Search Results (2,949)

Background: Individuals with inflammatory bowel disease (IBD) are at substantially increased risk for Clostridioides difficile infection (CDI), which leads to significantly higher morbidity and mortality compared to the general population. However, comprehensive national-level analyses of long-term mortality trends in this population remain limited. This study examines mortality trends associated with IBD and CDI in the United States from 1999 to 2023. Methods: This descriptive study utilized the CDC WONDER Multiple Cause-of-Death database. Deaths involving IBD (ICD-10: K50, K51) and CDI (A04.7) were identified among adults aged 25 years and older. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated with 95% confidence intervals and stratified by sex, race/ethnicity, urbanization, and census region. Joinpoint regression was applied to estimate the annual percent change (APC) in mortality. Results: Between 1999 and 2023, 76,084 deaths were recorded. Medical facilities accounted for 46% of deaths, followed by decedents’ homes (28.3%) and nursing home/long-term care facilities (16.5%). Overall mortality declined gradually from 1999 to 2018 (APC: −0.23, p < 0.05), increased sharply through 2021 (APC: +12.75, p < 0.05), and was then followed by a non-significant change through 2023 (APC: −2.69; 95% CI: −8.24 to 3.19), consistent with a plateau. Men consistently exhibited higher AAMRs than women. Non-Hispanic White individuals had the highest AAMRs (1.844 in 2023), while Non-Hispanic Black individuals experienced a sustained increase from 2016 onward (APC: +7.11, p < 0.05). Hispanic mortality increased steadily throughout the study period (APC: +1.31, p < 0.05). Rural populations had higher overall AAMRs than urban populations. The Midwest recorded the highest regional AAMRs by 2023 (1.867). Conclusions: Mortality increased significantly between 2018 and 2021, coinciding with the COVID-19 pandemic, though our study design cannot prove causation. Disparities by race/ethnicity, urbanization, and region persisted. These findings underscore the need for ongoing antibiotic stewardship, equitable healthcare access, and targeted public health interventions for this vulnerable population. Full article

Background: Patients with inflammatory bowel disease (IBD) are prone to low vitamin D levels; however, data from Southeast Europe on this topic remain sparse. We measured serum 25-hydroxyvitamin D [25(OH)D] concentrations in Albanian patients with inflammatory bowel disease (IBD) to determine the prevalence of deficiency and its association with clinical disease activity. Methods: We enrolled 96 patients with IBD (82 with ulcerative colitis [UC] and 14 with Crohn’s disease [CD]) and 563 healthy controls at the University Hospital Center Mother Teresa in Tirana, Albania. Serum 25(OH)D concentrations were measured using an electrochemiluminescence immunoassay (Elecsys Vitamin D total III, Roche Diagnostics). Vitamin D levels were classified as deficient (<10 ng/mL), insufficient (10–29 ng/mL), or sufficient (≥30 ng/mL). Disease activity was scored using the Total Mayo Score (TMS) for UC and the Crohn’s Disease Activity Index (CDAI) for CD. The analysis was performed using SPSS version 26.0. Results: Patients with IBD had lower mean serum 25(OH)D concentrations than controls (18.0 ± 9.9 vs. 23.8 ± 11.1 ng/mL; p = 0.001). After adjustment for age and sex, vitamin D sufficiency (≥30 ng/mL) remained less common among patients with IBD than among healthy controls (adjusted OR, 0.494; 95% CI, 0.260–0.939; p = 0.031). Only 12 of the 96 IBD patients (12.5%) had sufficient vitamin D levels. Vitamin D insufficiency and deficiency were observed in 65.6% and 21.9% of patients, respectively. A weak inverse correlation with Total Mayo Score was observed among UC patients with complete disease activity data (r = −0.266, p = 0.044). No such correlation was observed for CDAI in patients with CD. The relationship between vitamin D and CRP was negative but did not reach significance (r = −0.213, p = 0.051). Conclusions: Low vitamin D levels are common among Albanian patients with IBD and showed a weak inverse association with disease activity in UC. Whether correcting this deficiency changes the disease course remains to be determined in prospective trials. Full article

