Introduction

​Crohn's disease (CD) is characterized by a rare, chronic disease that requires lifelong treatment, representing a burden on healthcare systems. Considering that in Brazil, through the Unified Health System (SUS), patients have access to all treatment, it is important to know how the costs are being distributed in these patients, to better plan they care.

Aims & Methods

Objective: The present study aims to evaluate the costs for the hospital and SUS reimbursement for outpatient treatment of patients with CD. Methodology: This is a retrospective cohort of patients with CD followed between 2006 and 2020 in a Brazilian public tertiary hospital. Patients over 18 years of age and with complete information in their medical records were included. Through medication and exams carried out during follow-up, SUS reimbursement values were calculated using the SIGTAP-SUS table and hospital costs using the table provided by the hospital. The values for the acquisition of medications were provided by the State Health Department. Conversion to dollars was carried out each year, as well as correction for inflation. The statistical difference was evaluated across disease phenotypes according to the Montreal classification using the ANOVA test and the Scheffe post hoc test.

Results

One hundred and ninety-one patients were included, 50.26% being female. The SUS reimbursement cost was $6741.40 ± 2526.87, the hospital cost was $7162.88 ± 2732.30, and adjusted for inflation was $11274.36 ± 5806.85. In post hoc analysis, there was a statistical difference between groups A2 and A3 (age at disease onset between 16 and 40 years and over 40 years) in the reimbursement group, and between the inflammatory and fistulizing phenotypes in the cost and reimbursement groups.

Conclusion

​In Brazil, the treatment of CD has lower costs but maintains differences between phenotypic profiles similar to international studies. Showing the difference in cost, reimbursement and inflation, questions are raised about the updating of SIGTAP-SUS tables and the credibility of cost studies and its management planning.

Introduction

Pfizer's Institute for Translational Equitable Medicine and our Chief Medical Officer, Aida Habtezion, MD, hosted an IBD Health Equity Summit at DDW 2023 in Chicago, Illinois on May 5, 2023 with a group of 22 key opinion leaders in the gastroenterology field. The purpose of the Summit was to uncover health equity research gaps and quality of care gaps that will enable Pfizer and our partners to determine future directions in IBD research and contribute to achieving healthcare equity by providing opportunities to improve patient outcomes, as well as address practice-based disparities.

Aims & Methods

A full day Summit was designed and developed, bringing together thought leaders and experts (representing research, HCPs and patients) to discuss health disparity gaps and possible solutions. The day was split into two parts: a morning session focused on research, with IBD researchers presenting different facets of the research construct with follow-on discussion with the audience. The afternoon was dedicated to clinical care and also included IBD experts addressing Health Equity concerns and opportunities. A follow-on summary report was developed, distributed and serves as the basis for current and future strategies aimed at closing disparity gaps among IBD patients.

Results

Several overarching themes emerged, highlighting IBD as a global affliction, and challenges that transcend geographical borders. Addressing these challenges will require solutions tailored to local and regional contexts that consider factors such as race, ethnicity, socio-economic status, culture, diets, and sexual orientations. It was also recognized that many of the challenges posed by IBD are not unique to this disease, and that valuable insights can be gained by examining other complex disease states to improve the quality of care and address health disparities in patients with IBD.

Conclusion

IBD Research
Key gaps include low clinical trial participation of patients from diverse communities due to lack of healthcare literacy, low historical representation, bias in recruitment, lack of diversity in providers.
Strategies to address these gaps include improving health literacy, workforce development and educating providers, adequate compensation for time, flexibility for participating in trials, and incorporation of digital health tools for follow-ups.
Clinical Care
There are groups of patients in several regions that lack any care, and addressing healthcare disparities in IBD care for these patients cannot be done online but will need to be done on a local and regional level on the ground.
When addressing health inequities, the heterogeneities within underserved populations like Black and Hispanic patients need to be considered.
Gaps in data on the effectiveness of therapies in specific patient populations (ie, response to anti-TNFs in black patients and patients with comorbidities).
Sponsorship is lacking to establish efforts in underserved communities on a global level; There is an opportunity to provide connection for minority physicians to resources.
By identifying gaps and potential strategies to close them, the participants have provided Pfizer and our partners a roadmap to address health disparities among IBD patients worldwide. These data and information have served as the basis for a go-forward plan to support and invest in change initiatives to close gaps. Our desire is to enlist additional partners and collaborators through a Call to Action to identify solutions at the local level that can accelerate improved IBD care and outcomes for some of the most vulnerable populations in the world.

