Introduction

Severe acute colitis (SAC) <represents a critical complication of inflammatory bowel disease (IBD), requiring prompt and appropriate management. Opportunistic infections, particularly those caused by cytomegalovirus (CMV) and Clostridioides difficile (C. difficile), can significantly influence clinical outcomes and therapeutic responses, especially in immunocompromized individuals. This study aims to evaluate the incidence of these opportunistic infections in patients with SAC complicating IBD and to analyze their impact on clinical progression and treatment efficacy.

Aims & Methods

A retrospective study was conducted involving patients admitted for SAC, diagnosed based on Truelove and Witts criteria and a Lichtiger score exceeding 10. Initial assessments included CMV polymerase chain reaction (PCR) testing on colonic biopsies and/or blood samples, detection of C. difficile toxins A/B in stool specimens, and standard microbiological evaluations. Clinical, biological, and therapeutic response data were systematically collected.

Results

Fifty-five patients over the age of 18 were included, with a mean age of 42.36 years (range: 18–74) and a slight female predominance (55%). In 34% of cases, SAC was the initial manifestation of IBD. All patients met the Truelove and Witts criteria and had a Lichtiger score >10 upon admission. Endoscopic signs of severity were observed in 40% of patients.
Intravenous corticosteroid therapy using hydrocortisone hemisuccinate was administered as the first-line treatment for all patients, yielding a 60% response rate.
CMV co-infection was identified in 4 patients, all of whom were refractory to intravenous corticosteroids and subsequently received ganciclovir. Two patients responded favorably to second-line therapy with cyclosporine, while the remaining two did not respond to infliximab and required subtotal colectomy.
C. difficile co-infection was detected in 6 patients, treated with intravenous metronidazole and oral vancomycin. Among these, 3 patients did not respond to first-line medical therapy; one acheved clinical improvement with cyclosporine, whereas two required emergency subtotal colectomy due to the development of toxic megacolon.
Bivariate analysis revealed a statistically significant association between CMV co-infection and corticosteroid treatment failure (p=0.009). No significant association was found between C. difficile co-infection and first-line treatment failure in SAC.

Conclusion

Opportunistic infections, particularly CMV, are linked to unfavorable therapeutic responses in patients with SAC. Early detection of these co-pathogens is crucial for promptly adjusting treatment strategies, including the consideration of second-line therapies or surgical interventions. These findings underscore the importance of systematic screening for opportunistic infections in SAC patients to optimize management and improve clinical outcomes.

Disclosure

The authors report no conflicts of interest

Clinical Case Summary

A 44-year-old man was admitted because of acid reflux and heartburn for three years. The patient had undergone sleeve gastrectomy (SG) and tension-free repair of esophageal hiatal hernia three years and one year before admission, respectively. He was scheduled to undergo gastric per-oral endoscopic myotomy (G-POEM) after gastroscopy and gastric emptying examination, which showed esophagitis, pylorospasm (A), and gastric emptying disturbance. After submucosal injection, a 2-cm mucosal incision was made 5cm above the antrum pylorus (B). After the submucosal tunnel was extended to 3cm below the pylorus, the muscle bundle was completely transected using the hybrid knife (C). After hemostasis with hot biopsy forceps, the mucosal entry on the stomach was closed with clips. After myotomy, the pylorus was remarkably enlarged, and the gastroscope passed smoothly without resistance (D). The patient recovered uneventfully and was discharged on the postoperative day 2. The patient did not experience any discomfort during the two-year postoperative follow-up. Pylorospasm is a rare adverse event after SG. G-POEM after SG was more complicated and riskier than normal due to distortion of the gastric cavity and limited space for the procedure. This case provides the possibility of applying G-POEM to treat pylorospasm after SG.

Introduction

Early gastric cancer (EGC) represents a critical stage in preventing and controlling the progression from gastritis to advanced gastric cancer (AGC). Therefore, identifying the single-cell characteristics of EGC, particularly the cellular composition of the tumor microenvironment (TME), as well as identifying potential predictive markers and therapeutic targets, could significantly enhance the monitoring of gastric cancer and improve clinical cure rates.

Aims & Methods

We constructed a comprehensive single-cell RNA sequencing atlas for 184,426 high-quality gastric cancer cells from various stages, utilizing clinical biopsies and surgical samples. The cell composition, differential gene expression, lineage differentiation, intercellular communication, immune infiltration, and clinical correlations between tumor and microenvironment cells were analyzed. Furthermore, through the integration of clinical sample detection, ex vitro and in vivo cell function tests, organoid and endothelial cell co-culture, mouse tumorigenic models, ultrasonic vascular detection, and transcriptome sequencing, key target cell subsets and their molecular roles in EGC were identified.

