Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure for class 1 and 2 obese subjects¹. The effects of smoking habits on weight are well known regarding bariatric surgery^2-6. However, given that this patient population is inherently weight-concerned, understanding the effects of tobacco use on post-operative weight loss in bariatric endoscopy is essential to guiding clinicians in counselling patients in this field.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in an Italian tertiary referral centre was assessed retrospectively. Data on smoking habits (smoker, non-smoker, and previous smoker) were collected. Efficacy and safety between the three smoking categories was evaluated using an ANOVA test.

Results

Between May 2017 and October 2021, 290 subjects underwent ESG. Out of the total, smoking habits were available for 275 subjects: 144 non-smokers (NS; 52,4%), 51 smokers (S; 18,5%) and previous smokers (EX-S; 29,1%). No statistically significant differences in BMI was observed between the three groups.
In each group, no major complication were reported in the perioperative period. Adherence to follow-up was 93,1%, 92,4% and 73,5% for non-smokers, 90,2%, 84,3% and 82,4% for smokers, 91,3%, 90,0% and 71,9% for EX-smokers, at 6,12 and 24 months.
Average TBWL, EWL and WL were similar between the three groups at 6,12 and 24 months (see Table below). In the non-smoker group, five subjects underwent revision procedures (4 Re-ESG, 1 Surgery) after 24 months, whereas one previous smoker underwent Re-ESG after six months. No revision was reported in the smoker group.

Conclusion

Our analysis, with the strengths of a large cohort and a long-term follow-up, showed that smoking habits do not influence the efficacy and safety of ESG for up to 24 months.
Finally, proper counseling of patients should advise the cessation of the smoking habit.

References

¹ Abu Dayyeh BK, et al. Lancet. 2022
² Dittrich L. Surg Obes Relat Dis. 2020
³ łuszyńska P. J Clin Med. 2022
⁴ Chow A. Surg Endosc. 2021
⁵ Mohan S. Surg Endosc. 2021
⁶ Srikanth N. J Addict Dis. 2021

Introduction

The global burden of overweight and obesity-related diseases has been a growing public health concern over the past few decades. These conditions contribute significantly to morbidity and mortality worldwide and are associated with a wide range of chronic diseases. Understanding the trends and sex differences in disease burden attributable to overweight and obesity is essential for developing effective prevention and intervention strategies. This study aims to assess the burden of overweight and obesity-related diseases in males and females.

Aims & Methods

We analyzed data from the Global Burden of Diseases (GBD) study, covering overweight and obesity-related disease burdens in 26 diseases across 204 countries and territories. Key disease burden indicators, including mortality and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change.

Results

In 2019, the global burden of overweight and obesity-related diseases reached 160.2 million DALYs, and the number of deaths associated with these conditions was approximately 5.02 million in males and females. The age-standardized death rates in males showed an increase from 58.19 per 100,000 person-years in 1990 to 66.55 per 100,000 person-years in 2019 (APC =0.36%, 95% CI 0.30% to 0.42%, P <.001), while in females it decreased from 59.31 per 100,000 person-years in 1990 to 58.14 per 100,000 person-years in 2019 (APC =-0.22%, 95% CI -0.29% to -0.14%, P <.001). There was a higher increase in age-standardized DALY rates in males, from 1632.5 per 100,000 years in 1990 to 2070.34 per 100,000 years in 2019 (APC =0.74%, 95% CI 0.70% to 0.78%, P <.001), while females experienced a smaller increase from 1618.26 per 100,000 years in 1990 to 1789.67 per 100,000 years in 2019 (APC =0.24%, 95% CI 0.19% to 0.29%, P <.001). These trends resulted in a higher male-to-female rate ratio in deaths and DALYs in 2019, which did not exist in 1990. The higher male-to-female rate ratio in deaths and DALYs were found in more than half of countries and territories. A large proportion of the higher burden in males compared to females can be explained by an increase in development.

