Introduction

Inflammatory bowel diseases (IBDs), primarily ulcerative colitis (UC) and Crohn's disease, are complex chronic immune-mediated disorders. Although etiopathogenesis of UC is still unknown, several studies suggest a clear association to altered gut microbiota, impaired mucous layer and epithelial barrier disfunction. Fecal microbial transplantation (FMT) emerged as a promising therapeutic approach aimed at repopulating gut microbiota with beneficial taxa from a healthy donor, and indirectly influencing the recipient's immune system. At present, FMT represents a well-established effective therapy for patients suffering from recurrent C. difficile infections. Promising data suggest FMT efficacy in patients with mild to moderate UC, but mechanism of actions are still yet to be fully understood.

Aims & Methods

Our study aims to evaluate the impact that FMT, using feces from UC patients with active and inactive disease, on microbiota composition and mucosal integrity in a murine model of colitis. We used mice (n=40) that were pre-conditioned for a week with a cocktail of broad spectrum antibiotics to deplete most of the intestinal microbiota, then a 7-day DSS 3% treatment was carried out to induce the colitis and, during those days, two FMT infusion were performed. The mice were sacrificed at the end of seven days of recovery, and feces, colon and whole blood were collected.

Results

The use of antibiotics allowed the engraftment of FMT colitis in mice. Disease activity index of murine colitis was ameliorated by the infusion of feces from inactive UC patients, associated with the decrease of LPS in serum, lower levels of pro inflammatory cytokines (such as IFNgamma, TNFalpha, IL17), an increase of FOXP3 and MUC2 as a marker of intestinal integrity. A modulation of gut microbiota was assessed after each phase of treatment.
Our study suggests the infusion of fecal suspension from inactive UC patients is able to induce an anti-inflammatory response at mucosal level and to induce proliferation of those bacterial families associated with remission.

Conclusion

These data open new scenario about the use of autologous FMT in UC. Autologous FMT reduces the potential for donor-recipient microbial-interactions/incompatibilities which have been shown to influence strain engraftment outcomes.

Clinical Case Summary

A 64-year-old male patient presented with acute epigastric pain over 7 days, worsening after meals, nausea, vomiting 2 times without signs of bleeding, diarrhea 5-6 times/day, high blood pressure 180/100 mmHg. He had a 6-year history of recurrent epigastric pain, after multiple EGDSs was diagnosed as gastric ulcer and atrophic gastritis. The patient had undergone HP eradication and received standard anti-ulcer therapy several times, with no clinical improvement. On physical examination, the patient appeared pale. The abdomen was soft, without pain, guarding or rebound tenderness. The patient's medical history was significant for arterial hypertension. Lab abnormalities included WBC 16.32-10x10⁹/L, ESR 94mm/sec, CRP at 184.3 mg/L, FBG 767 mg, Total protein 50.9 g/L, CREA 147 mmol/L, Urea 13.42 mmol/L, Na 129 mmol/L. Intestinal infections were negative. New EGDS revealed an ulcerative lesion with 0.8cm diameter, in the region from antrum to greater curvature, covered with fibrin. Colonoscopy was normal. Duplex ultrasound revealed a 70% stenosis of the celiac trunk and superior mesenteric artery, with atherosclerotic wall deformation and intima-media thickening. A thrombosis was detected in the region of the aortic bifurcation. CT angiography revealed up to 70% stenosis of the suprarenal abdominal aorta, no contrast enhancement was observed in the origins of the celiac trunk, superior mesenteric artery, left renal artery (left kidney appeared atrophic), total occlusion of bilateral common, external, and internal iliac arteries.
Conclusion: Gastric ulcers are mostly associated with HP. However, in rare cases, underlying vascular pathology may be critical in their pathogenesis. This case highlights an overlooked cause of gastric ulcers, particularly in patients with atherosclerotic risk factors. In patients with persistent symptoms despite medical therapy ischemic ulceration should be included in the differential diagnosis.