Results

Our single-cell atlas highlights the cellular and molecular characteristics of EGC. Eight distinct cell lineage states were identified, and it was observed that the number of epithelial cell meta-clusters gradually decreased. In contrast, the number of T&NK, B, plasma, fibroblast, myeloid, and endothelial cells increased with disease progression. Certain epithelial subclusters ((metaplastic stem-like cells (MSCs), metaplastic stem-like cells (PMC-like), proliferating cells), T-cell subclusters (T_reg, CCR7⁺ naive, CH25H⁺ CD4⁺, TEM CD8⁺, and GFPT2⁺ CD8⁺ T cells), and endothelial subclusters (IL-33⁺ Venous-1 and AMAMTSL2⁺ Artery-2) were found to be increased in EGC. The Venous-1 subcluster was found to express high levels of IL-33. Mechanistically, it was revealed that IL-33 enhances the survival and angiogenesis of endothelial cells by upregulating the expression of adhesion proteins CD34 and PECAM1. Patient-derived EGC and AGC organoids were subsequently generated, and it was demonstrated that endothelial-derived IL-33 promoted the growth of both EGC and AGC organoids ex vitro and in vivo. Furthermore, IL-33 was found to increase the expression of KRT17 in EGC organoids. Notably, we also found that high expression of IL-33 was positively correlated with the depth of invasion and malignancy of EGC.

Conclusion

This study provides novel insights into the single-cell components involved in EGC and reveals the role of the IL-33⁺ endothelial subcluster in EGC progression.

Introduction

Endoscopic mucosal resection (EMR) of colonic lesions is widely used for the removal of superficial gastrointestinal neoplasms, but intraprocedural and postprocedural bleeding remain significant adverse events. Current strategies often involve epinephrine injection, which has uncertain efficacy and potential systemic side effects, including hypertension and increased postprocedural pain. Tranexamic acid (TXA), an antifibrinolytic agent with a well-established safety profile, has shown efficacy in reducing bleeding across various surgical fields and may be an alternative to epinephrine use.

Aims & Methods

The primary aim was to assess whether the addition of TXA into the submucosal injection solution during colonic EMR is non-inferior to epinephrine in reducing the rates of intraprocedural and postprocedural bleeding. Secondary aims included comparing pain levels, the need for opioid analgesia, and the incidence of other complications such as deep mural injury and delayed bleeding. A prospective, double-blinded, controlled, non-inferiority pilot study was conducted at the Shamir Medical Center. Patients aged >18 years undergoing EMR for colonic lesions ≥20 mm were randomized into two groups. The study group received a standard injectate solution with 100 mg TXA in 10 ml, while the control group received the same solution with 1:100,000 epinephrine. Outcome measures included intraprocedural bleeding, delayed bleeding, pain (and analgesic use), perforation, hospitalization, and post-polypectomy syndrome.

Results

A total of 112 patients were included (57 TXA, 55 epinephrine). The mean age of the entire cohort was 69.0 years, and 47.3% were women. The average polyp size was 33.4 mm. The groups were comparable in most baseline characteristics, although TXA patients were slightly older (p = 0.032) and had higher rates of diabetes (p = 0.042). No significant difference was observed in lesion size, morphology, or pathology. Intraprocedural bleeding was similar across groups. Clinically significant delayed bleeding occurred in 7% of TXA vs 7.3% of epinephrine patients (p = 0.958). Notably, postprocedural pain was significantly reduced in the TXA group (5.3% vs 41.8%, p < 0.001), as was opioid requirement (0% vs 47.8%, p < 0.001). Although not statistically significant, there were no cases of deep mural injury or hospitalization due to post-polypectomy syndrome in the TXA group, compared to four in the epinephrine group (p = 0.055).

Conclusion

The addition of TXA to the submucosal injection solution during colonic ER procedures is non-inferior to epinephrine in preventing intraprocedural and delayed bleeding. Moreover, TXA is associated with significantly reduced postprocedural pain and opioid use, suggesting it may offer a safer and more comfortable alternative to epinephrine. These findings support the feasibility of larger-scale trials to further evaluate the efficacy and safety of TXA in endoscopic interventions.

