Introduction

Inflammatory Bowel Diseases (IBD) are multifactorial diseases, including Ulcerative Colitis (UC) and Crohn's Disease (CD).
Up to 50% of IBD patients show a primary or secondary non-response to standard biological therapy. Therefore, Randomized Clinical Trials (RCTs) represent a significant therapeutic opportunity for them.

Aims & Methods

This study aims to compare the clinical characteristics of "real-life" IBD patients of our tertiary IBD centre to "trial patients" and to identify novel therapeutic targets from real-life populations to be considered for RCTs. We prospectively enrolled consecutive patients who started biologic therapy from August 2019 to August 2020 at Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome. We divided patients into three sub-groups: (1) "real-life" patients, patients treated according to clinical practice with standard biologic therapy that did not meet the inclusion and exclusion criteria for RCTs, (2) patients "real-life suitable for trial", potentially eligible in RCTs, but treated with standard of care, and (3) "trial" patients". Trial patients were treated with drugs from 14 phases 2b and 3 studies actively recruiting in our centre.

Results

We enrolled 134 patients: 72 with UC and 62 with CD. "Real-life" patients were 41 in UC and 38 in CD, "real-life suitable for trial" were 6 in UC and 14 in CD, and "trial" were 25 in UC and 10 in CD.
According to the existing inclusion and exclusion criteria, the study showed that only 43% of UC patients and 39% of CD were suitable for a potential enrollment in RCTs. However, only 16% of CD was finally enrolled in RCTs. At the enrollment, UC patients were excluded due to topical therapy use, cancer, recent Clostridium difficile infection or laboratory abnormalities. In contrast, CD patients were excluded mainly for a low CDAI but also due to complications of the disease that might require surgery, previous total or subtotal colectomy or major abdominal surgery in the previous six months. Both "trial" UC and CD patients showed more extraintestinal manifestations of disease, especially the articular ones (p<0,05). Moreover, "trial" patients presented, both in CD and UC, a higher significant concomitant use of systemic corticosteroids at the dose < or = 20mg/die (p < 0,05). Percentages of patients treated previously with other biological drugs were superior in "trial" patients compared to "real-life" in UC (88% vs 29%); instead, in CD, there was no significant difference (60% vs 45%).
We observed different baseline clinical disease activity scores in CD: the mean HBI of "real-life" patients was 4.8, and the mean HBI of "trial" patients was 9.1.
In addition, patients enrolled in RCTs waited longer before accessing the proposed biological therapy.

Conclusion

This study highlights some differences between clinical practice and research, particularly regarding the criteria for starting biological therapy in CD.
Firstly, “trial patients” presented more complex diseases, significantly impacting their clinical status.
Furthermore, RCTs use clinical scores (CDAI) as determinants for enrollment and decision-making, although endoscopy and radiological imaging are more widely used in clinical practice for decision making.
These differences could cover the actual effectiveness of a new drug compared to the theoretical efficacy derived from registration RCTs.
Therefore, we believe that new therapeutic targets, such as mucosal or histological healing in UC and transmural healing or new radiological scores in CD, should be considered and perhaps used in RCTs.

Clinical Case Summary

The ubiquitous availability of digital media does not only have advantages. Inexperienced mushroom pickers increasingly frequently use APPs for mushroom identification and consume forest mushrooms with false security. Currently, for example, life-threatening Amanita phalloides poisoning is becoming more frequent.
A 65-year-old patient presented with a latency period of approximately 40 hours after consumption of the mushrooms. Nausea and vomiting, as well as loss of strength and cramps in arms and legs, had already been present for about 24 hours. Laboratory tests revealed coagulation failure and markedly elevated transaminases (INR 2.1, GOT 2590 U/l, GPT 3119 U/l). The Meld Score was 33. Only when asked explicitly the patient reported eating wild mushrooms he had collected. The vomit and mushroom debris were recovered and immediately examined by a mushroom expert. Immediately after admission to our intensive care unit, liver protective therapy with Silibinin and N-Acetylcysteine was initiated.
Analysis by a fungal expert revealed evidence of Amanita phalloides. At an INR of 3.3 with massive diffuse skin hemorrhages and rising transaminases (GOT 4825U/l, GPT 4104U/l), repeated therapeutic plasma exchange (exchange of 1.3 times the plasma volume) was performed to control the complications of liver failure. In the course, transaminases and coagulation parameters stabilized, and liver transplantation was not necessary. The patient is now in excellent general health.
Our patient case shows that early diagnosis, as well as therapy, are crucial to reducing the lethality of tuberous leaf fungus poisoning. Patients are often unaware of the danger, so if they have symptoms, they should be asked explicitly about consuming collected mushrooms. As a bridging therapy for the stabilization and regeneration of liver function, therapeutic plasma exchange is an excellent option.

