Clinical Case Summary

A 46-year-old man from Bolivia consulted for abdominal pain with watery diarrhoea and occasional rectorrhagia for the last 2 months, associated with asthenia and weight loss. Laboratory tests showed microcytic anaemia, elevated C-reactive protein, positive faecal occult blood and negative stool culture. Colonoscopy (Images 1, 2) revealed deep ulcers in the ileum and colon with discontinuous areas of respected mucosa. Treatment was started with oral methylprednisolone at a dose of 1 mg/kg, with a decrease in the stool rhythm. He returned to the emergency department due to worsening abdominal pain, and was admitted for follow-up care. Histology (Image 3) showed epithelioid granulomas of probable infectious origin, due to the intramacrophagic inclusions, so the corticosteroid treatment was suspended. The quick test for HIV was positive, with a viral load of 79,000 copies/ml and a CD4 count of 88 CD4/ml. Mantoux and IGRA were negative. PCR amplification for Histoplasma spp in ileal biopsy was positive. Amphotericin B was prescribed with prophylaxis of opportunistic infections with trimethoprim-sulfamethoxazole. After 2 weeks, antiretroviral treatment was started. The patient improved, the abdominal pain disappeared and his intestinal rhythm normalised, and he was discharged from hospital. On outpatient follow-up, he was asymptomatic, with resolution of the ulcers in the control colonoscopy and no evidence of fungal structures in the histological examination.
The infection by Histoplasma capsulatum is the most frequent endemic mycosis in the American continent. Intestinal involvement is rare, with a preference for the ileocecal region in the form of deep ulcers that can simulate an outbreak of Crohn disease, as in our case. The use of immunosuppressants, especially anti-TNF-alpha, may worsen its course, highlighting the importance of a broad differential diagnosis, taking into account the patient's epidemiological characteristics.

References

Image 1. Colonoscopy. Terminal ileum with large ulcer with fibrin background, oedema and perilesional erythema.
Image 2. Colonoscopy. Transverse colon with two large deep ulcers with fibrin background and raised edges.
Image 3. Biopsy of ileum. Non-caseating epithelioid granulomas with intramacrophagic inclusions in ileal tissue. HE 40x.

Introduction

Personalizing biologic therapies in inflammatory bowel disease (IBD) remains a critical unmet need. Here, we investigated circulating and stool microRNAs (miRNAs) as prognostic markers for treatment response across three biologics - anti-TNF, vedolizumab (VEDO), and ustekinumab (UST) - and explored their relationship with gut microbiome to uncover potential host-microbe predictors of response.

Aims & Methods

This study included 43 IBD patients (mean age 40.4 years, 25.6% female, 20.1% with ulcerative colitis) enrolled in the ILEITIS cohort at National University Hospital, Singapore. The majority had received anti-TNF (n=35), whilst others were given VEDO (n=9), or UST (n=15) therapies. Clinical non-response was defined as disease flare within 48 weeks post-induction, indicated by C-reactive protein >5 mg/L, fecal calprotectin >150 μg/g, or moderate to severe endoscopic inflammation. Baseline serum and stool samples were collected and isolated for miRNA profiling by the ID3EAL^TM PanoramiR microRNA Knowledge Panel (MiRXES) via the QuantStudio5-384-well qPCR system (Applied Biosystems). Fecal microbial communities were assessed via shotgun metagenomic sequencing. Differential expression analysis and Spearman correlation with false discovery rate (FDR) adjustment were performed to explore miRNA–microbe associations and treatment response patterns.

Results

Among 376 paired serum and stool miRNAs analyzed, only six exhibited significant positive correlations, indicating largely compartment-specific expression patterns. Stool miRNAs demonstrated stronger and more numerous correlations with gut microbial taxa (11 significant pairs, FDR < 0.05), whereas serum miRNAs showed no strong associations. Biologic-specific miRNA signatures were identified. Predictive modelling identified top-ranked miRNA with high discriminative performance for treatment response; serum miR-296 and stool miR-134 perfectly predicted VEDO response (AUROC = 1.0); serum miR-146 predicted UST response (AUROC = 1.0); and stool miR-302 robustly predicted anti-TNF response (AUROC = 0.897). Correlation analysis between biologic-responsive miRNA and microbial taxa revealed 12 significant correlations for stool-derived miRNA and 14 for serum-derived miRNA. Notable microbial species involved in these associations include Bacteroides uniformis, Parabacteroides distasonis, Phocaeicola dorei, Clostridium scindens, Streptococcus sanguinis, Bilophila wadsworthia, Hungatella hathewayi, and Clostridium leptum, all taxa implicated in IBD-associated dysbiosis, showed significant correlations (FDR < 0.05).

Conclusion

Stool- and serum-derived miRNAs capture non-overlapping but complementary dimensions of host response to biologic therapy in IBD. There are significant overlaps between host miRNAs and microbiome readouts suggesting plausible links between key microbial responders to therapy and host regulatory miRNAs, especially in the luminal compartment. Our findings highlight the value of integrating compartment-specific miRNA and microbiome profiling to improve precision medicine approaches in IBD.

Introduction

Sex-based differences in clinical outcomes are increasingly being recognised in acute care, yet few studies have examined whether upper gastrointestinal bleeding (UGIB) risk scores perform differently in male versus female patients. This study evaluated the discriminatory performance of five established UGIB risk scores in predicting inpatient mortality by sex.