Disclosure

Employee of Pfizer Inc

Clinical Case Summary

Background: Although mesalazine preparations are the first-line drug for induction of remission in ulcerative colitis, the number of intolerant cases is increasing.¹⁾ An association between mesalazine oral administration and decreased risk of cytomegalovirus(CMV) reactivation has been suggested.²⁾
Presentation of Case: A 63-year-old male was diagnosed with UC 2022 and started taking mesalazine. One week later, he developed fever and his stool frequency increased, so mesalazine intolerance was suspected and stopped taking.He was hospitalized in November. After admission, a blood test showed CMV quantitative PCR 6.7×10. And he was positive for MMX-mesalazine DLST. Colonoscopy revealed a left-sided colitis, Mayo 3. In December, the colonoscopy was performed again and found that the rectum was Mayo 3 with residual ulceration, but other areas had improved to about Mayo 1, so the patient was judged to be steroid-dependent and was induction maintained in remission with infliximab and azathioprine. As the stool frequency gradually increased from February 2024, he was judged to be secondarily invalid on infliximab. He was suspected to have renal failure due to diarrhea and was admitted to the hospital in April. Endoscopy showed punched-out ulcer and CMV enteritis was suspected. Treatment was initiated with prednisolone in combination with ganciclovir and antibiotic.
Discussion: Standard therapy for ulcerative colitis with mesalazine intolerance and CMV reactivation is not settled; JAK inhibitors are not suitable for remission induction therapy because reactivation of Herpes spp. is likely to be problematic. Anti-α4β7 integrin inhibitors are also difficult to introduce because of their intestinal selectivity. It is necessary to consider introducing anti-IL23 antibodies. Treatment of mesalazine-intolerant ulcerative colitis with CMV reactivation is challenging.
Conclusion: Further accumulation of cases in which anti-IL23 antibodies were used to induce remission is desirable.

References

1 Hiraoka S. Journal of Gastroenterology and Hepatology 2021;36:137-143
2 Qin U.Diagnostics 2021;11(11):1952

Introduction

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), often manifests around the fertile age. It is known that disease activity affects pregnancy outcomes. However, little is known about how IBD affects pregnancy outcomes and vice versa. Both IBD and pregnancy complications, particularly those in which placental insufficiency is implicated, are accompanied by oxidative stress. Oxidative stress is defined as an imbalance between reactive oxygen species (ROS) production and antioxidant availability. Free thiols (FT) are circulating biomarkers of oxidative stress since they readily scavenge ROS. Previous research has shown reduced levels of FT in both IBD¹ and pregnancy complications². Classical biomarkers of placental insufficiency include soluble FMS-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PLGF), and their ratio is reflective of maternal pregnancy complications². However, the behavior of these biomarkers in pregnant women with IBD remains unclear.

Aims & Methods

In this study, we aimed to investigate the relationship between FT, sFlt-1, and PLGF and the occurrence of pregnancy complications in patients with IBD, and to assess their dynamics before, during, and shortly after pregnancy.
In this retrospective clinical pilot study, we investigated a cohort of pregnant women with IBD and healthy pregnant controls who were pregnant between 2000 and 2023. Serum samples taken before (IBD n=41), during (IBD n=33, controls n=14), and after (IBD n=25) pregnancy were analyzed for PLGF, sFlt-1 and FT levels. FTs were measured using a colorimetric detection method. sFlt-1 and PLGF were measured using an immunofluorescent assay. Extensive clinical data were collected, including data about pregnancy complications such as pre-eclampsia, fetal growth restriction, and gestational diabetes, and IBD disease parameters, including fecal calprotectin and clinical disease scores.

Results

In total, 40 patients (n=32 CD, n=7 UC, and n=1 IBD-U) with 47 pregnancies and 14 non-IBD control pregnancies were included. Comparing patients with IBD to controls during pregnancy, serum FT levels were significantly reduced in patients, even after adjustment for gestational age (p=0.043). FT levels significantly decreased during pregnancy compared to preconception (p=0.001), suggesting increased systemic oxidative stress during pregnancy. The sFlt-1/PLGF ratio was significantly higher in IBD compared to controls (p=0.011), which was partially due to a difference in gestational age (median (IQR): controls 32.6 weeks (29.4-33.1) vs. 15.4 weeks (7.0-22.7) in IBD). In total, 32 patients (56%) and 3 controls (21%) developed pregnancy complications. The sFlt-1/PLGF ratio was higher in those developing maternal complications, almost reaching significance (p=0.053), while FT showed a trend towards decreased levels in those developing maternal complications (mean (SD): 368.9 µM (38.7) without vs. 349.1 µM (21.9) with maternal pregnancy complications, p=0.082).

Conclusion

This study provides evidence for increased systemic oxidative stress (reflected by lower systemic FT levels) during pregnancy in IBD, when compared to both healthy controls and their own pre-conceptional levels. These results suggest a difference in redox status between pregnant women with IBD compared to those without. Further research is necessary to substantiate these findings and evaluate the utility of these biomarkers in predicting pregnancy complications and guiding clinical decision making in IBD pregnancy.

