Clinical Case Summary

A 35-year-old woman referred to the emergency department with vomiting, hyporexia, abdominal distension and worsening of her chronic diarrhea.
Laboratory tests revealed neutrophilic leukocytosis (20x10⁹/L), eosinophilia (8.00x10⁹/L) and increased PCR values. The patient was hospitalized and scheduled for further examination:

• CT scan showed intra-abdominal ascites with thickening of some loops of the jejunum.
• Stool tests revealed a C. Difficile infection, which was treated with vancomycin. Calprotectin was in the normal range.
• Esophagogastroduodenoscopy and pancolonoscopy with terminal ileoscopy were within normal limits.
• PET scan revealed an extensive intra-abdominal ascitic effusion with an intense uptake along the jejunum.
• Paracentesis showed an exudate rich in eosinophilic granulocytes and negative for neoplastic cells. Bacterial culture and BK research were negative.

Lastly, a bone marrow biopsy and an anterograde push enteroscopy with biopsies were performed.
The first one showed no signs of myeloproliferative disease, but a normal marrow with an important eosinophilia. On the other hand, the enteroscopy highlited a hyperemic jejunal mucosa without macroscopic lesions. (FIGURE A.)
The histological examination revealed a regular architecture with normal villo/crypt ratio and focally >30x100 intraepithelial enterocytes. (FIGURE B.)
Although not all diagnostic criteria were satisfied for the diagnosis of primary eosinophilic gastroenteritis (diagnostic cut-off limit is >50/HPF), multidisciplinary evaluation diagnosed an idiopathic hypereosinophilic syndrome with prevalent gastrointestinal involvement and steroid therapy (1mg/kg) was started. In just two days of therapy, the blood eosinophils were reduced to normal values and the symptoms were significantly improved.
She has currently tapered steroid therapy to start a treatment with the monoclonal antibody mepolizumab. At latest laboratory tests eosinophils amount to 0.09x10³/µL.

Introduction

The increasing accessibility of upper gastrointestinal endoscopy has led to a rise in its prescription. However, its overuse and inappropriate indications result in environmental and economic costs, potential iatrogenesis, and a paradoxical reduction in access. This study aims to assess the indications for elective diagnostic upper gastrointestinal endoscopy (UGE) requested in the hospital setting.

Aims & Methods

A retrospective analysis was conducted on elective diagnostic UGE requests from both outpatient and inpatient settings. The appropriateness of the requests was classified according to the recommendations of the American Society for Gastrointestinal Endoscopy and the European Society of Gastrointestinal Endoscopy.

Results

A total of 314 requests were analyzed over a three-month period: 90.8% (n=285) from outpatient consultations and 7.6% (n=24) from inpatient settings. A previous UGE had been performed in 53.8% (n=169) of patients, with an average interval of 27.13 ± 2.12 months between requests. Overall, 59.6% (n=187) of the requests were deemed appropriate, with the most frequent indications being the need for biopsies (15%, n=28), gastrointestinal bleeding or anemia (14.4%, n=27), and post-endoscopic intervention surveillance (10.7%, n=20).
Clinical information indicated the presence of alarm symptoms in 27.7% (n=87) cases, the most frequent being gastrointestinal bleeding or anemia (33.3%, n=29), age >50 years with new-onset symptoms or suspected structural disease (21.8%, n=19), and progressive dysphagia (17.2%, n=15). Conversely, 40.4% (n=127) of requests were considered inappropriate, mainly due to non-compliance with guidelines and surveillance intervals. The most common inappropriate indications included symptoms attributed to disorders of the gut-brain axis (20.5%, n=26), surveillance of atrophic gastritis, fundic gland polyps, hyperplastic polyps, and gastric intestinal metaplasia (11.8%, n=15), as well as post-gastric surgery surveillance for benign conditions in asymptomatic patients (8.7%, n=11). Additionally, 39 (28.3%) UGEs were requested for gastric cancer screening.

Conclusion

This study identified a significant proportion of UGE requests lacking appropriate and timely indications. These findings emphasize the need for well-defined criteria to ensure the rational and optimized use of this resource.

