Introduction

Endoscopic sleeve gastroplasty (ESG) is a less invasive alternative to surgery for patients with obesity. The post procedure recovery is quicker and patients can be discharged one day after procedure.

Aims & Methods

We aimed to determine the outcome after ESG in patients with obesity and benefit of adding GLP1 agonist after ESG. All patients undergoing ESG at our center from 2017 up to 2020 were retrospectively recruited. Patients with BMI ranging from 30 to 40 kg/m² were eligible for ESG. The baseline demographic and clinical profile and reports of investigations were recorded. The date of procedure and follow up details including weight at various time points were noted. The procedure was done by Apollo^TM overstitch device. The primary outcome was loss of at least 10% weight from baseline after ESG. The secondary outcome was loss of >20% weight after surgery. Multivariate analysis was performed using logistic regression to asses the predictors of weight loss after ESG including use of GLP1 agonist.

Results

	Weight loss >10% (n=28)	Weight loss <10% (n=13)	p
Age (Years)	39.9+9	37.4+9.2	0.3
Gender (Female)	25 (89.3%)	12 (92.3%)	0.98
Weight before ESG (Kg)	90.4+12.8	88.9+8.6	0.76
Use of GLP1 agonist after ESG	11 (39.3%)	8 (61.5%)	0.2

Forty-six patients underwent ESG during the study period. Their mean age was 39.9+8.8 years and 91.3% were females. The mean BMI before ESG was 35.1+2.9 kg/m² and mean weight was 90.2+11.5 kg. Follow-up data was available for 41 patients: the mean duration of follow-up was 29.4+14.8months. The primary outcome (weight loss >10%) was achieved in 68.3% patients. Weight loss >20% was noted in 19.5% subjects. The mean weight 6-12 months after ESG was 80.8+11.2 Kg and after 2 years was 87.6+12.6 Kg. Multivariate analysis was done using age, gender, baseline weight and use of GLP1 agonist as variables for predicting weight loss after ESG (Table 1). We did not find any significant predictors including use of GLP1 agonist (p=0.2).

Conclusion

ESG leads to weight loss in about two-third of patients although the effect is not sustained after 2 years. Use of GLP1 agonist does not have additional impact on weight loss.

Introduction

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4β7) integrin, suppresses immune cell migration by blocking the interaction between α4β7 integrin and mucosal addressin cell adhesion molecule 1, and is used to treat patients with UC with moderate-to-severe activity. Reports about histological features that predict vedolizumab efficacy are scarce.

Aims & Methods

We evaluated the infiltration of inflammatory cells in the colonic mucosa prior to the induction of vedolizumab and examined the association between histological features and vedolizumab efficacy.
This was a multicenter, retrospective study. Patients with UC who were treated with vedolizumab between November 2018 and April 2021 were enrolled in this study. All eligible patients had moderate-to-severe disease activity at the time of the initial treatment with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 per unit area of the lamina propria were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified.

Results

A total of 42 patients were included in this study. 17 (40.5%) patients achieved clinical remission at week 22. Significantly more CD4+ cells were found in the colonic mucosal tissues of patients with remission than in those without remission (odds ratio [OR]=1.44, P=0.014). In contrast, the CD68-positive area and the CD45-positive were not significantly different between the two groups. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR=0.11, P=0.008 and OR=0.50, P=0.009, respectively).

Conclusion

A high CD4+ infiltration in the colonic mucosa was associated with remission after vedolizumab treatment. Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.

Introduction

Although CADe/x systems increase colorectal polyp detection, their ability to predict histological diagnosis is limited.

