Introduction

Inflammatory bowel diseases (IBD) are chronic, heterogeneous, and inflammatory conditions mainly affecting the gastrointestinal tract. Currently, endoscopy is the gold standard test for assessing mucosal activity and healing in clinical practice; however, it is a costly, time-consuming, invasive, and uncomfortable procedure for patients. There is, therefore, a need for sensitive, specific, fast and non-invasive biomarkers for the diagnosis of IBD.

Aims & Methods

Label-free quantification by nanoscale liquid chromatography coupled to tandem mass spectrometry (nLC MS/MS) was performed to profile the urinary and serum proteomes of 100 patients with newly diagnosed IBD, before starting any treatment [50 patients with Crohn´s disease (CD) and 50 patients with ulcerative colitis (UC)] and 50 healthy controls (HC). Data Mining and Pattern Recognition techniques were used to identify hidden relationships that are not detectable by using the classical and most commonly used lineal classifiers; thus, identifying potential markers able to discriminate the studied cohorts. Finally, we applied Ingenuity Pathway Analysis (IPA) to analyze the pathways and functions of differentially expressed proteins.

Results

Serum proteomics results revealed 45 differentially expressed proteins in the comparison between UC and HC groups, 32 proteins significantly expressed in CD versus HC, and 12 proteins in CD compared with UC. In urine samples, 110 proteins were significantly changed in UC versus HC, 50 proteins were differentially expressed between CD and HC, and a total of 31 proteins were significantly changed in CD compared with UC patients. Receiver operating characteristic curve (ROC) analysis found multiple proteins with a high area under the curve values, up to 0.94, indicating that these serum and urine proteins are of value as new non-invasive diagnostic classifiers of IBD patients. For each study comparative, the 5 most significant classifiers were selected. IPA revealed multiple signaling pathways, including prothrombin activation, acute phase response signaling, complement and coagulation system and liver X receptor/retinoid X receptor (LXR/RXR) activation, altered in IBD patients compared to HC (p-value < 0.05).

Conclusion

Our findings indicate that analysis of the urine and serum proteome using nLC MS/MS is a feasible approach for biomarker discovery. We identified several serum and urine proteins that could serve as new non-invasive markers for the diagnosis of IBD patients after further validation. After bioinformatic analyses, we found multiple proteins that may play important roles in the pathogenesis of IBD.

Introduction

In the years to follow we anticipate a rise in the prevalence of an aging population of inflammatory bowel disease (IBD) patients and a rise in cancer incidence. We are in urgent need of data to help us manage these patients.
We therefore followed a cohort of patients from a referral oncology hospital with prior and active cancer who received biologic therapy to control their IBD.

Aims & Methods

We first recorded data regarding inflammatory bowel disease characteristics: disease type, disease duration, disease severity, previous surgery or hospitalization and received therapy: type and duration of biologic therapy, prior use of immunosuppressants. We also recorded all available data regarding cancer disease: cancer site, stage, virus related cancer, family history of cancer, smoking status and received therapy (curative surgery, chemotherapy, hormone therapy, radiotherapy, immunotherapy). We monitored outcomes of IBD (steroid free clinical remission, IBD-related surgery or hospitalization) and outcomes of cancer (recurrence free survival, progression free survival, overall survival).
A blinded oncologist was asked to retrospectively evaluate all available data regarding cancer prognosis (stage, histology, response to therapy) and to categorize patients in 3 groups: low, intermediate or high risk to recur or progress.

