Introduction

Recent research has highlighted significant health risks associated with pregnancy among female surgeons in USA. They reported increased risks of infertility and pregnancy complications among female surgeons, attributed to work schedules and delayed childbearing due to professional demands (1).

Aims & Methods

This joint study by the Young Gastroenterology (JUGA) and Surgical Working Group of Young Surgeons (CAJC) of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the German Society for General and Visceral Surgery (DGAV) focuses on the prevalence and factors of major pregnancy complications among female visceral medicine doctors in Germany and compares their experiences with a non-doctor control group from lawyers and teachers. Utilizing an anonymous online survey, responses from 352 doctors detailing 757 pregnancies and 92 non-doctors with 172 pregnancies were collected and analyzed. Generalized Linear Mixed Models (GLMM) were employed to assess risk factors linked with pregnancy complications, with particular attention to work conditions and use of assisted reproductive technologies.

Results

The study revealed no differences in maternal age at first live birth, number of births as well as the overall frequency and number of pregnancy complications between female visceral medicine doctors and non-doctors. However, visceral medicine doctors experienced higher rates of pregnancy loss (23.1% vs. 13.7%, p = 0.008) and intrauterine growth restriction (3.0% vs. 0.0%; p = 0.025). Work hours, especially close to end of pregnancy and during nights and weekends, were significantly longer for doctors (p ≤ 0.001) and associated with pregnancy complications. Additionally, a higher proportion of doctors expected pregnancy to have more impact on their career compared to non-doctors (90.3% vs. 70.1%; p = 0.001), with both groups commonly aligning family planning with career goals.

Conclusion

These results reveal significant differences in pregnancy-related complications, with a higher prevalence among medical professionals, likely influenced by working hours and times. Further analysis is warranted to better understand the underlying factors contributing to these disparities and to inform targeted interventions.

References

1. Rangel EL, Castillo-Angeles M, Easter SR, et al. Incidence of Infertility and Pregnancy Complications in US Female Surgeons. JAMA Surg. 2021;156(10):905–915. doi:10.1001/jamasurg.2021.3301

Introduction

Rectal sensory function plays a critical role in normal bowel function. For example, rectal hypersensitivity is associated with Irritable Bowel Syndrome (IBS), whereas rectal hyposensitivity is linked to constipation.
The International Anorectal Physiology Working Group (IAPWG) (1) has established a standardised investigation protocol for anorectal physiological function. According to this protocol, the rectal sensory function is evaluated by simple balloon distension using an elastic balloon during a standard high-resolution anorectal manometry investigation (HRAM). However, the gold standard for rectal sensory assessment is the rectal barostat investigation, as described by the European COST action GENIEUR group (2).
The correlation between these two methods is largely unknown. The two methods use different balloons (elastic vs. non-elastic balloons, different size and shape). Moreover, the barostat is pressure-controlled whereas the HRAM is volume-controlled. For this reason, assessment of the level of agreement is not feasible.

Aims & Methods

We assessed the correlation between rectal sensory testing with the HRAM and rectal barostat investigations for each sensory threshold, in a group of healthy volunteers.
Twenty-six healthy volunteers (mean age 42 years, 50% females) were recruited and investigated using both HRAM according to the IAPWG protocol and rectal barostat using the GENIEUR protocol on the same day.
Sensory thresholds for first sensation (FS), first urge (FU), intense urge (IU) and maximum tolerable volume (MTV) were recorded for both methods.
Spearman’s rank correlation coefficient was used for analysis, since it does not assume normal distribution.

Results

Median values, along with the 1^st and 3^rd quartile are presented in Table 1.
There were statistically significant positive correlations between the sensory thresholds for first urge, intense urge and maximum tolerable volume. However, the correlation coefficients were generally weak, with only MTV showing a correlation coefficient above 0.5.

Table 1. Quartiles of the four sensory thresholds used and Spearman’s correlation factor between HRAM and barostat based investigations.

Conclusion

There is a weak correlation between the two methods, suggesting that HRAM balloon distension and barostat cannot be used interchangeably with respect to rectal sensory testing. Standardisation of rectal sensory testing is warranted to improve the accuracy and reliability.

