Introduction

In Crohn’s disease (CD), 10% of patients present with fibrostenosis with a further 10% progressing from inflammatory to a fibrostenotic disease behaviour over 7 years^[1]. The prevalence of CD fibrostenosis is >20%^[2]. 40% of fibrostenotic CD patients need surgery at 5 years compared to ~10% with inflammatory disease^[2]. Fibrotic tissues exhibit excessive accumulation of collagen type 1 and 3, with amide protons in the collagen backbone showing potential for quantification using MT imaging [3].
GI-Seg by Motilent is a tool that uses advanced image analysis algorithms to segment the gastrointestinal tract in MRI scans. The software creates a three-dimensional model of the GI tract, allowing clinicians to visualize and analyse the structure and volume of the organs in detail. GI-Seg is designed to save clinicians time and increase the accuracy of their diagnoses by automating the segmentation process, which can be a time-consuming and error-prone task when done manually.

Aims & Methods

The primary objective of this study is to undertake biological validation of the candidate MRI measures as independent imaging biomarkers of histological fibrosis with the primary outcome being the correlation between MRI measures and histological fibrosis measures. Patients with CD histological diagnosis and in need of surgical resection for stenosis attended a one-hour 3T MRI scanning session within 12 weeks prior to their intestinal resection surgery.
After the surgical resection, consecutive sections were cut in the sample and scored by a specialized gastrointestinal pathologist for inflammation, fibrosis, and muscular hypertrophy. A global score was derived for these variables for each individual bowel wall layer and for the whole bowel wall.
An expert radiologist with the help of the histopathologist located the strictures on the magnetisation transfer (MT) and T2 weighted scans. Z-spectrum quantification involved fitting z-spectra to a three-pool model using the Levenberg-Marquardt algorithm, with voxel-wise mapping of the fitted parameters. The GI-seg tool was also used to generate a 3D model of the stricture on T2 weighted scans measuring bowel wall volume and mean signal intensity of each stricture.
Pearson correlation coefficient was used to quantify the correlation between the variables.

Results

A total of 8 CD (19 strictures) patients were recruited. Strictures were identified in histopathology and located on the in-vivo T2 weighted and MT scans by the radiologist. Out of the 8 patients, 6 were used for Z-spectrum quantification. Bowel wall volumes in mm³ and Mean signal intensity were calculated using the GI-seg tool.
MT Z- spectrum amplitude fit showed a high correlation with global fibrosis (r(10) = .775, p = .008), and inflammation scores (r(10) = .824, p = .003).
Mean T2 signal intensity measured using GI-Seg highly correlated with global fibrosis scores (r(19) = .617, p = .005) , global inflammation scores (r(19) = .692, p = .001) and MT Z- spectrum amplitude fit (r(10) = .941, p < .001).
The volume of each stricture showed a moderate correlation to global fibrosis scores (r(19) = .383, p = .106), global inflammation scores (r(19) = .425, p = .069) and muscular hyperplasia (r(19) = .404, p = .086).

Conclusion

This study reveals a strong correlation between mean T2 signal intensity and global fibrosis, muscular hyperplasia, and inflammation scores in CD strictures. The GI-seg tool accurately measured bowel wall volume and signal intensity, indicating potential as independent imaging biomarkers for fibrosis, inflammation, in CD strictures.

References

[1] Lo B, Vester-Andersen MK, Vind I, et al. Changes in Disease Behaviour and Location in Patients With Crohn's Disease After Seven Years of Follow-Up: A Danish Population-based Inception Cohort. J Crohns Colitis 2018;12:265-272.
[2] Moran GW, Dubeau MF, Kaplan GG, et al. Phenotypic features of Crohn's disease associated with failure of medical treatment. Clin Gastroenterol Hepatol 2014;12:434-42.e1.
[3] Fang ZN, Li XH, Lin JJ, Huang SY, Cao QH, Chen ZH, Sun CH, Zhang ZW, Rieder F, Rimola J, Chen MH, Li ZP, Mao R, Feng ST. Magnetisation transfer imaging adds information to conventional MRIs to differentiate inflammatory from fibrotic components of small intestinal strictures in Crohn's disease. Eur Radiol. 2020 Apr;30(4):1938-1947.

Disclosure

Prof Gordon W Moran is in receipt of research funding from Astra Zeneca, Johnson and Johnson and Bristol Myers Squibb. He is also a consultant for Alimentiv Inc.
Dr Alex Menys and Dr Andrew Bard are employed by Motlient.

