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Evidence on ustekinumab safety in pregnancy is gradually expanding, but its clearance in the postnatal period is unknown. The aim of this study was to investigate ustekinumab concentrations in umbilical cord blood and rates of clearance after birth, as well as how these correlate with maternal drug concentrations, risk of infection, and developmental milestones during the first year of life. Pregnant women with inflammatory bowel disease were prospectively recruited from 19 hospitals in Denmark and the Netherlands between 2018 and 2022. Infant infections leading to hospitalization/antibiotics and developmental milestones were assessed. Serum ustekinumab concentrations were measured at delivery and specific time points. Nonlinear regression analysis was applied to estimate clearance. In 78 live-born infants from 76 pregnancies, we observed a low risk of adverse pregnancy outcomes and normal developmental milestones. At birth, the median infant-mother ustekinumab ratio was 2.18 (95% confidence interval, 1.69–2.81). Mean time to infant clearance was 6.7 months (95% confidence interval, 6.1–7.3 months). One in 4 infants at 6 months had an extremely low median concentration of 0.015 μg/mL (range 0.005–0.12 μg/mL). No variation in median ustekinumab concentration was noted between infants with (2.8 [range 0.4–6.9] μg/mL) and without (3.1 [range 0.7–11.0] μg/mL) infections during the first year of life (P =.41). No adverse signals after intrauterine exposure to ustekinumab were observed with respect to pregnancy outcome, infections, or developmental milestones during the first year of life. Infant ustekinumab concentration was not associated with risk of infections. With the ustekinumab clearance profile, live attenuated vaccination from 6 months of age seems of low risk. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Little is known about the involvement of gut microbiota in the disease course of diverticulitis and the potential benefits of manipulating the gut milieu. We propose to conduct a randomised placebo-controlled feasibility trial of faecal microbiota transplantation (FMT) given as capsules to patients with acute uncomplicated diverticulitis. Objectives: The objective is primarily to investigate the feasibility of clinical safety, explore efficacy associated with FMT in this patient population, and examine changes in patient-reported quality of life and the composition and function of the gut microbiota. Design: Study protocol for a randomised placebo-controlled trial. Methods and analysis: Participants with acute, uncomplicated diverticulitis, as confirmed by computed tomography (CT) scan, will be recruited from Odense University Hospital (Denmark) and randomly assigned to either the intervention group or the control group. The intervention group will consist of 20 patients who receive encapsulated FMT. The control group will also consist of 20 patients, receiving placebo capsules. Primary safety endpoint : Patient safety is monitored by (a) the number of re-admissions and (b) the number of adverse events within 3 months of FMT/placebo; Primary efficacy endpoint : Reduction in the proportion of patients treated with antibiotics within 3 months following FMT/placebo; Secondary outcome : Change from baseline to 3 months in the GI-QLI questionnaire. Results will be analysed using an intention-to-treat approach. Adverse events or unintended consequences will be reported. Ethics and discussion: This is the first study to investigate the safety and efficacy of FMT in patients with acute uncomplicated diverticulitis. The project has the potential to broaden the knowledge and literature on the role of the intestinal microbiota in diverticulitis, and we believe it will elevate our understanding of cause and effect. Trial registration: Informed consent is obtained from all participants. The study is approved by the regional ethics committee (ref. S-20230023) and the Danish Data Protection Agency (ref. 24/2435). The trial was registered on clinicaltrials.gov (NCT06254625) on 10th February 2024. [ABSTRACT FROM AUTHOR]

