Introduction

Minimal hepatic encephalopathy (MHE) is the mildest form of hepatic encephalopathy (HE), and is defined as presence of signs of brain dysfunction (only detectable by specific psychometric tests) in absence of disorientation and asterixis. One of the neuropsychological test which is being frequently used in order to evaluate patients psychomotor speed and cognitive flexibility, and therefore detect MHE, is Stroop test (via EncephalApp).

Aims & Methods

The aim of this study was to evaluate the Stroop test for the screening and diagnosis of MHE. This prospective case-control study was performed at Clinic for Gatroenterology and Hepatology, University Clinical Center of Serbia (February 2020-August 2022), and included patients with cirrhosis and MHE and healthy controlos. Patients with uncontrolled overt HE (defined as mini mental status examination score <25), and those who consumed alcohol or psychoactive substances at least one month prior to testing were excluded. In all patients the presence of MHE was confirmed using animal naming test. In each participant the Stroop test was performed, and the results were compared between the two groups. The test itself has two components, the “OFF” and “ON” state. The specific outcomes recorded after the Stroop test are: 1. OFFTIME (total time for five correct runs in the “OFF” state), 2. number of runs needed to complete the five correct “OFF” runs, 3. ONTIME (total time for five correct runs in the “ON” state), and 4. number of runs needed to complete the five correct “ON” runs.

Results

A total of 111 participants were included (59 cases and 52 healthy controls). The majority of patients were classified as Child-Pugh class B (n=37, 62.7%), while the etiology of liver disease was most commonly alcohol-related (n=22, 37.3%). Median OFFTIME did not differ between the two groups (106.3 (84.5-126.3) and 91.4 (79.8-124.6), p>0.05). However, in patients with MHE median values of ONTIME and total time (OFF+ON) were significantly higher (122.3 (97.8-150.2) and 105.3 (84.5-136.3); 228.0 (180.7-274.9) and 195.6 (166.0-262.6); respectively, p<0.05). Participants were further divided into subgroups based on age and education level. Statistical significance between patients and controls in examined parameters was detected in younger participants, as well as in the group with higher educational level (Table 1).

Table 1. The difference in Stroop test parameters in respect with educational level.

Conclusion

Stroop test could be a valuable tool in detecting MHE in patients with cirrhosis, especially younger population and those with higher educational level.

Introduction

Microbiome analysis is a promising approach for the application of findings from basic research in the clinical field. However, there is an ongoing debate about the consistency of different bioinformatics analysis platforms. The lack of established standards affects the implementation of research findings.

Aims & Methods

In our study, we demonstrated that the results on the microbial composition of gastric mucosal biopsies are only slightly influenced by the efficacy of different microbiome analysis platforms. Furthermore, we investigated whether recent revisions to the International Code of Nomenclature for Prokaryotes and consequent alterations in taxonomic classification influenced the findings.
Gastric biopsy specimens were obtained from gastric cancer patients with well-defined clinical profiles (n=40), including individuals with and without Helicobacter pylori (H. pylori) infection, and from control subjects (n=39) with and without H. pylori infection. DNA extraction and 16S rRNA gene sequencing (V1-V2) was performed at one site, and the resulting fastQ files were distributed to five expert teams for independent analysis. Three widely used bioinformatics pipelines for microbiome analysis, namely DADA2, MOTHUR and QIIME2, were used for the analysis.

Results

The generated fastQ files exhibited no platform-dependent clustering, indicating the comparability of the sequences. Microbial diversity was slightly reduced in both GC groups and significantly reduced in the H. pylori positive controls. This is due to an extreme increase in the relative abundance of H. pylori in this group. It also follows that the samples of the H. pylori positive control group have a very high similarity and form the clearest cluster in the corresponding analysis. Regardless of the protocol used, H. pylori status, microbial diversity and relative bacterial abundance were reproducible on all platforms. Although minor differences in performance were detected and assessed, similarity analysis and bacterial enrichment assessment also yielded consistent results. The introduction of the new taxonomy only had a major impact on the Proteobacteria phylum, as it originally also included H. pylori according to the old taxonomy, but this is now assigned to the new Campilobacterota phylum.

Conclusion

In summary, our findings demonstrate that disparate microbiome analysis methodologies employed by independent research teams can yield comparable results from identical datasets.

