Clinical Case Summary

We report the case of a 49-year-old male with primary sclerosing cholangitis and acute severe worsening of ulcerative pancolitis. Patient failed intravenous corticosteroids. Rescue infliximab (10 mg/kg) induction achieved partial initial clinical response, but no long term success. Colectomy was advised but declined. Following multidisciplinary team review, upadacitinib was initiated with informed patient consent. At week 8, despite evident clinical response and biochemical response allowing corticosteroid tappering, rectoscopy showed large ulcers, prompting extension of induction to 16 weeks. At week 12, the patient reported discoloration of the dorsal aspect of the 1st and 2nd left toes. Examination revealed pallor, violaceous hue, reduced skin temperature, and delayed capillary refill (>2 seconds). CTA identified occlusions of the distal posterior tibial and medial plantar arteries. Endovascular revascularization included balloon angioplasty, intra-arterial nitrates, and alteplase thrombolysis. He was started on aspirin, statins, and calcium channel blockers. Upadacitinib was discontinued due to suspected association with arterial event. Two weeks later, the patient developed toe pain and dry ulcer. MR angiography showed a new distal anterior tibial artery occlusion. No further intervention was performed; rivaroxaban (2 × 2.5 mg) was added. Within one month, ulcers healed and pain resolved. Despite repeated colectomy recommendations, the patient declined and was transitioned to ustekinumab. Extensive workup, including CTA/MR of the aorta, echocardiography, fundus exam, capillaroscopy, and autoimmune thrombophilia testing, was unremarkable. The vascular event likely reflects a synergistic effect of upadacitinib (1) and active severe colitis (2). Current evidence on the treatment and prevention of cardiovascular adverse events in IBD is limited, highlighting the need for further research. To our knowledge, this is the first reported case of such a complication.

References

1. Setyawan J, Mu F, Yarur A, Zichlin ML, Yang H, Fernan C, Billmyer E, Downes N, Azimi N, Strand V. Risk of Thromboembolic Events and Associated Risk Factors, Including Treatments, in Patients with Immune-mediated Diseases. Clin Ther. 2021 Aug;43(8):1392-1407.e1. doi: 10.1016/j.clinthera.2021.06.008. Epub 2021 Jul 6. PMID: 34238587.
2. Massironi S, Mulinacci G, Gallo C, Viganò C, Fichera M, Villatore A, Peretto G, Danese S. The oft-overlooked cardiovascular complications of inflammatory bowel disease. Expert Rev Clin Immunol. 2023 Apr;19(4):375-391. doi: 10.1080/1744666X.2023.2174971. Epub 2023 Feb 8. PMID: 36722283.

Clinical Case Summary

Acute Esophageal necrosis (AEN) is a rare clinical entity, with fewer than 150 reported cases in literature and endoscopic prevalence ranging from 0.01 to 0.28%(1). First described by Goldenberg and later characterized by Gurvits in 2007, this condition predominantly affects the distal esophagus due to its relatively poor blood supply, resulting in its characteristic black appearance. AEN typically occurs in male patients with predisposing risk factors such as chronic liver disease, chronic kidney disease, alcoholism, malnutrition and cardiovascular comorbidities(2). It is also associated with sepsis and carries a high mortality rate. Upper gastrointestinal endoscopy remains the gold standard (3). Given the rarity of AEN, the standardized management guidelines are not well defined and the primary therapeutic focus remains on optimizing medical condition.
We present the case of an 81-year old female, marking the first documented instance of AEN in Ireland, who presented with septic shock, profound hypoglycemia with hypothermia and workup revealed Acute Esophageal Necrosis. The development of AEN in our patient was multifactorial, with esophageal ischemia secondary to septic shock induced hypotension playing a key role. The condition may have been exacerbated by reduced cardiac output and vasoconstriction of splanchnic blood vessels secondary to hypothermia. Furthermore, gastric reflux likely contributed to additional mucosal injury. The patient was managed successfully with conservative yet aggressive approach with inotropic support, antibiotics and total parenteral nutrition.
We conclude that AEN should be considered in any patient with predisposing risk factors, particularly in presence of critical illness. This case highlights the urgent need for development of standardized guidelines to ensure timely diagnosis and optimal management for this rare but serious condition.
The poster will include pictures of Upper GI endoscopy of the patient

References

1. Goldenberg SP, Wain SL, Marignani P. Acute necrotizing esophagitis. Gastroenterology. 1990 Feb;98(2):493-6. doi: 10.1016/0016-5085(90)90844-q. PMID: 2295407.