Introduction

In recent years, evidence shows that long non-coding RNAs (lncRNAs) are key regulators of gene transcription and play important roles in the pathogenesis of inflammatory bowel diseases. LncRNAs are involved in the regulation of intestinal epithelial cell apoptosis, cell-cell interactions, and enhancing inflammation, among others. Biological therapies, which are considered the most potent for disease control, only benefit one-third of patients. For this reason, a deeper understanding of the mechanisms by which biological drugs elicit their effect on intestinal mucosal is needed. Hence, we aimed to unravel the ex vivo modulator effect of infliximab on the lncRNAs expression in intestinal biopsies from patients with Crohn´s Disease (CD).

Aims & Methods

We performed an unbiased transcriptomic analysis of intestinal biopsies from the ileum and colon from 30 patients [active CD = 10, quiescent CD = 10, healthy controls (HC) = 10] to identify lncRNA differentially expressed in the setting of infliximab modulation. Endoscopic biopsies were cultured with or without infliximab and the transcriptome was determined by Illumina gene expression array. We used different databases (Ensembl Biomart, RNAcentral and ToppGene) to search for non-annotated lncRNA information and data on the location (cellular component), biological process and molecular function of differentially expressed lncRNAs.

Results

Transcriptomic results revealed a widespread dysregulation of lncRNAs in ileum biopsies from patients with active CD, quiescent CD and HC compared to the colon at baseline and after infliximab culture. These differentially expressed lncRNAs were enriched in such pathways as proliferation, apoptosis, migration, inflammatory response of fibroblasts, response to wounding, posttranscriptional regulation of inflammatory genes and activation of the mitogen-activated protein kinase signaling pathways. Regarding the effect of infliximab according to intestinal location, presence of disease and activity, no significant lncRNAs were identified in the different study comparatives.

Conclusion

We have characterized the basal transcriptomic landscape of lncRNAs in patients with CD (active and quiescent) and HC both in ileum and left colon. However, we have not found differential lncRNA expression due to the effect of infliximab, suggesting that the location (ileum or colon) is more relevant when analyzing differences in lncRNA expression in the intestinal tissue.

Introduction

Superficial esophageal squamous cell carcinoma (SESCC) was enabled detection by the innovation of Narrow Band Imaging (NBI). However, NBI has insufficient sensitivity for detecting SESCC when used by inexperienced endoscopists.¹⁾ To solve these problems, the construction and usefulness of endoscopic detection models for SESCC using artificial intelligence (AI) have been reported.²⁾ On the other hand, the assistant effect of the AI model for endoscopists has not been fully examined.

Aims & Methods

The aim of this study is to create an AI model to assist in detecting SESCC and to assess the effect of the AI assistance on the endoscopist's diagnostic performance using endoscopic video. We collected endoscopic videos of cases with lesions and without lesions from May 2020 to September 2021 for training data to create an AI model for detecting SESCC and from October 2021 to January 2022 for test data. All videos were taken 3 to 5 seconds at National Cancer Center Hospital East by using NBI. Eligibility criteria for cases with lesions were as follows: i) histopathologically diagnosed ESCC or high-grade intraepithelial neoplasia (HGIN); ii) the depth of lesion shallower than cMM/SM1. Residual lesions after endoscopic resection for ESCC were excluded. The eligibility criteria for cases without lesions were the absence of ESCC or HGIN by endoscopic diagnosis. Patients with a history of chemotherapy, radiotherapy, chemoradiotherapy, or surgery for ESCC were excluded. The performances of the AI model and 18 endoscopists (8 experts and 10 non-experts) for detecting SESCC were evaluated using the test data. Furthermore, to explore the assistance ability of the AI model, the endoscopists were required to diagnose again on the same test data after 4 weeks, referring to the results predicted by the AI model. The diagnostic performance of the endoscopists with and without the AI assistance was compared to assess the sensitivity, specificity, accuracy, and interobserver agreement. The recognition to the lesions by the AI model was defined to detect with Intersection over the Union > 0.3 for 5 consecutive frames for each video. The results of the endoscopists were presented as averages.