Chronic inflammatory diseases (CIDs) pose a growing healthcare challenge, with a substantial proportion of patients showing inadequate response to biological treatment. There is renewed interest in dietary changes to optimize treatment regimens, with a growing body of evidence suggesting beneficial effects with adherence to a gluten‐free diet. This study compared the likelihood of achieving clinical response to biological treatment after 14–16 weeks in patients with CID with high versus low‐to‐medium gluten intake. Secondary outcomes of interest included changes in disease activity, health‐related quality of life and C‐reactive protein. The study was a multicentre prospective cohort of 193 participants with a CID diagnosis (i.e. Crohn's Disease, Ulcerative Colitis, Rheumatoid Arthritis, Axial Spondyloarthritis, Psoriatic Arthritis or Psoriasis) who initiated biological treatment between 2017 and 2020. Participants were stratified based on their habitual gluten intake: the upper 33.3% (high gluten intake) and the remaining 66.6% (low‐to‐medium gluten intake). The proportion of patients achieving clinical response to biological treatment after 14–16 weeks was compared using logistic regression models. The median gluten intake differed significantly between groups (12.5 g/day vs. 5.9 g/day, standardized mean difference = 1.399). In total, 108 (56%) achieved clinical response to treatment, with no difference between 35 (55%) in the high gluten group and 73 (57%) in the medium‐to‐low gluten group (OR = 0.96 [0.51–1.79], p = 0.897). No differences were found with secondary outcomes. In conclusion, this study found no association between gluten intake and response to biological treatment in patients with CID. [ABSTRACT FROM AUTHOR]

Background and Aims To investigate if treatment with non-pooled, multidonor faecal microbiota transplantation [FMT] for 4 weeks was superior to placebo to induce clinical remission in patients with chronic pouchitis. Methods The study was a randomised, double-blinded, placebo-controlled study with a 4-week intervention period and 12-month follow-up. Eligible patients with chronic pouchitis were recruited from five Danish hospitals. Participants were randomised to non-pooled, multidonor FMT derived from four faecal donors, or placebo. Treatment was delivered daily by enema for 2 weeks, followed by every second day for 2 weeks. Disease severity was accessed at inclusion and 30-day follow-up, using the Pouchitis Disease Activity Index [PDAI]; PDAI <7 was considered equivalent to clinical remission. Faecal samples from participants and donors were analysed by shotgun metagenomic sequencing. Results Inclusion was stopped after inclusion of 30 participants who were randomised 1:1 for treatment with FMT or placebo. There was no difference in participants achieving clinical remission between the two groups at 30-day follow-up, relative risk 1.0 (95% CI [0.55; 1.81]). Treatment with FMT resulted in a clinically relevant increase in adverse events compared with placebo, incidence rate ratio 1.67 (95% CI [1.10; 2.52]); no serious adverse events within either group. Faecal microbiota transplantation statistically significantly increased the similarity of participant faecal microbiome to the faecal donor microbiome at 30-day follow-up [ p  = 0.01], which was not seen after placebo. Conclusions Non-pooled, multidonor FMT was comparable to placebo in inducing clinical remission in patients with chronic pouchitis, but showed a clinically relevant increase in adverse events compared with placebo. ClincialTrials.gov number, NCT04100291. [ABSTRACT FROM AUTHOR]

Objectives: The influence of comorbidity on long-term hospitalization and mortality after COVID-19 in adults (40–59 years) and older adults (≥60 years) is yet to be explored. Methods: This is a Danish population-based cohort study of patients with a first-time positive PCR test for COVID-19 from 1 March 2020, to 28 February 2022 (N = 1,034,103). Exposed cohorts were patients with 1) a Charlson Comorbidity Index (CCI) score of 1–2 and 2) a CCI score ≥3, who were compared to patients without comorbidity (CCI of zero) within the groups of adults (67.9%) and older adults (32.1%) for the risk of hospitalization and mortality. Next, within the age groups, each disease category of the CCI was considered as an exposed cohort and compared to patients who did not have the specific disease of interest. Adjusted hazard ratios (HR) for hospitalization and mortality were estimated by Cox regression models adjusted for confounders. Results: The highest HRs were in adult patients with a CCI score of ≥3. The adjusted HR was 4.54 (95%CI: 4.38–4.70) for hospitalization, and among older adults it was 3.05 (95%CI: 2.99–3.11). The adjusted HR for mortality among adults with a CCI score ≥3 was 21.04 (95%CI: 18.86–23.47), and the adjusted HR for mortality among older adults was 4.61 (95%CI: 4.44–4.78). The underlying disease influenced the risk estimates among adults and older adults, and "dementia" had the highest impact on mortality. Conclusion: A CCI score of 1 or above increases the risk of hospitalization and mortality up to 2 years after a positive PCR test of COVID-19 for adults and older adults. Further, the type of underlying disease in older adults highly influences the risk of hospitalization and mortality. [ABSTRACT FROM AUTHOR]