Introduction

A range of criteria have been created to evaluate the appropriateness of gastrointestinal (GI) endoscopy. The most widely recognized were set by the American Society for Gastrointestinal Endoscopy and the European Panel of Appropriateness of Gastrointestinal Endoscopy (EPAGE), updated EPAGE-II criteria. Nevertheless, the application of general rules is not sufficient, especially in hospitalized patients. The complexity, singularity, and dynamic clinical evolution demands the proactive involvement of an experienced endoscopist to make the decision whether or not to perform the exam.

Aims & Methods

Our aim was to analyze the appropriateness of endoscopic exam requests in hospitalized patients over the course of one year.
A prospective observational study was conducted in an endoscopic unit of a tertiary hospital center. The requested exams were triaged by a gastroenterologist after reviewing the patient’s medical record, assessing clinical status and complementary diagnostic tests. In cases of unclear indication, and no absolute contraindication, the decision to proceed was discussed with the referring physician.

Results

A total of 184 requests for inpatient endoscopy and/or colonoscopy were received during 1 year (table 1). 154 (84%) of the requests were thought to be appropriate. 12 (6%) were cancelled during triage: 2 were patients on best supportive care, 1 died, 3 had other diagnosis which plausibly justified the clinical situation, 2 had recent endoscopic exams, and 4 presented no clinical/analytical evidence of GI bleeding). 18 (10%) requests were initially postponed (8 were awaiting imaging results; 5 had poor clinical status and 5 respiratory distress) and ended up being cancelled (8 had another diagnosis in imaging tests, 8 maintained clinical deterioration contraindicating exam and 3 died). In total 30 (16%) of the requests were cancelled.
The most frequent exam requested was endoscopy, and the most common indication was suspected GI neoplasia. From a total of 58 suspected GI neoplasms, 11 were confirmed as gastric neoplasia, which was the most common finding.
None of the patients with a cancelled exam was diagnosed with a GI disease during follow up.
Mortality rate was considerably higher in the group with cancelled exams (33% vs 11% during hospitalization, 50% vs 32% during follow up, 15% vs 1.8% within 30 days after discharge). Mean age was similar between groups. This findings reveal a frail group of patients, with little likelihood of benefiting from an invasive exam.

Total, n=184	GI endoscopy performed	GI endoscopy deferred and/or cancelled
N, %	154 (84)	30 (16)
Sex, male (%)	89 (58)	16 (53)
Age (years), mean (±SD)	72 (12.8)	71 (14)
Type of exam Endoscopy, n (%) Colonoscopy, n (%) Endoscopy + Colonoscopy, n (%) Flexible sigmoidoscopy, n (%)	68 (44) 28 (18) 55 (36) 3 (19)	13 (42) 6 (19) 10 (33) 1 (33)
Indication, n Anemia Diarrhea Dysphagia Epigastric pain Chronic liver disease Suspected GI neoplasia¥ Suspected upper GI neoplasia Suspected colorectal neoplasia Suspected GI bleeding	42 5 8 3 7 44 14 15 4	5 - - 1 - 20 - - 4
Relevant endoscopy findings, n Hypopharyngeal neoplasm Grade C, D esophagitis Esophageal neoplasia Esophagogastric varices Gastric angiodysplasia Gastric neoplasia Neoplastic infiltration of duodenum Colorectal neoplasia Inconclusive (poor bowel preparation)	2 2 2 6 3 11 2 7 3	-
Motive to defer and/or cancel, n Awaiting imaging results Clinical deterioration Respiratory distress End-of-life care Evidence of myeloma Evidence of ovarian cancer Recent endoscopic evaluation Without analytical or clinical evidence of bleeding Death	-	8 5 5 2 1 2 2 4 1
Death during hospitalization, n (%)	17 (11)	10 (33)
Death within 30 days after discharge, n (%)	2 (1.8)	3 (15)

¥ Suspected GI neoplasia includes constitutional syndrome, evidence of metastases without a known primary source, ascites and/or pleural effusion.