Results

We collected 280 cases (140 with lesions and 140 without lesions) videos as training data and 115 cases (52 with lesions and 63 without lesions) videos as test data. The clinicopathological characteristics of the lesions were as follow: median lesion size was 15mm (range:1-100mm), and the pathological depth of tumor were EP/LPM/MM/SM1/SM2=10/17/0/4/4/4. The sensitivity, specificity, and accuracy of the AI model were 76.0%, 79.4% and 77.2% respectively. With the AI assistance, the sensitivity and accuracy of the endoscopists were significantly improved (without vs with the AI assistance: 57.4% vs 66.5%, P<0.05, 68.6% vs 75.9%, p<0.05), while the specificity were slightly improved (87.0% vs 91.6%, P=0.059). For experts, the sensitivity and accuracy were significantly improved (59.1% vs 70.0%, P<0.05, 72.1% vs 79.3%, p<0.05). For non-experts, the accuracy was significantly improved (65.8% vs 73.3%, P<0.05), while the sensitivity and specificity were slightly improved (56.1% vs 63.7%, P=0.07, 81.9% vs 89.2%, p=0.07). The interobserver agreement for diagnosis among the endoscopists was improved with the AI assistance (κ=0.429 vs κ=0.547).

Conclusion

The assistance of the AI model improved the endoscopist's sensitivity of detection of SESCC without reducing the specificity, regardless of their experience. The AI model would be effective in improving the endoscopist's ability to detect SESCC in practice.

References

1) Ishihara R, Takeuchi Y, Chatani R et al. Prospective evaluation of narrow-band imaging endoscopy for screening of esophageal squamous mucosal high-grade neoplasia in experienced and less experienced endoscopists. Dis Esophagus 2010; 23: 480–6.
2) Waki K, Ishihara R, Kato Y et al. Usefulness of an artificial intelligence system for the detection of esophageal squamous cell carcinoma evaluated with videos simulating overlooking situation. Digestive Endoscopy 2021; 33: 1101–1109.

Introduction

Endoscopic colonic stenting is a treatment method in which a colonoscope is used to insert a self-expandable metal stent (SEMS) into a stenotic site and allow its expansion to alleviate colonic obstruction and permit urgent colonic decompression. It is an effective and extensively practiced minimally invasive procedure compared with emergency surgery. However, perforation, stent migration, and reocclusion may occur. Perforation is particularly a serious adverse event with a mortality rate of 50%. There are three possible causes of perforation:
(1) Local perforation due to stimulation of the stent itself directly into the intestinal tract;
(2) Perforation due to guidewire or catheter manipulation during stent insertion; and
(3) Perforation due to increased pressure in the intestinal tract at the oral side of the obstruction (especially in the cecum) caused by air supply during colonoscopy insertion.
For the first possible cause, an improved colonic stent was developed to reduce irritation to the intestinal tract, and for the second possible cause, a strategy for safe stent insertion was established.
However, perforation due to the third possible cause remains a concern, and appropriate countermeasures should be urgently developed.
In endoscopic colonic stenting, we hypothesized that colonoscope insertion using the gel immersion method, which uses a recently developed endoscopic view-securing gel, would allow safe and rapid access to the lesion without increasing intestinal pressure, thereby decreasing the incidence of perforation.

Aims & Methods

This study aimed to clarify the usefulness of the gel immersion method during colonoscope insertion with endoscopic view-securing gel for colonic stenting. Eight patients in whom colorectal stenting was performed using the gel immersion method between May 2022 and January 2023 were included.
The primary endpoint was the endoscopic lesion reach rate, and the secondary endpoints were the technical and clinical success rates of SEMS deployment, colonoscope insertion time, total procedure time, and adverse event rate.

Results

Of the included patients, four were males (50%), and the mean age of patients was 67.6 ± 15.6 years. Seven patients (87.5%) had colorectal cancer and one patient (12.5%) had gastric cancer. The cancer was localized at the following sites: sigmoid colon in three patients, descending colon in three patients, transverse colon in one patient, and ascending colon in one patient. The purpose of SEMS deployment was bridge to surgery in four (50%) and palliation in four (50%) patients. In all cases, the endoscope was inserted without the preparation and insertion of the endoscope into the lesion at the origin of the obstruction without insufflation, and the endoscopic lesion reach rate was 100% (8/8). No worsening of intestinal dilatation was observed. The technical and clinical success rates each were 100% (8/8). The scope insertion time was 9.8 ± 5.2 min, total procedure time was 27.3 ± 6.5 min, and the adverse event rate was 0% (0/8).

Conclusion

For endoscopic colonic stenting, endoscope insertion using the gel immersion method could be performed safely and effectively and has the potential to become the standard method.

