in Inflammatory Bowel Disease (IBD) patients, despite complete vaccination. METHODS: Patients who reported a COVID-19 at least 3 weeks after complete vaccination were asked to answer an on-line anonymous questionnaire which included patient and disease characteristics, vaccination history, and the evolution of COVID-19. RESULTS: Among 3240 IBD patients who reported complete vaccination between 1st May 2021 and 30thJune 2022, 402 (12.4%) were infected by SARS Cov-2 [223 male, 216 Crohn's disease (CD), 186 Ulcerative Colitis (UC), mean (SD) age 42.3 (14.9) years, mean (SD) IBD duration 10.1 (9.7) years]. Three hundred and sixty-nine patients (91.8%) were infected once and 33 (8.2%) twice. The mean (SD) time between last vaccination and infection was 4.1 (1.6) months. Overall, 351 (87.3%) patients reported mild constitutional and/or respiratory symptoms, 34 (8.4%) were asymptomatic and only 17 patients (4.2%) required hospitalization. Of hospitalized patients, 2 UC patients died of COVID-19 pneumonia. The remaining hospitalized patients did not need high flow oxygen supply or ICU admission. CONCLUSIONS: A minority of completely vaccinated IBD patients developed COVID-19 which evolved with mild symptoms and a favorable outcome. These results reinforce the importance of vaccination especially in vulnerable populations.

Genetic polymorphisms and risk of MALT lymphoma in Greek population.

PURPOSE: MALT lymphoma is thought to have a genetic component. Genetic studies in the greek population are rare and genetic determinants remain to be established. The current study aimed to seek correlations between genetic polymorphisms and risk of MALT lymphoma in the Greek population. PATIENTS AND METHODS: 83 MALT lymphoma patients and 60 age-matched healthy outpatients were recruited. SNPs in TNFa, LTA and CTLA-4 genes and IL1RN-VNTR and GSTT1 and GSTTM1 null polymorphisms were genotyped using published PCR/PCR-RFLP methods, while two novel PCR-RFLP methods were developed for IL-22 rs7314777 and TCF19 rs7750641 SNPs. Part of the results was validated by DNA-sequencing. Statistical analysis was performed using SPSS and the SNPstats bioinformatic tool. RESULTS: The mean age of the patients and controls were 55.9 and 56.2 years respectively. The majority of patients (63) suffered gastric marzinal zone lymphoma (GMZL) and 71.1% were stage I at diagnosis. A statistically significant association was noted for the CTLA-4 49A/ G G variant (OR:2.56,p: 0.006) and the TCF19 rs7750641 SNP T variant (OR: 3.86, p:0.023). CONCLUSIONS: Our study confirmed a role for CTLA-4 49A/G and TCF19 rs7750641 SNPs in the Greek population. Additional studies could help confirm these associations and possibly link them to prognosis or response to treatment parameters.

The Pathogenesis of Extraintestinal Manifestations: Implications for IBD Research, Diagnosis, and Therapy.

This article reports on the sixth scientific workshop of the European Crohn's and Colitis Organisation [ECCO] on the pathogenesis of extraintestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. This paper has been drafted by 15 ECCO members and 6 external experts [in rheumatology, dermatology, ophthalmology, and immunology] from 10 European countries and the USA. Within the workshop, contributors formed subgroups to address specific areas. Following a comprehensive literature search, the supporting text was finalized under the leadership of the heads of the working groups before being integrated by the group consensus leaders.

Sphingosine-1-phosphate receptor-1 (S1P1) is expressed by lymphocytes, dendritic cells, and endothelium and modulated during inflammatory bowel disease.

