Introduction

Chronic liver disease remains one of the most common causes for hospital admission and is associated with high morbidity and mortality rates. Timely and adequate management within the first 24 hours is crucial for improving clinical outcomes in cases of decompensated cirrhosis. This study aimed to evaluate the impact of implementing a care bundle checklist during the first 24 hours of hospital admission on management and outcomes of decompensated cirrhosis.

Aims & Methods

We developed an adapted care bundle (based on the BSG/BASL care bundle, AASLD quality measures proposal, Baveno VII consensus, and EASL guidelines) and compared two patient groups from two Portuguese hospital centers: Group-A (retrospective, pre-care bundle implementation) and Group-B (prospective, post-care bundle implementation).

Results

A total of 224 patients (Group-A: 148; Group-B: 76) were included. More than one decompensation was observed in 118 patients (52.7%), and 69 patients (30.8%) were experiencing their index hospitalization for liver decompensation. Regarding etiology, alcoholic liver disease was the most common (n=200; 89.3%). The groups were similar in terms of gender, age, length of hospital stay, and Child-Pugh and MELD-Na scores at admission. The most common decompensations were gastrointestinal bleeding (n=91; 40.6%), ascites (n=75; 33.5%), and hepatic encephalopathy (n=72; 32.1%). Group B was more likely to present with multiple decompensations at admission and exhibited significantly higher rates of acute kidney injury, hepatocellular carcinoma, acute-on-chronic liver failure, and portal vein thrombosis (p<0.05). Following care bundle implementation, we found significant improvements in patient care. At admission, patients were significantly more likely to undergo urine and blood cultures, chest X-ray, and abdominal ultrasound (p<0.05), receive diagnostic paracentesis (p<0.05), and have an accurate alcohol history documented (p=0.04). During admission, Group-B was significantly more likely to be prescribed lactulose for encephalopathy prophylaxis, vasopressor therapy for gastrointestinal bleeding, and venous thromboembolism prophylaxis, as well as undergo nutritional assessment (p<0.05). While in-hospital mortality rates were similar (4.7% vs. 5.3%; p=1), 6-week mortality rates (8.8% vs. 3.9%; p=0.01) and 3-month readmission rates (31.1% vs. 15.8%; p=0.02) were significantly lower in the post-intervention cohort.

Conclusion

The implementation of a standardized care bundle was associated with higher rates of appropriate investigation and treatment within the first 24 hours of hospital admission and improved patient outcomes, reducing 6-week mortality and 3-month readmission rates.

Introduction

Heyde syndrome is the co-occurrence of aortic stenosis and gastrointestinal bleeding secondary to vascular lesions, including angiodysplasias. Several studies have demonstrated cessation of gastrointestinal bleeding after transcatheter aortic valve implantation (TAVI), but the etiology and effects on vascular lesions are largely unknown.

Aims & Methods

We aimed to establish the effects of TAVI on gastrointestinal vascular lesions and identify the factors associated with recovery. In this prospective, single-center cohort study, patients with iron-deficiency anemia on the TAVI waitlist from September 2020 to February 2022 were assessed by capsule endoscopy. Those with vascular lesions were reassessed six months after TAVI. Endoscopic images were anonymized and evaluated by two independent researchers.

Results

Twenty-four patients underwent capsule endoscopy, and vascular lesions were present in 18 (prevalence 75%). TAVI was performed in 15/18 patients with vascular lesions, of which 11 agreed to a second capsule endoscopy. The mean number of vascular lesions across the gastrointestinal tract decreased from 6.4 (SD 5.6) to 2.0 (SD 2.1) (P = .036). The number of vascular lesions decreased in 9/11 (82%) patients, including 6/11 (55%) who no longer had typical angiodysplasias. Cessation of angiodysplasias was less frequent in patients who had multiple valvular heart disease before TAVI (0/3 [0%] vs 6/8 [75%]) and patients with significant paravalvular leakage after TAVI (2/5 [40%] vs 4/6 [67%]).

Conclusion

Angiodysplasias are present in 75% of anemic patients with severe aortic stenosis. TAVI effectively reduces the size and number of angiodysplasias in these patients.