Aims & Methods

The aim of this study is to determine which factors related to morphology, histology and the image characteristics are associated with histology prediction by PolyDeep, a CADe/x system.
For this analysis, 5546 still images of colorectal polyps collected in PIBAdb database (https://www.iisgaliciasur.es/home/biobanco/colorectal-polyp-image-cohort-pibadb/?lang=en) were used. The images were obtained from videos recorded by endoscopist. Each image was associated with the endoscopy description (morphology, size), the final histology diagnosis and the characteristics (size, area) related with the Red, Green and Blue model (RGB model) and the Hue, Saturation and Value model (HSV model). Finally, the Convolutional Neural Network (CNN) determined the probability a polyp was classified as neoplastic lession (adenomatous, Traditional Serrated Adenoma,TSA, Sessile Serrated Lession, SSL). We determined Polydeep classified lesions as neoplastic if the probability was ≥0.5. We performed three analysis: (1) linear multiple regression in order to determine which variables are associated with the probability of classification as neoplastic lesions. (2). A multivariate logistic regresion analysis to define the variables associated with the classification as a neoplastic lesions. (3) A multivariate logistic regression to establish which variables are associated with missclassification of polyps. We use the R software for statistical computing.

Results

PolyDeep classified 84,51% of the lesions as neoplastic lession and managed to correctly classify 85.02% of the evaluated polyps (92.8% adenomas, 82.5% TSA, 84.2% SSL and 51.6% hyperplastic). The R² in the multiple linear regression is the 0.3655. The model associated to the neoplastic diagnosis has an Akaike Information Criterion (AIC) of 3363.3 and the model associated with missclassification, has an AIC of 3547.5. The variables associated to each regression model showed in the attached table.

Predictor variables		Neoplastic lesion classification - Predictive model		Missclassification - Predictive model
		Multiple linear regression OR / (CI 95%) R2 = 0.3655	Multivariate logistic regression OR / (CI 95%) AIC = 3363.3	Multivariate logistic regression OR / (CI 95%) AIC = 3547.5
Histology	TSA SSL Hyperplastic	-0.09 / (-0.11 - 0.07) -0.05 / (-0.07 - 0.02) -0.37 / (-0.39 - 0.35)	0.44 / (0.32 - 0.61) 0.65 / (0.47 - 0.92) 0.17 / (0.13 - 0.22)	1.88 / (1.34 - 2.60) 2.52 / (1.77 - 3.53) 15.67 / (11.98 - 20.63)
NICE classification	Type 2 Type 3	0.10 / (0.09 - 0.12) 0.03 / (-0.11 - 0.17)	1.55 / (1.23 - 1.96) 8.29 / (0.00 - NA)	1.23 / (0.97 - 1.57) 0.00 / (NA- 5,36x10+87)
Paris classification	Slightly elevated Sessile Pedunculated	0.06 / (0.02 - 0.10) 0.04 / (-0.01 - 0.07) 0.04 / (-0.01 - 0.07)		1.31 / (0.80 - 2.19) 0.88 / (0.54 - 1.46) 0.42 / (0.23 - 0.79)
Polyp size (mm)		0.23 / (0.23 - 0.24)	1.25 / (1.20 - 1.30)	1.06 / (1.02 - 1.09)
Width (píxels)		-0.31 / (-0.31 - 0.31)	0.99 / (0.98 - 0.99)
Area (píxels2)		0.68 / (0.68 - 0.68)
Mean model RGB	Mean box red (0º-255º) Mean box blue (0º-255º) Mean box color (0º-255º) Mean image green (0º-255º) Mean image blue (0º-255º) Mean outside box red (0-255º) Mean outside box green (0º-255º) Mean outside box blue (0º-255º)	0.02 / (0.02 - 0.02) -0.52 / (-0.53 - 0.52) 0.36 / (0.35 - 0.36) 0.60 / (0.59 - 0.60) 0.82 / (0.81 - 0.82)	0.97 / (0.96 - 0.97) 0.73 / (0.67 - 0.79) 1.50 / (1.35 - 1.68)	3.38 / (2.30 -5.02) 1.82 / (1.54 - 2.16) 0.20 / (0.12 - 0.32) 2.91 / (2.12 - 4.01) 0.53 / (0.36 - 0.78) 0.76 / (0.66 - 0.89) 0.70 / (0.65 - 0.76)
Mean Model HSV	Mean box Hue (0º-179º) Mean box saturation (0º-179º) Mean image hue (0º-179º) Mean image saturation (0º-179º) Mean image value (0º-179º) Mean outside box hue (0º-179º) Mean outside box saturation (0º-179º) Mean outside box value (0º-179º)	0.02 / (0.02 - 0.02) 0.19 / (0.19 - 0.20) -0.21 / (-0.22 - 0.21) 0.17 / (0.17 - 0.17) -0.84 / (-0.85 - 0.83)	1.09 / (1.07 - 1.12) 1.07 / (1.05 - 1.08) 1.20 / (1.14 - 1.26) 0.74 / (0.68 - 0.79) 1.25 / (1.16 - 1.34)	0.97 / (0.94 - 0.99) 1.26 / (1.10 - 1.43) 0.55 / (0.47 - 0.64) 0.88 / (0.85 - 0.92) 0.84 / (0.75 - 0.94) 1.71 / (1.49 - 1.95)