Disclosure

No conflicts of interests

Introduction

Individuals with the Dutch founder CDKN2A/p16-Leiden pathogenic variant (PV) have an increased lifetime risk of melanoma (70%) and pancreatic cancer (20%). Consequently, skin surveillance is offered from the age of 12 to those with a confirmed or suspected PV, while pancreatic cancer surveillance is exclusively offered to confirmed carriers from the age of 40. It is unknown whether the CDKN2A PV impacts quality of life (QoL). Therefore, we aimed to assess QoL and psychological distress in individuals from affected families.

Aims & Methods

This cross-sectional study included confirmed carriers and those with a 50% risk of the CDKN2A PV (at-risk carriers) undergoing cancer surveillance. Individuals ≥18 years were identified from the skin and pancreatic cancer surveillance programs at the Leiden University Medical Center and invited for a one-time, validated self-report questionnaire, including the 12-Item Short Form Health Survey (SF-12), Hospital Anxiety and Depression Scale (HADS), and Cancer Worry Scale (CWS).

Results

A total of 537 individuals were screened for eligibility, of whom 59/249 (24%) individuals under skin surveillance (skin surveillance group) and 188/288 (65%) individuals under combined pancreatic cancer and skin surveillance (pancreatic cancer surveillance group) responded. In both surveillance groups, health-related QoL and general distress levels were within the general population norms (Table 1). However, more than 40% of all study participants reported melanoma-related distress. Pancreatic cancer-related distress was experienced by 45% of the pancreatic surveillance group. Determinants of cancer-related distress were a first-degree relative with melanoma or pancreatic cancer, increased cancer risk perception, and poor general health perception. Over 80% of the participants felt that the benefits of cancer surveillance outweigh the disadvantages.

Table 1. Descriptive statistics and summary of group comparisons for psychological variables

Scale	Scale range / threshold	Skin surveillance group (N = 59)	Pancreatic surveillance group (N = 188)	General population
		Mean (±SD) % > threshold	Mean (±SD) % > threshold	Mean (±SD) % > threshold
Health-related QoL
SF-12 PCS	Range 0-100	54.7 (6.6)**	50.4 (8.1)**	51.7 †/ 48.1‡
SF-12 MCS	Range 0-100	46.9 (10.1)	51.4 (8.8)	48.0 †/ 51.0 ‡
General and cancer-related distress
HADS - anxiety	Range 0-21 Abnormal threshold ≥ 11	4.7 (3.7) 6 (10%)	4.0 (3.6)** 11 (6%)	5.1 (3.6) § -
HADS - depression	Range 0-21 Abnormal threshold ≥ 11	2.8 (3.1) 2 (3%)	2.7 (2.8)* 3 (2%)	3.4 (3.3) § -
CWS - melanoma-related worries	Range 8-32 Abnormal threshold ≥ 14	12.7 (3.2) 26 (44%)	13.4 (3.9) 76 (40%)	-
CWS - pancreatic-related worries	Range 8-32 Abnormal threshold ≥ 14	11.4 (3.0) 10 (17%)	13.6 (3.9) 84 (45%)	-

**P<0.01. *P<0.05. SF-12, 12-item Short Form Health Survey; PCS, Physical Component Scale; MCS, Mental Component Scale; HADS, Hospital Anxiety and Depression Scale; cancer worries measured by the adapted Cancer Worry Scale (CWS). Scores of the SF-12 ranged from 0-100, with higher scores indicating better health. The HADS cut-off score was ≥ 11, indicating a clinically significant anxiety or depressive disorder. The CWS cut-off score was ≥ 14, indicating increased cancer-related distress. ^† age-matched QoL norm scores from Dutch general population with skin surveillance group. ^‡ age-matched QoL norm scores from Dutch general population with pancreatic surveillance group.^1§ HADS scores were compared with 199 individuals from the general Dutch population.²

Conclusion

In conclusion, confirmed and at-risk carriers of the CDKN2A PV experienced similar levels of QoL and general distress compared with the general population. However, cancer-related worry was substantial was substantial in this population. These findings can help identify individuals who may benefit from psychological support.