Introduction

Gastroenterology (GE) is a medical discipline that studies all diseases of the digestive system. It comprises several areas of study and offers a large variety of sub-specializations: proctology, interventional endoscopy or even digestive oncology. The decisive elements in the choice of this specialty vary among interns. The aim of our study is to determine the various factors influencing the choice of gastroenterology as a specialty among medical interns.

Aims & Methods

This is a cross-sectional, multicentric, survey-type study, conducted from September 1 to 30, 2023, involving 7 national medical faculties. All medical interns, regardless of sex or age, participated in our study.
An electronic survey with 29 items was created using Google Forms®. It was divided into two parts: the first part contained 13 questions on socio-demographic characteristics and exposure to GE during the academic curriculum, while the second part concerned the factors motivating the choice or not of GE as a specialty.
A statistical analysis using the Fisher’s exact test was performed. P values of <0.05 were considered statistically significant. Data were analyzed using Jamovi (Version 2.3).

Results

A total of 329 responses were collected: the majority were women 208 (63.2) with a F/M sex ratio of 1.7 and a median age of 27 [25; 28] years. The majority had already completed a GE rotation during their training course n=205 (62.3), of which 90 (44.1) had found it "satisfactory". More than half of the participants n= 178 (54.1) had already considered GE as a future specialty, and this choice was mostly made during GE lectures given in medical school n= 66 (36.9). Among those who had never considered GE, the main reasons were lack of interest in the specialty, the fact that it is a medical specialty, lack of information about GE, potential remuneration, and dissatisfaction with GE rotation during the training course (59.2%, 28.9%, 13.9%, 10.4% and 10% respectively).
Among those who finally opted for GE, the majority were women (70.2% vs. 29.8%, p=0.004). Satisfaction with the GE rotation during the training course had an impact on the final choice: "satisfactory" vs. "mediocre" (43.8% vs. 6.3% p=0.009).
Multivariate analysis showed that early interest in fields such as endoscopy (OR= 4.46, CI95%: 1.44-13.78, p=0.009) or proctology (OR= 4.26, CI95%: 1.01-18.01, p=0.05) increased the chance of choosing GE.

Conclusion

This study showed that there is a gender disparity in the choice of GE as a specialty. The fact that it is a medical discipline may lead men to choose another path. Our study also highlighted the importance of GE training courses during the medical curriculum to motivate interns to join our specialty, as well as the need to spotlight certain areas such as endoscopy or proctology.

Introduction

The need for endoscopic necrosectomy (EN) has increased dramatically, as endoscopic EUS-guided drainage has become gold standard for treatment of pancreatic walled-off-necrosis (WON)[1,2]. Although snares and baskets are commonly used in EN procedures, they can be ineffective and dedicated instruments specifically designed for EN are scarce. Recently, an innovative powered endoscopic debridement system (EndoRotor, Interscope Inc., Northbridge, MA, USA) designed to excise and remove necrotic tissue within the WON was introduced specifically for EN with promising results[3,4]. While the first generation EndoRotor catheter was limited to 3.2 mm diameter, a larger catheter that fits into a large-channel gastroscope with a working channel of 6.0 mm has now been introduced. This study evaluates the clinical outcomes, safety, and feasibility of the novel 6.0 catheter for EN of WON.

Aims & Methods

This retrospective study was performed using prospectively collected data from all patients who underwent EN with the 6.0 catheter between December 2021 and March 2023 at Gastro Unit, Copenhagen University Hospital Hvidovre, a tertiary referral center in Denmark. All patients with symptomatic WON and need for necrosectomy were considered eligible for this study. Technical feasibility, safety, and clinical outcomes were evaluated.