2. https://pubmed.ncbi.nlm.nih.gov/17322991/

3. Sina (2023). Acute Esophageal Necrosis: A Rare and Serious Cause of Digestive Bleeding - Clinical Case Reports Journal (ISSN 2767-0007). [online] Clinical Case Reports Journal. Available at: https://clinicalcasereportsjournal.com/article/1000264/acute-esophageal-necrosis-a-rare-and-serious-cause-of-digestive-bleeding [Accessed 28 Feb. 2025].

Clinical Case Summary

A 52-year-old male, liver-transplanted in 2014 for alcohol- and HCV-related cirrhosis (HCV eradicated in 2017 with DAAs), was evaluated in May 2024 due to low-grade evening fevers. His immunosuppression regimen included tacrolimus 1 mg b.i.d., with stable trough levels around 11.5 ng/mL. However, during a routine check-up, tacrolimus levels spiked to 27 ng/mL. The result was confirmed on repeat testing despite Tacrolimus discontinuation.

No changes in liver function were observed, and tacrolimus was temporarily discontinued. The patient was hospitalized and developed mild upper limb tremors. Erythrocytapheresis was performed due to suspected tacrolimus toxicity, reducing levels only modestly (from 22 to 21.2 ng/mL). Given the discrepancy between assay results and clinical context, the lab performed a dilutional linearity test, revealing non-linearity suggestive of assay interference.

Autoantibody screening (RF, ANA, ASMA, LKM, ANCA, etc.) was negative. However, treatment of the sample with heterophile antibody blocking reagent (HBR) significantly reduced tacrolimus concentrations, confirming heterophile antibody interference. The patient underwent plasmapheresis to eliminate interfering antibodies, which normalized tacrolimus readings. Unfortunately, he developed candidemia (Candida parapsilosis) and died from cardiovascular complications.

This case illustrates how heterophile antibodies may falsely elevate tacrolimus levels in immunoassays, potentially leading to inappropriate clinical decisions. Clinicians must consider assay interference when pharmacokinetics and clinical findings are discordant, and collaborate closely with laboratory services to ensure accurate therapeutic drug monitoring.

Introduction

Emerging experimental and clinical data suggest that the gut microbiome can significantly influence the antitumor efficacy of key chemotherapy agents, including 5-fluorouracil, oxaliplatin, and docetaxel. These agents form the backbone of the neoadjuvant chemotherapy (NAC) regimen, FLOT, which is widely used for the treatment of locally advanced gastric cancer (GC). However, despite growing evidence from preclinical models, clinical studies investigating the direct association between gut microbiome composition and the response to NAC in GC patients remain scarce.

Aims & Methods

This study aims to address this gap in knowledge by exploring the relationship between the gut microbiome and therapeutic outcomes in this clinical context. In this longitudinal observational study, we explored the association between pre-treatment fecal microbiome composition analyzed via 16S rRNA gene sequencing and histological tumor regression, as assessed by the Becker score, in GC patients undergoing NAC with the FLOT regimen, followed by gastrectomy.