Results

A total of 30 patients were included, 57 % female, median age 60 years, 60% Crohn's Disease, median disease duration 9.5 years, 26% prior IBD surgery, 33% prior azathioprine use, 36% smokers. They were treated with anti-TNF therapy (n=19) anti-integrin therapy (n=8) and anti-IL 12/23 therapy (n=4). The majority (20%) of patients had a history of hematologic malignancy (lymphomas, myeloproliferative disorders, leukemias), 13% with a virus related cancer and 66% with curative surgery. Patients were classified retrospectively as 63% low risk, 13% intermediate risk and 10% high risk. Four patients ) with active cancer (2 with lung cancer and 2 with myeloproliferative disorders) continue to receive biologic therapy for IBD and oncological therapy with no signs of progression from both diseases. All but 3 patients have remained in steroid free clinical remission: 3 had IBD-related surgery. Median follow up under biologic therapy was 5.5 years: only 2 patients showed cancer recurrence: 1 patient with breast cancer developed bone metastases and finally died, and 1 patient with colon cancer developed bladder cancer and died as well. Both patients were classified as high risk.
In both patients biologic therapy was interrupted and that resulted in administration of high-dose steroids and IBD-related hospitalizations and infections (pneumonia, C Difficile colitis).

Conclusion

In this cohort of cancer patients with IBD treated with biologics and followed up for more than 5 years the risk of cancer recurrence was low and not unexpected in oncology terms.
Biologic therapy was successful in the majority of patients and kept them off surgeries and steroids for their underlying IBD. We need more smart and innovative ways to study this particular clinical scenario in the future.

Introduction

Proton Pump Inhibitors (PPIs) are commonly prescribed for gastrointestinal disorders. Several studies have reported an overprescription of PPIs in patients with liver cirrhosis^1,2, yet their use in these patients increases the risk of spontaneous bacterial peritonitis and mortality rates. HAS-BLED score is a tool used to evaluate bleeding risk in individuals on chronic anticoagulation therapy, and cardiologists use it to prescribe PPIs in patients on anticoagulants, to reduce the risk of gastrointestinal bleeding³.

Aims & Methods

This study aimed to assess the appropriateness of PPI prescriptions in patients with liver cirrhosis and anticoagulant treatment. A secondary objective was to investigate whether the guidelines for administering PPIs based on a patient's HAS-BLED score align with the indications for PPI prescription recommended in established gastroenterological guidelines.
This study was retrospective. From January 2022 to December 2023, we included consecutive cirrhotic patients who had anticoagulant treatment for various indications (atrial fibrillation, deep vein thrombosis, pulmonary embolism). All patients were counted only once, even if hospitalized multiple times. To establish the validity of PPI prescription, we used the current guidelines^4–7. Anticoagulant treatment alone, is not a valid indication for PPI prescription in patients with liver cirrhosis, in the absence of concomitant antiplatelet treatment⁴. HAS-BLED scores were calculated⁸, and patients with a score ≥ 4 were considered at high risk for bleeding. We looked for an association between high HAS-BLED score and PPI prescription, and whether these prescriptions were aligned with the current gastroenterological guidelines.

Results

We found 577 hospitalizations for cirrhosis, among these, 61 patients (mean age 71.3 years old ± 8,88, 46 males) were under chronic anticoagulant treatment. We identified 32 patients on PPIs during the hospital stay. Fourteen (43.7%) had no valid indication, but 5 had a high HAS-BLED score. The remaining patients (n=18) were prescribed PPIs for the following reasons: gastritis (n=10), antiplatelet with high risks (n=3), NSAID and corticosteroid (n=2), peptic ulcer disease (n=2), gastroesophageal reflux disease (n=1). In our cohort, 27 (44.3%) patients had a high HAS-BLED score. Among these patients, 18 were on PPI. In the patients with low HAS-BLED (n=34), 14 were on PPIs, and 9 of them didn’t have a valid indication based on current gastroenterological guidelines. We computed the Chi2 statistic to assess the association between PPI prescription and a high HAS-BLED score: the chi-square statistic yielded 3.921 (p=0.048). A similar association was observed at discharge: the chi-square statistic was 3.994 (p=0.046). No association was observed between HAS-BLED score and inappropriate PPI prescription (Chi2 = 0.147, p = 0.7).

Conclusion

In our cohort of patients with liver cirrhosis, over 50% were prescribed PPIs during their hospital stay, with 43.7% lacking a valid indication. An association was observed between the HAS-BLED score and the prescription of PPIs; however, only a portion of the non-valid indications can be attributed to the high HAS-BLED score.