Table 1. Patient’s characteristics and exam indications and findings.

Conclusion

16% of the requests were considered inappropriate, which allowed to avoid 30 unnecessary exams.
Developing standardized indications for endoscopic exams in inpatient care is difficult, and an individualized approach is critical in order to reach an equilibrium between overusage and overlooking, while considering the principle of primum non nocere.

References

1. American Society for Gastrointestinal Endoscopy. Appropriate use of gastrointestinal endoscopy. Gastrointest Endosc 2000;52:831-7
2. Juillerat P, Peytremann-Bridevaux I, Vader JP, et al. Appropriateness of colonoscopy in Europe (EPAGE II). Presentation of methodology, general results, and analysis of complications. Endoscopy 2009;41:240-6
3. Gimeno García AZ, González Y, Quintero E, et al. Clinical validation of the European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE) II criteria in an open-access unit: a prospective study. Endoscopy. 2012 Jan;44(1):32-7.
4. Shaheen NJ, Fennerty MB, Bergman JJ. Less Is More: A Minimalist Approach to Endoscopy. Gastroenterology. 2018 May;154(7):1993-2003.
5. Leal C, Almeida N, Silva M, et al. Appropriateness of Endoscopic Procedures: A Prospective, Multicenter Study. GE Port J Gastroenterol. 2021 May 25;29(1):5-12.

Introduction

Patients with acute-on-chronic liver failure (ACLF) have traditionally been considered with a tendecy for bleeding however, they frequently display a paradoxical prothrombotic state. ACLF is characterized systemic inflammation and an increased risk of both bleeding and thrombosis. Bleeding arises from decreased pro-coagulation factors and platelet sequestration due to portal hypertension, while thrombosis is exacerbated by endothelial dysfunction and elevated heparinoids, thrombomodulin, or von Willebrand factor.

Aims & Methods

The aim of this study was to evaluate platelet aggregation pattern in patients with ACLF compared to acute decompensated (AD) liver cirrhosis.
The study took place in between the 1^st of July 2024- 31^st of January 2025 and we prospectively included cirrhotic patients, divided in two groups: ACLF group and AD group. The exclusion criteria were people with compensated liver cirrhosis, antiaggregant or anticoagulant treatment and patients with hepatocellular carcinoma or other malignancies. We investigated platelet aggregability in whole blood, by using multiplate aggregometry. For analysis, platelet aggregometry was performed induced by: adenosine diphosphate (ADP), arachidonic acid (ASPI), prostaglandin E2 (PGE2) and thrombin receptor-activated peptide (TRAP-6) as agonist were determined. TRAP‑6 is a peptide that stimulates protease-activated receptor 1 (PAR1) on platelet membrane.

Results

In this study we included 52 patients – 25 patients with ACLF and 27 patients with AD. There were no differences regarding demographic parameters and liver disease etiology between the two study groups. Compared to AD group, patients with ACLF showed an enhanced maximal platelet aggregation with TRAP-6 (AUC 85±12 U vs 45±10 U, p<0.0001). In contrast, we did not detect any differences in platelet aggregation between the two groups after ADP, ASPI or PGE2 activations. We observe that PAR-1 stimulation induces the highest aggregation curve and area under the curve in patients with ACLF and AD, but ACLF patients show the strongest response, highlighting that the degree of liver decompensation influences aggregation results. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

Conclusion

Our results indirectly indicate that platelet reactivity is higher in patients with ACLF likely due to enhanced PAR-1 receptor activity. Severe decompensation correlates with a stronger TRAP response, suggesting that there are more PAR-1 receptors on platelets of this patients.

References

1. EASL Clinical Practice Guidelines on acute on liver failure; J. Hepatol. 2023
2. Napolitano et al. European Journal of Internal Medicine 2017
3. Tripodi et al. Hepatology 2006
4. Lisman et al. Hepatology 2006
5. Nassar et al. BIOMEDICINES 2023
6. Rogalski et al. Scandinavian Journal of Gastroenterology 2019
7. Zanetto et al. Liver International 2022
8. Vecerzan et al. Cureus 2024
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Introduction

Celiac disease, a chronic autoimmune enteropathy caused by exposure to gluten in genetically predisposed individuals, is characterized by a broad clinical spectrum often with multisystem involvement. Symptoms related to the reproductive system include delayed menarche, early menopause, fertility disorders, miscarriages, and prematurity.

