Introduction

As inflammatory bowel disease (IBD) is frequently diagnosed in young adults, the disease often coincides with pregnancy. About one in four female patients will have their first pregnancy after diagnosis. Current guidelines advise treatment through specialized clinics for IBD patients wishing to conceive, which are increasingly implemented. However, recent outcome data from these centers is scarce. In this study we therefore describe the pregnancy-course in three specialized Dutch IBD university clinics.

Aims & Methods

For this multicenter, retrospective cohort study, all adult female IBD-patients who had been pregnant during treatment in any of the three participating Dutch university medical centers between the inception of the respective electronic patient records and 2022 were included. Data on patient- and disease characteristics, lab values, medication usage and pregnancy outcomes was extracted from the electronic patient records. Topics relevant to pregnancy were logged, including intoxications, the use of folic acid and vitamin D, and gestational weight gain.

Results

Data was collected on 620 women who had been pregnant in the study period, including 376 (60.6%) with Crohn’s disease (CD), 230 (37.1%) with ulcerative colitis (UC), and 13 (2.1%) with inflammatory bowel disease unclassified (IBDU). Of the CD-patients, 68 (18.1%) had a history of perianal disease. The mean age at conception of the first pregnancy was 29.9 years. Altogether, 983 pregnancies were included, of which 10.3% was conceived using assisted reproductive technologies, including in vitro fertilization (IVF) in 3.6% of pregnancies. During 9.8% of pregnancies, the mother actively smoked tobacco at conception. Medication was used during 71.0% of pregnancies, most often consisting of thiopurines (27.1%) and amino salicylates (24.4%). Appropriate gestational weight gain was achieved in 31.1% of pregnancies. 152 (15.5%) pregnancies resulted in miscarriage, 12 (1.2%) pregnancies were ectopic. In the remaining pregnancies, 511 (62,4%) newborns were delivered vaginally. A caesarean section (CS) was performed in 234 cases (23.8%). Overall, 54 mothers (23.1%) who underwent a CS had perianal disease. An adverse pregnancy outcome was noted in 159 (21.3%) of pregnancies, including low birth weight in 78 (10.5%), prematurity in 85 (11.4%) and dysmaturity in 89 (11.9%). Adverse outcomes occurred more often in the group of women who experienced disease activity in any point during pregnancy, but this difference was not statistically significant (30.8% vs 21.7%, p=0.120). Two patients developed deep venous thromboembolism during or within six weeks after pregnancy.

Conclusion

In IBD the mean age at conception and the rate of pregnancies conceived using IVF were comparable with the general Dutch population. A CS was performed more frequently in this cohort when compared to healthy pregnancies in the Netherlands (23.8% vs 17.6%). In these specialized centers low birth weight (10.5% vs 5.7%), prematurity (11.4% vs 6.6%) and dysmaturity (11.9% vs 9.7%) occurred more often in comparison to the known rates in Dutch pregnancies, emphasizing that adequate counseling before and during pregnancy in IBD is essential.

Introduction

Recurrent abdominal pain is the predominant symptom of chronic pancreatitis (CP), contributing to significant morbidity and reduced quality of life. Medical management includes analgesics, antioxidants, neuromodulators, and pancreatic enzyme replacement therapy (PERT). While PERT is used for pancreatic exocrine insufficiency (PEI), it is also thought to reduce pain by suppressing pancreatic secretion via negative feedback. However, previous meta-analysis did not show pain reduction, though subgroup analysis suggested potential pain relief with non-enteric (NE) coated enzymes1. Unlike currently available enteric-coated formulations, high in lipase but low in proteas, non-enteric coated enzymes with high protease content dissolve rapidly and may more effectively suppress cholecystokinin-mediated pancreatic stimulation, potentially improving pain outcomes.