References

1. Netherlands S. Gezondheid en zorggebruik; persoonskenmerken. Accessed 05-01-2024.
2. Spinhoven PH, Ormel J, Sloekers PPA, Kempen GIJM, Speckens AEM, Hemert AMV. A validation study of the Hospital Anxiety and Depression Scale (HADS) in different groups of Dutch subjects. Psychological Medicine. 1997;27(2):363-370. doi:10.1017/S0033291796004382

Introduction

Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) offers advantages over duodenal stenting and surgical bypass. EUS-GE technique, however, remains non-standardized. A parallel enteric tube (PET) facilitates luminal distention, a critical step during EUS-GE.

Aims & Methods

We primarily aimed at standardizing PET-assisted EUS-GE, secondarily assessing reproducibility and outcomes.
Prospective multicenter study on consecutive adult patients with unresectable malignant gastric outlet obstruction undergoing primary EUS-GE between August 2019-April 2021. Hierarchical task analysis predefined procedural steps into tasks and subtasks. Subtasks were further categorized into essential (performed in all centers and in over 85% of the procedures) or optional. Subtask methodology was considered established if performed similarly in all centers or variable if not. Procedure times, injected fluid volume, luminal diameters obtained, accessories used, and clinical outcomes were recorded.

Results

Seven endoscopists performed EUS-GE in 65 patients (50.8% male, median [IQR] age 77.5 [65.7-86.5] years). EUS-GE was categorized into 4 tasks and 10 subtasks (Table 1). Five essential subtasks involved an established methodology (guidewire and PET placement, endoscope exchange, delivery system insertion and LAMS deployment).
Technical and clinical success rates were 98.5% and 83.3%, respectively. AEs occurred in 10 (15.4%) patients (2 mild, 7 moderate, 1 severe). Success and AE rates were not different between expert and non-experts. Median (IQR) procedure time was 26.2 (19.7-37.1) min. The short and long axis of the targeted small bowel loop was 27 (23-30) x 40 (33-60) mm. Procedure time was longer (35 [30.6-43.7] vs 21.8 [16.4-29.5] min, p<0.001) and injected fluid volume higher (510 [439-870] vs 415 [255-480] ml, p=0.01) in non-experts.

Table 1. Proposed taxonomy for the PET-assisted EUS-GE

Tasks	Subtasks	Methods	Material
PET placement	Advance guidewire beyond the stricture (E)	Aim distal end past into jejunum (Es)	Three layer catheter (S) 0.025” or 0.035” guidewire
	Through the catheter enterography (O)	Enterography (V)	-
	Advance PET beyond the stricture (E)	Aim distal end next to Treitz into jejunum (Es)	R: 8.5 Fr drain
Endoscope exchange	Remove initial endoscope, advance echoendoscope (E)	Endoscopic and fluoroscopic monitoring of PET position (Es)	-
Small bowel distention and targeting	Through the PET enterography (O)	Enterography (V)	-
	Small bowel distention (E)	Saline + contrast +/- methylene blue (V)	R: Flushing pump S: Tap adaptor
	Target acquisition (E)	EUS +/- fluoroscopic guidance (V)	-
LAMS placement	Stent insertion (E)	Freehand technique, bowling water sign (Es)	R: 20x10 mm LAMS S: 15x10 mm LAMS
	Stent deployment (E)	Intra-channel stent release technique (Es)	-

PET: Parallel enteric tube; EUS-GE: Endoscopic ultrasound-guided gastroenterostomy; (E): Essential; (O) Optional; (Es) Established; (V): Variable; (S): Suggested; (R): (Recommended); LAMS: Lumen apposing metal stent.

Conclusion

PET-assisted EUS-GE was standardized, identifying its key steps and technique variants. PET-assisted EUS-GE appears to be a reproducible procedure among advanced endoscopists with different levels of experience. (Clinical Trials Identification Number: NCT04660695).

Disclosure

Carlos Chavarríareceived research and training support by a grant from The Foundation of the Institute of Health Sciences Studies of Castilla y León (IECSCYL).
Vanessa Martín-Álvarezhas nothing to declare.
José Ramón Aparicio is a consultant for Boston Scientific.
Jose Carlos Subtil has nothing to declare.
Francisco Javier Garcia-Alonso has nothing to declare.
Juan J. Vila is a consultant for Boston Scientific and speaker for Cook Endoscopy and Olympus.
Belén Martínez-Moreno has nothing to declare.
Victoria Busto-Bea has nothing to declare.
Ramon Sanchez-Ocaña has nothing to declare.
Carlos de la Serna-Higuera has nothing to declare.
Manuel Perez-Miranda Miranda is a consultant and speaker for Boston Scientific, Olympus, and M.I.Tech.

