Faecal microbiota transplantation and Helicobacter pylori: transmission from donors to recipients?
Anne Karmisholt Grosen, Department of Clinical Medicine, Department of Clinical Immunology, Aarhus University Hospital
S. Mikkelsen, Department of Clinical Immunology; S. M. D. Baunwall, Department of Hepatology and Gastroenterology; J. F. Dahlerup, Department of Hepatology and Gastroenterology; L. T. Erikstrup, Department of Clinical Microbiology; C. L. Hvas, Department of Hepatology and Gastroenterology; C. Erikstrup, Department of Clinical Immunology, Aarhus University Hospital
BACKGROUND: Donor screening for faecal microbiota transplantation (FMT) ensures patient safety and should perferably avoid unnecessary screening. Helicobacter pylori may colonise the stomach of healthy faeces donors, but its potential transmission to recipients during FMT is uncertain. Some, but not all, FMT centers exclude H. pylori positive donors, and there is a need to qualify if H. pylori should lead to exclusion of faeces donors.
AIM: To determine whether H. pylori is transmitted from donors to recipients by FMT.
Furthermore, to investigate whether FMT application method impacts transmission.
METHODS: The study was a cohort study with a retrospective quality assurance study on H.
pylori transmission. Forty faeces donors were included in the study. Donor and recipient, pre- and post-FMT, archive faeces samples were screened for H. pylori antigen.
RESULTS: Of the 40 faeces donors screened, 13 (33%) were H. pylori positive. Samples from recipients treated with faeces from H. pylori positive donors will be analyed.
PERSPECTIVES: This is the first study to investigate H. pylori transmission from donors to recipients by FMT. If H. pylori is not transmitted by FMT, regardless of application method, a high proportion of donors can be included instead of excluded. Knowledge on H. pylori transmission, positive as well as negative results, will help optimise donor screening protocols and contribute to the establishment of evidence based faeces donor criteria.
Keywords: Gastroenterology and hepatology, Infection, Laboratory science
Study Macrophage and Monocyte Subsets in the healthy and NAFLD liver by the single-cell genomic analysis
Wenfeng Ma, Department of Clinical Medicine
Yonglun Luo, Department of Biomedicine, Aarhus University & Steno Diabetes Center Aarhus, Aarhus University Hospital; Henning Grønbæk, Department of Hepatology and Gastroenterology, Aarhus University Hospital
Background: Non-alcoholic Fatty Liver Disease (NAFLD) is a clinical challenge associated with obesity and insulin resistance and may progress to end-stage liver diseases. There is an urgent need to gain novel insights into NAFLD pathophysiology and identify new treatment targets. Hepatic macrophages are involved in disease development and progression and new knowledge on macrophage diversity is key to overcoming this disease.
Methods: We analyzed the single-cell and bulk transcriptome data of the NAFLD and healthy subjects in public databases, and collected liver biopsies from NAFLD patients. We also collected the clinical information and stored the serum and PBMC referred for further investigations. The biopsy tissues were prepared for single-cell RNA sequencing (scRNA- seq) and spatial sequencing respectively. In this study, we will include 24 NAFLD patients:
12 with simple steatosis and 12 with inflammation and fibrosis.
Results: We analyzed the scRNA-seq data (GSE136103) of CD45+ cells from 2 end-stage NAFLD and 2 healthy liver samples. We confirmed that macrophage-specific expression genes CD163, MRC1, CD5L and SDC3 are mainly expressed in the macrophage cell cluster. The gene VCAN was mostly expressed in the monocyte cell cluster, and has a lower expression in NAFLD. With these marker-genes, we will further study the recruitment of macrophages from the peripheral monocytes in liver during NAFLD progression.
Conclusion: The CD163, MRC1, CD5L, SDC3 genes are mainly expressed in the macrophage cell cluster, and the VCAN was decreased in NAFLD liver monocytes
compared with the healthy. The function of these marker-genes during NAFLD progressing remains to be explored.
Keywords: Gastroenterology and hepatology, Genetic engineering, Cell biology
Predictors for adverse pregnancy outcomes in women with IBD include preconception disease activity and debuting with IBD during pregnancy – a Danish prospective cohort study
Thea Vestergaard, Department of Clinical Medicine
M. Julsgaard, Department of Gastroenterology and Hepatology, AUH; J. Røsok, Department of Gastroenterology and Hepatology, AUH; R. Bek-Helmig, Department of Obstetrics and Gynaecology, AUH; Jens Kelsen, Department of Gastroenterology and Hepatology, AUH
Background and aims: Women with Inflammatory Bowel Disease (IBD) are often informed of risks of adverse pregnancy outcomes as a consequence of their disease. We
investigated the pregnancy outcome in a tertiary IBD center, and aimed to identify predictors for adverse outcome.