Clinical Case Summary

Background: Syphilis is a chronic systemic infection caused by the spirochete Treponema pallidum, often referred to as "the great imitator" due to its ability to affect nearly any organ. Syphilitic hepatitis, or "luetic jaundice," is a rare manifestation, indicating spirochete dissemination to the liver.
Case Report: A 26-year-old female was admitted to the hospital with fever (39.5 °C), fatigue, sweating, tremor, dark urine, pale stools, and significant weight loss (15 kg over two months). She also reported lower extremity muscle and joint pain, cough and slowing of speech. On examination, she had icteric skin, a generalized maculopapular rash, and enlarged cervical lymph nodes. No history of alcohol or drug use was noted.
Laboratory tests revealed elevated levels of both cytolytic and cholestatic liver enzymes, along with increased bilirubin an elevated C-reactive protein.
Abdominal ultrasound and contrast CT showed hepatomegaly, hilar and retroperitoneal lymphadenopathy and splenomegaly.
Viral hepatitis markers (HBsAg, HBV PCR, HCVAb, HCV PCR, anti-HAV IgM, anti-HEV IgM) and antibodies for CMV, EBV, HIV, HSV-1,2 were negative. Wright-Hedelson test for brucellosis and serological markers for autoimmune hepatitis were negative while IgG and cerulopasmin levels were within normal range. Given systemic findings and history, syphilis was considered. Serologic tests were positive for Treponema pallidum (ELISA, TPHA, MRP). Liver biopsy revealed mild active hepatitis. The diagnosis of ^secondary syphilitic hepatitis was made. The patient was started on antimicrobial therapy. During follow-up, liver function tests normalized, and systemic symptoms resolved.
Conclusion: This case underscores the importance of considering syphilis in the differential diagnosis of unexplained hepatitis. Although rare, syphilitic hepatitis should be considered in patients with liver enzyme elevations and nonspecific symptoms, particularly when no clear alternative diagnosis is found.

References

1) Malvar G, Cardona D, Pezhouh MK, Adeyi OA, Chatterjee D, Deisch JK, Lamps LW, Misdraji J, Stueck AE, Voltaggio L, Gonzalez RS. Hepatic Secondary Syphilis Can Cause a Variety of Histologic Patterns and May Be Negative for Treponeme Immunohistochemistry. Am J Surg Pathol. 2022 Apr 1;46(4):567-575. doi: 10.1097/PAS.0000000000001848. PMID: 34864775.
2)Supronowicz Ł, Rogalska M. Syphilitic hepatitis. Clin Exp Hepatol. 2024 Mar;10(1):9-13. doi: 10.5114/ceh.2024.136235. Epub 2024 Mar 12. PMID: 38765910; PMCID: PMC11100338.
3)Al Dallal HA, Narayanan S, Alley HF, Eiswerth MJ, Arnold FW, Martin BA, Shandiz AE. Case Report: Syphilitic Hepatitis-A Rare and Underrecognized Etiology of Liver Disease With Potential for Misdiagnosis. Front Med (Lausanne). 2021 Nov 29;8:789250. doi: 10.3389/fmed.2021.789250. PMID: 34912834; PMCID: PMC8666961.
Figure 1: Histological images of the liver biopsy
Figure 2: Abdominal CT images
Figure 3: Images of maculopapular rash

Introduction

Functional dyspepsia (FD) is a common gastrointestinal disorder with limited treatment options. Itopride, a compound that combines dopamine D2 receptor antagonism with inhibition of acetylcholinesterase, may offer benefits over other prokinetics.

Aims & Methods

This meta-analysis evaluates the therapeutic efficacy of Itopride compared to placebo and other prokinetic agents in managing FD symptoms.
A total of 19 randomized controlled trials were included in the analysis, comprising six placebo-controlled studies (n=1981, 976 on placebo and 1005 on Itopride) and 13 trials comparing Itopride to another prokinetic (n=1077, 515 on Itopride and 562 on control prokinetics including mosapride citrate, levosulpiride, metoclopramide, domperidone, and cisapride). Meta-analyses were conducted using a random-effects (DerSimonian and Laird) model. Outcome measures included overall responder rate and symptom assessment, comparing Itopride to 1) all prokinetics and 2) placebo. In addition, Itopride was compared to placebo and domperidone for symptom scores of epigastric pain and early satiation. Results are presented as Cohen’s d (95% CI) or odds ratios(OR) (95% CI).

Results

Analysis of responder rates from seven placebo-controlled and nine active comparator studies showed a statistically significant benefit of Itopride over placebo (OR=1.25, 1.07 to 1.45, p=0.01), with no significant difference when compared to other prokinetics (OR=1.11, 0.93 to 1.34).
When assessing overall symptom scores, three placebo-controlled and four prokinetic-controlled trials were analyzed. Itopride showed a moderate effect size compared to other prokinetics (Cohen’s d=0.51, 0.13 to 0.88, p=0.01) and a large but not statistically significant effect compared to placebo (Cohen’s d=1.14, -0.43 to 2.71).
Early satiation was assessed in six domperidone-controlled trials, yielding a significant odds ratio of 1.37 (1.02 to 2.67, p=0.04). A large but not statistically significant difference was found compared to placebo (two trials, Cohen’s d=1.10, -0.47 to 2.67). For epigastric pain, a moderate but not statistically significant difference was found with placebo (two trials, Cohen’s d=0.68, -0.01 to 1.38) or domperidone (four trials, OR=0.85, 0.63 to 1.16).

Conclusion

This meta-analysis suggests that Itopride provides significant symptom relief in patients with FD compared to placebo, particularly in overall responder rates. While Itopride’s benefits over other prokinetics were modest in general symptom relief, it demonstrated a statistically significant advantage over domperidone for early satiation.