Conclusion

The study uncovers a significant increase in the burden of overweight and obesity-related diseases, with a marked disparity between males and females. These findings underscore the need for further research to investigate the underlying causes of this gender difference in overweight and obesity-related deaths and DALYs. Identifying the contributing factors will facilitate the development of targeted interventions and public health policies to address and resolve these disparities. It is crucial to ensure that both genders benefit equitably from efforts to combat the global burden of overweight and obesity-related diseases.

Introduction

Double-headed capsules enable the non-invasive one-step endoscopic evaluation of both the small bowel and colon (pan-intestinal capsule endoscopy, PCE).

Aims & Methods

We aim to evaluate the diagnostic accuracy and safety of PCE vs. the current standard of care (conventional colonoscopy) as the first-line examination in patients with iron deficiency anaemia (IDA) and/or overt bleeding after a non-diagnostic upper endoscopy (suspected mid or lower gastrointestinal bleeding, MLGIB).
We conducted a prospective, single-centre, single-blinded cohort study including consecutive patients with suspected MLGIB. All patients were submitted to PCE, followed by same-day colonoscopy under deep sedation. The physicians performing PCE and conventional colonoscopies were independent and blinded to each other’s observations. The diagnostic yield for potentially haemorrhagic lesions (PHL) was compared for efficacy analysis, and adverse events were assessed for both examinations. The gold standard diagnosis was defined by consensus panel. This trial has been registered in ClinicalTrials.gov (ID NCT04782986).

Results

We included 100 consecutive patients with suspected MLGIB, mean age 66.5 (18-92) years, 65% female gender, presenting with IDA (81%) or overt bleeding (19%). Mean haemoglobin level was 8.4 (4.1-12.8) g/dL and 40% were inpatients. For PCE, the PillCam Crohn’s® capsule was used in 88 patients, and PillCam COLON® 2 in the remaining. Patients with overt bleeding performed PCE within 2 weeks in 70% of cases, 15% in the first 72h after the bleeding episode. PCE was complete in 76% of cases, vs. colonoscopy 95% (p<0.01). The quality of bowel preparation was adequate in 72% of PCE vs. 85% of colonoscopies (p=0.012). Overall, PHL were diagnosed, based on the combination of PCE + colonoscopy, in 46% of patients, corresponding to small bowel and/or colon angioectasias in more than two-thirds (69.6%) of cases. PHL were detected by both examinations in 13/46 (28.3%), only by colonoscopy in 3/46 (6.5%), and only by PCE in 30/46 (65.2%) of cases (p<0.01). Overall, colonoscopy detected PHL in 23% of the entire cohort, which means 50% (23/46) of all patients with PHL according to the consensus panel, while for PCE the overall diagnostic yield was 44%, meaning 95.7% (44/46) of all PHL (p<0.01). Considering the gold standard diagnosis for PHL, colonoscopy had a sensitivity of 23/46=50%, specificity 54/54=100%, positive predictive value (PPV) 23/23=100% and negative predictive value (NPV) 54/77=70,1%, while for PCE the sensitivity was 44/46=95.7%, specificity 54/54=100%, PPV 44/44=100% and NPV 54/56=96.4%. Thirty-one percent of patients had PHL accessible to ileocolonoscopy; in those cases, the PCE was able to make the diagnosis in 29/31 (93.5%) vs. conventional colonoscopy in 23/31 (74.2%) of cases, p<0.01. Regarding safety, no significant adverse events occurred with PCE, vs. 2% (cardiopulmonary) with conventional colonoscopy.

Conclusion

PCE is safe and more effective than conventional colonoscopy in identifying PHL both in the small bowel and the colon, and could be considered as a first-line examination in patients with IDA or overt bleeding after a non-diagnostic upper endoscopy. In more than half of patients with suspected MLGIB, PCE does not detect any PHL either in the small bowel or the colon, dismissing any further invasive endoscopic investigations.