Clinical Case Summary

29-year-old male with bloating, early satiety and frequent stools for last 8 years. He reported loss of around 30 kg weight in the past 6-8 years. His physical examination showed gross emaciation and BMI of 11.75 kg/m². He had pallor, oedema and bradycardia with heart rate of 46–54 per minutes.
Blood investigations showed Hemoglobin 8 gm%, total protein 4.8 gms with albumin 2.1 gms. Serum tissue transglutaminase antibody was negative. Contrast enhanced CT showed multifocal symmetric mural thickening involving short segment of small bowel with proximal dilatation and mild thickening of ileocecal junction. Barium meal-follow through and enteroclysis corroborated these findings. Colonoscopy and upper GI endoscopy were normal.
Diagnosis of Crohn’s Disease was considered and oral prednisolone and mesalamine were started. He continued to be symptomatic over next two years. Laparotomy showed multiple dilated small bowel loops and no stricture. Ileal biopsy showed lipofuscinosis.
The final diagnosis was confirmed to be Brown Bowel Syndrome. Patient was then started on Vitamin E, multivitamins, anti-oxidants and mesalamine.
Intestinal lipofuscinosis is a rare disorder that presents as brown pigmentation, occasionally with bowel dilatation and pseudo-obstruction. It co-exists with malabsorption of fat soluble vitamins, especially Vitamin-E. Pathologically, mitochondrial malfunction and degeneration lead to lipofuscin deposition followed by smooth muscle mitochondrial myopathy. Clinical features show motility disorders along with malabsorption features. Treatment involves treating the underlying cause and early initiation of Vitamin-E supplementation.
Conclusion
We present a rare intestinal disorder, Brown bowel syndrome, characterised by the deposition of lipofuscin in the intestinal cells following chronic malabsorption syndrome and vitamin E deficiency.

Introduction

Invariant Natural Killer T (iNKT) cells are lipid-specific T lymphocytes endowed with antitumor activities and whose infiltration is considered a positive prognostic factor in colorectal cancer (CRC). In this context, we have previously demonstrated that, at steady state, iNKT cells eliminate human CRC cells by releasing perforin and granzyme B (1).
However, we reported that the tumor-associated pathobiont Fusobacterium nucleatum is capable of inducing IL17 and GM-CSF expression in iNKT cells, promoting iNKT-mediated recruitment of neutrophils with PMN-MDSCs- like phenotype and functions. Tumor co-infiltration by iNKT cells and neutrophils in a large cohort CRC patients of correlates with negative clinical outcomes (2). Since the gut microbiota is an oncogenic driver of CRC and intestinal microbes represent potent stimulators of iNKT cell responses we analyzed the tumor-associated mucosal microbiota of the 35 CRC patients by 16S rRNA gene sequencing, revealing the presence in a large fraction of patients of Porphyromonas gingivalis, an opportunistic oral pathobiont often associated with inflammatory diseases and cancers.

Aims & Methods

Very little is known about how the function of iNKT cells is influenced by Porphyromonas gingivalis. Our aim is to assess changes in human iNKT cell phenotype and function provoked by this bacterium, and how these changes might contribute to colon cancer progression.
Human iNKT cell phenotype, functional profile and cytotoxic capabilites were evaluated upon stimulation with P. gingivalis isolates in vitro. Subsequently, as validation, P. gingivalis was administered to AOM/DSS-treated mice and evaluated iNKT cell phenotype and tumor progression. P. gingivalis-exposed human iNKT cells were sequenced and candidate molecules were tested in vitro in killing assays with human CRC epithelial cells.

Results

We observed that, compared to cells stimulated with aGalCer (a prototypical iNKT cell antigen), iNKT cells primed with P. gingivalis showed lower levels of interferon gamma, together with impaired cytotoxicity against CRC cell lines. These cells were also characterized by an increased expression of GM-CSF, and interleukins -17 and -10, as well as an increased capability of neutrophil chemotaxis. This pro-tumorigenic phenotype was confirmed in AOM/DSS-treated mice, as P. gingivalis-treated animals showed tumors of greater size, together with an increase in IL-17+ and GM-CSF+ iNKT cells. Pg-primed iNKT cells showed an enriched neutrophil chemotaxis gene signature, which included the chemokines CXCL1, CXCL2, CXCL5, CXCL8, CCL2 and CCL4 and of proinflammatory proteins acting on the cytotoxic machinery of NKT cells inhibiting their killing functions.

Conclusion

These results demonstrate that P. gingivalis can promote colon tumorigenesis by acting on iNKT cells, both by hampering antitumor properties and promoting the release of pro-tumorigenic cytokines and chemokines, which further act on myelo-phagocytic cells.

References

1. Díaz-Basabe, A., et al. (2021). Human intestinal and circulating invariant natural killer T cells are cytotoxic against colorectal cancer cells via the perforin–granzyme pathway. Mol Oncol, 15: 3385-3403. https://doi.org/10.1002/1878-0261.13104

Introduction

Managing tumoral bleeding poses a significant challenge for endoscopists. Traditional tools such as clips and heat-probes frequently prove inadequate in controlling stubborn bleeding caused by mucosal invasion from these tumors. Hemostatic powder sprays provide a novel solution by applying a combination of minerals and polymers directly onto the tumor surface, forming a mechanical barrier to seal the bleeding site. However, there is a scarcity of data regarding their effectiveness in treating hemorrhagic gastrointestinal neoplasms. This study seeks to evaluate the efficacy of Hemostatic powder spray in patients suffering from gastrointestinal bleeding related to malignancies.