References

(1). Carrington E. et al. The international anorectal physiology working group (IAPWG) recommendations: Standardized testing protocol and the London classification for disorders of anorectal function. Neurogastroenterology & Motility. 2020;32: e13679.
(2). https://genieur.eu/Downloads/PhenotypingTool/SOP_Rectal_barostat.pdf

Introduction

Fecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (CDI), but its safety is jeopardized by the potential risk of transmitting microbial pathogens. Stool biobanks have established to provide both a widespread and equitable access to FMT and high safety, quality, and traceable workflows. To guarantee the safety of each donor stool batch, international guidelines recommend either a quarantine or a direct stool testing with a rapid molecular assay for gut pathogens. While reports of the quarantine-based approach are emerging, data on the direct testing-based approach are still limited

Aims & Methods

Our aim is to report outcomes of a donor screening program for FMT including a direct stool testing-based approach based on a rapid molecular assay for gut pathogens.We prospectively evaluated all candidates enrolled in our FMT donor program since the introduction of a direct stool testing with a rapid molecular assay for gut pathogens, in 2019. Following international guidelines, donor screening consisted of a five-step framework, including: 1) collection of clinical history; 2) blood and stool testing; 3) a further questionnaire the day of each donation; 4) nasopharyngeal swab and stool RT-PCR assay for SARS-CoV-2 the day of each donation (after March 2020); 5) a direct stool testing with a rapid molecular assay for gut pathogens and cultures for MDRO evaluation. Specifically, the RT-PCR Allplex™ Gastrointestinal Panel Assay (Seegene, Korea) was used for a comprehensive identification of common gastrointestinal pathogens. The QIAamp Fast DNA Stool Mini Kit (QIAGEN, Hilden, Germany) was used for nucleic acid extraction. We evaluated rates of donations per year, rates and reasons of candidates’ exclusion at each step of the donor screening, as well as the rate of unsuitable fecal donations and the intestinal pathogens that caused their rejection. Finally, we recorded the number of total fecal aliquots provided by eligible donors, and related safety outcomes at 12 weeks after their use within FMT.

Results

From January 2019 to December 2022, 227 candidates were assessed for eligibility. Of them, 122 were excluded at different steps of the screening process. Finally, we enrolled 69 eligible donors (37 females, 53,6%; mean age 37, 30% of the total pool). Thirty-seven fecal aliquots were collected in 2019 (13 donors), 39 in 2020 (20 donors); 51 in 2021 (24 donors), and 104 in 2022 (43 donors). Overall, we collected 231 fecal donations, of which 136 (58.8%) were considered eligible and stored at -80°C for FMT. Eight donations were discarded for insufficient amount of feces (<50 g - 3%), and 87 (37.6%) for positivity to intestinal pathogens, including Enteropathogenic E. coli (EPEC) (n=31 samples – 13.4%), ESBL (extended-spectrum beta-lactamase) E. coli (n=15 samples, 6.5%), Blastocystis hominis (n=17 samples, 7.3%).Notably, we found a seasonal variation among pathogen positivity, as most pathogens were observed in Autumn (from September to December: n=48/87, 55.8%).All donations have been used, and no serious adverse events or infections have been observed at 12 weeks after FMT.

Conclusion

Our screening of donor feces based on direct stool testing guarantees high safety of FMT, although with high rates of donor exclusion, with the need of a well-established framework to guarantee a continuous availability of eligible donors to avoid shortages of fecal aliquots.

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.

Introduction

The sex differences in the incidence of gastric cancer have been well known. However, uncertainty still exists in terms of prognosis of GC. For example, the US SEER data reports a significantly better prognosis in females than in males, but the prognosis is better in males than in females in Korean Central Cancer Registry data. Roles of molecular markers and gut microbiota as new prognostic factor are emerging recently, but few studies seem to try to reveal sex differences.

Aims & Methods

In this background, we aimed to analyze the differences in GC characteristics according to sex in Korean patients, mainly focused on survival. This was a single-center retrospective study. A total of fifteen thousand patients diagnosed with GC at the Seoul National University Bundang Hospital between 2003 and 2023 were included. Clinicopathological characteristics, histologic types, survival rates with age- and stage-stratification, and associated risk factors were analyzed. Information related to death was cross-verified using medical record review and data from the National Statistical Office.