Aims & Methods

To primarily assess the effect of a high-protease, non-enteric-coated pancreatic enzyme preparation on pain in patients with painful chronic pancreatitis. The study was registered under ClinicalTrials.gov (NCT05042284).
We conducted a randomized, double-blind, placebo-controlled trial where we randomly assigned participants to a high protease (30,000 U)-containing, non-enteric-coated enzyme preparation (n=54) and a placebo (n=53) group. The study duration was 24 weeks. Patients with painful CP (per Mayo Clinic criteria) with chronic pain were enrolled. The primary outcome was to see a difference in mean Izbicki pain score at 12 and 24 weeks and a change in pain scores (VAS 0-10) using pain diaries. Secondary outcomes were changes in the number of painful days, analgesic requirements, patient’s global impression of change (PGIC), quality of life, and adverse effects. Weekly pain data were collated. Repeated measures, linear, and mixed-effects models were used to analyze the primary outcome. Analysis was intention-to-treat.

Results

107 out of 256 screened patients fulfilled enrollment criteria. The mean age was comparable between groups (35.1±10.6 vs. 33.6±12.3 years; p=0.51), and baseline characteristics were similar. The primary outcome using mixed model analysis showed no significant differences in the change in Izbicki pain scores between the two groups at 12 and 24 weeks (Table: Results). The mean difference in VAS pain score was -3.7(95%CI: -4.3to-3.1) in enzyme group vs. -3.5(95%CI: -4.2to-2.9) in placebo group (p=0.64) at 12 weeks. The changes were -4.2(95%CI: -4.7to-3.6) vs. -4.1(95%CI: -4.7to-3.5), respectively (p=0.79), at 24 weeks indicating no significant difference. The median number of painful days was also similar, at 12 weeks, 16 (IQR: 9–35) in the enzyme group vs. 16 (IQR: 4–36.5) in placebo (p=0.31); at 24 weeks, 3(IQR: 0–8.5) vs. 3(IQR: 0–7)(p=0.30) respectively. Analgesic use was higher in the enzyme group at 12 weeks (45(83.3%) vs. 37(69.8%); p=0.11) and 24 weeks (42(77.8%) vs. 35(66%); p=0.20). Differences in the change in global health status, quality of life, PGIC, and adverse effects at both time points were also non-significant.

Conclusion

Despite the high protease content, Non-enteric coated enzyme preparations did not improve pain and quality of life in patients with painful chronic pancreatitis. Further RCTs are needed to evaluate benefits in distinct subgroups.

References

1. Yaghoobi, Mohammad, Julia McNabb-Baltar, Raheleh Bijarchi, and Peter B. Cotton. “Pancreatic Enzyme Supplements Are Not Effective for Relieving Abdominal Pain in Patients with Chronic Pancreatitis: Meta-Analysis and Systematic Review of Randomized Controlled Trials.” Canadian Journal of Gastroenterology and Hepatology. Doi: https://doi.org/10.1155/2016/8541839

Clinical Case Summary

A 70-year-old patient with diabetes mellitus and cholecystectomy performed six months earlier was admitted to the emergency department for generalized abdominal pain, hyporexia and weight loss.
An abdominal CT scan showed a solid-cystic pancreatic lesion suggestive of mucinous neoplasia, together with peritoneal nodules in the right paracolic gout. In view of the suspicion of malignancy, an echoendoscopy with fine needle aspiration puncture (EUS-FNA) was performed, identifying an irregular lesion with heterogeneous and hypovascular ultrastructure in the pancreatic neck-body and a discrete dilatation of the main pancreatic duct. Finally, the histological study didn´t show neoplastic cells.
Suddenly the patient experienced a clinical worsening with severe pain and high fever. Laboratory tests showed a progressive increase in C-reactive protein and leukocytosis with left shift. In a control CT scan, a reduction in the size of the pancreatic lesion is observed, together with an increase in the peritoneal lesions which present a polyglobulated contour, hypercapillary margins and rarefaction of the surrounding fat. These finding suggesting the presence of peritoneal abscesses secondary to dropped gallstones. After broad-spectrum antibiotic therapy, the intra-abdominal abscesses improved radiologically, but the collection persisted in the right posterior pararenal space which was drained under ultrasound control with subsequent disappearance of fever and normalization of analytical parameters.
Dropped gallstones occur in approximately 7% of cholecystectomies. The secondary granulomatous reaction in paucisymptomatic patients can simulate peritoneal tumor processes in imaging tests, being one of the adverse effects described in relation to this pathology. In our case, the concomitant presence of peritoneal lesions together the pancreatic lesion oriented the initial case as a malignant process; however, the patient's evolution were key to the final diagnosis.