Table 1: The table show the results of the multiple linear regression and both multivariate logistic regressions with the variables associated to correct classifications or missclassification of colorectal lesions. Traditional Serrated Adenoma (TSA); Sessile Serrated Lesion (SSL); Odd Ratio (OR); Confindence Interval (CI)

Conclusion

The results obtained in this study allow us to establish strategies to improve Polydeep predicted histological diagnosis.

Introduction

Limited evidence is available about predictors of response to specific medications for ulcerative colitis (UC). OCTN1, an organic cation transporter, with its variants, could modulate the inflammatory response and potentially modify drug response to immune-modulatory therapy (anti-TNFα and Vedolizumab), perhaps predicting individual response.

Aims & Methods

We first confirmed the ability of OCTN1 to differentially modulate IL1β secretion under different stimuli in a human leukemia monocytic cell line (THP-1) and in human peripheral blood mononuclear cells. We therefore prospectively enrolled a cohort of UC patients starting either anti-TNFα or Vedolizumab, determined their OCTN1 genotype and evaluated their clinical features at baseline and clinical response to therapy or disease remission (according to clinical Mayo score) after six weeks (T1) and six months (T2). We finally enrolled a cohort of UC patients in clinical and endoscopic remission (according to full Mayo score) under immune-modulatory therapy (anti-TNFα or Vedolizumab) for at least two years.

Results

OCTN1-deficient THP1 cells showed reduced IL-1β secretion in response to peptidoglycan (PGN) and Fusobacterium nucleatum (Fn), whilst primary monocytes bearing OCTN1 503F variant displayed an increased production of IL-1β in response to PGN and live bacteria. We therefore enrolled 90 patients, 50 starting anti-TNFα and 40 Vedolizumab. Patients with 503F genotype showed higher rates of pancolitis as compared to 503L genotype. Among patients with 503L phenotype, Vedolizumab results highly associated with long-term response (OR 8.92, 95%CI 0.50-11.0; p=0.019), whilst conversely co-presence of 503F genotype and Vedolizumab therapy disclosed an opposite role on the long-term response rate (OR 0.02, 95%CI 0.00-0.81; p=0.038).
The population of UC patients in clinical and endoscopic remission was composed by 92 patients, 63 under anti-TNFα and 29 under Vedolizumab. Of note, similar trends of disease extension were observed across genotypes: higher rates of pancolitis were observed in the 503F population as compared to 503L (62.5% vs 44%). Furthermore, among patients in remission with 503F genotype, the percentage of subjects receiving Vedolizumab was sensibly lower than among patients with 503L genotype (87.5% anti-TNFα vs 12.5% Vedolizumab among 503F genotype; 56% anti-TNFα vs 44% Vedolizumab among 503L genotype).

Conclusion

Mutated OCTN1 genotype (503F) favors an increased IL1β secretion from human stimulated leukocytes, thus suggesting a worse disease course with higher rate of pancolitis and lower response to Vedolizumab as compared to 503L.

Introduction

Chronic constipation (CC) is one of the most frequent non-motor features of Parkinson’s Disease (PD). Previous studies highlighted the association of CC with PD duration and severity [1]. Furthermore, gut microbiota changes and brain-gut-axis (BGA) dysregulation are common in PD and these alterations are related with clinical manifestations [2,3]. For this reason, probiotics, balancing the gut microbiota, are emerging as a potential therapeutic approach in PD patients.