Results

The ratio of males and females was about 2:1, and there was no differences in stage between sexes. Female patients were significantly younger than males, had more gastric body cancers and tumors with diffuse type or poorly differentiated histology. Females underwent less endoscopic treatment and more surgery, and tumors with microsatellite instability was more common in females, while mutation of p53 was less common. In histological types according to Lauren classification, diffuse type histology was more common in younger patients in both males and females. The proportion of intestinal type GC increased with age, but the proportion increased rapidly in males while increased gradually in females. In Cox multivariate regression analysis for GC-related death, older age, proximal tumor location, diffuse type histology and advanced tumor stage were risk factors. In terms of survival, overall and GC-specific survival did not show significant differences between sexes in the analysis of the total population. However, sex differences in survival reversed with age, that younger females under 50 showed survival disadvantages, but the survival became similar in 50s, and older females over 60 showed survival advantages in both overall and GC-specific survival. Furthermore, in the stratification analysis according to the stage, there were no significant differences in stages I to III. But, stage IV female patients showed significant survival disadvantages. In subgroup analysis of stage IV patients, the differences between males and females in median survival were two months, and female patients were significantly younger and had a higher proportion of diffuse type GC than male patients, which shows aggressive feature and is related to poorer survival.

Conclusion

Significant differences in survival between sexes were observed with stratification analysis, although sex itself was not an independent prognostic factor. These age-dependent changes are thought to suggest the effect of sex hormones. These differences should be considered in clinical practice and later research in terms of tailored medicine.

Introduction

Endoscopic ultrasound-guided biliary drainage (EUS-BD) is reported to be useful as an alternative treatment for patients who are unable to undergo transpapillary bile duct drainage. EUS-hepaticogastrostomy (HGS), which involves a transgastric approach to the left intrahepatic bile duct, has been suggested as the first-line approach for EUS-BD because of a lower risk of bile leakage in patients with dilated intrahepatic bile ducts. However, there are few reports comparing the effectiveness and safety of EUS-BD procedures between EUS-HGS and EUS-HGS with antegrade stenting (EUS-AS+HGS).

Aims & Methods

Therefore, we compared the efficacy and safety of EUS-AS+HGS and EUS-HGS as drainage methods in EUS-BD. From April 2017 to December 2020, we retrospectively evaluated patients who underwent EUS-AS+HGS or EUS-HGS in our hospital for unresectable malignant biliary obstruction for which transpapillary biliary drainage had failed. We compared the time to recurrence of biliary obstruction (TRBO), overall survival, technical success rate, clinical success rate, adverse event rate, reintervention rate, and length of hospital stay between each procedure.

Results

A total of 68 patients, 22 in the EUS-AS+HGS group and 46 in the EUS-HGS group, were included in the study. In the EUS-HGS group, 38 patients underwent HGS only, while EUS-AS+HGS was attempted in another 8 patients who ultimately underwent EUS-HGS because of unsuccessful guidewire penetration. In the EUS-AS+HGS group, the TRBO was significantly longer, and the re-intervention rate significantly lower than in the EUS-HGS group (both p=0.03). However, there were no significant differences in technical success rate, overall survival, clinical success rate, adverse event rate, and length of hospital stay.

Conclusion

EUS-AS+HGS was superior to EUS-HGS regarding the length of biliary patency and re-intervention rate in patients with unresectable malignant biliary obstruction. The results suggest that EUS-AS+HGS is the preferred treatment when guidewire penetration of the biliary stricture is possible.

Introduction

Intestinal microbiota are prominent in the etiology of irritable bowel syndrome (IBS). In this exploratory study, we investigated short- and long-term changes in the microbiota of IBS patients after intervening with a low-FODMAP diet (LFD) or probiotics (an 8 strains lactobacilla) using a standardized microbiota characterization test intended for routine use.

Aims & Methods

We analyzed data and fecal samples collected in a previous trial from non-comorbid IBS patients before treatment, and then again after four weeks and one year of treatment. Response to treatment was defined by a reduction in the IBS-SSS score, and the gut microbiota were characterized using the standardized and GA-map® Dysbiosis Test Lx.

Results

Of the 25 responders to either treatment, two of the 22 with fecal samples available were dysbiotic at baseline, increasing to eight out of 19 after four weeks; after one year all responders providing a sample were normobiotic (n=15). After four weeks, the abundance of Bacilli, Lactobacillus spp. and Streptococcus salivarius ssp. thermophilus were temporarily increased in the probiotic responder group (p<0.05), while for LFD responders Anaerobutyricum hallii had decreased. There was a greater abundance of R. gnavus at baseline in those responding to probiotics than in those responding to LFD.

Conclusion

In addition to improving IBS symptoms, sustained LFD or repeat probiotics tended to temporarily alter the microbiota profile in responders. Microbiota characterization is a promising tool for monitoring IBS treatments; however, more extensive studies are needed.