Results

Sixteen patients underwent a total of 25 EN procedures with the 6.0 catheter. The mean age of the patients was 51.8 years (SD 17.7 years) and 11 (68.8%) were male. The etiology of the acute necrotizing pancreatitis was alcohol in 4 patients (25.0%), gall stones in 7 patients (43.8%), post-endoscopic retrograde cholangiopancreatography (ERCP) in 3 patients (18.8%), and idiopathic in 2 patients (12.5%). The mean size of the WON was 27.5 cm (SD 10.5 cm). The median computed tomography severity index (CTSI) was 8.5 (P25-P75: 6.0-9.0) and median modified CTSI (mCTSI) was 9.0 (P25-P75: 8.0-10). Two patients did not achieve clinical resolution (12.5%), as they died from multisystem organ failure before resolution of the WON was achieved. The median length of stay in hospital for the patients who achieved clinical resolution was 56.0 days (P25-P75: 36.5-96.0 days) and the median number of necrosectomy procedures performed to achieve clinical resolution was 5.0 (P25-P75: 2.0-8.5). All patients had EN procedures performed with snares in addition to the procedures with the powered debridement system. Five patients had necrosectomy performed with the 3.2 catheter (31.0%) as well as the 6.0 catheter. The median duration of EN with the 6.0 catheter was 60.0 minutes (P25-P75: 45.0-100 minutes) per procedure.
A device-related adverse event was noted in one instance (4.0%). The patient exhibited symptoms of peritoneal reaction in the hours following the procedure, which may have been caused by perforation of the WON into the peritoneal cavity. The patient was treated with laparoscopic peritoneal lavage and drainage and recovered without further interventions. No other procedure-related adverse events were identified. Malfunction of the catheter was observed in 7 procedures (28.0%).

Conclusion

To perform necrosectomy procedures optimally, dedicated endoscopic instruments designed for debridement of pancreatic WON are required. This study suggests that EN with the novel EndoRotor 6.0 catheter is safe and feasible with promising clinical results for EN of pancreatic WON. To assess the efficacy relative to standard techniques, comparative studies are warranted.

References

[1] Karstensen JG, Novovic S, Hansen EF, et al. EUS-guided drainage of large walled-off pancreatic necroses using plastic versus lumen-apposing metal stents: A single-centre randomised controlled trial. Gut 2022; 0: 1–7. doi:10.1136/gutjnl-2022-328225
[2] Ebrahim M, Werge MP, Hadi A, et al. Clinical outcomes following endoscopic or video-assisted retroperitoneal management of acute pancreatitis with large (>15 cm) walled-off pancreatic necrosis: Retrospective, single tertiary center cohort study. Dig Endosc 2022; 34: 1245–1252. doi:10.1111/den.14295
[3] Stassen PMC, de Jonge PJF, Bruno MJ, et al. Safety and efficacy of a novel resection system for direct endoscopic necrosectomy of walled-off pancreas necrosis: a prospective, international, multicenter trial. Gastrointest Endosc 2022; 95: 471–479. doi:10.1016/J.GIE.2021.09.025
[4] Wiel SE van der, May A, Poley JW, et al. Preliminary report on the safety and utility of a novel automated mechanical endoscopic tissue resection tool for endoscopic necrosectomy: a case series. Endosc Int Open 2020; 08: E274–E280. doi:10.1055/A-1079-5015

Introduction

Patients with ulcerative colitis (UC) report that UC negatively affects their quality of life (QoL), including sexual functioning, satisfaction, and drive.^1,2 These effects are rarely discussed with or by gastroenterologists in clinical practice. The CONFIDE study aims to elucidate the impact of symptoms on the lives of patients with moderate to severe UC in the United States (US), Europe (EU5; France, Germany, Italy, Spain, and UK), and Japan. Data presented here are from the US and EU5.

Aims & Methods

Online, quantitative, cross-sectional surveys were conducted (July–September 2021). Criteria based on previous treatment, steroid use, and/or hospitalization were used to define moderate-to-severe UC. Data collected included patient perspectives on the impact of UC on sexual activity. Sexual activity was not limited to intercourse and included activities such as masturbation.

Results

Surveys were completed by 200 US patients (male [M]=62%, mean age 40 years) and 556 EU5 patients (M=57%, mean age 39 years). Of these, 77% US and 54% EU5 patients were receiving advanced therapy (biologic/novel oral) and 52% and 73% were receiving steroids at the time of survey completion, respectively. Overall, 63% US patients (M=55%, female [F]=77%) and 53% EU5 patients (M=47%, F=60%) reported avoiding or decreasing sexual activity due to UC in the 3 months prior to the survey. Among these patients (US: N=126; EU5: N=292), most frequently reported reasons for avoidance of sexual activity were bowel urgency (BU; 41%), decreased sexual desire (37%), and fear of BU-related accidents (34%) in the US and fear of faecal seepage (37%), fear of BU-related accidents (36%), and BU itself (31%) in EU5. Although reasons for avoiding sexual activity were broadly similar between sexes, higher percentage of male patients from both US and EU5 (US: M=33%, F=24%; EU5: M=42%, F=33%) reported fear of faecal seepage as a factor affecting sexual activity. Conversely, higher percentages of female patients reported perianal pain (M=13%, F=19%) and self-consciousness (M=13%, F=24%) as reasons for avoiding sexual activity in the US and decreased sexual desire (M=16%, F=26%), BU (M=26%, F=36%) and fatigue (M=14%, F=22%) in EU5.