Disclosure

Medtronic provided financial support to the acquisition of some of the capsules which were used in the trial

Introduction

Capsule endoscopy is the first-line examination for digestive bleeding with likely origin in the small bowel, in hemodynamically stable patients. In the 2022 update, ESGE guidelines recommend that, in the context of overt bleeding, capsule enteroscopy should be performed as soon as possible, ideally within the first 48 hours. In the previous guidelines, published in 2015, the recommended window was 14 days.

Aims & Methods

This study aimed to evaluate the improvement in yield offered by the new recommendations regarding the timing of urgent capsule enteroscopy. Patients with suspected overt middle gastrointestinal bleeding between January 2005 and November 2022 were retrospectively analyzed. Diagnostic and therapeutic yield, rebleeding rate, and mortality were compared when capsule enteroscopy was performed within the first 48 hours, within the first 14 days, or between the 3rd and 14th day after admission.

Results

A total of 138 patients were included (58.7% men, median age 66 years), 87 of whom (63.0%) underwent capsule enteroscopy within the first 48 hours after hospital admission. The median follow-up was 55 months (5-180). The diagnostic yield (presence of blood or lesions with bleeding potential) was slightly higher when capsule enteroscopy was performed within the first 48 hours (81.6% versus 76.5%, p=0.349). On the other hand, capsule enteroscopy within the first 48 hours was significantly associated with higher therapeutic yield (endoscopic, radiologic, or surgical treatment) - 54.0% versus 39.2%, p=0.02. The rebleeding rate was significantly lower in patients undergoing enteroscopy within 48 hours after admission (19.5% versus 29.4%, p=0.04). On the other hand, overall mortality at 36 months did not differ between strategies (21.8% and 25.5%, p=0.401).

Conclusion

Performing capsule endoscopy within the first 48 hours, as recommended by recently published guidelines, is associated with favourable short- and long-term clinical outcomes.

Introduction

Chronic fatigue is a debilitating symptom and has major impacts on the quality of life of patients with chronic inflammatory conditions. In IBD, an estimated 50% of patients suffer from persistent fatigue despite successful treatment of intestinal inflammation. During active disease flares, this number jumps to 80% (Borren et al. 2018). Tryptophan metabolites are not only associated with disease activity in UC and CD, but also with chronic fatigue (Kavyani et al. 2022). Thus, our aims are (1) to characterize the relationship between fatigue and tryptophan derivatives and (2) to understand the metabolic dynamics arising when fatigue symptoms improve following therapeutic intervention.

Aims & Methods

In a prospective open label cohort of patients with moderate-to-severe Crohn’s disease (CD, n = 71) and ulcerative colitis (UC, n = 94) assigned to biologics therapy or JAK inhibitors, fatigue was assessed by the fatigue subscale of the Functional Assessment of the Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire at therapy induction and 2 and 14 weeks thereafter. A FACIT-F score of <30.1 was considered severe fatigue while a score of >40 was considered no relevant fatigue. Clinical response at week 14 was defined as Crohn’s Disease Activity Index (CDAI) <150 and reduction of Partial Mayo Clinical Score (PMCS) >50% vs. baseline, respectively. We used targeted mass spectrometry to quantify the levels of 13 tryptophan derivatives and neopterin in a subset of patient serum in the weeks following therapy induction (at 0, 2, and 14 weeks, n = 120 individuals).

Results

Half of the recruited patients had severe fatigue at baseline (50.3%). Of the 120 patients who reached week 14 and had FACIT-F scores available, severe fatigue was experienced by 45.9% of the patients who did not respond to therapy and the rate was reduced to 13.2% in therapy responders. We found 8 metabolites positively associated with FACIT-F: tryptophan, kynurenic acid, kynurenine, picolinic acid, xanthurenic acid, serotonin, indole-3-proprionic acid, and quinaldic acid, while neopterin was negatively associated (FDR < 0.05). Four of these metabolites changed dynamically as a function of the extent of fatigue improvement: tryptophan, kynurenine, xanthurenic acid, and serotonin (FDR < 0.05). In all cases, the rate of change of these metabolites increased as a function of fatigue improvement.