Aims & Methods

To study the impact of celiac disease on fertility in a female Greek population. A retrospective review of all patient records from the celiac disease outpatient clinic at our hospital.

Results

Medical histories of 231 female patients were reviewed (69% of the total patient population) with a mean age of 44.3 years and a mean age at diagnosis of 35.3 years. The mean age of menarche was 12.7 years. Menstrual irregularities were reported in 27% (20% instability, 7% dysmenorrhea). A total of 28% (65/231) were in menopause, with an average age of menopause onset at 50.7 years. A history of miscarriages was recorded in 15% of all women (35/231), but in 29% of women in menopause (19/65). 82% (53/65) of women in menopause had children, with 98% (52/53) having been pregnant before the diagnosis of the disease. Among all women who gave birth, only 12/113 (11%) had been diagnosed before pregnancy. 56% (63/113) and 44% (50/113) had a vaginal delivery and cesarean section, respectively. Pregnancy complications were recorded in 24 women (18 preterm births, 15 low birth weight infants, 1 intrauterine death).

Conclusion

Women with celiac disease tend to have relatively late menarche and an increased rate of miscarriages. However, the disease does not seem to significantly affect fertility.

References

1.Ehud Galron MD, Rayna Boyarsky MD,Ido Sold MD, Chen Ben David MD,and Eyal Gal MD,Interactions between celiac disease and pregnancy:A literature review, Isr Med Assoc J.2023 Dec;25(12):830-835
2.Giovanni Casella et. Al. Celiac disease and obstetrical-gynecological contribution, Gastroenterol Hepatol Bed Bench. 2016 Autumn; 9(4): 241–249.
3.Stephanie M. Moleski et. Al., Increased rates of pregnancy complications in women with celiac disease, Annals of Gastroenterology (2015) 28, 236-240
4.Nafeesa N. Dhalwani et Al., Women With Celiac Disease Present With Fertility ProblemsNo More Often Than Women in the General Population, Gastroenterology 2014;147:1267–1274

Introduction

Granulocyte–monocyte apheresis (GMA) selectively removes activated leukocytes and immune mediators, and it has shown to be safe and effective in treating ulcerative colitis (UC). Previous reports have also described its combination with biologics.

Aims & Methods

The aim of our study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. A retrospective, multicentre study was performed in 7 IBD Units, including all patients with refractory UC who received combined plus GMA and TOFA. The number of GMA sessions, its frequency, filtered blood volume and length of each session were compiled, along with the clinical data. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, CRP and faecal calprotectin. Data regarding TOFA intensification, need for new immunomodulators/biologics and colectomy were also compiled. Descriptive statistics and non-parametric tests were used in the statistical analysis.

Results

Twelve patients with UC were included (median 46 years [IQR, 37-58]; 67% female; 67% E3; 75% non-smokers). Patients were receiving TOFA 10 mg bid (75%), 5 mg bid (16%), or 15 mg bid (8%), with 33% receiving steroids at baseline. All patients had prior exposure to anti-TNF agents, 42% to vedolizumab and 8% ustekinumab. Median baseline Mayo score was 7 (IQR, 5-7), median CRP of 11 mg/L (IQR, 5-32) and faecal calprotectin 800 mg/kg (IQ, 715-2,094). GMA was started mostly after PNR (73%), and the median number of GMA sessions was 11 (IQR, 3-20) and 50% received maintenance GMA. Partial Mayo score significantly decreased 1 month after the last GMA session (p=0.027). Four patients (36%) were switched to a new therapy and no patient required colectomy during follow-up. All patients under steroids at baseline were able to stop them. No patient reported adverse events related to the combination therapy.

Conclusion

Combination of GMA with TOFA can be an effective and safe therapy in selected cases of UC after PNR or LOR to this drug.