Introduction

Gender differences are gaining increasing attention in autoimmune diseases, such as autoimmune atrophic gastritis (AAG). AAG is a chronic inflammatory pre-neoplastic condition that leads to atrophy of the oxyntic mucosa, resulting in hypochlorhydria and potentially leading to gastric neoplastic lesions. Recently, also the human microbiota has gained interest in the scientific community. Previous studies showed that AAG may be associated with modifications in the gastric microbiota composition likely due to hypochlorhydria, that makes plausible the overgrowth of intragastric bacteria. To our knowledge, data on gender differences in gastric microbiota are lacking.

Aims & Methods

In this study we aimed to investigate gender differences in the gastric microbiota composition in subjects with healthy stomachs and patients affected by AAG. This is a post-hoc analysis conducted on 52 adult subjects undergoing gastroscopy for dyspepsia: median age 61 years, range 18- 83, 32 females and 20 males; 30 (57.7%) with healthy stomach and 22 (42.3%) with AAG. Gastric biopsies were obtained for both histopathology and genomic DNA extraction. Gastric microbiota was assessed by sequencing hypervariable regions of the 16SrRNA gene. Bacterial profile at phylum and genus level was reported as relative abundance expressed as 16SrRNA OTUs (>0.5%) and biodiversity calculated as Shannon-diversity index-H. All data were stratified for female and male gender separately in healthy subjects and AAG patients.

Results

Healthy women had a significantly higher bacterial abundance compared to men; differently, in AAG patients, gastric bacterial abundance was similar in both genders (at 13333 reads, 704.65 in healthy women vs 470.40 in healthy males, p= 0.03; 467.2 in AAG females vs 433 in AAG males, p=0.32). In healthy subjects, the gastric microbiota showed a significantly lower biodiversity in females compared to males (3.2 vs 3.4, p=0.003). In contrast, in AAG patients, the gastric microbiota showed a significantly lower biodiversity in males than in females (Shannon index 2.3 vs 3.5, p<0.0001). Compared to healthy subjects, in AAG patients, the biodiversity of the gastric microbiota was significantly lower in males (2.3 vs 3.4, p<0.001), while it was higher in females (3.5 vs 3.2, p=0.002). Taxa frequency at phylum level in females and males is shown in the table. Concerning taxa frequency at genus level, Streptococcus was the most prevalent being higher in healthy females compared to males (11.26 vs 7.88, p=0.03), but similar in both genders in AAG (15.94 vs 15.49, p= 0.77).

Taxonomy phyla Healthy stomach	Females median	Males median	p - value	Taxonomy phyla AAG	Females median	Males median	p - value
Firmicutes	22.67	15.83	0.5677	Firmicutes	27.46	33.11	0.0155
Proteobacteria	18.70	26.41	0.8489	Proteobacteria	19.13	19.32	0.1425
Bacteroidetes	10.55	10.46	0.1824	Bacteroidetes	5.17	2.36	0.4042
Actinobacteria	2.97	1.75	0.6424	Actinobacteria	2.19	2.10	0.0042
Fusobacteria	0.19	1.31	0.0124	Fusobacteria	0.58	0.18	0.4634

Conclusion

Gastric microbiota gender differences in healthy subjects, seem to be reset in AAG, likely due to hypochlorhydria. Differences between genders on taxa frequency at phylum and genus level were observed in healthy subjects and AAG patients. The impact of these findings on the gender-specific natural history of AAG remains to be elucidated.

Introduction

C-reactive protein (CRP) and fecal calprotectin (FeCal) are non-invasive inflammatory biomarkers used to assess disease activity in UC. The Phase 3 QUASAR induction study evaluated the efficacy and safety of guselkumab (GUS), an IL-23 p19 subunit antagonist, in patients (pts) with moderately to severely active UC. Here, we analyze the effect of GUS treatment on CRP and FeCal through Week (Wk) 12 in pts with elevated CRP and/or FeCal.