Introduction

Societal trends in recent decades have led to greater expression and awareness of gender and identity. This was demonstrated by the 2021 census in England and Wales asking, for the first time, whether respondents still identified as the same sex as at their birth. Inflammatory bowel disease (IBD) affects close to 500,000 people in England and Wales and is known to have long term effects on patients’ physical, mental and sexual health. However, it’s prevalence within the LGBTIQ+ population and the specific service provisions this population requires, given that LGBTIQ+ individuals may have greater psychological needs¹, has not been previously studied.

Aims & Methods

To calculate the prevalence of individuals identifying with LGBTIQ+ and living with IBD within England and Wales, census data for England and Wales from 2021 were analysed to calculate the percentage of population identifying as LGBTIQ+². Data was also collected from the Crohn’s and Colitis UK (CCUK) national report 2021 on disease prevalence as well as the provision of psychological support³. This data was then cross-referenced with census data to determine the estimated prevalence of LGBTIQ+ people diagnosed with IBD.

Results

45.7 million census responses were received in 2021 across England and Wales. 262,000 (0.5%) respondents identified as a gender different to their sex at birth. 48,000 (0.10%) identified as a trans man, 48,000 (0.10%) identified as a trans woman, 30,000 (0.06%) identified as non-binary, 118,000 (0.24%) did not give further information regarding their gender and 18,000 (0.04%) provided another response. The highest levels were seen in London (0.46%) and the lowest in Wales (0.14%). 1.5 million (3.2%) people answered as gay, lesbian, bisexual or other sexual orientation with the highest prevalence in London (2.23%) and lowest in the West Midlands and East of England (1.21%). CCUK data suggests 485,000 people suffer from IBD in England and Wales⁴. The calculated number of IBD patients identifying as lesbian, gay, bisexual or other sexual orientation was 15,520 whilst the calculated number identifying as a gender different to their sex at birth was 2,425. The CCUK National IBD report from 2020 identified that 2% of services were sufficiently staffed with psychologists to meet the previously defined IBD standards³.

Conclusion

This analysis suggests that there are over 17,000 people in England and Wales suffering from IBD who identify as LGBTIQ+ however the true prevalence is likely to be higher. Whilst there is no specific data on the impact of IBD in this population, individual statements published by patient support groups show that these patients have unique requirements in simultaneously navigating a chronic disease and the challenges of identifying as LGBTIQ+⁵. There is extensive data suggesting that both LGBTIQ+ people¹ and IBD patients⁶ have a higher burden of mental health disorders and thus these patients are more likely to require, and benefit from, increased psychological support. However, the national provision of psychologists as part of the IBD multi-disciplinary team is extremely low and this represents an unmet need. Further research is required to gain more insight into LGBTIQ+ patient experience to identify deficiencies in service provision and help modify IBD services to better support the holistic needs of this patient group.

References

1. Bachmann C, 2018, ‘LGBT in Britain: Stonewall Health Report’.
2. Office for National Statistics, ‘Sexual orientation, England and Wales: Census 2021’.
3. Crohn’s & Colitis UK, 2021, ‘Crohn’s and Colitis Care in the UK – The Hidden Cost and a Vision for Change’.
4. Crohn’s & Colitis UK, ‘New research shows over 1 in 123 people in UK living with Crohn’s or Colitis. March 2022’. Available at: https://crohnsandcolitis.org.uk/news-stories/news-items/new-research-shows-over-1-in-123-people-in-uk-living-with-crohn-s-or-colitis Last accessed April 2023.
5. Crohn’s & Colitis Foundation, ‘Recognising the needs of LGBTQ+ IBD patients during pride month’, Available at: https://www.crohnscolitisfoundation.org/blog/recognizing-the-needs-of-lgbtq-ibd-patients-during-pride-month Last accessed April 2023.
6. Tribbick D, Salzberg M, Ftanou M et al, 2015, 'Prevalence of mental health disorders in inflammatory bowel disease: an Australian outpatient cohort', Clinical and Experimental Gastroenterology, Volume 8, 197-204