References

1. Bourgonje AR, Gabriëls RY, de Borst MH, Bulthuis MLC, Faber KN, van Goor H, Dijkstra G. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease. Antioxidants (Basel). 2019 Sep 1;8(9):351. doi: 10.3390/antiox8090351.
2. Schoots MH, Bourgonje MF, Bourgonje AR, Prins JR, van Hoorn EGM, Abdulle AE, Muller Kobold AC, van der Heide M, Hillebrands JL, van Goor H, Gordijn SJ. Oxidative stress biomarkers in fetal growth restriction with and without preeclampsia. Placenta. 2021 Nov;115:87-96. doi: 10.1016/j.placenta.2021.09.013.

Introduction

The ability to achieve endoscopic R0 resection in colorectal T1 cancer depends on the submucosal (SM) invasion distance of the malignancy. In this study, we looked for correlations between the SM invasive distance and achievement of R0 resection.

Aims & Methods

We classified fibrosis of the SM layer as noncancerous (Type B) and cancerous (Type C) and further categorized each into three phases from mild (1) to severe (3). Measurements of SM invasion distances for each tumor were based on the criteria specified by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). For 142 patients (70 male and 72 female, average age of 68.1 years), 143 lesions were diagnosed as cancerous fibrosis in subjects who underwent ESD and 1,813 lesions were scored as colorectal epithelial neoplasms, with T1 cancer being diagnosed by postoperative pathological diagnosis. We evaluated the diagnostic ability of cancerous fibrosis in 308 patients including 165 Type B cases. We also compared the degree of SM invasion in Type C-1, C-2, and C-3 malignancies in which we observed macroscopic typing of the 143 Type C lesions. We then scored the degree of SM invasion in R0 resected Type C lesions. Using an ROC curve and a 95% cutoff index, we calculated the maximal SM invasion distance for which R0 resection could be achieved.

Results

The macroscopic subtypes of Type C lesions were as follows: 0-Is+IIa (LST-G (nodular mixed type)): 55, 0-IIa (LST-NG (flat elevated typ)): 23, 0-IIc+IIa (LST-NG(pseudodepressed typ)): 19, 0-Is: 23, 0-IIa+IIc: 15, 0-IIc: 8. Perioperative endoscopy was able to accurately diagnose 83.9% Type C cases and 93.9% of Type B cases. With regard to diagnostic potential, perioperative endoscopy had 83.9% sensitivity, 93.9%, and specificity. Diagnostic precision was 92.3%, PPV was 92.3%, and NPV was 87.0%. Pathology was used to sub-classify the 143 Type C cases based on severity. Seventy-one patients were C-1, 34 were C-2, and 38 were C-3. The mean SM invasion distances in C-1, C-2 and C-3 cases were 801.2 ± 956.1 mm, 1,745 ± 891.6 mm, and 3063.5 ± 2008.4 mm, respectively; differences between each group were significant (p<0.01). We classified macroscopic types of Type C into Flat and Depressed (FD:0-IIa, 0-IIc+IIa, 0-IIa+IIc, 0-IIc) and Protruded (P: 0-Is+IIa, 0-Is ).Although the corresponding values in the P group were larger (C-1:970.6 mm, C-2:2292.3 mm, and C-3:3483.3 mm, respectively), this difference was not statistically significant. The R0 rate according to the invasive distance was 94.7% when SM was <1,500 mm, and 92.9% when SM was <1,000. For SM between 1,000 mm and 1,500 mm the R0 rate was 19/19 (100%).The percentage of cancer-positive cases in the vertical margin (VM (+)) increased proportionally with the degree of invasion. For SM values between 1,500 and 2,000, VM (+) was 79.2%, whereas for SM values of 2,000 or more, the R0 rate decreased to 45.5%. We identified a statistically significant difference (p=0.037) between less than 1,500 mm and 1,500-2,000 mm. The maximum Youden Index was 0.636 and the R0 rate was 95.4%, when the upper limit was less than 1,625 mm.

Conclusion

An SM of less than 1,625 mm (regardless of the macroscopic type) is predictive of an R0 resection for colorectal T1 cancer, and provided the possibility of curative treatment. Also, we infer that the quantitative and qualitative advantages of ESD can help endoscopists avoid the pitfalls associated with preoperative endoscopic diagnosis, which may be useful in clinical practice.

Introduction

The role of inhaled and subsequently swallowed aeroallergens in treatment outcomes of adults with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of dietary therapy in EoE. In this international two-centre study, we compared six-food elimination diet (SFED) outcomes of EoE patients assessed during versus outside the pollen season.

