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.

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

Melanosis coli (MC) is the benign hyperpigmentation of the colorectal mucosa.¹ Known risk factors for MC include the use of anthraquinone laxatives and chronic constipation.¹ Prior studies have suggested a link between MC and colorectal cancer (CRC), though this remains unresolved.² Here, we describe a case of MC coinciding with CRC.
A 71-year-old gentleman with no obvious risk factors for MC presents with abdominal pain and altered bowel habit. His abdominal and rectal examinations were insignificant. His colonoscopy revealed extensive MC along nearly the full colonic length and a circumferential tumour at the hepatic flexure, alongside multiple small polyps. Histopathological investigations identified the tumour as an adenocarcinoma. He subsequently underwent a right hemicolectomy.
A study proved that proteins identified in CRC are similarly up-regulated in MC, suggesting a contributory role.² It has also been postulated that the aberrant Hedgehog signalling pathway activation seen in CRC is also detected in MC, albeit at a different cellular level, suggestive of a link between the pathophysiology of both conditions.³ MC is associated with higher detection rates of polyps, precursor lesions for CRC during colonoscopy. ¹ This is attributable to the ‘enhance effect’, where the visibility of polyps is increased against the pigmented colonic mucosa in MC.²
Our case demonstrates that MC may arise without known risk factors like the use of anthraquinone laxatives. While some studies have demonstrated a possible link between MC and colorectal malignancy, a true pathophysiological link has yet to be established.
More studies are warranted to demonstrate a possible pathophysiological relationship between MC and CRC. Irrespective of causality, the enhanced detection of colonic polyps in coincidental MC may have implications for earlier interventions in colonic malignancies, and its presence on colonoscopy should prompt increased vigilance by clinicians.

References

1. Abu Baker F, Mari A, Feldman D, Suki M, Gal O, Kopelman Y. Melanosis coli: A helpful contrast effect or a harmful pigmentation? Clinical Medicine Insights: Gastroenterology. 2018;11:117955221881732. doi:10.1177/1179552218817321
2. Yuan S, Wang P, Zhou X, Xu J, Lu S, Chen Y, Zhang Y. Differential proteomics mass spectrometry of melanosis coli. Am J Transl Res. 2020 Jul 15;12(7):3133-3148. PMID: 32774690; PMCID: PMC7407713
3. Wang ZC, Gao J, Zi SM, Yang M, Du P, Cui L. Aberrant expression of sonic hedgehog pathway in colon cancer and Melanosis Coli. Journal of Digestive Diseases. 2013;14(8):417–24. doi:10.1111/1751-2980.12060

Introduction

The brain-gut axis plays a crucial role in the regulation of gastrointestinal (GI) function, with the activity of the autonomic nervous system (ANS) being significantly important. Increased stress, correlated with socioeconomic, behavioral, dietary, and environmental factors, may lead to an overactive sympathetic nervous system response. The aim of this study was to evaluate the correlation between stress and autonomic nervous system responses in gastrointestinal patients.

Aims & Methods

The study comprised 136 GI patients, divided into three groups: the Dyspepsia Group (DG) with 39 patients, a mean age of 37.8 ±11.2 years; the IBS Group (IBS) with 41 patients, a mean age of 45±15 years; and the Celiac Group (CG) with 53 patients, a mean age of 38.2±14 years. ANS activity was assessed using parameters from Heart Rate Variability (HRV) analysis, including time domain, frequency domain, and nonlinear analysis. The severity of stress was assessed using stress indices calculated based on hemodynamic parameters and indicators from linear and nonlinear HRV analysis with the HRV Kubios Premium software.

Results

Patients in the IBS Group exhibited the highest stress indicators and sympathetic ANS activity parameters compared to those in the DG and CG groups (SNS index [stress] p=0.038, SNS index AVG p=0.038). Furthermore, the IBS Group had higher stress indices compared to the DG Group (Stress Index 14.0 vs 9.0; p=0.024). Positive correlations were found between the Stress Index, SNS index (stress), and average heart rate (R=0.525; p=0.0001), as well as with sympathetic ANS activity indices. Negative correlations were observed with indicators of parasympathetic nervous system activity across all investigated groups (R=0.433; p=0.001). A high level of stress, indicated by a Stress Index value above 12, was found in 18% of patients with CD, 38% with IBS, and 28% with DG.

Conclusion

Approximately 27% of GI patients experienced significant levels of stress. The stress indicators positively correlated with sympathetic ANS activation and/either impaired function of the parasympathetic system. Assessing the severity of stress will enable targeted therapy to improve the dysfunctions of the brain-gut axis.

Clinical Case Summary

Introduction: Von Hippel-Lindau (VHL) syndrome is a rare hereditary neurocutaneous disorder distinguished by its propensity for the development of both benign and malignant tumors such as cerebellar hemangioblastomas, retinal angiomas, clear cell renal carcinomas, pancreatic neuroendocrine tumors, and others. Additionally, multiple pancreatic, renal, and urogenital cysts may also develop, potentially giving rise to localized symptoms and the risk of malignant transformations (1).
Case report: This case study centers on a 54-year-old male patient who was flagged for potential tumorous lesions in both kidneys upon undergoing a comprehensive health assessment. Following a multi-sliced computed tomography (MSCT)-guided biopsy, the presence of clear cell renal carcinoma was bilaterally confirmed. An abdominal MSCT delineated an enlarged pancreas featuring multiple cystic formations. Then, an Endoscopic Ultrasound (EUS) examination detailed the presence of multiple cysts in the pancreatic region, forming conglomerates with a collective dimension of up to 80 mm. Following an EUS-FNA (fine needle aspiration) procedure, cuboidal epithelium within the cyst was identified, and a biochemical analysis revealed normal levels of CEA, amylase, and glucose. The combination of these findings, along with the patient's medical history, raised suspicions of serous cystadenoma and prompted consideration of VHL syndrome. Finally, a heterozygous missense variant in the VHL gene was detected by sequencing genes included in the clinical exome panel.
Conclusion: Distinguishing cystic pancreatic lesions, which can give rise to endocrine and/or exocrine insufficiency or be asymptomatic, from potentially malignant lesions is of paramount importance. Therefore, diligent tumor surveillance associated with VHL syndrome is crucial for timely detection and treatment.

References

1. van Asselt SJ, de Vries EG, van Dullemen HM, Brouwers AH, Walenkamp AM, Giles RH, Links TP. Pancreatic cyst development: insights from von Hippel-Lindau disease. Cilia. 2013 Feb 5;2(1):3.