Conclusion

In both US and EU5 populations, >50% patients with moderate-to-severe UC reported avoiding or decreasing sexual activity due to UC, with bowel urgency and bowel urgency-related accidents being among the top three reasons. In addition to other QoL parameters, impact of UC on patients’ sexual health needs to be assessed in routine clinical practice.

References

¹Bulut AE, et al. Turk J Gastroenterol. 2019;30:33-39.
²Jedel S, et al. Inflamm Bowel Dis. 2015;21:923-38.

Disclosure

Simon Travis, Grants: Ferring Pharmaceuticals, AbbVie, Schering-Plough, MSD, Procter & Gamble, Warner Chilcott, International Organization for the Study of IBD, ECCO, UCB, Vifor Pharma, Normal Collision Foundation, Buhlmann, Takeda, Janssen, Pfizer, and Eli Lilly and Company.
Marla C. Dubinsky, Consultancy fees: AbbVie, Arena Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Celgene Corporation, Eli Lilly and Company, F. Hoffman-La Roche Ltd, Genentech Inc., Gilead Sciences, Janssen, LLC, Pfizer, Prometheus Biosciences, Takeda Pharmaceuticals USA, Inc., and UCB; Stockholder: Trellus Health Inc.; Research support: AbbVie, Janssen, LLC, Pfizer, and Prometheus Biosciences.
Toshifumi Hibi, Consultancy fees/grant/research support/speaker: AbbVie GK, ActivAid, Alfresa Pharma Corporation, Apo Plus Station, Aspen Japan K.K, Bristol-Myers Squibb, Celltrion, EA Pharma, Eli Lilly and Company, Ferring Pharmaceuticals, Gilead Sciences, Janssen, JIMRO, JMDC Inc., Kyorin, Mitsubishi-Tanabe Pharma Corporation, Mochida Pharmaceutical, Nichi-Iko Pharmaceutical, Nippon Kayaku Co. Pfizer, Takeda Pharmaceutical, Zeria Pharmaceutical, and MIYARISAN Pharmaceutical.
David T. Rubin, Grants/contracts: Takeda; Consultancy fees: AbbVie, Altrubio Inc., Allergan, Inc., American College of Gastroenterology, Arena Pharmaceuticals, Athos Therapeutics, Bellatrix Pharmaceuticals, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Celgene Corp/Syneos, Cornerstones Health, Inc. (non-profit), GalenPharma/Atlantica, Genentech/Roche, Gilead Sciences, GODURN, LLC, InDex Pharmaceuticals, Ironwood Pharmaceuticals, Iterative Scopes, Janssen, Eli Lilly and Company, Materia Prima, Pfizer, Prometheus Biosciences, Reistone Biopharma, Takeda, and Techlab Inc; Stockholder: Altrubio and Datos Health.
Remo Panaccione, Consultancy/speaker fees and/or advisory board member: AbbVie, Amgen, Arena Pharmaceuticals, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Ferring, Fresenius Kabi, Gilead Sciences, Janssen, Merck, Organon, Pfizer, Roche, Sandoz, Shire, and Takeda; Consultancy fees and/or advisory board member: Alimentiv, AstraZeneca, Biogen, Boehringer Ingelheim, Genentech, Glaxo-Smith Kline, JAMP Bio, Mylan, Novartis, Oppilan Pharma, Pandion Pharma, Progenity, Protagonist Therapeutics, Sublimity Therapeutics; Consultancy fees: Abbott, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Galapagos, JAMP Bio, Pendopharm, Satisfai Health, Theravance Biopharma, Trellus, Viatris, and UCB.
Stefan Schreiber, Consultancy and lecture fees: AbbVie, Amgen, Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Falk, Ferring Pharmaceuticals, Galapagos/Gilead, Genentech/Roche, Eli Lilly and Company, Janssen, MSD, Pfizer, and Takeda.
Christian Atkinson, Employee: Adelphi Real World; Consultancy: Eli Lilly and Company in connection with this study.
Alison P. Bleakman, Cem Kayhan, Theresa H. Gibble, Christophe Sapin, and Eoin J. Flynn are employees and stockholders of Eli Lilly and Company.