Introduction

Loss of skeletal muscle mass (SMM), one of the hallmarks in the diagnosis of sarcopenia, is a frequent condition in patients with inflammatory bowel disease (IBD) and it is a negative predictor of disability and poor clinical outcomes.¹ Despite its clinical relevance, its diagnosis remains challenging due to limited access to standard methods like dual-energy X-ray absorptiometry (DEXA), computed tomography (CT), and magnetic resonance imaging (MRI). More practical alternative, such as bioelectrical impedance analysis (BIA) and ultrasound (US), should be investigated.^2-4

Aims & Methods

This study aims to evaluate the feasibility, reproducibility, and diagnostic accuracy of US measurement of psoas muscle thickness compared to BIA in assessing SMM in IBD patients.
US psoas muscle thickness adjusted for body mass index (BMI) was compared with BIA-derived SMM normalized to squared height. Feasibility and reproducibility between the two investigators were evaluated by intra-class correlation coefficient (ICC). SMM normalized to squared height and US thickness adjusted for BMI values were compared with Pearson’s test. Results were considered significant with a p value <0.05. The diagnostic accuracy of US psoas muscle thickness measurement in comparison to SMM with BIA was assessed by calculating sensitivity (Sens), specificity (Spec), positive and negative likelihood ratios (LR+, LR-) with their 95% confidence intervals (95% CI). This study was approved by the local Ethics Committee (no. 0049113).

Results

A total of 86 consecutive patients with IBD were prospectively enrolled, including 67.4% with CD and 32.6% with UC. The cohort had a male predominance (68.6%), with a mean age of 50.4 ± 17 years and a mean BMI of 23.68 ± 3.73 kg/m². US assessment of psoas muscle thickness was feasible in all patients. Inter-operator reproducibility was excellent with an ICC of 0.951. A significant positive correlation (r = 0.54, p < 0.0001) was observed between the US-derived psoas thickness adjusted for BMI and SMM as measured by BIA and normalized to squared height. Receiver operating characteristic (ROC) curve analysis revealed an area under the curve (AUROC) of 0.753 for men and 0.758 for women. Sex-specific cut-offs of psoas thickness × BMI were determined (≤108.18 cm·kg/m² for men, ≤66.9 cm·kg/m² for women), yielding sensitivities of 93.5% and 78.5% and specificities of 53.6% and 69.2%, respectively. Low SMM was defined according to BIA-based thresholds normalized to height squared, with cut-offs of <6.68 kg/m² for females and <8.97 kg/m² for males, as proposed by Peine et al. ⁵

Table 1. Ultrasound psoas thickness compared to skeletal muscle mass values at bioelectrical impedance analysis

Conclusion

US measurement of psoas muscle thickness is a feasible, low-cost, non-invasive and reproducible method for evaluating SMM in IBD patients. It shows promising diagnostic accuracy compared to BIA and, since the psoas muscle is a key anatomical landmark for evaluating the terminal ileum, it could be used as a practical first-line screening tool for sarcopenia especially in routine bowel US. Further prospective studies are needed to refine cut-off values, validate findings in diverse populations, and assess the long-term prognostic implications of this technique within the framework of personalized IBD management.

References

1. Nishikawa, H. et al. Inflammatory bowel disease and sarcopenia: Its mechanism and clinical importance. Journal of Clinical Medicine vol. 10 Preprint at https://doi.org/10.3390/jcm10184214 (2021).
2. Oshima, Y., Shiga, T., Namba, H. & Kuno, S. Estimation of whole-body skeletal muscle mass by bioelectrical impedance analysis in the standing position. Obes Res Clin Pract 4, (2010).
3. Smith, R. L., Taylor, K. M., Friedman, A. B., Gibson, R. N. & Gibson, P. R. Systematic Review: Clinical Utility of Gastrointestinal Ultrasound in the Diagnosis, Assessment and Management of Patients with Ulcerative Colitis. Journal of Crohn’s and Colitis vol. 14 Preprint at https://doi.org/10.1093/ecco-jcc/jjz163 (2020).
4. Mulinacci, G. et al. P466 Ultrasound muscle assessment for sarcopenia screening in patients with Inflammatory Bowel Disease: A prospective study (SarcUS-IBD). J Crohns Colitis 18, (2024)
5. Peine, S. et al. Generation of normal ranges for measures of body composition in adults based on bioelectrical impedance analysis using the seca mBCA. Int J Body Compos Res 11, (2013).

Disclosure

No conflict of interest

Introduction

Gastroesophageal reflux disease (GERD) and asthma are commonly co-occurring conditions, with shared genetic factors identified. However, the specific loci and the influence of common genetic architecture remain undefined.