Treat-to-target management in inflammatory bowel disease (IBD) combines symptoms, fecal and serum biomarkers, endoscopy, histology, and cross-sectional imaging, but these measures frequently diverge. Discordance may reflect analytical variation, timing, disease location, phenotype, comorbidity, or partially non-overlapping biological processes. We performed a critical narrative review using a structured PubMed/MEDLINE search, supplemented by citation chaining and publisher searches. Guidelines, systematic reviews, diagnostic studies, cohorts, randomized trials, and selected mechanistic studies were prioritized. Fecal calprotectin (FC) and lactoferrin primarily reflect intestinal neutrophilic inflammation, whereas C-reactive protein (CRP) and related serum indices reflect a nonlocalizing systemic response. The fecal immunochemical test (FIT) detects gastrointestinal bleeding, and leucine-rich alpha-2 glycoprotein (LRG) remains promising but insufficiently standardized. We distinguish five biological biomarker domains—namely, fecal–neutrophil; serum–systemic; epithelial/barrier; restitution/resolution; and fibrosis/extracellular matrix (ECM) remodeling—from symptoms and clinical indices, pharmacologic measurements, and phenotype-directed reference assessments. Circulating barrier, repair, and matrix-turnover markers remain investigational. Reactive therapeutic drug monitoring (TDM) for anti-tumor necrosis factor (anti-TNF) agents has the most mature evidence. Vedolizumab and ustekinumab show exposure–response associations, but actionable thresholds are unvalidated, and clinical TDM is not established for newer biologics or oral small molecules. After objective confirmation of disease activity, the framework may support phenotype-directed therapeutic decisions but is not a validated algorithm. Clinically important disagreement should prompt assessment of sampling, assay, timing, infection, medication-related confounding, and pretest probability before phenotype-directed endoscopy, histology, imaging, or reactive TDM is selected. A single discordant result should neither trigger treatment escalation nor exclude active or structural disease. Full article

Inflammatory bowel disease (IBD) and colorectal cancer (CRC) are heterogeneous intestinal disorders that pose significant threats to human health and share common pathological features, including intestinal mucosal barrier disruption and gut microbiota dysbiosis, in which fucosylation acts as a critical regulatory mediator. Fucosylation is a highly conserved post-translational glycosylation modification involving the enzymatic transfer of fucose residues to glycoproteins and glycolipids. This tightly regulated process plays essential roles in maintaining intestinal homeostasis, mediating host–microbiota interactions and regulating immune responses. This review adopts a physiology-to-pathology framework, delineating fucosylation’s operational principles in healthy intestines and its dysregulation in IBD and CRC. It summarizes the spatial distribution of fucosylation, its regulatory mechanisms, and its roles in disease pathogenesis, and also discusses its potential as a diagnostic biomarker and therapeutic target. Finally, this review highlights future research directions to bridge mechanistic insights with clinical translation, emphasizing the promise of fucosylation in the precision diagnosis and treatment of intestinal disorders. Full article