Disclosure

Lia Goltstein, Maxim Rooijakkers, Naomi Thierens, Selene Schoormans, Charles Houdeville, Marlijn Hoeks, and Sanna Rijpma do not have potential conflicts of interest or disclosures to report. Hanneke Beaumont has received speaker fees from Medtronic. Erwin van Geenen has received research funding from Viatris, Boston Scientific, and Olympus and serves as a consultant for MTW-Endoskopie and Microtech. Xavier Dray is cofounder and shareholder of Augmented Endoscopy, has served as a consultant for Norgine and Provepharma, and received speaker fees from Bouchara Recordati, Fujifilm, Medtronic, Norgine, and Sandoz. Niels van Royen has received research funding from Abbott, Philips, Medtronic, and Biotronik, has served as a consultant for RainMed, Castor, and Medtronic, and received speaker fees from Abbott. The Radboudumc, on behalf of Joost Drenth, has received research funding from Gilead to support Hepatitis C elimination in The Netherlands.

Clinical Case Summary

Introduction: A rare but serious side effect of SGLT-2 inhibitors is the euglycemic diabetic ketoacidosis (DKA), which is usually triggered by acute disease (e.g. infection), reduced food and fluid intake, reduced insulin doses, or alcohol consumption.^1-4
Case report: A 53-year-old patient, with a history of type 2 diabetes mellitus treated with metformin and empagliflozin, presented with abdominal pain, jaundice and abnormal liver function tests (AST: 338 U/l, ALT: 508 U/l, γ-GT: 2020 U/l, ALP: 483 U/l, TBL: 2.65 mg/dl, DBL: 2 .22 mg/dl). Abdominal U/S revealed intrahepatic and extrahepatic bile duct dilatations. The patient underwent ERCP (Figure A) where a stenosis in the intrapancreatic segment of the bile duct was revealed and a fully covered metal stent of 6 cm length was placed, while a cytological smear was positive for adenocarcinoma. Abdominal CT scan (Figure B) revealed a hypodense lesion (d. 3cm) in the head of the pancreas. Postoperatively, the patient manifested abdominal pain, fever, vomiting, lethargy, tachypnea and tachycardia with increased inflammatory markers and cholestatic enzymes and normal serum glucose. Arterial blood gases revealed metabolic acidosis (PH: 7.21, HCO3: 13 mmol/l, Lac: 0.8 mmol/l) with an increased anion gap (25 mmol/l) and ketonuria (ketone > 43 mg/dl). Euglycemic diabetic ketoacidosis was treated with an insulin pump with co-administration of glucose solution and intravenous administration of crystalline fluids and potassium replenishment. SGLT-2 inhibitor was discontinued. Microbemia due to Pseudomonas aeruginosa was detected and due to lack of apyrexia, an imaging re-evaluation with CT scan was performed where a liver abscess was detected (Figure C). Eventually, liver abscess was treated with drainage under CT guidance (Figure D).
Conclusion: Euglycemic diabetic ketoacidosis is a rare but serious complication of SGLT-2 inhibitors, which requires a high level of awareness from physicians for early recognition.

References

1. Sethi SM, Vohra M, Ali SA. EUGLYCEMIC DIABETIC KETOACIDOSIS (EDKA) IN A PATIENT RECEIVING DAPAGLIFLOZIN. Acta Endocrinol (Buchar). 2021 Apr-Jun;17(2):266-269.
2. Acevedo-Mendez BA, Ye Y, Hajizadeh N, Myers A. Hypertriglyceridemia-Induced Acute Pancreatitis, Euglycemic Diabetic Ketoacidosis and COVID-19 Infection in a Patient With Type 2 Diabetes Taking a Sodium-Glucose Cotransporter 2 Inhibitor. Cureus. 2021 Nov 23;13(11):e19828.
3. Sampani, E., Sarafidis, P., Dimitriadis, C. et al. Severe euglycemic diabetic ketoacidosis of multifactorial etiology in a type 2 diabetic patient treated with empagliflozin: case report and literature review. BMC Nephrol 21, 276 (2020).
4. Yii ESS, Azli AW, Sitaram PN. Sodium-glucose cotransporter 2 inhibitor-induced euglycemic diabetic ketoacidosis in a patient with coronavirus disease 2019: a case report. J Med Case Rep. 2022 Jan 4;16(1):17.