References

1. Gamelas Vet al. Prescription Pattern of Proton Pump Inhibitors at Hospital Admission and Discharge. GE Port J Gastroenterol. 2019;26(2):114-120. doi:10.1159/000488506
2. Ct C, et al. Inappropriate use of proton pump inhibitors in a local setting. Singapore Med J. 2014;55(7). doi:10.11622/smedj.2014087
3. Pisters R, et al. A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey. Chest. 2010;138(5):1093-1100. doi:10.1378/chest.10-0134
4. Scarpignato C et al. Italian Society of Pharmacology, and the Italian Association of Hospital Gastroenterologists. Effective and safe proton pump inhibitor therapy in acid-related diseases - A position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016;14(1):179. doi:10.1186/s12916-016-0718-z
5. http://www.ncbi.nlm.nih.gov/books/NBK552570/
6. Lanza FL, et al, Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728-738. doi:10.1038/ajg.2009.115
7. Freedberg et al. The Risks and Benefits of Long-term Use of Proton Pump Inhibitors: Expert Review and Best Practice Advice From the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031
8. Gallego P et al. Relation of the HAS-BLED bleeding risk score to major bleeding, cardiovascular events, and mortality in anticoagulated patients with atrial fibrillation. Circ Arrhythm Electrophysiol. 2012;5(2):312-318. doi:10.1161/CIRCEP.111.967000

Introduction

Dietary therapies have revolutionised treatment for irritable bowel syndrome (IBS). However, response rates to the diet with the highest evidence of efficacy (the low FODMAP diet) remain at 50-75%, suggesting other potential drivers of symptom onset. A low food chemical elimination-rechallenge diet targeting bioactive food chemicals (including salicylates, amines, glutamate and other additives), is commonly applied in Australia in patients exhibiting both gastrointestinal and extra-intestinal symptoms. However, data supporting the low chemical diet is scant, and safety concerns exist due to its restrictive nature potentially causing nutritional deficiencies and disordered eating.

Aims & Methods

This cross-sectional survey in patients with IBS and healthy controls aimed to evaluate the frequency of co-existing extra-intestinal symptoms, as well as explore patient perceptions and use of the low chemical diet. Participants with IBS (IBS-Severity Scoring System¹ (IBS-SSS) >75), and healthy controls (not meeting Rome IV and ≤75 on IBS-SSS) were recruited via online advertisement. Validated questionnaires were used to assess gastrointestinal symptoms (IBS-SSS¹), extraintestinal symptoms (extended PHQ-12²), and food additive intake (IBD-Food additive questionnaire³). Additional questionnaires assessed use of dietary therapies with specific focus on food chemicals. Data was analysed using independent samples t-test and chi-square test.

Results

204 IBS and 22 healthy controls completed the study. Total IBS-SSS for the IBS participants was 277±79, compared to 36±28 in the healthy control group (p<0.01). IBS participants were more likely to report extra-intestinal symptoms including headaches (p<0.01), migraines (p=0.03), fatigue (p<0.01), difficulty sleeping (p=0.03), rhinitis (p=0.02), urticaria (p=0.04) and mood disturbance (p<0.01). Twenty-one (10%) of IBS participants were following a low chemical diet compared to none in the control group. Of these 21 participants, dietary advice was provided by a dietitian (n=13), general practitioner (n=6), gastroenterologist (n=6), naturopath (n=3), family/friend (n=4) and/or the diet was self-initiated (n=7). IBS participants were more likely to report at least one food chemical as a trigger for gastrointestinal (38% vs 13%, p=0.03) and/or extra-intestinal (30% vs 9%, p=0.04) symptoms (Table 1). There was no significant difference in consumption (g/day or g/kg/day) of ultra-processed, additive containing foods.

Table 1. Suspected dietary triggers (food chemical specific) for gastrointestinal and extra-intestinal symptoms

Conclusion

Patients with IBS are more likely to report experiencing extra-intestinal symptoms compared to healthy controls. Despite limited evidence, a low food chemical diet is utilised by patients with IBS to manage both gastrointestinal and extra-intestinal symptoms. Further data is needed to understand the efficacy and safety of the low chemical diet in IBS.

