Clinical Case Summary

Eosinophilic esophagitis is characterized by dysphagia, GERD and impactions. It is related to environmental and genetic factors resulting in an altered Th2 immune response that allows overexposure to circulating antigens.
We present the case of a 46-year-old male with EoE since 2016 and no treatment, who came to the ED for dysphagia, odynophagia and fever. No notable alterations in X-ray, ECG and blood tests. A gastroscopy showed rounded ulcers in distal esophagus with biopsies showing changes compatible with herpetic infection and positive IHC for HSV1. Treatment was started with Acyclovir 10 days + PPI, with disappearance of symptoms and resolution of ulcers in gastroscopy after 8 weeks.
HSV esophagitis is frequent in immunocompromised patients related to viral reactivation. In immunocompetent patients it is infrequent and self-limited manner in most cases.
In recent years, the relationship between EoE and HSV esophagitis has been postulated through three possible hypotheses.
Firstly, inadequately treated EoE produces chronic inflammation and increased permeability. This leads ruptures of the epithelial barrier, increased intracellular spaces, alteration of binding proteins and decreased activity of desmosomes, reversing these findings with the treatment. Alteration of these defense mechanisms may be the gateway for HSV infection.
On the other hand, HSV infection causes damage to the mucosa what favors contact with swallowed antigens and a Th2 response with eosinophilic infiltration.
The third hypothesis is related to the use of topical corticosteroids that has been associated with fungal infections, thanks to the local immunosuppression that they entail, increasing the risk of viral infections.
Although more studies are needed, it has been established that the lack of EoE treatment is an essential factor in the increased risk of HSV esophagitis. Therefore, adequate treatment of EoE to contain tissue inflammation is key to prevent this and other complications.

Introduction

Esophagogastric junction contractile integral (EGJ-CI) is a metric of EGJ barrier function on high-resolution manometry (HRM), which may be limited by measurement discrepancies and unclear clinical utility. Mean EGJ basal pressure is a novel, simple HRM metric assessing barrier function. We compared their performance to predict conclusive gastroesophageal reflux disease (GERD).

Aims & Methods

Consecutive patients (Nov 2022-Oct 2023) undergoing combined HRM and 24 hour pH-impedance testing OFF antisecretory therapy (except for Barrett's patients) for known or suspected GERD were eligible, all with prior upper endoscopy. Mean (between end-expiration and end-inspiration) basal EGJ pressure, referenced to mean intragastric pressure, was calculated manually using the isobaric contour tool. EGJ-CI was calculated using the smart box tool, with the isobaric contour set 2 mmHg above intragastric pressure, over three respiratory cycles and normalized for its duration. On pH-impedance testing, Lyon classification 2.0 was applied. Conclusive GERD was defined as acid exposure time (AET) >6% or histologically confirmed Barrett’s. Mann-Whitney U and Kruskal-Wallis test, with Bonferroni correction, were used. ROC curves were plotted.

Results

125 patients were included (mean age 51.6 ± 16.5 years, 60% males). Upon applying Lyon 2.0 classification, 45 (36%) patients had conclusive GERD (25 Barrett’s), 7 (6%) borderline GERD, 16 (13%) reflux hypersensitivity (RH), while 57 (45%) had functional symptoms. Patients with conclusive GERD, on HRM, had a significantly lower mean basal EGJ pressure (11.0 vs 18.5 mmHg; p<0.001) than patients without conclusive GERD, while EGJ-CI was not statistically different (26.1 vs 35.1 mmHg∙cm; p=0.101). Mean basal EGJ pressure was significantly different across Lyon v2.0 subgroups (median values in GERD: 11, borderline GERD: 16, RH: 19, FH: 20 mmHg; p<0.001), while EGJ-CI did not differ (p=0.283). Mean basal EGJ pressure (AUROC: 0.73, 95%CI 0.64-0.82) showed greater predictive performance of conclusive GERD than EGJ-CI (AUROC: 0.59, 95%CI 0.49-0.69). The optimal cut-off of 13 mmHg had 72% sensitivity and 62% specificity; a cut-off of 9.5 mmHg had 86% sensitivity, while a cut-off of 23.5 mmHg had 91% specificity.

Conclusion

Mean EGJ basal pressure is a simple HRM metric to predict conclusive GERD, well differentiating GERD phenotypes, with greater performance than EGJ-CI. This metric could be preferred over EGJ-CI as a useful adjunctive measure to support GERD diagnosis.

Introduction

Collagenous colitis (CC) is a debilitating, non-destructive inflammatory bowel disease (IBD) that causes intense watery, non-bloody diarrhoea. The abnormal immune response is thought to be initiated by deficient tolerance to commensal gut microbiota, and fecal sample analyses indicate similarities with classic IBD forms as ulcerative colitis and Crohn’s disease. Yet, the exact members of the microbiome that might trigger and maintain the disease remain unknown.

Aims & Methods

To identify primary microbial triggers of CC pathogenesis that could directly interact with intestinal epithelial and submucosal cells, we isolated subepithelial mucosa from CC and healthy control (Hc) formalin-fixed paraffin-embedded samples (n=7-10) by using a laser microdissection microscope (PALM MicroBeam LCM, Zeiss, Germany). Isolated nucleic acids were sequenced using shotgun metagenomics in a NovaSeq 6000 platform (Illumina, USA). Microbial communities were identified using MetaPhlan3/4, and microbial metabolic and molecular function pathways using Humann3.2 algorithms.