Disclosure

Marwah Al-sheikh, Dorit Vedel Ankersen and Mette Bennedsen declare no conflict of interest
Christina Casén is an employee of Genetic Analysis AS and owns stocks and shares in Genetic Analysis AS.
Kristin Gravdal and Graceline Tina Kirubakaran are employees of Genetic Analysis AS.
Johan Burisch reports personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work.
Pia Munkholm has received consulting or lecture fees from AbbVie, Calpro A/S, Ferring Pharmaceuticals, Jansen-Cilag, Celgene, Takeda, Tillotts Pharma, Merck Sharp & Dohme, Pfizer, and research funds from Coloplast, Ferring Pharmaceuticals, Jansen-Cilag, Merck Sharp and Dohme, Pharmaforce, Svar A/S, Takeda, Tillotts Pharma, Novo Nordic.

Introduction

Paediatric-onset inflammatory bowel disease (PIBD) is a distinct phenotype with more aggressive and extensive gut inflammation at diagnosis in comparison to adult-onset IBD.¹ Disease activity in paediatric IBD is typically monitored using a combination of clinical, endoscopic, and laboratory parameters. Circulating cell-free DNA (cfDNA) and mitochondrial DNA (mtDNA) are damage-associated molecular patterns (DAMPS) released into the bloodstream during tissue damage and cell death and can be detected in peripheral blood samples. There is a growing interest in the use of cfDNA and mtDNA as potential non-invasive biomarkers for disease activity. Recent studies have suggested that levels of cfDNA and mtDNA may correlate with disease activity in adult IBD² but their utility in paediatric populations, where mitochondrial dysfunction is strongly implicated,³ remains largely unexplored. This study aims to present initial data on the potential use of cfDNA and mtDNA as biomarkers for disease activity in paediatric-onset IBD.

Aims & Methods

GI-DAMPs/MUSIC is an ongoing cross-sectional and longitudinal multi-centre translational research study in Scotland (2020 – 2025) with a primary aim of investigating the inflammatory mechanisms of IBD with a focus on multi-omics, immune- and microbiome-profiling aligned to careful clinical prospective follow-up. We measured circulating cfDNA and mtDNA, using mtDNA-specific ND2 gene dPCR, in the peripheral blood of patients diagnosed under 17 years (A1 phenotype)⁴ and correlated this with detailed phenotypic data, clinical disease activity scores and standard biomarkers.

Results

24 patients, out of a total GI-DAMPS cohort of 338, were A1 phenotype and included in the analysis (14/24 (58%) male, 23 Crohn’s disease (CD), 1 Ulcerative colitis (UC)) with a median (IQR) age at diagnosis of 13 (11.5-15 years). Patients with highly active disease had higher levels of cfDNA levels compared to those in remission (median 0.435 (0.246-0.700 ng/µl) vs 0.123 (0.066-0.160 ng/µl), p=0.005). mtDNA levels were also significantly higher in those with highly active disease compared to those in remission (median 363.6 (135.2-639.6 copies/µl) vs 96.4 (78.2-129.8 copies/µl), p=0.024). cfDNA was moderately correlated with total white cell count (Pearson correlation, r=0.41, p=0.48) and negatively correlated with haemoglobin (r=-0.42, p=0.41), though these correlations were not seen with mtDNA (all p=>0.05).

Conclusion

In conclusion, our initial data demonstrate that the levels of circulating cell-free DNA (cfDNA) and mitochondrial DNA (mtDNA) in the blood are potentially valuable biomarkers for differentiating disease activity in paediatric IBD. These findings suggest that measuring cfDNA and mtDNA levels could provide a non-invasive method for monitoring disease activity in young patients with IBD, enabling early detection of disease flare-ups and facilitating prompt intervention. Further investigation is needed to validate these results and determine the clinical utility of these biomarkers in the management of paediatric IBD.

References

1. van Rheenen, P. F. et al. The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update. J. Crohn’s Colitis 15, 171–194 (2021).
2. Boyapati, R. K. et al. Mitochondrial DNA Is a Pro-Inflammatory Damage-Associated Molecular Pattern Released During Active IBD. Inflamm. Bowel Dis. 24, 2113–2122 (2018).
3. Haberman, Y. et al. Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response. Nat Commun 10, 38 (2019).
4. Levine, A. et al. ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents. J. Pediatr. Gastroenterol. Nutr. 58, 795–806 (2014).