Background: Fecal Microbiota Transplant (FMT) is an effective treatment for recurring Clostridioides Difficile Infections (rCDI). FMT administered via oral capsules (caFMT) offers several practical advantages to conventional liquid FMT. We began using caFMT in 2021 imported from an external institution. Based on similar production methods, we began our own caFMT production in 2022. We aimed to evaluate the quality of our caFMT. Study Design and Methods: We created a database of all FMT treatments (n = 180) provided by our institution. Quality of all FMT was evaluated by treatment success rates. We compared our caFMT to the imported caFMT. Results: Our caFMT yielded similar success rates compared to that of the imported caFMT, 65% (CI 95% 58–72%) and 72% (CI 95% 66–79%) respectively. FMT administered via colonoscopy had a significantly higher success rate, 79% (CI 95% 73–85%) than own our caFMT and other routes of administration. The combined success rate of treatments increased notably for all routes of administration when repeating FMT after prior failure. Discussion: The fact that our caFMT compared similarly to the imported caFMT was viewed as a success in terms of quality assurance. Our caFMT had a slightly lower success rates compared to data from other studies, but could be affected by several other factors than our FMT-production methods. A lower success rate of caFMT compared to FMT via colonoscopy is acceptable due to the practical advantages offed by caFMT. Our study serves as a practical example, proving that of the standardization of caFMT production is indeed viable. [ABSTRACT FROM AUTHOR]

Recent research on crisis communication has focused on the challenges of complex and protracted crises. In this essay, it is argued that such crises must be handled communicatively by putting the communication challenges, constraints and opportunities at the centre. To this end, the combination of the notions of the rhetorical situation and kairos is suggested as a keystone that provides a bottom‐up, context‐sensitive approach needed to cope with the fluid and changing situations of such crisis. Importantly, the life cycle of a protracted crisis can not only be understood in terms of physical factors (e.g., infection rates in a pandemic) but is also formed through the public's perceptions and the communicative choices of crisis communicators calling for action to mitigate or end a crisis. The rhetorical situation and kairos highlight the importance of spatial temporality, the uniqueness of the situations and the constitutive dimension of communication in a crisis. This implies the identification of the opportune moments to present a response and recognising the important 'spaces' between typical crisis situations. [ABSTRACT FROM AUTHOR]

Background Elderly patients with inflammatory bowel disease [IBD] are fragile in many respects. Therefore, in these patients, we studied postoperative complications [new abdominal surgery and serious infections after the first IBD surgery]. Methods This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis [UC] and Crohn's disease [CD]. The exposed cohort [elderly] constituted those at an age of ≥60 years at first IBD surgery, and the unexposed [adults] those with surgery at the age of 18–59 years. We estimated adjusted hazard ratios [aHRs] of: a] new abdominal surgery within 2 years; and b] serious [hospital-diagnosed] infections within 6 and 12 months. We adjusted for several confounders including type of index surgery [laparoscopic or open]. Results The aHR for a new surgery among elderly with UC and CD were 0.69 [95% CI 0.58-0.83] and 0.98 [95% CI 0.83-1.15], respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 [95% CI 0.81-1.40] and 0.85 [95% CI 0.67-1.08], respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 [95% CI 1.12-1.88] and 1.26 [95% CI 1.00-1.59], respectively. Conclusion The elderly with IBD did not have an increased risk of new abdominal surgery within 2 years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery. [ABSTRACT FROM AUTHOR]

The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non‐smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non‐smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144. [ABSTRACT FROM AUTHOR]