Results

Among the 38 enrolled patients, 19 (50%) achieved a Becker score of 1–2 and were classified as ‘Responders,’ while the other 19 (50%) were classified as ‘Non-responders’. Responders exhibited a higher abundance of Parabacteroides distasonis, Alistipes sp. AL-1, and Bacteroides plebeius. A combined biomarker of these species demonstrated robust predictive accuracy for a favorable response to NAC, with sensitivity of 89%, specificity of 63%, and an AUC of 0.8 (95% CI: 0.66–0.94). In contrast, non-responders showed a predominance of bacterial genera, including Ruminococcaceae UCG-014, Ruminococcus 1, Ruminococcaceae UCG-005, and the [Eubacterium] eligens group. The combined biomarker of these genera demonstrated excellent predictive performance for poor NAC response, with sensitivity of 89%, specificity of 95%, and an AUC of 0.93 (95% CI: 0.85–1.0).

Conclusion

The results of our study support the hypothesis that the pre-treatment gut microbiome composition can serve as a reliable biomarker for predicting both positive and negative responses to NAC in GC patients. By identifying specific microbial signatures associated with chemotherapy outcomes, this research provides critical insights into how microbiome-based strategies might enhance personalized treatment regimens for GC. Future studies are needed to validate these findings and explore potential therapeutic interventions targeting the microbiome to improve clinical outcomes in GC patients.

Clinical Case Summary

The patient was a 39-year-old man admitted to the emergency department for sudden onset of diffuse abdominal pain. The patient had a pathological history of chronic smoking. The clinical history dates back 10 hours to the onset of abdominal pain, initially localized to the epigastrium and rapidly generalized to the entire abdomen, unrelieved by usual treatment and without other associated signs. The patient was conscious, normocardiac, normotensive, slightly tachypneic and apyretic. A diffuse abdominal tenderness was noted, with no other particular pathological signs. Biological work-up revealed hyperleukocytosis at 20430/mm3 , C-reactive protein (CRP) at 5.80 mg/L , no hydroelectrolytic disorders, and the rest of the biological work-up returned normal. Abdominal CT revealed pneumo bubbles with infiltration of mesenteric fat, predominantly at the supra-mesocolic level, in favor of a hollow organ perforation. The patient underwent surgery, which revealed a pre-pyloric gastric perforation measuring approximately 1 cm with a clean edge and the presence of 2 hepatic nodules measuring 0.25 and 0.5 cm in segment II. The rest of the exploration was without anomalies, and the gastric perforation was sutured, with biopsy of the edges of the gastric perforation and biopsy of the hepatic nodules. Histopathological examination revealed the presence of subacute and chronic nonspecific inflammatory remodeling in the gastric margin biopsy, whereas the liver biopsy showed epithelial and gigantocellular granulomatous inflammation with caseous necrosis consistent with tuberculosis.The diagnosis of hepatic tuberculosis was made.The patient was put on standard anti-tuberculosis treatment for 6 months.

Clinical Case Summary

A 36-year-old man with a history of chronic diarrhea was admitted with isolated oedemato-ascitic syndrome and general deterioration.On examination,he had conjunctival subicterus bilateral lower limb edema, thoracoabdominal collateral venous circulation and ascites.As part of the etiological work-up of the oedemato-ascitic syndrome,Cardiac and renal causes were ruled out.Chest X-ray showed a hilar opacity with tracheal retraction.GeneXpert test on sputum confirmed pulmonary tuberculosis.Paracentesis showed non-infected transudate ascites with a serum-ascites albumin gradient at 11 g/L.Blood tests showed microcytic hypochromic anemia,normal platelet count,and elevated liver tests with AST at 18 times the upper limit of normal (ULN), ALT at 11× ULN, alkaline phosphatase at 3.3× ULN,normal GGT,prothrombin time at 25%,and a direct hyperbilirubinemia of 24 mg/L.Viral serologies were negative.Serum protein electrophoresis showed a beta-gamma bridging pattern with hypergammaglobulinemia.Antinuclear antibodies were positive, while the remaining autoimmune panel and Wilson's disease screening were negative.Abdominal CT angiography showed hepatomegaly with hypertrophy of the caudate lobe,a “flip-flop” pattern,stenosis of the intrahepatic inferior vena cava, and non visualization of the hepatic veins confirming Budd-Chiari syndrome(BDS).The etiological work-up of the chronic diarrhea revealed negative HIV serology,normal TSH,and elevated IgA anti-transglutaminase antibodies.Ileocolonoscopy showed partial villous atrophy in the ileum,supporting the diagnosis of coeliac disease (CD).Given the radiological features suggestive of BDS,a thrombophilia work-up was performed and was negative.An autoimmune etiology related to CD was retained as the most likely cause of BDS.A gluten-free diet resolved the diarrhea.Anticoagulation was started, but persistent portal hypertension and difficulty maintaining therapeutic anticoagulation led to referral for a portosystemic shunt.