Aims & Methods

This retrospective study included 1,003 patients who underwent inpatient oesophagogastroduodenoscopy (OGD) for UGIB between January 2025 and August 2023 at a UK tertiary care centre. Glasgow-Blatchford Score (GBS), CHAMPS, ABC, Japanese score, and MAP(ASH), were calculated for each patient. Binary Logistic regression examined sex as an independent factor for 30-day inpatient mortality, with UGIB aetiology also accounted for (variceal vs non-variceal). Receiver operating characteristic (ROC) curves were used to assess each score's performance in predicting inpatient mortality separately for male and female subgroups.

Results

Out of the 1,003 admissions, 59.2% and 40.8% were males and females, respectively, with crude analysis demonstrating female mortality being slightly higher (10.5%) compared to male (8.6%). However, this was found not to be significant (p: 0.304, OR 1.251, CI: 0.816-1.917). These findings were consistent regardless of UGIB aetiology (variceal vs non-variceal).
For the 30-day inpatient mortality outcome, the ABC score demonstrated strong discriminative performance in both males (AUC: 0.804) and females (AUC: 0.835). CHAMPS and MAP(ASH) also performed consistently, with CHAMPS yielding AUCs of 0.788 in males and 0.793 in females, and MAP(ASH) showing 0.767 and 0.781 in males and females respectively. GBS performed slightly better in females (AUC: 0.743) compared to males (AUC: 0.691). The Japanese score showed poor discrimination in both sexes, particularly in females (AUC: 0.577). Overall, ABC, CHAMPS, and MAP(ASH) performed reliably across sexes.

Conclusion

Whilst crude mortality rates were higher in females than males, gender did not show to be an independent predictor of inpatient mortality, which could, however, necessitate a larger cohort size to ascertain validity. Risk scores, particularly the ABC score, maintained high and consistent predictive accuracy for inpatient mortality in both male and female patients with UGIB. These findings support the use of these tools across genders and suggest minimal gender-related performance bias in risk stratification.

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic conditions with alternating phases of flare-ups and remission. Due to the persistent and often severe course of these diseases, effective treatment significantly improves patients' daily activities and overall functioning. [1] Given the uncertain prognosis and the frequent disease progression despite pharmacotherapy, it is important to explore additional interventions that could support traditional treatments. While physical activity may provide both anti-inflammatory and functional benefits in IBD, data on its efficacy and safety during disease exacerbation remain scarce. [2] This pilot study is the first real-world investigation into the effects of a supervised physical exercise training in patients hospitalized due to IBD flare.

Aims & Methods

This study aimed to evaluate the effects of an individualized, moderate-intensity, supervised physical exercise training on exercise tolerance, inflammation, and fatigue resistance in patients hospitalized due to IBD flare, and to explore baseline factors associated with greater benefit from the intervention. Patients were randomly assigned to an intervention group, receiving individual cycloergometer training during hospitalization, or to a control group without exercise. Both groups were well balanced at baseline, with no significant differences in demographic, clinical, or laboratory parameters. At both admission and discharge, all patients underwent standardized graded exercise tests to establish their exercise tolerance based on the lactate threshold and heart rate/power output response. Furthermore laboratory assessments, and the Functional Assessment of Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire were conducted.

Results

A total of 22 patients were included in the study, with 13 patients in the intervention group and 9 patients in the control group. Although FACIT-F scores improved in both groups, the intervention group demonstrated a significantly greater improvement (median change –39 points; IQR –49 to –11; p = 0.014) compared to the control group (median change –25 points; IQR –52 to –6; p = 0.30). Baseline FACIT-F scores were significantly correlated with changes in heart rate response response during exercise: patients with greater baseline fatigue and poorer functional status experienced greater improvement in exercise tolerance (r = –0.62, p = 0.028). Platelet counts remained more stable in the intervention group (median change +10 ×10³/µl; IQR –65 to +45) compared to a significant increase in the control group (median +74 ×10³/µl; IQR +44.5 to +101.75; p = 0.046). In the intervention group, greater reductions in calprotectin were strongly correlated with more favorable heart rate responses during a graded exercise test (r = –0.92, p = 0.009).

Conclusion

Supervised training program during hospitalization for IBD flare was associated with improved fatigue resistance and more favorable inflammatory responses. Patients with worse baseline functioning obtained greater benefit in exercise tolerance. These findings support the feasibility and potential therapeutic role of individualized physical activity in acute IBD care and highlight the need for further investigation in real-world settings.

References

1. Farrell D, Artom M, Czuber-Dochan W, Jelsness-Jørgensen LP, Norton C, Savage E. Interventions for fatigue in inflammatory bowel disease. Cochrane Database Syst Rev. 2020 Apr 16;4(4):CD012005. doi: 10.1002/14651858.CD012005.pub2.
2. Achtenberg M, Cibor D, Zwolińska-Wcisło M. Structured exercise in patients with inflammatory bowel disease: a literature review. Gastroenterology Review/Przegląd Gastroenterologiczny. 2025;20(1):36-40. doi:10.5114/pg.2025.148473.

Disclosure

Magdalena Achtenberg has received lecture fees and/or travel grants from Ferring and Eli Lilly, unrelated to the present work. Tomasz Dziubyna has received travel grants from Fresenius, unrelated to the present work. Małgorzata Zwolińska-Wcisło, Dorota Cibor, Karolina Gazda, Magdalena Wyrzykowska, Piotr Kosieniak, Maria Wiśniewska, Jerzy A. Żołądź, Marcin Grandys and Joanna Majerczak declare no conflict of interest.