Methods: Between 2008 and 2021, 608 pregnancies in women with IBD were enrolled in a prospective cohort. Predictors examined for increased risk of adverse pregnancy outcomes included debut of IBD during pregnancy and disease activity before or during pregnancy.
All data was collected through review of medical records.
Results: 322 women remained in remission throughout pregnancy. 282 experienced disease activity in one or more trimesters. 36 women debuted with IBD during pregnancy.
167 experienced flaring within 6 months of conceiving. Sustained remission was not associated with an increased risk of preterm birth, intra uterine growth retardation (IUGR), low birth weight or still birth. Flaring or debuting with IBD during pregnancy was, however, associated with a lower birth weight when adjusting for potential confounders. Flaring within 6 months of conceiving was associated with increased risk of continuous disease activity during pregnancy (RR=2.13 [1.83-2.49]).
Conclusion: Conception while in remission increases the probability of remaining in
remission throughout pregnancy. Reassuringly, sustained remission is associated with a low risk of adverse birth outcomes, comparable to that of the background population.
However, experiencing disease activity in one or more trimesters or debuting with IBD was associated with IUGR, cesarean section and lower birth weight.
Keywords: Gastroenterology and hepatology, Inflammation, Gynecology and obstetrics
Fear of cancer recurrence and quality of life in a circulating tumor DNA based surveillance program following curative intended treat-ment of colorectal cancer – a substudy of IMPROVE-IT2
Jesper Berg Nors, Department of Clinical Medicine, Department of Molecular Medicine (MOMA)
T. Juul, Department of Surgery; L.H. Iversen, Department of Surgery; K.A. Gotschalck, Department of Clinical Medicine; C.L. Andersen, Department of Molecular Medicine
INTRODUCTION: The IMPROVE-IT2 study is a randomized controlled trial investigating the benefit of ctDNA guided postoperative surveillance for colorectal cancer patients
compared to the current standard-of-care CT scan surveillance. The present IMPROVE-IT2- substudy aims to assess the potential effects of intensified recurrence surveillance with regards of fear of recurrence and health related quality of life (QoL).
MATERIAL & METHODS: The aim is 1:1 randomization of 255 patients to either a ctDNA- guided sur-veillance program (experimental group) with ctDNA analysis will be performed every 4 months postoperatively (4, 8, 12, 16, 20 and 24) or standard of care surveillance according to current Danish Guidelines with CT scans at months 12 and 36 postoperatively (control group). Both groups com-plete QoL questionnaires at baseline (prior to
randomization and start of surveillance), and at 12, 18, 24 and 36 months. The
questionnaire includes EORTC QLQ-C30 and Fear of Cancer Recurrence Inventory (FCRI).
RESULTS: By 25th of October 2021 a total of 110 patients have been randomized with 55 in the ex-perimental group and 55 in the control group. Sixty-six patients have completed questionnaire at 12 months. No differences were found between the groups when
analyzing global health status or summary score from the EORTC QLQ-C30 questionnaire at baseline and 12 months. We see a trend towards higher risks of clinical fear of cancer recurrence in the experimental group at 12 months (RR=1.58 (0.99-2.41)).
CONCLUSIONS: No significant effect of ctDNA guided surveillance were found on health related QoL or fear of cancer recurrence in this preliminary analysis of the IMPROVE-IT2 study.