References

An actual image of the thoracoabdominal collateral venous circulation of the patient, and his abdominal CT angiography.

Introduction

Spontaneous bacterial peritonitis(SBP) is the most common type of infection in patients with cirrhosis, with high mortality and recurrence rates^[1]. The intestinal immune barrier is an important link in blocking intestinal bacterial translocation^[2-3], but the mechanism of immune barrier changes in SBP in cirrhosis is unclear. The gut microbiota influences antitumor immunity by producing immunomodulatory metabolites^[4]. However, microbial consumption of multiple metabolites may also influence host immune responses^[5]. Here, we investigated the role of Stenotrophomonas maltophilia and its metabolites in the development of SBP.

Aims & Methods

We detected the bacterial composition of ascites and stool in patients with spontaneous bacterial peritonitis by 16S sequencing. The Stenotrophomonas maltophilia-SBP rat model was established by oral administration of carbon tetrachloride and Stenotrophomonas maltophilia. Metabolomics analysis was performed by liquid chromatography-mass spectrometry and single-cell sequencing was used to analyze changes in intestinal cell composition and gene expression. The biological functions of Stenotrophomonas maltophilia-conditioned medium and metabolites were determined in rat CD8⁺T cells.

Results

16S sequencing found that the abundance of Stenotrophomonas maltophilia in SBP ascites samples was high and positively correlated with inflammatory indicators. Among 1876 patients with cirrhosis and ascites, patients infected with Stenotrophomonas maltophilia had significantly increased levels of procalcitonin, C-reactive protein, ascites lactate dehydrogenase, and polymorphonuclear leucocytes count. Animal experiments showed that Stenotrophomonas maltophilia derived from human ascites can promote the occurrence of SBP in rats. Single-cell sequencing results showed that it significantly increased CD8⁺T cell exhaustion in the ileum and reduced memory T cells. Metabolomics analysis revealed that arginine was a significantly decreased metabolite in the supernatant of Stenotrophomonas maltophilia, and its downregulation was verified in rat serum and intestinal tissue. Mechanistically, Stenotrophomonas maltophilia degrades arginine through arginine decarboxylase, inhibits mTORC1 activity, thereby reducing CD8⁺T cell effector function and ultimately promoting the progression of SBP. Arginine supplementation significantly inhibited the formation of SBP and improved intestinal barrier function.

Conclusion

Stenotrophomonas maltophilia has been shown to promote SBP in rats by degrading arginine. Arginine supplementation is a potential preventive measure for SBP.

References

[1] Serper M, Tang H, Zhang S, et al. Clinical outcomes and care for spontaneous bacterial peritonitis: A national
cohort study. Hepatology. 2025.

• [2] Piano S, Singh V, Caraceni P, et al. Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide. Gastroenterology. 2019. 156(5): 1368-1380.e10.
• [3] Pabst O, Hornef MW, Schaap FG, Cerovic V, Clavel T, Bruns T. Gut-liver axis: barriers and functional circuits. Nat Rev Gastroenterol Hepatol. 2023. 20(7): 447-461.
• [4] Cong J, Liu P, Han Z, et al. Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8(+) T cell effector functions. Immunity. 2024. 57(4): 876-889.e11.
• [5] Meza-Perez S, Liu M, Silva-Sanchez A, et al. Proteobacteria impair anti-tumor immunity in the omentum by consuming arginine. Cell Host Microbe. 2024. 32(7): 1177-1191.e7.