Results

Bray-Curtis and Jaccard similarity coefficients showed that CC subepithelial microbiome was similar to that from Hc samples. Still, further analyses indicated that microbial metabolic pathways and molecular functions could differ. Microbiota that was associated with CC included Anoxybacillus and Barnesiella, whereas microbiota associated with Hc comprised Bacteroides, Leuconostoc and Lactobacillus.

Conclusion

Mucosa-associated microbiota in CC did not significantly differ from healthy microbiota. However, our results point to a relation of CC with bacteria that form biofilms (Anoxybacillus) and affect the variability of colitis development (Barnesiella). Thus, validation and further follow-up of these results could help us identify CC triggers in the future.

References

Carstens A. The Gut Microbiota in Collagenous Colitis Shares Characteristics With Inflammatory Bowel Disease-Associated Dysbiosis. Clin Transl Gastroenterol. 2019 Jul;10(7):e00065

Disclosure

AM has received salary for consultancies from Tillotts Pharma AG, Ferring, Vifor and Dr Falk Pharma; speaker’s honoraria from Tillotts Pharma AG and Vifor. The remaining authors declare no conflicts of interest.

Introduction

Benign pancreatic disorders pose significant challenges in diagnosis, treatment, and management due to their complex nature and diverse etiology. As the prevalence of pancreatic diseases continues to rise, the demand for specialized care and expertise becomes imperative.
Thus the Section of Interdisciplinary Pancreatology (SIP) has been launched in 2023 at Ulm University Hospital to manage a broad spectrum of pancreatic disorders, encompassing cystic pancreatic lesions, autoimmune pancreatitis and IgG4-related disease (IgG4-RD), and all types of chronic pancreatitis.
Here, we will present insights from two years of experience within this unit, focusing on the disease spectrum, the impact of a multidisciplinary board structure, and the direct advantages of Patient-Reported Outcome Measures (PROMs) in enhancing patient care.

Aims & Methods

To basically show the structure of an interdisciplinary section of pancreatoloy and emphasise resulting advantages and chances in pancreas care. Moreover, descriptive analyses from PROMs, impact on decision making and paths will be shown.

Results

The structured implementation of the SIP created a level of interdisciplinarity that has not been achieved before. Thus collaborative efforts resulted in relevant changes of daily-patient care and patient paths. This is assessed and further shown by the integration of PROMs that are continuously recorded. By systematically collecting patient-reported data on symptoms, functional status, and treatment outcomes, the division gains valuable insights into the patient experience and treatment efficacy and allows patient centered therapy management. Specifically by the integration of a dedicated multidisciplinary board to review cases of benign pancreatic disorders, consensus-driven decision-making optimized diagnostic accuracy and therapeutic planning, fostering individualized approaches. One of these successful approaches that has been established are high numbers of hybrid procedures in robotic enucleation of pancreatic cysts.

Conclusion

In conclusion, our two-years experience in a division of interdisciplinary pancreatology underscores its efficacy in addressing the diverse array of pancreatic disorders. Through collaborative decision-making, regular case reviews, and the integration of PROMs, the SIP exemplifies a patient-centric approach to pancreatic care that prioritizes clinical excellence, interdisciplinary collaboration, and continuous quality improvement.

Introduction

Patients with metabolic-dysfunction associated steatohepatitis (NAFLD activity score ≥4) and significant fibrosis (≥F2) (fibrotic MASH) are at increased risk for disease progression and development of cirrhosis. Following the recent approval of the first agent for the management of noncirrhotic MASH, timely identification of these patients is of major importance. Fibroscan-aspartate aminotransferase (FAST^TM) score enables the noninvasive diagnosis of fibrotic MASH, and has been assessed in several studies.

Aims & Methods

To assess the overall performance of FAST^TM score for diagnosing fibrotic MASH. We searched Medline, Cochrane library, Web of science and Scopus up to January 2024. We included diagnostic accuracy studies assessing the performance of FAST^TM score for ruling out (FAST^TM score ≤0.35) and ruling in (FAST^TMscore ≥0.67) fibrotic MASH using liver biopsy as the reference standard. We calculated pooled diagnostic accuracy estimates using bivariate random-effects models, and assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool.

Results

We included 16 studies with 8838 participants. Most studies (87.5%) were at high or unclear risk of bias due to concerns regarding patient selection, interpretation of FAST score without knowledge of biopsy results, and length of biopsy specimens for fibrotic MASH diagnosis. Across all participants, 54.8% were females and 31% had type 2 diabetes. Mean age and body mass index (BMI) were 52.4 years and 32.4 kg/m². Mean aspartate aminotransferase and alanine aminotransferase were 45.0 IU and 57.6 IU, respectively. The prevalence of fibrotic MASH across studies was 32.9% ranging from 14% to 55%. Using the rule out cut off (≤0.35), FAST^TM yielded a pooled sensitivity of 0.88 (95 % CI; 0.83, 0.91), specificity 0.52 (0.45, 0.60), positive likelihood ratio (LRp) 1.8 (1.6, 2.1) and negative likelihood ratio (LRn) 0.23 (0.18, 0.30). By applying the rule in cut off (≥0.67), pooled sensitivity, specificity, LRp, and LRn were 0.45 (0.39, 0.52), 0.87 (0.82, 0.90), 3.4 (2.8, 4.1) and 0.63 (0.58, 0.69) respectively. Assuming a pre-test probability (prevalence) of 30% for fibrotic MASH, a FAST^TM score ≥0.67 resulted in a positive predictive value of 60%, while with a FAST^TM score ≤0.35 the negative predictive value was 91%.

Conclusion

FAST^MT score has acceptable accuracy for the diagnosis of fibrotic MASH. Proposed thresholds of ≤0.35 and ≥0.67 might be useful for ruling out/in fibrotic MASH respectively.