Aims & Methods

Pts with a modified Mayo score of 5-9 and a Mayo endoscopy subscore ≥2 at baseline (BL) were randomized 3:2 to receive either GUS 200mg IV or placebo (PBO) IV at Wks0, 4, and 8. CRP and FeCal were assessed at BL, Wk4, Wk8 (for CRP only), and Wk12.

Results

A total of 701 pts were evaluated and approximately 50% of randomized pts had a history of inadequate response/intolerance to advanced therapies (ADT) for UC; 47.4% of these pts had inadequate response/intolerance to ≥2 ADT classes. Median BL concentrations of CRP and FeCal were similar between the GUS-treated and PBO-treated pts (4.34 vs 3.83mg/L and 1651 vs 1606mg/kg, respectively). Among pts with elevated CRP and/or FeCal at BL, greater reductions in CRP and FeCal were observed at the earliest timepoint assessed (Wk4) with GUS and continued through Wk12 compared with PBO (Table).
At BL, 248 GUS-treated pts and 160 PBO-treated pts had elevated CRP (>3mg/L); the proportions were similar between treatment groups (58.9% vs 57.1%, respectively). Among these pts, median change from BL in CRP concentration (mg/L) at Wk12 for the GUS and PBO cohorts were -3.99 and -0.51mg/L, respectively (nominal p<0.001); the proportions of pts achieving 50% and 75% reduction in CRP levels (or ≤3mg/L) at Wk12 were higher for GUS-treated pts than those receiving PBO (59.7% vs 28.1% and 47.2% vs 19.4%, respectively; both nominal p<0.001). Similarly, a higher proportion of GUS-treated pts achieved CRP≤3mg/L at Wk12 than PBO-treated pts (40.3% vs 16.3%, nominal p<0.001).
At BL, 333 GUS-treated pts and 225 PBO-treated pts had elevated FeCal (>250mg/kg); the proportions were similar between treatment groups (79.1% vs 80.4%, respectively). Median change from BL in FeCal concentration (mg/kg) for pts with elevated FeCal at BL at Wk12 were -800 and -86mg/kg for the GUS and PBO cohorts, respectively (nominal p<0.001); the proportions of pts achieving 50% and 75% reduction in FeCal levels (or ≤250 mg/kg) at Wk12 were higher for GUS-treated pts than those receiving PBO (51.1% vs 33.8% and 41.4% vs 23.6%, respectively; both nominal p<0.001). A larger percentage of pts treated with GUS achieved FeCal≤250mg/kg at Wk12 than pts treated with PBO (29.4% vs 17.3%, nominal p<0.001).

Table. Change from baseline in CRP and FeCal through Week 12 among patients with elevated CRP (>3mg/L) or FeCal (>250mg/kg) at baseline
	Placebo IV	Guselkumab 200 mg IV
CRP (mg/L) Baseline, N Median [IQR]	160 8.02 [5.40; 16.85]	248 9.26 [5.31; 18.05]
Wk 4, N Median change from baseline [IQR]	158 -2.06 [-5.70; 1.58]	245 -3.35 [-8.60; -0.23]***
Wk 8, N Median change from baseline [IQR]	156 -1.75 [-5.68; 1.46]	239 -3.80 [-10.77; -0.19]***
Wk 12, N Median change from baseline [IQR]	153 -0.51 [-4.64; 2.72]	239 -3.99 [-11.46; -0.85]***
FeCal (mg/kg) Baseline, N Median [IQR]	225 1743 [1120; 3395]	333 1787 [920; 4009]
Wk 4, N Median change from baseline [IQR]	213 -227 [-1041; 658]	308 -603 [-1866; 230]***
Wk 12, N Median change from baseline [IQR]	201 -86 [-1254; 504]	293 -800 [-2532; 0]***
***Nominal P≤0.001. Patients who had a prohibited change in UC medication, an ostomy or colectomy, or discontinued study agent due to lack of efficacy or an AE of worsening of UC or other reasons except for COVID-19 related reasons (excluding COVID-19 infection) or regional crisis in Russia and Ukraine prior to the designated timepoint had their baseline value carried forward from the time of the event onward. The p-values of treatment comparison were based on the mixed-effect model repeated measures with CRP and FeCal values being log-transformed.