Background/Objectives: Inflammatory bowel disease (IBD) may require topical rectal treatment for distal colonic inflammation. Rectal foams or rectal enemas can reach deeper bowel sections but are complex to administer, especially for pediatric patients with IBD. Furthermore, it is a challenge to visualize this administration process in a structured manner. We aimed to design a rectal demonstration model to enable the visualization of rectal foam administration and to assess the clinical risk potentially associated with detectable errors. Methods: A rectal demonstration model was developed, handling errors were defined, and their clinical risk was rated. The model was tested for rectal foam administration by 19 adolescent patients (aged 12–18 years). Results: A total of 12 observable administration steps, including their clinical risk, were defined by an expert panel of physicians and pharmacists. Seven handling errors were rated with a high clinical risk, such as “Not shaking the spray can at all before administration”. In demonstrations by adolescent patients, a median of three (Q25/Q75; 2/4.5; min/max 1/7) handling errors were identified. The most frequent error was releasing the pump dome too quickly after pushing down (11/19, 58%). At least one error with high clinical risk (score: 5–6) was identified in 15/19 (79%) of patients’ administrations. Conclusions: The developed demonstration model facilitates the visualization of handling errors in rectal foam administration that would otherwise not be accessible in routine care. A high rate of clinically relevant handling errors was identified in adolescents. Prospectively, the model can be used to practice rectal foam administration and address patient handling errors to increase patient safety. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder influenced by environmental factors including cold stress. While cold exposure exacerbates intestinal inflammation, the specific microbial metabolites linking environmental stress to colitis remain unclear. 3-Hydroxypropionate (3-HPA) is a gut microbial metabolite elevated following cold exposure, but its pathogenic role in intestinal inflammation has not been investigated. This study aimed to determine whether 3-HPA contributes to colitis progression and to characterize its effects on gut microbiota and intestinal epithelial function. Methods: We employed a dextran sulfate sodium (DSS)-induced colitis mouse model to assess the impact of cold exposure and exogenous 3-HPA administration. Paired shotgun metagenomic and metabolomic analyses were performed to evaluate gut microbial composition and metabolic outputs. Mechanistic studies using NCM460 intestinal epithelial cells were conducted to examine mitochondrial respiration and tight junction integrity under nutrient-limited conditions. Results: Cold exposure increased fecal 3-HPA levels and aggravated DSS-induced colitis, characterized by enhanced weight loss, histological damage, and immune cell infiltration. Direct 3-HPA supplementation alone was sufficient to worsen colitis severity. Multi-omics profiling revealed that 3-HPA reshaped gut microbiota composition, depleted short-chain fatty acids (SCFAs), and disrupted microbial tryptophan and bile acid metabolism. In vitro, 3-HPA impaired mitochondrial oxidative phosphorylation, reduced ATP production, and compromised tight junction organization in intestinal epithelial cells. Conclusions: These findings identify 3-HPA as a gut microbial metabolite elevated by cold exposure that contributes to colitis progression by disrupting beneficial microbial metabolism while also impairing epithelial mitochondrial function and barrier integrity. Modulating 3-HPA production or its downstream epithelial effects may represent a potential therapeutic approach for IBD exacerbated by environmental stress. Full article

Background/Objectives: Although the exact etiology of Inflammatory Bowel Diseases (IBD) is not yet fully understood, recent evidence suggests that both genetic and dietary factors are involved in their pathogenesis. The aim of the present exploratory study was to investigate how first-degree relatives (FDRs) of individuals with IBD perceive familial risk and the role of diet in IBD onset and prevention. Methods: A mixed methods approach was followed. A total of 103 unaffected FDRs of individuals living with IBD in Greece participated in an online questionnaire examining demographic characteristics, disease-related knowledge, risk perception, and beliefs about the role of diet in IBD. In parallel, 16 semi-structured interviews explored participants’ beliefs, self-reported dietary practices, and the factors shaping them using a framework analysis guided by the Health Belief Model. Results: Exploratory quantitative findings indicated that belief in the role of diet was associated with higher odds of self-reported family dietary changes, while belief in genetic risk was associated with lower odds of self-reported family dietary changes. The findings did not characterize the nature, maintenance, or motivation of these changes. Qualitative findings provided a deeper understanding of participants’ beliefs, highlighting that diet was mainly viewed as relevant to IBD management rather than prevention. Fear of disease onset and healthcare professional guidance were perceived as key facilitators of dietary changes. Conclusions: Our findings highlight heterogeneous beliefs regarding familial IBD risk and self-reported family diet changes, and support future research addressing balanced familial-risk communication for unaffected FDRs. Full article