Aims & Methods

This study aimed to evaluate the effectiveness of Hemostatic powder spray compared to standard clinical treatment in controlling gastrointestinal bleeding originating from malignant lesions. The primary outcome measures included the combined rates of rebleeding within 30 days, while secondary outcomes encompassed the combined rates of mortality over any time period.
We gathered relevant data, an extensive search of electronic databases was conducted up to April 2024. Only randomized controlled trials (RCTs) were included in the study, focusing specifically on cases where Hemostatic powder spray was pitted against conventional endoscopic techniques for managing bleeding caused by gastrointestinal tumors.

Results

Three studies involving a total of 162 patients were included in this meta-analysis. Among them, 83 patients underwent treatment with Hemostatic spray powder alone, while 79 patients received conventional hemostatic techniques. The pooled results of the analysis revealed that Hemostatic powder spray was associated with a lower incidence of re-bleeding beyond 30 days from the onset of treatment (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15-0.84), demonstrating a significant advantage over standard endoscopy in the management of gastrointestinal tumor bleeding (p-value 0.01). Additionally, there was no significant difference observed in all-time mortality between the two treatment groups (OR 0.40, 95% CI 0.19-0.83, p-value 0.09).

Conclusion

Hemostatic spray powders demonstrate significant efficacy in achieving hemostasis for gastrointestinal bleeding associated with malignancies. They should be regarded as a viable alternative to conventional endoscopic methods in such cases. Subsequent research should be structured to assess both the effectiveness and safety of hemostatic spray powders as a primary hemostatic approach compared to traditional endoscopic techniques.

References

1. Pittayanon, Rapat et al. “The efficacy of Hemospray in patients with upper gastrointestinal bleeding from tumor.” Endoscopy international open vol. 4,9 (2016): E933-6. doi:10.1055/s-0042-109863
2. Chen YI, Wyse J, Lu Y, et al. TC-325 hemostatic powder versus current standard of care in managing malignant GI bleeding: a pilot randomized clinical trial. Gastrointest Endosc 2020;91:321–328.
3. Bruno da Costa Martins, et al. Mo1140. Preliminary results of a randomized controlled trial comparing hemostatic powder versus optimal clinical treatment in the management of gastrointestinal bleeding from malignancy, Gastrointestinal Endoscopy, Volume 87, Issue 6, Supplement, 2018, Pages AB415-AB416, ISSN 0016-5107.
4. Martins BC, Abnader Machado A, Scomparin RC, et al. TC-325 hemostatic powder in the management of upper gastrointestinal malignant bleeding: a randomized controlled trial. Endosc Int Open 2022;10:E1350–E1357.
5. Minhem MA, Nakshabandi A, Mirza R, et al. Gastrointestinal hemorrhage in the setting of gastrointestinal cancer: anatomical prevalence, predictors, and interventions. World J Gastrointest Endosc 2021; 13:391–406.
6. Hussein, Mohamed et al. “Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes.” Journal of gastroenterology and hepatology vol. 36,11 (2021): 3027-3032. doi:10.1111/jgh.15579

Introduction

Use of antithrombotics including antiplatelet agents and anticoagulants is associated with upper and lower GI bleeding, thus a higher rate of positive findings is reasonable to be expected when patients receiving these drugs undergo SBCE for the investigation of SBB. However, the results of published studies concerning the impact of antithrombotics on the SBCE diagnostic yield remain conflicting. Furthermore, the clinical outcome of patients under antithrombotics who undergo SBCE for the investigation of SBB is not currently known.

Aims & Methods

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). Multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient’s bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode.

Results

During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) patients receiving antithrombotics, compared to 1113/5866 (18.9%) not receiving these drugs (p<0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occured in 927 (36.5%) of patients receiving antithrombotics (36.5%), compared to 795 (13.5%) not receiving these drugs (13.5%, p<0.00001).

Conclusion

Both the diagnostic yield of SBCE and the rebleeding rate were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real world setting only in a minority of patients with positive findings.

References

1. Sherwood MW, Nessel CC, Hellkamp AS, et al. Gastrointestinal bleeding in patients with atrial fibrillation treated with rivaroxaban or warfarin: ROCKET AF trial. J Am Coll Cardiol 2015; 66: 2271–2281.
2. Abraham NS, Hlatky MA, Antman EM, et al. ACCF/ACG/AHA 2010 expert consensus document on the concomitant use of PPI and thienopyridines: focused update of the ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. Am J Gastroenterol 2010; 105:2533–2549.
3. Maiden L, Thjodleifsson B, Seigal A, et al. Long-term effects of nonsteroidal anti-infammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study. Clin Gastroenterol Hepatol. 2007;5:1040–1045.
4. Nagata N, Niikura R, Yamada A, et al. Acute middle gastrointestinal bleeding risk associated with NSAIDs, antithrombotic drugs, and PPIs: a multicenter case-control study. PLoS ONE. 2016;11:e0151332.
5. Lepileur L, Dray X, Antonietti M, et al. Factors associated with diagnosis of obscure gastrointestinal bleeding by video capsule enteroscopy. Clin Gastroenterol Hepatol. 2012;10:1376–1380.
6. Shiotani A, Honda K, Murao T, et al. Combination of low-dose aspirin and thienopyridine exacerbates small bowel injury. Scand J Gastroenterol. 2011;46:281–286.