Aims & Methods

Objective: To evaluate the patients’ satisfaction rates as well as gastroenterological and neurological effects of the administration of a synbiotic in PD patients with CC.
Methods: This study enrolled patients with stable PD who fulfilled Rome IV Criteria for CC or irritable bowel syndrome with constipation (IBS-C). Patients received a synbiotic treatment (Enterolactis ® duo, 4 sachets/day, containing probiotic Lactobacillus casei and prebiotic inulin) for 12 weeks. Two primary endpoints were chosen to monitor the satisfaction with therapy (SWT). SWT was defined when patients were satisfied (satisfaction score >4 on a 7-point Likert scale) or improved after therapy (increase in the global rating of change scale of at least two points on a -7 to +7 visual analogue scale). In addition, a gastrointestinal (GI) evaluation with the Patient Assessment of Constipation-symptoms questionnaire (PAC-SYM), number of complete bowel movements per week, Bristol stool Scale (BSS) were calculated before and after the treatment. The neuropsychological evaluation was performed by the Montreal Cognitive Assessment (MoCA), Movement Disorder Society-Sponsored Revision of Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), SCales for Outcomes in Parkinson’s disease - Autonomic Dysfunction (SCOPA-AUT), Toronto Alexithymia Scale (TAS-20), Reading the Mind in the Eyes Test (RMET), Parkinson Anxiety Scale (PAS), State-Trait Anxiety Inventory (STAI-Y), Beck Depression Inventory (BDI II), Hamilton depression rating scale (HAM-D) pre- and post-intervention.

Results

30 patients (10 F) were consecutively enrolled. Satisfaction >4 (endpoint 1) significantly changed from 17% to 60% patients after treatment, p = 0.002. The calculated satisfaction score significantly increased from 4(1) to 5(2) (median (IQR), p = 0.003. Improvement after treatment (endpoint 2) was achieved by 83% of patients. The Global Rating of Change Score changed significantly from 0(3) to 4(2)(median (IQR), p < 0.001. Moreover, a beneficial effect of treatment was shown on GI symptoms. Specifically, PAC-SYM Questionnaire score changed from 1.42(0.94) to 0.91(0.77), p < 0.001, number of complete bowel movements per week from 3(3.5) to 5.5(4.1) p < 0.001 and Bristol stool Scale (BSS) from 2(2) to 3(2) p < 0.001. After treatment PD patients performed better in motor and non-motor features. Specifically, the scores (median (IQR) of TAS-20 significantly changed from 55.0 (22) to 49.5 (21), p=0.03, SCOPA-AUT from 17.0 (7) to 13.5 (10), p = 0.002, MDS-UPDRS part 1 from 13.5 (13) to 9.0 (6), p = 0.001, HAM-D score from 12.5(10) to 9.0 (12), p = 0.045. PAS-A showed a trend towards significance from 7.0(6) to 5.0(7), p = 0.06.

Conclusion

Our results showed that a considerable number of PD patients with CC or IBS-C were satisfied with their defecation after treatment. GI symptoms as well as motor and non-motor features in PD patients improved. Our data suggest that the addition of a synbiotic Enterolactis ® duo may be a useful therapeutic approach in PD possibly acting on the gut-brain-gut axis.

References

References
[1] Krogh K, Ostergaard K, Sabroe S, Laurberg S. Clinical aspects of bowel symptoms in Parkinson’s disease. Acta Neurol Scand. 2008;117(1):60-64.
[2] Shen T, Yue Y, He T, Huang C, Qu B, Lv W, Lai HY. The Association Between the Gut Microbiota and Parkinson’s Disease, a Meta-Analysis. Front Aging Neurosci. 2021 Feb 12;13:636545.
[3] Scheperjans F, Aho V, Pereira PA, et al. Gut microbiota are related to Parkinson’s disease and clinical phenotype. Mov Disord. 2015;30(3):350-358.