Probiotic interventions for inflammatory bowel disease (IBD) have become a hot research topic in this field. However, no previous studies have investigated whether fox-derived probiotics exert therapeutic effects against colitis. The present investigation evaluated the effects of Lactiplantibacillus plantarum (syn. Lactobacillus plantarum) J3, sourced from the intestines of healthy Arctic foxes, on colitis. In an in vitro LPS-stimulated Caco-2 cell model, strain J3 exhibited prominent anti-inflammatory and antioxidant capacities, indicating potential to preserve intestinal barrier integrity. Furthermore, in an in vivo DSS-induced colitis mouse model, oral J3 supplementation markedly alleviated body weight loss, lowered disease activity index (DAI), and ameliorated histopathological lesions in colon tissues. Mechanistic analyses revealed that the J3 group displayed significantly decreased colonic levels of TNF-α, IL-1β, IL-6, MPO, PGE₂, along with downregulated COX-2 mRNA expression (p < 0.05). By contrast, the levels of IL-10, TJ protein mRNA, and MUC2 mRNA were markedly upregulated, whereas serum LPS and D-Lac concentrations were significantly reduced (p < 0.05). In an exploratory analysis of 16S rDNA and short-chain fatty acids (SCFAs) in a subset of mice, J3 treatment showed a trend toward colonic microbial remodeling, accompanied by a significant increase in short-chain fatty acid production (p < 0.05). Overall, these findings indicate that Lactiplantibacillus plantarum J3 derived from foxes may alleviate DSS-induced colitis in mice, providing a basis for future translational research. Full article

Background: Patients with inflammatory bowel disease (IBD) often follow restrictive diets. Data on dietary habits and beliefs in pediatric IBD are scarce. Our aim was to assess dietary habits, beliefs, and knowledge regarding nutrition and IBD among children with IBD. Method: In this single-center, cross-sectional study, pediatric patients aged 12–18 years with IBD completed a non-scoring, 25-item questionnaire assessing general dietary habits, beliefs about diet’s role in IBD pathogenesis and treatment, food avoidance, and food-related experiences since diagnosis. Results: We included 72 IBD patients (mean age [SD]: 15.2 [2.3] years; 41 (57%) were male, 32 (45%) had Crohn’s disease (CD)). Almost half of the participants did not believe that eating habits contributed to the pathogenesis of IBD. One-third of patients considered diet to be more important than medication. Approximately two-thirds changed their eating habits after diagnosis, regardless of disease type (χ²: 0.70, p = 0.40), or induction therapy (nutritional vs. non-nutritional, χ²: 0.02, p = 0.88). At least one food was avoided by 65% of the participants. Conclusions: Most children have changed their dietary habits and avoided one or more food groups. The type of induction therapy did not relate to the knowledge and dietary beliefs after induction. Our findings suggest that repeated education and dietary counseling should be an integral part of the management of pediatric IBD. Full article

Major histocompatibility complex class II (MHC-II) expression by intestinal epithelial cells (IECs) has emerged as a critical mechanism regulating mucosal immune homeostasis at the interface between the intestinal microbiota, epithelial barrier, and immune system. Beyond professional antigen-presenting cells, IEC-intrinsic MHC-II shapes CD4⁺ T-cell responses, influencing tolerance to commensal microorganisms, immunity to enteric pathogens, and maintenance of barrier integrity. Recent studies have revealed that epithelial MHC-II expression is dynamically regulated by cytokines, the gut microbiota, dietary factors, and microbiota-derived metabolites, linking environmental signals to local adaptive immune responses. Dysregulation of epithelial antigen presentation has been implicated in chronic intestinal inflammation, including inflammatory bowel disease (IBD). This review summarizes current knowledge regarding the molecular regulation, spatial organization, and immunological functions of epithelial MHC-II and discusses its emerging role in host–microbiota interactions, mucosal barrier homeostasis, and intestinal disease. Full article

