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.

Table. Comparison of age-standardized mortality and disability-adjusted life years (DALYs) rates between males and females, 1990-2019
Metric	1990	2000	2010	2019	Annual percentage change (95% CI)	P-value
Mortality Rate (per 100,000 person-year)
Male	58.2	62.5	64.0	66.6	0.36% (0.30% to 0.42%)	<0.001
Female	59.3	61.0	58.3	58.1	-0.22% (-0.29% to -0.14%)	<0.001
Male to Female Ratio	0.98	1.02	1.10	1.14	0.58% (0.55% to 0.61%)	<0.001
DALYs Rate (per 100,000 year)
Male	1633	1798	1927	2070	0.74% (0.70% to 0.78%)	<0.001
Female	1618	1704	1719	1790	0.24% (0.19% to 0.29%)	<0.001
Male to Female Ratio	1.01	1.06	1.12	1.16	0.50% (0.48% to 0.52%)	<0.001

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

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure in class 1 and 2 obese subjects.The effects of menopause on weight are well known. However, given that this patient population is inherently weight-concerned, understanding the effects of ESG on women in menopause is essential to guiding clinicians in counselling this patient population.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in a tertiary referral centre was assessed retrospectively. Data on fertility status (menopause and non-menopause women) were collected. A comparison was performed using the Mann-Whitney U test.

Results

Between May 2017 and October 2021, 209 women underwent ESG. Out of the total, fertility status was available for 204 women: 79 menopause (M; 38,7%) and 125 non-menopause women (NM; 61,3%).At baseline, non-menopause women were younger, whereas there were no differences in BMI and weight.
Adherence to follow-up was 92,4%, 87,3% and 80,0% for menopause, 88,8%, 90,4% and 72,9% for non-menopause, at 6,12 and 24 months, respectively.
Six months after the procedure, non-menopause women showed significantly higher TBWL, WL and BAROS score compared to the menopausal group. In contrast, EWL showed no significant difference between the groups.Average TBWL, WL and EWL were not significantly different between the groups at 12 and 24 months (as shown in Table below).
Seven menopausal women needed revision procedures (5 Re-ESG, 1 Surgery), whereas ten non-menopausal women underwent revision (8 Re-ESG, two surgery).

Table. Weight loss trajectories of subjects who underwent Endoscopic Sleeve Gastroplasty, based on menopausal status. Data are reported as median (Interquartile range).

		WL (kg)	EWL (%)	TBWL (%)	BAROS
6-months follow-up	Menopause (n=73)	15,0 (10)	50,8 (24,7)	15,2 (8,6)	3,5 (1,5)
	Non-menopausa (n=111)	17,0 (9,0)	54,9 (34,6)	17,2 (8,6)	4,0 (2,0)
	p	0,017	0,068	0,0190	0,039
12-months follow-up	Menopause (n=69)	13,0 (11,0)	47,8 (31,4)	14,1 (13,0)	3,5 (2,3)
	Non-menopausa (n=113)	16,0 (13,5)	52,5 (41,5)	16,3 (13,5)	3,5 (2,8)
	p	0,162	0,318	0,223	0,506
24-months follow-up	Menopause (n=40)	13,0 (15,6)	40,5 (39,3)	13,6 (14,8)	2,6 (2,9)
	Non-menopausa(n=62)	10,0 (11,8)	35,4 (45,0)	10,4 (13,4)	2,5 (3,4)
	p	0,4	0,716	0,519	0,776

Conclusion

Non-menopausal women who undergo ESG show better outcomes in the short term. However, this advantage does not persist in the medium and long term.

Introduction

Obesity, one of the most common co-morbidities in women of reproductive age, contributes to infertility and obesity-related pregnancy complications. On the other hand, pregnancy is a condition in which, physiologically, the pregnant woman undergoes weight gain. Endoscopic Sleeve Gastroplasty (ESG), an organ-sparing bariatric procedure aimed to reduce gastric volume and modify gastric motility with full-thickness endoscopic sutures, may be used for the treatment of obesity in women of childbearing age.

Aims & Methods

A retrospective analysis of a prospective database was conducted to evaluate weight trajectories, the evolution of obesity-related comorbidities, and lifestyle modification in women who became pregnant after ESG.
A comparison was made between childbearing-age women who became pregnant after ESG and non-pregnant women who reached at least the 6-month follow-up after ESG.