References

1. Francis., et al (1997). Aliment Pharmacol Ther., 95(4), 999-1007
2. Spiller., et al. (2010). Aliment Pharmacol Ther., 32(6), 811-820
3. Trakman., et al. (2020). Nutrients, 12(3). 812.

Disclosure

No conflicts to declare

Introduction

Due to the daily rhythm of insulin level, an increase of the morning fasting blood sugar value was known in prediabetes statements. ECG heart rate variability (HRV) parameters like low-frequency (LF) and high-frequency (HF) also have a circadian pattern. The ratio of LF/HF can show the activity of the autonomic nervous system.
The evaluation of the epidemiological and metabolic aspects of lifestyle (effects of missing meals, high carbohydrate intake, night shift etc.) could help find a more accurate pathophysiological knowledge to improve overweight in therapy-resistant patients and clearing the risk of it.

Aims & Methods

Our aim was to compare the results of the mother-child group described in our reference abstract and the group performing physical work during night shift. Searching long-term effects of regular night shift physical work and staying awake, such as anaerobic exercise. Could more objective effects on weight loss or on cardiovascular risk be identified than mentioned in other night shift studies?
17 mothers (M) and 24 children (Ch) consecutively, and 24 night shift employees (NS) were examined in the morning after their night shift. The epidemiological parameters were evaluated, then the oral loading test with orally intake of 75 g of glucose was performed. We checked the venous blood gas parameters to follow mitochondrial function indirectly. The function of the autonomic nervous system was determined by a 2-minute resting HRV and LF/HF values.

Results

Our groups (mean+SD): age were M=48.8 +/- 5.1 vs. Ch=23.5+/-5.4, vs. NS=45.7+/-10.0. The averages of BMI were M=28.59 vs. Ch=31.65 vs. NS=31.56.
The 0-minute insulin: M=5.4 +/- 3.43 vs. Ch=9.0+/-4.13, vs. NS=10.17+/-5.06 which is significant according to Student's t-test, p(M-Ch)=0.003. p(M-NS)= 0.001. The lifestyle differences were irregularity and skipping of the breakfast in the NS group.
The venous lactate was after 120 minutes of the glucose intake (mean +/- SD) M=1.37 +/-0.52 vs. Ch=1.56 +/-0.43, vs. NS=1.51 +/-0.19. Lactate reference value (Siemens Epoc Reader) <0.75 mmol/l, p (M-Ch)=0.005, vs. p(M-NS)=0.003. The 0-minute lactate values were M=1.03+/-0.44 vs. Ch = 1.02 +/- 0.31, vs. NS = 1.17 +/- 0.48. p>0.05. HRV LF/HF values (mean+/- SD) were M= 1.2+/-0.54, vs. Ch=1.05 +/-0.59 vs. NS=0.74+/-0.23, p(M-NS) =0.025, p(M-Ch)>0.05. The venosus partial pressure of oxygen (average +/- SD) were M=28.2 +/- 7.22 vs. Ch=29.8+/-7.26, vs. NS=26.8+/-6.55. p(M-NS)>0,05.

Conclusion

The higher basal insulin and lactate level and lower venosus partial pressure of oxygen in the NS group could be explained by a relative tissue hypoxia which a factor of anaerobic metabolism and could increase the consumption of glucose in the muscles by GLUT4 transporters and elevating the level of circulating glucose.
The vagus tone helped in the dynamic autonomic regulation and it was responsible for cardiovascular health. Its decreasing correlates with the lower LF/HF ratio, which could be a marker for physical overload of the NS group.
Unsuccessful weight loss could be explained with the proportionally higher insulin level in NS group, which causes a feeling of hunger and helps the fat storage. On the other hand, the lower effectiveness of calorie-restricted diets should be improved with regular meals during night shift.
We presented a possible clinically measurable sign of the pathophysiological features of the adipose tissue hypoxygenisation as in hypoxia inducible factor 1-alpha studies presented.
We were planning a long-term health risk study to demonstrate the effectiveness of these parameters.

References

UEG 2023 Abstract 642 and 1400