Introduction

Infection with SARS-CoV-2 leads to pronounced changes in the intestinal microbiome and also decay of tryptophan that are both related to disease severity. Supplementation of tryptophan metabolism using ileocolonic-release nicotinamide may stabilize the microbiome and alleviate COVID-19 symptoms.

Aims & Methods

This prospective, double-blind, randomized, placebo-controlled trial evaluated safety and efficacy of a 4-week intervention with a novel oral formulation of nicotinamide (1,000 mg/d) in symptomatic, unvaccinated, non-hospitalized outpatients with PCR-proven early COVID-19. The primary outcome was full recovery from reduced physical performance after 2 weeks in the prespecified symptomatic primary analysis population with at least one risk factor for severe COVID-19. Stools from a part of the patients (4 timepoints) were submitted to 16S rRNA (n=70) and shotgun metagenomics (n=18) sequencing.

Results

Screening of 7,013 patients resulted in randomization of 900 participants (nicotinamide or placebo (1:1), from which 867 received the investigational product and 500 qualified for the acute disease analysis population. 110 of 191 patients (57.6%) receiving nicotinamide and 80 of 188 patients receiving placebo (42.6%) recovered from their performance drop at week 2 (absolute difference, 15.0 percentage points; odds ratio, 1.33; 95% confidence interval, 1.03 to 1.70; P=0.004). Nicotinamide was also superior in the secondary endpoints ability to perform normal activities (P=0.009) and shortness of breath (P=0.012). Substantial effects on gut microbiome constitution were seen counteracting COVID-19 related changes. Reduction of tryptophan biosynthesis in the microbiome in placebo patients was restored and NAD salvage pathways were activated in nicotinamide-treated individuals. No relevant safety signals were observed.

Conclusion

Oral treatment with nicotinamide stabilized the gut microbiome against COVID-19 related changes and led to faster recovery of physical performance in symptomatic patients at risk for severe Covid-19. (Funded by the German Research Foundation [DFG], the State of Schleswig-Holstein and the UEG Research Prize; ClinicalTrials.gov number: NCT04751604)

Disclosure

SS reports indirect stock ownership in Gerion Biotech GmbH as well as consulting and personal fees from AbbVie, Allergosan, Amgen, Arena, BMS, Biogen, Celltrion, Celgene, Falk, Ferring, Fresenius, Galapagos/Gilead, HIKMA, I-Mab, Janssen, Lilly, Morphic, MSD, Mylan, Pfizer, Prometheus, Protagonist, Provention Bio, Sandoz/Hexal, Takeda, and Theravance.
GHW is employed part-time by CONARIS Research Institute AG (Kiel, Germany).
TB reports consulting fees, honoraria or other support from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Merck, MSD, Novartis, Pfizer, and Roche.
KA reports consulting fees, honoraria or other support from AbbVie, Falk, Galapagos, Janssen, Pfizer, and Takeda.
ML reports a lecture honorarium and travel support by AstraZeneca.
PR reports stock ownership in Gerion Biotech GmbH and consulting fees from Takeda.

Introduction

Cholangiocarcinoma (CCA) prevalence is high in East and Southeast Asia, especially in northeast Thailand. The first line of treatment for unresectable CCA is systemic chemotherapy which a median OS of less than 1 year under palliative systemic therapy. Albumin-Bilirubin (ALBI) prognosis score is the new method for the evaluation of liver performance status and prediction of treatment outcome but there is a lack of data in CCA patients.

Aims & Methods

Aim: To study the association of overall survival and ALBI prognostic score in unresectable CCA patients who received systemic chemotherapy.
Methods: This retrospective cohort study was conducted in Maha Chakri Sirindhorn Medical Center, Thailand. Demographic data, Clinical information, Laboratory profile, and survival analysis were extensively reviewed in the patient who received systemic chemotherapy from 2012 - 2022. All patients were monitored for at least 1 year after initial treatment with chemotherapy or until death.