Results

Between January 2018 and December 2021, a total of 150 childbearing-age women underwent ESG at a large Italian tertiary medical center. Out of the total, 18 patients (12,0 %) reported a desire for pregnancy associated with unsuccessful attempts in the 12 months preceding ESG.
Eleven patients (mean age 33,4±6,2 years) became pregnant after the procedure, following a mean time interval of 5,5±3,9 months. The mean preconception BMI was 31,9±4,0 kg/m² (with a mean reduction of 7,24±4,0 kg/m² after ESG). Three patients were affected by hyperinsulinemia (H-INS), while an additional patient had both H-INS and high blood pressure (HBP). Three women reported difficulty in becoming pregnant before the ESG: two were affected by PCOS.
Total body weight loss (TBWL) of at least 5% was achieved before pregnancy in all patients (73% reached a TBWL ≥ 10%).
Six out of eleven (55%) patients had weight gain in the ranges recommended by the Institute of Medicine (IOM) during pregnancy. Among the 18 women with a reported desire for maternity associated with difficult attempts in the previous 12 months, 16,6 % (3/18) managed to start and carry out a pregnancy.
TBWL (%) was 18,08±8,00, 10,35±11,53, and 12,08±8,49, at the beginning of pregnancy, at the delivery, and at the first follow-up (mean interval, 5,18±3,57 months).
No significant differences in WL, TBWL, EWL, BMI, BAROS, and QoL were found between the pregnancy and non-pregnancy groups (99 childbearing-age women) up to 24 months after ESG.

Conclusion

ESG produces adequate weight loss before pregnancy in patients with obesity and is potentially a useful treatment option for women who have difficulty becoming pregnant, such as those with PCOS. Pregnancy after ESG does not adversely affect weight loss outcomes after delivery as lifestyle changes induced by ESG are maintained after pregnancy and allow for a gradual loss of weight gained during pregnancy.

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

Non-invasive biomarkers are needed to improve the management of eosinophilic esophagitis (EoE). We investigated whether eosinophil and lymphocyte counts could be used to diagnose EoE among patients with dysphagia and assess histological, endoscopic, and clinical disease activity in patients with known EoE.

Aims & Methods

This was a prospective study conducted at four EoE referral centers (Pisa, Padova, Humanitas Research Hospital, Milano Policlinico San Donato). We enrolled consecutive patients undergoing esophagogastroduodenoscopy (EGD) for suspected or known EoE who had performed blood counts within one month before EGD. Histological remission and non-EoE-related dysphagia (NED) were defined according to current guidelines on EoE. Endoscopic characteristics were classified according to the EoE reference score (EREFS). Demographic, clinical and full blood count data were collected. After the EGD, all patients completed the Dysphagia Symptom Questionnaire over 14 days (DSQ). Kruskal-Wallis Rank Sum Test and Pearson’s Chi-squared were used for comparisons. ROC curve analysis was used to assess the diagnostic accuracy. Spearman’s test was used for correlations. Significance threshold was p<0.05.

Results

We included 210 consecutive patients. Of these, 123 had EoE (58.5% active; 41.5% in histological remission) while 87 had non-EoE dysphagia (NED). Characteristics in Table 1. Absolute eosinophil count (AEC) of active EoE was significantly higher than NED (335 vs 90/mm3; p<0.001), and so was eosinophil percentage (4.6% vs 1.1%; p<0.001), and median lymphocyte percentage (30 vs 27%; p<0.001). ROC curve analysis showed that a cut-off of 155 eosinophils/mm3 had an AUC of 0.85, with 71% specificity and 87% sensitivity for the identification of EoE among patients with dysphagia (Figure 1a). Other ROC analyses on the diagnosis of EoE reported in Table 2. With regards to disease monitoring, only eosinophil counts differed significantly between EoE and NED. Median AEC of active EoE was higher than EoE in remission (335 vs 200/mm3; p<0.01), and so was eosinophil percentage (4.6 vs 1.4%; p<0.001) (Table 3). Based on ROC analysis, a cut-off of 325 eosinophils/mm3 had and AUC of 0.70 for the identification of histological remission in EoE, with a specificity of 52.7%% and sensitivity of 82.3% (Figure 1b) (Table 3). There was modest positive correlation between AEC and the EREFS with Spearman’s Rho of 0.4 (p<0.0001), but there was no correlation between AEC and DSQ scores (Rho= -0.01; p=0.9).