Conclusion

In this phase 3 induction study, pts with moderately to severely active UC and elevated inflammatory markers treated with GUS 200mg IV induction showed greater improvement from BL in both CRP and FeCal levels compared with PBO. Differences were observed as early as the first assessments at Wk4 and continued through Wk12.

Disclosure

Tadakazu Hisamatsu received consulting fees from Janssen Research & Development, LLC.
Laurent Peyrin-Biroulet reports personal fees from Janssen.
Axel Dignass reports fees for participation in clinical trials, review activities such as data monitoring boards, statistical analysis and end point committees from Janssen; consultancy fees from Janssen; and payment from lectures including service on speakers bureaus from Janssen.
Kuan-Hsiang G. Huang, Matthew Germinaro, Nicole Houck,Ye Miao, and Hongyan Zhang are employees of Johnson & Johnson and own company stock/stock options.
Marjorie Argollo reports consulting fees from Janssen.
Ken Takeuchi has served as a speaker for Janssen.
Rafal Filip reports lecture fees and research/education support from Janssen.
Jessica R. Allegretti is a consultant and speaker for Janssen.
Brian G. Feagan received consulting fees from Janssen; a member of the speakers bureau for Janssen; support for attending meetings and/or travel from Janssen; and participation on a Data Safety Monitoring Board or Advisory Board from Janssen.
Bruce E. Sandsreports grants, consulting and speaking fees and other support from Janssen.

Introduction

Pancreatic cysts are a common finding in imaging studies, and, considering the different malignant potentials of mucinous and non-mucinous cysts, it is necessary to develop accurate methods and algorithms to differentiate between them. We conducted this study to compare the diagnostic performance of glucose levels and CEA levels in the diagnosis of mucinous pancreatic cysts.

Aims & Methods

We conducted a retrospective study of patients who underwent EUS-FNA of pancreatic cystic lesions between September 2020 and March 2023 at a tertiary referral center. We included patients whose glucose and CEA levels had been measured. Indicators of mucinous cysts include glucose levels less than 2.7 mmol/l and CEA levels greater than 192 ng/ml. It was compared to the final pathology (obtained after surgery or by EUS-FNB) result to determine their accuracy.

Results

	Non-mucinous	Mucinous
Gender (%male)	47.3%	33.3%
Age ( Median)	50.2	58.3
Cyst location
head	9	3
body	2	5
tail	8	4

A total of 31 patients were included in the study, 13 males and 18 females. The mean age was 55.7 years. Of the 31 patients, 12 (38.7%) were diagnosed with mucinous cysts (6 mucinous cystic neoplasms, 6 intraductal papillary mucinous neoplasms), and 19 (61.2%) were diagnosed with non-mucinous cysts (9 serous cystic neoplasm, 8 pseudocysts, 1 solid pseudopapillary neoplasm, and 1 lymphoepithelial cyst). There was a female prevalence in patients with mucinous cysts (8 females and 4 males) with a mean age of 59,6 years. From the cyst fluid analysis, the sensitivity, specificity, and accuracy of glucose in diagnosing mucinous cysts were 91.7%, 89.5%, and 90.3%, respectively. CEA’s sensitivity, specificity, and accuracy were 81.8%, 85.0%, and 83.9%, respectively.

Conclusion

In the diagnosis of pancreatic cystic lesions, glucose levels have high diagnostic performance with high sensitivity and accuracy. In contrast, CEA levels have a lower diagnostic performance. The findings of our study support the use of EUS-FNA and glucose levels in the diagnosis of pancreatic cystic lesions, as well as EUS-FNB to obtain histological specimens for a more accurate diagnosis of pancreatic cysts. Further studies are needed to validate these findings and explore the potential of other biomarkers in diagnosing and managing pancreatic cystic lesions.