The sphingosine-1-phosphate receptor-1 (S1P1) agonist ozanimod ameliorates ulcerative colitis, yet its mechanism of action is unknown. Here, we examine the cell subsets that express S1P1 in intestine using S1P1-eGFP mice, the regulation of S1P1 expression in lymphocytes after administration of dextran sulfate sodium (DSS), after colitis induced by transfer of CD4+CD45RBhi cells, and by crossing a mouse with TNF-driven ileitis with S1P1-eGFP mice. We then assayed the expression of enzymes that regulate intestinal S1P levels, and the effect of FTY720 on lymphocyte behavior and S1P1 expression. We found that not only T and B cells express S1P1, but also dendritic (DC) and endothelial cells. Furthermore, chronic but not acute inflammatory signals increased S1P1 expression, while the enzymes that control tissue S1P levels in mice and humans with inflammatory bowel disease (IBD) were uniformly dysregulated, favoring synthesis over degradation. Finally, we observed that FTY720 reduced T-cell velocity and induced S1P1 degradation and retention of Naïve but not effector T cells. Our data demonstrate that chronic inflammation modulates S1P1 expression and tissue S1P levels and suggests that the anti-inflammatory properties of S1PR agonists might not be solely due to their lymphopenic effects, but also due to potential effects on DC migration and vascular barrier function.

Colonic casts: unexpected complications of colonic ischaemia.

Introduction Extensive colonic ischaemia can result in passage of a colonic 'cast' (CC) through the rectum. Case Study We report a 69-year-old male who initially underwent surgery to remove a sessile polyp. On postoperative day (POD)15, he was febrile, suffering from diarrhoea, and was treated conservatively. On POD18, the patient returned to our hospital with a CC that presented after defaecation. Computed tomography of the abdomen revealed a CC extending from the descending colon to the anal orifice with presentation of air between the affected colonic wall and the CC. The patient was treated conservatively and discharged on POD20 without complications having passed the CC (≈80cm) completely and becoming afebrile. Conclusions In most cases, the cause of CC passage is surgery for colorectal cancer or repair of an abdominal aortic aneurysm. A mild-to-severe presentation is dependent upon the bowel-wall layers affected by ischaemia and which therefore are included in the CC.

KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation.

Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor κB (NFκB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation.

Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis.

Interactions between TNF-like Cytokine 1A (TL1A) and its receptors, death receptor-3 (DR3) and decoy receptor-3 (DcR3) may be important in atherogenesis. We hypothesized that dysregulation of this system predicts formation of new atheromatic plaques in rheumatoid arthritis (RA). Forty-five patients were prospectively followed up for 40.5 ± 3.6 months. Serum concentrations of TL1A and DcR3 were measured at baseline and carotid and femoral arteries examined by ultrasound at baseline and at the end of follow-up. Individual serum levels of TL1A correlated with the progression of carotid atheromatic plaque height (Spearman rho = 0.550, p = 0.003). Patients with low TL1A and undetectable DcR3 serum levels at baseline showed significantly fewer newly formed carotid plaques during the next 3.5 years than the remaining patients (P = 0.016). Univariate analysis showed that a "low TL1A/DcR3" immunophenotype predicted a preserved atherosclerosis profile in carotid (P = 0.026), or carotid and/or femoral arteries (P = 0.022). Dysregulated TL1A-induced signaling may be associated with risk for accelerated atherosclerosis in RA.

Sedation in digestive endoscopy: the Athens international position statements.

BACKGROUND: Guidelines and practice standards for sedation in endoscopy have been developed by various national professional societies. No attempt has been made to assess consensus among internationally recognized experts in this field. AIM: To identify areas of consensus and dissent among international experts on a broad range of issues pertaining to the practice of sedation in digestive endoscopy. METHODS: Thirty-two position statements were reviewed during a 1 (1/2)-day meeting. Thirty-two individuals from 12 countries and four continents, representing the fields of gastroenterology, anaesthesiology and medical jurisprudence heard evidence-based presentations on each statement. Level of agreement among the experts for each statement was determined by an open poll. RESULTS: The principle recommendations included the following: (i) sedation improves patient tolerance and compliance for endoscopy, (ii) whenever possible, patients undergoing endoscopy should be offered the option of having the procedure either with or without sedation, (iii) monitoring of vital signs as well as the levels of consciousness and pain/discomfort should be performed routinely during endoscopy, and (iv) endoscopists and nurses with appropriate training can safely and effectively administer propofol to low-risk patients undergoing endoscopic procedures. CONCLUSIONS: While the standards of practice vary from country to country, there was broad agreement among participants regarding most issues pertaining to sedation during endoscopy.