Introduction

Eosinophilic esophagitis (EoE) is an inflammatory disease that is the leading cause of food impaction in children and young adults. EoE is thought to be a food antigen-driven allergic disease, best characterized by eosinophil-predominant inflammation, esophageal dysfunction, and expression of Th2 cytokines. Thymic stromal lymphopoietin (TSLP) is a cytokine primarily secreted by epithelial cells in barrier tissues in response to danger signals, infectious agents, Th2 cytokines and environmental antigens. TSLP is a master regulator of Th2 inflammation. Genetic studies have linked single nucleotide polymorphisms in TSLP to Th2 driven diseases, including eosinophilic esophagitis. Recent single-cell sequencing studies demonstrated memory CD4 T cells expressing TSLP receptor correlated with esophageal eosinophil counts. While some data suggest a key role of TSLP in the pathogenesis of EoE, its relative contribution has not been established in in vivo models.

Aims & Methods

Experimental EoE was induced in male wild type mice by an initial skin-sensitization using oxazolone (OXA, 17 days) followed by intraesophageal challenge with oxazolone or vehicle control (19 days, total duration 36 days). TSLP expression in the esophagus was measured during the sensitization and challenge periods. To determine the role of TSLP in EoE, treatment with a TSLP neutralizing antibody or isotype control began prior to esophageal challenge. Eosinophil counts, epithelial and lamina propria thickening, epithelial cell proliferation and esophageal vascularization were assessed in esophageal tissue on day 36.

Results

Intraesophageal challenge with OXA induced a transient upregulation of TSLP in the esophagus at day 29, with TSLP being expressed primarily in esophageal epithelial cells. Inhibition of TSLP activity with a blocking antibody in OXA sensitized mice resulted in 60% fewer eosinophils compared to isotype treated controls (p<0.001). Additionally, anti-TSLP treatment also induced statistically significant reductions in epithelial and lamina propria thickness and basal cell zone proliferation (Table 1). When assessed by region, TSLP neutralization statistically significantly reduced esophageal vascularization in regions with the highest degree of eosinophil infiltration.

Conclusion

This is the first time neutralization of TSLP in an experimental mouse model of EoE is reported, demonstrating a key role of TSLP in EoE disease pathogenesis. Inhibition of TSLP markedly decreased esophageal eosinophilia, a key diagnostic criterion for EoE. Other histologic features of EoE were also reduced upon TSLP neutralization. Together with genetic and mechanistic studies associating TSLP with EoE pathogenesis, this data suggests TSLP may serve as a treatment target for patients with EoE.

Disclosure

KK, LW, and HO are employees of Uniquity Bio

Clinical Case Summary

Case report: We report a case of a 51-year-old patient who initially presented in 2014 with thrombocytopenia, and splenomegaly. Liver parameters were within the normal range. Comprehensive diagnostic evaluations, including CT scans and liver biopsy, excluded cirrhosis, vascular occlusions, bypass circuits and other potential etiologies such as toxic, autoimmune, or infectious causes. Additional investigations, including bone marrow and spleen puncture as well as genetic tests did not reveal any hematological or neoplastic diseases.
At the age of 66, the patient suffered an episode of variceal hemorrhage due to grade IV oesophageal varices. Subsequently, after referral to our clinic in March 2020, a transjugular portosystemic shunt (TIPSS) was placed for persistent grade III varices (Figure 1), reducing the varices to grade I (2024). Despite successful management of varices, the patient developed mild hepatic encephalopathy, managed with lactulose and rifaximin.
Biopsy revealed nodular regenerative hyperplasia (Figure 2). We diagnosed idiopathic non-cirrhotic portal hypertension (INCPH), an infrequent yet significant clinical entity characterized by intrahepatic portal hypertension without cirrhosis or other liver diseases. Management challenges included the patient's intolerance to non-selective beta-blockers due to sinus bradycardia and ongoing low-grade hepatic encephalopathy, which precluded further TIPSS modification. Future management may include splenic vein embolization should varices recur.
Conclusion: The diagnosis of INCPH necessitates evident portal hypertension, no cirrhosis or advanced fibrosis, and no hepatic or portal vein thrombosis on imaging. Due to limited data, management typically mirrors that of cirrhosis-induced portal hypertension. This case highlights the diagnostic and management challenges of INCPH, stressing the importance of comprehensive assessments to rule out other causes and customize treatment for complications.