Introduction

According to the ROME IV criteria, functional dyspepsia (FD) can be subdivided into PDS (postprandial distress syndrome) with meal-related symptoms such as early satiation and postprandial fullness and EPS (epigastric pain syndrome) with meal-unrelated complaints such as epigastric pain or burning. Nausea can also co-exist in FD but the literature is poor in reporting whether this symptom is mainly triggered by meal ingestion. A recent global epidemiology study of gastroparesis-like symptoms showed that the prevalence of nausea or vomiting, in combination with postprandial fullness or early satiation varies between continents.¹

Aims & Methods

This study aims to compare the difference in prevalence rates of nausea within each FD subgroup between western and eastern secondary and tertiary care centers. Adult patients with disorders of gut-brain interaction (DGBI) recruited in 9 western and 7 eastern secondary and tertiary care facilities between the ages of 18 and 70 years completed the Enhanced Asian Rome IV questionnaire (Asian European Gastrointestinal Symptoms cohort or AEGIS). The western centers were located in Belgium, Bulgaria, France, Israel, Italy (2x), Slovakia, Sweden and The United Kingdom while the eastern centers were located in Australia, China, Iran, Japan, Malaysia and Singapore (2x). FD patients were divided into PDS, EPS and PDS-EPS overlap (OVP) subgroups. Patients were furthermore classified as having nausea when this symptom was reported at least once per week. The questionnaire EARQ4 questionnaire was also used to address the relationship between nausea and food intake. Patients were asked how often they experienced nausea, whether nausea was triggered or worsened by meal intake, how often nausea occurred after a meal and if so, how soon after a meal nausea started. A comparison of the prevalence of nausea and meal-related nausea was made between eastern and western patients and among FD subgroups. Continuous variables are reported as median (IQR) and compared with a Kruskal-Wallis test. Categorical variables were compared using a Pearson Chi-square test.

Results

Of the 1074 DGBI patients that completed the survey, 483 were classified as having FD (59.4% PDS, 27.5% EPS, 13.0% PDS-EPS overlap). FD patients from eastern (N=202) and western sites (N=281) had a similar body mass index (22.5 (19.6-25.7) vs. 21.3 (19.7-25.4)kg/m²) and age (39.0 (29.0-55.0) vs. 38.0 (26.0-54.0) years). Eastern sites included significantly more female patients than western sites (43 % vs. 17.5%, p<0.001). PDS and EPS patients from eastern sites had significantly less nausea than PDS and EPS patients from western sites (17.9% vs. 46.3% and 6.8% vs. vs 40.5% respectively, both p<0.001). The majority of FD patients with nausea experienced meal-related nausea with no difference between eastern and western sites (63.9% vs. 73.7%). In PDS patients with nausea, nausea was significantly more triggered or worsened by a meal (72.4%) than in PDS-EPS overlap and EPS (48.6% and 35.3% respectively; p<0.001). All groups reported that meal-related nausea started mostly (> 85%) within 60 minutes after the meal.

Conclusion

In contrast to previous literature, we found that western PDS and EPS patients report nausea more frequently than eastern PDS and EPS patients. In both eastern and western patients nausea was mostly meal-related. Meal-related nausea is more common in PDS than in PDS-EPS overlap and EPS patients. Further research is needed to investigate the role of ethnic factors in the pathophysiology of nausea in functional dyspepsia.

References

Huang IH, Schol J, Khatun R, et al. Worldwide prevalence and burden of gastroparesis-like symptoms as defined by the United European Gastroenterology (UEG) and European Society for Neurogastroenterology and Motility (ESNM) consensus on gastroparesis. United Eur Gastroenterol J. 2022;10(8):888-897.

Disclosure

Bert Broeders received lecture fees from the Rome Foundation.

Clinical Case Summary

We present a case of the extremely rare Sarcina Ventriculi infection in a 75-year-old female, adhering to a predominantly vegetarian diet, suffering with chronic dyspepsia, abdominal pain, vomiting and weight loss over a period of six months. Blood tests were consistent with iron deficiency anaemia. Imaging studies initially showed distended stomach with possible gastroparesis and later revealed significant gastric outlet obstruction (GOO) secondary to a suspected duodenal mass. Several gastroscopies were performed which initially showed gastric stasis and later revealed a strictured, oedematous duodenal wall with a duodenal ulcer. Biopsies from the duodenum showed chronic inflammation and bacterial colonies consistent with Sarcina Ventriculi. Biopsies were negative for Helicobacter pylori and there was no evidence of dysplasia or invasive malignancy on multiple levels examined. Although there are no treatment guidelines for Sarcina Ventriculi infection we tried a combination of Ciprofloxacin, Metronidazole and Omeprazole based on the results of the limited case reports^[1] of patients diagnosed with this infection. After completion of the 1-week antibiotic course, the stricture had significantly improved and Sarcina Ventriculi bacteria were not detected on repeat biopsy. Unfortunately, despite the treatment, our patient developed life-threatening complications of a bleeding duodenal ulcer and perforation requiring exploratory laparotomy. The incidence of Sarcina Ventriculi infection appears to be rising. This case highlights the urgent need for research to identify the most effective management for Sarcina Ventriculi infection and to create standardised treatment guidelines for its management. Clinicians managing patients with Sarcina Ventriculi infection should be vigilant about the potential complications ranging from gastroparesis and gastrointestinal ulcers to life threating presentations such as GOO, emphysematous gastritis and gastrointestinal perforation.

References

Figure 1 - Endoscopic view before treatment showing gastric food residue with pyloric obstruction secondary to distal duodenal stricture.
Figure 2 - Endoscopic view before treatment showing tight stricture with mucosal oedema at D2 causing complete gastric outlet obstruction.
Figure 3 - Histopathology slide of duodenal biopsy of the patient, showing Sarcina Ventriculi bacteria seen as the characteristic cuboidal and tetrahedral structures, on a background of chronic inflammation.
Figure 4 - Endoscopic view of duodenum after treatment with antibiotics showing improvement of the duodenal stricture and mucosal oedema, allowing a clearer view of the duodenum, and revealing a distal stricture bleeding duodenal ulcer.

[1] Tartaglia D, Coccolini F, Mazzoni A, Strambi S, Cicuttin E, Cremonini C, et al. Sarcina Ventriculi infection: a rare but fearsome event. A Systematic Review of the Literature. International Journal of Infectious Diseases. 2021;115: 48-61.
https://doi.org/10.1016/j.ijid.2021.11.027

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.