Keywords: Gastrointestinal surgery, Oncology, Public health
Treatment of bowel dysfunction following pelvic organ cancer
Mira Mekhael, Department of Clinical Medicine
H.M. Larsen, Department of Surgery Aarhus University Hospital; G. Sørensen, Department of Surgery Aarhus University Hospital; M. Majgaard, Department of Surgery Aarhus University Hospital; D. Kjær, Department of Surgery Aalborg University Hospital; K. Jacobsen,
Department of Surgery Aalborg University Hospital; M. Lauritzen, Department of Surgery Aalborg University Hospital; O. Thorlacius-Ussing, Department of Surgery Aalborg University Hospital; S. Laurberg, Department of Clinical Medicine Aarhus University, Department of Surgery Aarhus University Hospital; K. Krogh, Department of Clinical Medicine Aarhus University, Department of Hepatology and Gastroenterology Aarhus University Hospital;
A.M. Drewes, Department of Gastroenterology and Hepatology Aalborg University Hospital;
P. Christensen, Department of Clinical Medicine Aarhus University, Department of Surgery Aarhus University Hospital; T. Juul, Department of Clinical Medicine Aarhus University, Department of Surgery Aarhus University Hospital
Introduction: As cancer survival improves so does awareness on functional outcomes and the impact of late sequelae on quality of life (QoL). This study aims to present results on treatment of bowel dysfunction from our pelvic organ cancer late sequelae clinic.
Materials and methods: Patients with bowel dysfunction following pelvic organ cancer were offered treatment in a nurse-led clinic. Patients completed validated electronic patient-reported outcome measures assessing bowel function and QoL. Data collection is ongoing and is prospectively registered in an online database.
Results: To date, 345 cancer patients (50% rectal, 14% gynaecological, 12% anal, 11%
colonic, 10% prostate, 3% other cancers) have started treatment for bowel dysfunction in the late sequelae clinic. The mean age was 64 years (range; 27-93) with 54.5% women. Of the symptoms examined, the most frequent were faecal urgency (95%), fragmentation (93%), emptying difficulties (93%), incontinence (flatus 89%, liquid 60%, solid 35%) and obstructed defecation (80%). In total, 135 patients have completed treatment. At the end of treatment, 54% were treated with fibre supplement, 39% with anti-diarrheal medication, 21% with rectal emptying aids, 19% with oral laxatives and 24% with transanal irrigation.
Six patients received a stoma and one sacral nerve stimulation. Significant improvements in all the examined symptoms (p<0.001), bowel-related QoL (p<0.001) and generic QoL (p<0.001) were observed.
Conclusions: Treatment of bowel dysfunction significantly improved the symptom burden and QoL. This encourages a systematic screening for- and treatment of late sequelae following pelvic organ cancer.
Keywords: Gastrointestinal surgery, Other, Other
A protocol for studying the pharmacokinetics and side effects for
tetrahydrocannabinol and cannabidiol (Sativex) among patients with chronic kidney disease and patients on dialysis.
Marie Bach Nielsen, Department of Biomedicine, Department of Clinical Pharmacology, Aarhus University Hospital
E. A. Sædder, Department of Clinical Pharmacology, Aarhus University Hospital; N. Jessen, Department of Clinical Pharmacology, Aarhus University Hospital; J. B. Hasselstrøm,
Department of Forensic Medicine, Aarhus University; J. K. Madsen, Department of Renal Medicine, Aarhus University Hospital; D. S. Khatir, Department of Renal Medicine, Aarhus University Hospital; C. U. Andersen, Department of Clinical Pharmacology, Aarhus University Hospital
Background: Chronic kidney disease (CKD) is common and severe stages may be associated with a high burden of symptoms including anorexia, nausea, anxiety, muscle cramps and sleep disorders, which are often treated insufficiently. A possible effect of cannabinoids (tetrahydrocannabinol (THC) and/or cannabidiol (CBD)) on several of these symptoms has been suggested in previous studies. Therefore, cannabinoids may be an alternative treatment option. However, pharmacokinetic studies are lacking in patients with CKD.
Aim: To compare pharmacokinetics and side effects for Sativex between patients with different stages of CKD and healthy volunteers.
Methods: We aim to investigate the pharmacokinetics for THC, CBD and metabolites among patients with CKD, patients on dialysis and healthy volunteers over 24 hours after two oromucosal sprays of Sativex corresponding to 5.4 mg THC and 5.0 mg CBD. The CKD patients will be divided in two groups with an estimated creatinine clearance <15 ml/min and between 15-30 ml/min, respectively. In addition to blood sampling, the participants will regularly complete a numeric rating scale from 0-10 for questions regarding side effects of Sativex. Finally, we will investigate whether THC, CBD and metabolites are dialyzable. In total 85 participants will be included.
Perspectives: The study will provide fundamental knowledge regarding products containing THC and CBD in patients with different stages of CKD and thereby form the basis for precautions and dose selections, which is a necessary precondition before studies can be made to clarify a possible effect on symptoms in patients with CKD.
Keywords: Pharmacology, Nephrology, Other