Background/Objectives: Micronutrient deficiencies are common in inflammatory bowel disease (IBD) and contribute to anemia, impaired wound healing, neurologic injury, and adverse disease outcomes. Major societies, including ESPEN, ACG, and ECCO, recommend nutritional and micronutrient assessment in patients with IBD, yet few studies describe how comprehensively these recommendations are applied during hospitalization. This study aimed to characterize inpatient testing practices for vitamins B1, B6, B12, and zinc in hospitalized IBD patients, quantify deficiency frequency among those tested, and identify gaps between guideline-recommended and actual micronutrient assessment. Methods: A retrospective chart review was performed on adults with Crohn’s disease (CD) or ulcerative colitis (UC) hospitalized for an IBD flare at a tertiary care center. Demographics, comorbidities, and deficiency-associated clinical features were recorded. Yield was defined as the proportion of tested patients meeting institutional deficiency thresholds. Yield for each non-B12 micronutrient was compared with B12 as an internal benchmark. Results: Among 356 patients (285 CD, 71 UC), inpatient micronutrient testing was markedly imbalanced: B12 was tested in 97.2%, whereas B6, B1, and zinc were tested in only 34.8%, 30.6%, and 18.8%, respectively. Among those tested, deficiencies were common: B6 40.3%, zinc 32.8%, B1 22.9%, and B12 9.0%. Each non-B12 micronutrient yielded deficiency significantly more often per test than B12 (all p < 0.001), a testing-yield mismatch interpreted cautiously given selective testing of non-B12 nutrients. Deficiency frequencies did not differ significantly between CD and UC. Clinical contexts included tachycardia and edema (B1); elevated inflammatory markers and thromboembolism history (B6); anemia and neuropathy (B12); and diarrhea and hypoalbuminemia (zinc). Conclusions: Inpatient micronutrient assessment in IBD is heavily skewed toward B12, with B1, B6, and zinc under-tested despite a substantially higher yield of identified deficiency per test. This testing-yield mismatch represents a measurable implementation gap between guideline-recommended comprehensive assessment and actual inpatient practice; whether systematic panel-based assessment improves clinical outcomes warrants prospective evaluation. Full article

Differentiating active ulcerative colitis (UC) from Crohn’s disease (CD) is one of the unmet needs addressed by biomarkers in inflammatory bowel disease (IBD). The immune landscapes of UC and CD differ, justifying the search for discriminatory markers and novel therapy targets among their mediators. Herein, 27 systemic cytokines were measured using flow cytometry-based methodology in 138 IBD patients, with an additional 21 being determined in 67 of the patients. Their discriminatory power was assessed individually and as exploratory multivariable signatures generated using logistic regression, hierarchical clustering, and principal component analysis. Eotaxin-1, macrophage inflammatory protein (MIP)-1β, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) showed fair discriminatory potential, while multivariable models performed better. Interleukin (IL)-1β, IL-4, and MIP-1α were strongly associated with CD, whereas IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), MIP-1β, and TRAIL were associated with UC. Active UC was characterized by mediators linked to eosinophil-, mastocyte-, and neutrophil-driven inflammation and tissue repair (eotaxin-1, IL-5, growth-regulated oncogene (GRO), MIP-1β, stem cell factor (SCF), GM-CSF, IL-1 receptor antagonist, TRAIL, stem cell growth factor (SCGF)-β, and cutaneous T cell-attracting chemokine (CTACK)), whereas active CD was associated with Th1/Th17 immunity, myeloid activation, fibrosis, angiogenesis, and neuroimmune remodeling (IL-1β, IL-12p70, IL-15, ‘regulated on activation, normal T-cell expressed and secreted’ (RANTES), MIP-1α, stromal cell-derived factor (SDF)-1α, nerve growth factor β (β-NGF), and leukemia inhibitory factor (LIF)). In conclusion, integrated circulating immune signatures identify several understudied cytokines as potential contributors to disease-specific pathways and show potential in distinguishing active UC from CD warranting further mechanistic studies and independent validation in larger cohorts. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