Conclusion

Our results show that the AEC in peripheral blood has good accuracy for the diagnosis of EoE in patients with dysphagia and moderate accuracy for monitoring histological disease activity. In addition, AEC was modestly correlated with endoscopic disease activity (EREFS score) but not with symptoms.

Disclosure

Speaker or Consultancy for Apogee Therapeutics, Dr Falk Pharma, Malesci, JB Pharmaceuticals, Sanofi, Alfasigma

Introduction

The Epi-IBD cohort is a prospective European population-based cohort of 1,390 patients diagnosed with inflammatory bowel disease (IBD) in 2010 and 2011 according to Copenhagen criteria. Of these, 482 were diagnosed with Crohn’s Disease (CD), 817 with ulcerative colitis (UC) and 91 with IBD unclassified (IBDU). The Epi-IBD cohort was established to examine differences in incidence, treatment strategies, disease course and prognosis among IBD patients in Eastern and Western Europe.

Aims & Methods

This study aims to describe the use of biological therapy as well as the treatment prior to biological therapy. IBD patients were followed prospectively from the time of diagnosis until the 31^st December 2020, death, emigration or loss of follow-up. Clinical data on surgery, hospitalizations, and medical treatment, were captured throughout the follow-up period and entered into a validated web-database, www.epi-ibd.org.

Results

During a median follow-up period of 10.7 (interquartile range (IQR), 10.0-11.4) years, 34% (N=165/482) of CD and 15% (N=122/817) of UC patients were started on biological therapy. Biological therapy was initiated within the first year after diagnosis in 16.8% (N=81/482) of all CD and 3.8% (N=31/817) of all UC patients. In median biological therapy was started at 1.0 year (IQR, 0.3-3.1) and 2.7 years (IQR, 1.6-4.0) after CD and UC diagnosis, respectively. First-line biological therapy was infliximab in 74% (N=213/287) and adalimumab in 22% (N=64/287) of the patients. The remaing (N=10/287) received either Golimumab, Vedolizumab, Ustekinumab or were part of a trial/unknown. The sequences of biological therapies are displayed in Sankey diagrams, Figures 1 and 2. Herein illustrated is that 34% (N=56/165) CD and 34% (N=41/122) UC received at least two different biological drugs. Immunomodulators were initiated simultaneously to the first biological therapy in 19% (N=31/165) of CD patients and in 9% (N=11/122) of UC patients. Overall 63% (N=104/165) CD and 51% (N=62/122) UC patients were receiving concomittant immunomodulators with the first biological therapy.
The sequences of therapy leading up to biological therapy are displayed in Sankey diagrams, Figures 3 and 4. Herein illustrated is that the most common sequence of treatment before the first biological therapy for CD was 1) Steroids, 2) Immunomodulators (21%, N=34/165), and for UC was 1) 5-aminosalicylic-acid (5ASA), 2) Steroids, 3) Immunomodulators (39%, N=48/122). Prior to the first biological therapy one, two and three or more courses of systemic steroid were used in 41%, 28% and 17% (N=67, 47 and 28) of CD patients and 43%, 24% and 26% (N=52, 29 and 32) of UC patients. In 14% (N=23/165) and 7% (N=9/122) of CD and UC patients, systemic steroids were not used prior to first biological therapy. In patients having immunomodulators prior to biological therapy, these were administered for a median of 0.5 (IQR, 0.1-1.9) years and 1.1 (IQR, 0.2-3,2) years in CD and UC, respectively. For 5ASA this was 0.8 (IQR, 0.2-1.5) years for CD and 2.2 (IQR, 0.8-4.3) years for UC.

Conclusion

In this multicenter European population-based cohort, different prescribing patterns for biologics emerge: 34% of CD and 15% of UC patients received biologics within 10 years after diagnosis. Infliximab was the most common first-line biological therapy. Only about half of the patients received concomitant immunomodulators. Prior to the first biological therapy, most patients were exposed to systemic steroids and many to repeated courses.