Conclusion

Fatigue is linked to a diverse array of tryptophan metabolites. Notably, all of the significantly associated tryptophan derivatives were positively associated with FACIT-F, meaning that as fatigue symptoms improve, tryptophan metabolite levels increase. Many of these metabolites have previously been linked to symptom severity in IBD: for example, tryptophan, kynurenic acid and xanthurenic acid all tend to increase with symptom alleviation (Nikolaus et al. 2017, Michaudel et al. 2022). While the kynurenine-to-tryptophan ratio is elevated in active IBD (Nikolaus et al. 2017), this ratio did not convey a specific, fatigue-related signature. Considering that some patients continue to suffer from persistent fatigue even during disease quiescence, further work is needed to disentangle the impact of tryptophan metabolism on therapy response from its role on fatigue improvement.

Disclosure

F. Tran receives scientific funding from Sanofi, received consulting fee's from LEK Consulting and speaker's fees from Lilly, Janssen, Falk, Abbvie, Celltrion, onkowissen.de, CED Service GmbH. S. Schreiber reports consulting fees from Abbvie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Prevention Bio, Protagonist and Falk.

Introduction

Inflammatory bowel disease (IBD) shares many features with other chronic inflammatory diseases (CIDs), such as rheumatoid arthritis and psoriasis, which are characterized by dysregulated immune responses and systemic manifestations. While IBD is primarily associated with inflammation in the gut, it can also lead to extra-intestinal symptoms, including joint pain and skin lesions, which are commonly observed in these other diseases. Understanding commonalities and differences among these chronic inflammatory conditions is important for developing more effective therapies that can target the underlying immune dysregulation and improve patients' overall quality of life.

Aims & Methods

We aim to identify both the common disease signatures shared between IBD and other CIDs, as well as the disease-specific signatures unique to each condition. A cross-sectional cohort of 650 patients with CIDs, including Crohn's disease, ulcerative colitis, rheumatoid arthritis, psoriatic arthritis, psoriasis, and systemic lupus erythematosus (SLE), were recruited from the University Hospital Kiel. Peripheral blood samples were collected from this cohort, along with samples from 202 healthy controls, and subjected to RNA sequencing and methylation profiling. At the time of sample collection, the patients in the cohort underwent detailed clinical phenotyping including assessments of disease activity and symptoms. Additionally, these patients were followed up for up to 5 years to record any potential future complications that may arise.

Results

We performed differential expression and methylation analysis between each CID diagnosis and the healthy control group to identify shared molecular signatures. Our analysis showed that IBD shared the most differential signatures with rheumatoid arthritis, indicating common pathways in their pathogenesis. Psoriatic diseases also shared a significant proportion of differentially expressed and methylated patterns, while SLE had the least in common with other CIDs, suggesting distinct molecular pathways driving its pathogenesis. Interestingly, we were able to identify core transcriptomic changes that persisted even during inactive disease by separating the analysis by disease activity. These signatures were shared across different CIDs and were correlated with DNA methylation changes, reflecting the molecular mechanism of chronicity. Commonly upregulated genes across all CIDs were enriched in pathways related to inflammatory response, cytokine signaling, neutrophil chemotaxis, and humoral immune response. Disease-specific pathways included interferon-beta production in SLE, several metabolic processes in psoriasis, and complement activation in ulcerative colitis. Disease-specific methylation signatures were mainly located in CpG islands, while methylation signatures in enhancers were shared among most diseases. Our large cohort design enabled us to identify subgroup of patients across CIDs that share molecular characteristics, including a cluster of genes related to interleukin and interferon signaling upregulated in 71 samples belonging to different CIDs.

Conclusion

In conclusion, our study identified common and disease-specific molecular signatures in CIDs. Our findings suggest shared immune dysregulation pathways underlying the pathogenesis of IBD and rheumatoid arthritis, as well as potential commonalities between psoriatic diseases. We show the clear presence of core signatures of disease regardless of disease activity, which could represent insights into actionable targets for causative treatments and better disease control of CIDs.