Aims & Methods

Consecutive adult patients (≥18 years) with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Demographics, atopy, SPT results, endoscopy findings (EREFS), and the date of the endoscopy following SFED were retrospectively extracted. Individual sensitization profiles and historical and location specific pollen count data were scrutinized to define whether each patient had been assessed during or outside the pollen season following SFED. For patients without pollen sensitization, Spring was considered as pollen season for comparison purposes. Patients were divided into group A (positive SPT for pollens) or B (negative SPT for pollens). All patients had active EoE before SFED (eosinophils ≥15/high-power field, HPF) and adhered to SFED under the supervision of a dietitian. Response to SFED (eos<15/HPF) was assessed after a minimum of 6 weeks. Data are described as median/interquartile range (Q1-Q3) or as counts/percent. Kruskal-Wallis Rank Sum Test, Pearson’s Chi-Square and Fisher’s exact test were used as appropriate. Significance threshold was p<0.05.

Results

Fifty-eight patients were included, 62.0% had positive SPT for grass and/or birch (group A), while in 37.9% SPT was negative (group B). Significantly more patients from group A also had positive SPT for dust mite, cat and/or dog dander (85.7% vs 31.8%, p<0.001). The two groups were comparable in sex, age, baseline symptoms, atopy, baseline EREFS, and duration of SFED (Table1). The overall SFED response was 56.9%, (95% CI, 44.1%-68.8%) regardless of SPT results and pollen season. When stratifying SFED response according to whether the assessment of the assessment had been performed during or outside the pollen season, patients sensitized to pollens showed significantly lower response to SFED when the assessment was performed during compared to outside the pollen season (21.4% vs 77.3%; p=0.003). Additionally, during the pollen season, patients with positive SPT for pollens had significantly lower response to SFED compared to those with negative SPT (21.4% vs 77.8%; p=0.01). Patients without pollen sensitization did not show seasonal variations in SFED response (66.7% vs 53.8%; p=0.67) (Table 2).

Conclusion

Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. SPT for pollens may have a clinical utility in the dietary management of EoE by identifying patients less likely to respond to SFED during pollen season. Further studies are needed to clarify if alternative/combined therapy during pollen season will improve outcomes in sensitized EoE patients undergoing SFED or if elimination diets need to be undertaken outside of the pollen season.

Introduction

Colorectal cancer is one of the most common types of cancer worldwide. The majority of patients are operable at the time of diagnosis. One of the most severe surgical complications is anastomotic leakage (AL). The incidence of AL depends on where the anastomosis is located (1-2% for ileocolic anastomoses, increasing to 10-15% of anastomoses to the rectum). AL leads to prolonged hospital stay, decreased quality of life, increased risk of cancer recurrence, and increased mortality.
Experimental studies have shown that certain bacteria can contribute to the development of AL.
In Denmark, people aged 50-74 years are offered free of charge screening for colorectal cancer. They collect a stool sample at home to be analyzed for the presence for blood (a fecal immunochemistry sample). It is possible to extract bacterial DNA from the fecal sample, to characterize the gut microbiome at the time of sampling.

Aims & Methods

The objective of the study was to use third-generation sequencing methods to analyze screening fecal samples in a cohort of colorectal cancer patients, and to characterize and compare the gut microbiome between patients with or without postoperative AL.
Fecal samples sent to the Colorectal Cancer Screening Program that tested positive for blood, from 2016-2018, were place in a biobank and stored at -80 ⁰C. By combining the biobank with data from the Danish Colorectal Cancer Group, we identified 18 patients who had surgery for colonic or rectal cancer in the period and suffered a postoperative AL (AL group). We matched these patients in a 1:2-ratio, with 36 patients without AL (Control group). We analyzed the 16S ribosomal RNA genes in the screening fecal samples with third-generation sequencing (Oxford Nanopore Technologies).

Results

The data are preliminary, as the data analysis has not yet been completed.
The AL-group and Control group were similar on basic demographic parameters (age, gender, type of resection, smoker status and ASA classification). The gut microbiome composition was significant different in the two groups, based on the two main components of a principal coordinate analysis (PCoA) chart (PERMANOVA, p-value = 0.01).
The Bacteroidota phylum was more abundant in the Control group (p < 0.05). On the order level, Campylobacterales and Bacteroidales were more abundant in the Control group (p < 0.001). On family level, Campylobacteraceae were more abundant in the Control group (p < 0.001), whereas Burkholderiaceae were abundant in the AL-group (p < 0.001). The AL-group also had more Ralstonia and Burkholderia at genus level (p < 0.001), whereas the Control group had more Campylobacter and Oridobacter genera (p < 0.001).

Conclusion

The preoperative gut microbiome composition in colorectal patients with subsequent anastomotic leakage were significantly different from the control group without anastomotic leakage. Campylobacter and Oridobacter seem protective against AL, whereas Ralstonia and Burkholderia seem harmful. We are awaiting further analysis for the species level.
Further studies should focus on validating our results, including changes in the gut microbiome prior to surgery - for instance the impact of bowel preparation – and on estimating the predictive value of our findings.