Results

​69 patients of Unresectable CCA received systemic chemotherapy enrolled in this study. Most of the patients were men (45/69, 65.22%) and Intrahepatic type CCA (55/69, 79.71%). 17 patients (24.6%) need Biliary drainage before systemic chemotherapy which median pre-drainage TB was 11.35 mg/dL (10.7 – 20.6). Most ALBI prognostic score were group 2 (37/69, 53.6%) and anemia was significantly in ALBI 2 group (81.08%, P <0.001). The median overall survival was 10.23 months and the median progression-free survival was 5.77 months. Significantly better overall survival of the ALBI 1 group compared with the ALBI 2 group (ALBI 1, 13.76 months; ALBI 2, 6.33 months; log-rank test, P <0.001). The estimated 6, 12, 18, and 24-month survival rates were 72.46%, 40.58%, 18.84%, and 8.70%, respectively, whereas the estimated progression-free survival rate at 6, 12, 18, and 24 months were 47.83% and 10.14%, respectively.

Conclusion

ALBI prognosis score may serve as a surrogate marker in predicting the overall survival and progression-free survival of CCA patients who received Systemic chemotherapy.

References

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Disclosure

There is no any conflict of interest in this study

Introduction

Periodontitis (gum disease) and inflammatory bowel disease (IBD) are both chronic progressive inflammatory diseases with many similarities in their aetiopathogenesis. In addition, patients with IBD are reported to be at increased risk of developing periodontitis, which in turn seems to impact IBD activity and disability as shown in recent studies. However, these findings need to be validated. Thus, we aimed to assess whether the presence of periodontitis is associated with increased IBD activity, disability, and severity, and/or reduced IBD specific quality of life, in a Swedish patient cohort.

Aims & Methods

An on-line questionnaire was distributed to the members of the Swedish patient organisation for gastrointestinal diseases. The survey included questions on social demographics, oral health, as well as IBD-related characteristics. Oral health was assessed by the number of missing teeth, self-reported state of teeth and gums, and the Periodontal Screening Score (PESS), which is a validated instrument to screen for severe periodontitis. Disease activity in patients with Ulcerative Colitis (UC) and Crohn’s disease (CD) was assessed by the Simple Clinical Colitis Index (SCCAI) and the Harvey & Bradshaw’s Activity Index (HBI), respectively. Disease related disability was assessed by the Inflammatory bowel disease disability index (IBD-DI). IBD-specific health-related quality of life measured by the short inflammatory bowel disease questionnaire (sIBDQ).

Results

A total of 786 IBD patients responded to the invitation, including 371 patients with CD and 415 patients with UC. For both CD and UC, self-reported severe periodontitis was significantly associated with a higher level of current disease activity [OR 1.72 (1.86;2.49); p=0.004] based on the HBI (for CD) and the SCCAI (for UC), an increased IBD disability score [Coef. 5.07 (1.86;8.27); p=0.002], and an increased self-reported disease activity in the last 12 months [OR 1.44 (1.05;1.98); p=0.025]. Likewise, number of missing teeth (tooth loss is the ultimate outcome of untreated periodontitis and as such an indirect indicator of its severity), was associated with an increased IBD disability score [Coef. 4.47 (0.71;8.22); p=0.020]. IBD severity (analysed as composite parameter of history of IBD-related surgery and/or treatment with biological therapy) was neither associated with tooth loss [OR 1.57 (0.97;2.52); p=0.065], nor with self-reported severe periodontitis [OR 1.20 (0.80;1.80); p=0.367]. IBD-specific health-related quality of life measured by sIBDQ score showed a tendency to be decreased in the presence of self-reported severe periodontitis [OR -1.45 (-3.01;0.10); p=0.067] but was not associated with tooth loss [Coef. -1.20 (-3.01;0.62); p=0.194].

Conclusion

The present study provides further evidence that the presence of periodontitis is associated with an increased disease activity and disability in IBD patients. These results underline that increased attention should be given to the oral health of IBD patients.