Aims & Methods

We obtained genome-wide association study (GWAS) summary statistics for GERD (71,522 cases, 261,079 controls) and asthma (56,167 cases, 352,255 controls). Using linkage disequilibrium score regression (LDSC), we assessed genetic correlations between GERD and asthma. Bidirectional mendelian randomization (MR) was performed to investigate potential causal relationships, followed by cross-trait GWAS meta-analysis and colocalization analysis to identify shared risk loci. Additionally, summary-data-based mendelian randomization (SMR) and transcriptome-wide association study (TWAS) were conducted to pinpoint common functional genes. Finally, we analyzed gene expression profiles in both healthy individuals and GERD patients using esophageal single-cell RNA sequencing (scRNA-seq) data.

Results

We identified a significant genetic correlation between GERD and asthma (r_g = 0.37, P = 6.19×10^–38) and a significant causal effect of GERD on asthma (OR = 1.22, P = 1.54×10^-5). Cross-trait meta-analyses revealed 56 shared risk loci between GERD and asthma, including 51 loci that were newly identified. Three loci (rs61937247, rs7960225, and rs769670) exhibited evidence of colocalization. Gene-level analyses pinpointed three novel shared genes(RBM6, SUOX, and MPHOSPH9) between GERD and asthma. Single-cell RNA sequencing analysis uncovered heightened expression of these genes in immune cells of patients diagnosed with GERD.

Conclusion

Our study has discovered novel shared genetic loci and candidate genes between GERD and asthma, providing further insights into the genetic susceptibility of comorbidity and potential mechanisms of the two diseas​​​​es.

References

1. Broers C, Tack J, Pauwels A. Review article: gastro-oesophageal reflux disease in asthma and chronic obstructive pulmonary disease. Aliment Pharmacol Ther 2018;47:176–191.
2. Eapen AA, Gupta MR, Lockey RF, et al. Gastroesophageal reflux disease, laryngopharyngeal reflux, and vocal cord dysfunction/inducible laryngeal obstruction-overlapping conditions that affect asthma. J Allergy Clin Immunol. 2024;154(6):1369-1377.
3. Bulik-Sullivan B, Finucane HK, Anttila V, et al. An atlas of genetic correlations across human diseases and traits. Nat Genet. 2015;47(11):1236-1241.
4. Morrison J, Knoblauch N, Marcus JH, et al. Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics. Nat Genet 2020;52:740–747.
5. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559–575.
6. Stuart T, Butler A, Hoffman P, et al. Comprehensive Integration of Single-Cell Data. Cell 2019;177:1888-1902.e21.
7. Finucane HK, Bulik-Sullivan B, Gusev A, et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet 2015;47:1228–1235.
8. Freuer D, Linseisen J, Meisinger C. Asthma and the risk of gastrointestinal disorders: a Mendelian randomization study. BMC Med 2022;20:82.

Disclosure

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Introduction

Alcoholic hepatitis (AH) is a form of acute liver injury with significant morbidity and mortality. Several scoring systems have been developed and used to predict mortality, including Maddrey’s discriminant function (MDF), model for end-stage liver disease (MELD) and modified MELD including sodium (MELD-Na).

Aims & Methods

We conducted a systematic review of Pubmed, Embase, Cochrane Library and Web of Science to compare the accuracy of these scores in AH mortality prediction. The inclusion criteria include studies evaluating MDF, MELD and MELD-Na prognostic models for mortality, either as an assessment of a single score or in combination in patients with alcohol-related hepatitis.

Results

The pooled sensitivity and specificity of MDF for mortality prediction in 28 days were 0.862 (95%CI 0.714–0.940) and 0.538 (95%CI 0.322–0.741), respectively. In 90 days were 0.862 (95%CI 0.714–0.940) and 0.538 (95%CI 0.322–0.741), respectively. The pooled sensitivity and specificity of MELD for mortality prediction in 28 days were 0.809 (95%CI 0.676–0.896) and 0.753 (95%CI 0.636–0.842), respectively. In 90 days were 0.809 (95%CI 0.676–0.896) and 0.753 (95%CI 0.636–0.842), respectively. The pooled sensitivity and specificity of MELD-Na for mortality prediction in 28 days were 0.707 (95%CI 0.520–0.842) and 0.679 (95%CI 0.474–0.832), respectively. In 90 days were 0.707 (95%CI 0.520–0.842) and 0.679 (95%CI 0.474–0.832), respectively. No significant statistical difference was observed when comparing AUC of these scores.

Conclusion

Our study demonstrated no statistical difference between the prognostic models used at the admission of a patient with alcoholic hepatitis.