Background/Objectives: Patients with inflammatory bowel disease (IBD) frequently experience food-related symptoms and express a strong need for dietary guidance, yet evidence-based recommendations remain limited. This often leads to self-imposed dietary restrictions, potentially compromising nutritional intake and food-related quality of life (Fr-QoL). The primary aim of this study was to evaluate changes in Fr-QoL, following personalized feedback on an IBD-specific food frequency questionnaire and access to an online nutritional knowledge portal over a 6-month period. Secondary exploratory outcomes included changes in dietary intake and diet quality. Methods: In this nationwide pre–post study, 108 patients with IBD completed baseline and 6-month assessments. Dietary intake was measured using the validated GINQ-FFQ and Fr-QoL using a 29-item questionnaire. Nutrient intake was compared with EFSA reference values. Participants received automated personalized feedback and had access to educational tools and dietitian resources. Changes over time were analyzed using paired statistical tests. Results: A significant improvement in Fr-QoL was observed (mean difference 8.1 points, 95% CI 5.5–10.7; p < 0.001; Cohen’s d = 0.39). Baseline intake was characterized by high fat and low fiber consumption. After 6 months, total energy intake decreased (p < 0.001), along with reductions in protein, fat, carbohydrates, fiber, and several micronutrients, including iron, folate, vitamin B6, vitamin C, potassium, magnesium, and zinc. Diet quality did not improve, and adherence to EFSA guidelines remained suboptimal. The digital tools were positively evaluated. Conclusions: In this single-arm pre–post study, Fr-QoL scores were higher at follow-up than at baseline among participants who completed both assessments, whereas dietary intake and overall diet quality did not improve. The findings support the feasibility and acceptability of the developed digital tools for dietary assessment and nutrition education, although their effectiveness requires further evaluation in controlled studies. Additional strategies, including structured dietitian-led support combined with digital resources, may be required to optimize nutritional outcomes in patients with IBD. Full article

Background: Ankylosing Spondylitis (AS) and inflammatory bowel disease (IBD) exhibit substantial pathophysiological overlap, including dysregulated innate immunity, barrier dysfunction, and Th17-mediated inflammation. However, whether Na⁺ overload-related genes (NRGs) exhibit shared transcriptional alterations in IBD and AS remains unclear. This study aimed to characterize the expression patterns of NRGs across IBD and AS and to identify candidate genes associated with both diseases. Methods: Differential expression analysis was performed to identify differentially expressed NRGs (DE-NRGs) in diseased tissues relative to normal tissues. Shared DE-NRGs between IBD and AS were screened and defined as common differentially expressed NRGs (Co-DE-NRGs). We then analyzed the correlations of these Co-DE-NRGs and explored their relationships with immune cell infiltration in target tissues. Four machine learning algorithms were applied to screen key NRGs associated with both IBD and AS. Potential therapeutic agents targeting these core biomarkers were predicted using drug–gene interaction databases, and molecular docking was conducted for further validation. Results: A total of 32 shared Co-DE-NRGs were identified for IBD and AS, with nine key regulatory NRGs recognized: CALR, CD63, CYBA, DYSF, HYOU1, IL1B, JAK1, MMP9, and STAT3. Exploratory MR analysis identified disease-specific associations between genetically predicted expression of NRGs and CD, UC, and AS. Genetically predicted STAT3 expression showed positive associations with CD and UC but an inverse association with AS and therefore did not represent a consistent risk factor across the three diseases. Furthermore, transcriptome-based drug-response analysis identified four candidate agents shared between AS and at least one IBD dataset: ciclosporin, BCL-LZH-4, BRD-K79669418, and CID-5951923. Exploratory molecular docking generated STAT3 binding poses for BCL-LZH-4 and CID-5951923, with DOCK Grid Scores of −35.321896 and −28.361128, respectively. CID-5951923 was selected for representative visualization of its predicted interaction with STAT3. Single-cell RNA-sequencing analysis identified tissue- and cell-type-specific STAT3 mRNA expression patterns in the analyzed IBD colonic and AS peripheral-blood datasets, with monocytes representing a major cell population exhibiting detected STAT3 expression in the AS dataset. Conclusions: These findings identify shared NRG-related transcriptional alterations in IBD and AS, with STAT3 emerging as a candidate gene associated with both diseases. Further experimental studies are required to determine whether these alterations reflect the involvement of NECSO and to evaluate their potential diagnostic or therapeutic relevance. Full article