Current Gastroenterology Reports最新文献

{"title":"Switching from Intravenous to Subcutaneous Infliximab in Children with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.","authors":"Elizabeth A Spencer","doi":"10.1007/s11894-026-01061-2","DOIUrl":"10.1007/s11894-026-01061-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Subcutaneous infliximab (IFX-SC; CT-P13 SC/infliximab-dyyb/Remsima-SC/Zymfentra) is an approved maintenance option after intravenous (IV) induction in adults with inflammatory bowel disease (IBD), but it is not approved for patients < 18 years, and the pediatric evidence remains dispersed across small, largely observational cohorts. This review synthesizes the published pediatric experience of transitioning from IV to SC infliximab, examining maintenance of remission, drug concentrations, safety, and acceptability, and situates it within the adult evidence base and the distinctly pediatric concerns of access and dosing.</p><p><strong>Recent findings: </strong>A systematic search (PROSPERO: CRD420261465026) identified six independent, non-overlapping pediatric switch cohorts (n = 173). Random-effects proportional meta-analysis yielded pooled treatment persistence of 92% (95%CI 84-98), maintained clinical remission of 93% (95%CI 84-99), and any-cause discontinuation of 8% (95%CI 2-16), most often for injection-site intolerance, disease relapse, or paradoxical dermatitis. New anti-drug antibody formation was rare among the 129 children in cohorts measuring immunogenicity (four children, none sustained) while previously positive antibodies frequently resolved after switching. Steady-state SC concentrations ran roughly 2-fold above prior IV troughs, an expected step-up reflecting sustained subcutaneous exposure. Patient and caregiver satisfaction was high due to decreased school absence and travel, and cost analyses signaled net savings from avoided infusion-center use. The principal barrier was administrative: age-based denial. In appropriately selected children, transition to IFX-SC sustains remission with predictable pharmacokinetics, a reassuring immunogenicity profile, and excellent tolerability, mirroring the adult experience. These observations constitute a well-supported real-world signal and warrant prospective validation and pursuit of pediatric labeling.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149215221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial Intelligence in High-resolution Anorectal Manometry: Current Applications and Future Directions.","authors":"Myeongsook Seo, Segyeong Joo, Kee Wook Jung","doi":"10.1007/s11894-026-01056-z","DOIUrl":"10.1007/s11894-026-01056-z","url":null,"abstract":"<p><strong>Purpose of review: </strong>High-resolution anorectal manometry (HRAM) has improved anorectal physiological assessment but remains limited by conventional pressure-based metrics that incompletely reflect the complex spatiotemporal physiology of continence and defecation. This review summarizes recent advances in artificial intelligence (AI) and machine learning and their potential to enhance HRAM interpretation and clinical decision-making.</p><p><strong>Recent findings: </strong>Recent AI-based approaches have shown promising performance in automated HRAM interpretation, prediction of dyssynergic defecation and balloon expulsion abnormalities, implementation of the London Classification, and analysis of three-dimensional high-definition anorectal manometry datasets. In parallel, integrated physiological metrics such as integrated pressurized volume (IPV) and time-series IPV (TS-IPV) have improved characterization of anorectal function by incorporating pressure amplitude, spatial distribution, and temporal dynamics. Emerging deep-learning models have further demonstrated the potential to identify novel physiological patterns beyond traditional classification systems. AI has the potential to reduce observer variability, improve diagnostic standardization, and facilitate outcome prediction in anorectal physiology testing. Although challenges related to data standardization, external validation, and explainable AI remain, the integration of advanced physiological metrics and AI-driven analytics may transform HRAM from a descriptive diagnostic test into a platform for dynamic physiological phenotyping and precision medicine.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small Intestinal Bacterial Overgrowth in the Pediatric Population: A Review of Pathophysiology, Diagnosis, and Management.","authors":"Shaan Mody, Alison Laxer, Jermie Gandhi","doi":"10.1007/s11894-026-01059-w","DOIUrl":"10.1007/s11894-026-01059-w","url":null,"abstract":"<p><strong>Purpose of review: </strong>Small intestinal bacterial overgrowth (SIBO) remains a significant diagnostic and therapeutic challenge in pediatric gastroenterology. This review summarizes the epidemiology, pathophysiology, diagnosis, and management of SIBO in children, with emphasis on recent advances in microbiome science, evolving diagnostic paradigms, and pediatric-specific clinical considerations.</p><p><strong>Recent findings: </strong>SIBO is increasingly recognized across a broad range of pediatric conditions, including intestinal failure, motility disorders, disorders of gut-brain interaction, and systemic diseases associated with gastrointestinal dysmotility. Diagnosis remains challenging as currently available tests have important limitations and pediatric-specific diagnostic standards are lacking. Management requires a multifaceted approach that combines antimicrobial therapy, correction of underlying anatomic abnormalities or treatment of dysmotility, nutritional support, and emerging microbiome-directed strategies. Future research should focus on validating pediatric-specific diagnostic criteria, defining optimal treatment regimens, and advancing precision approaches to microbiome characterization and modulation.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking Restrictive Diets in IBD: Toward an Inclusion-Focused Nutritional Paradigm.","authors":"Brandon Cunha, Ari Alter, Madeline Berschback, Sunhee Park, Stephanie Gold, Yecheskel Schneider","doi":"10.1007/s11894-026-01047-0","DOIUrl":"10.1007/s11894-026-01047-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Patient-initiated elimination diets are widely adopted by those with inflammatory bowel disease (IBD), yet the evidence supporting their long-term use remains limited and their risks are increasingly recognized. Some common elimination diets utilized by patients include the specific carbohydrate diet (SCD), low-FODMAP diet, and gluten-free and dairy-free diets. This narrative review critically examines the role of self-initiated restrictive dietary strategies in IBD management, evaluating the evidence for and against common elimination-based approaches, and contrasts these with emerging data supporting more inclusive dietary patterns.</p><p><strong>Recent findings: </strong>Sustained elimination diets carry meaningful risks: malnutrition, micronutrient deficiency, sarcopenia, gut microbial dysbiosis, food anxiety, and avoidant/restrictive food intake disorder (ARFID). Current evidence demonstrates that the Mediterranean diet performs comparably to more restrictive approaches in inducing symptomatic remission, and generally is not associated with adverse nutritional and psychosocial consequences. Contemporary recommendations from several gastrointestinal societies discourage long-term elimination diets and favor inclusive, nutritionally adequate patterns, particularly the Mediterranean diet, as a preferred dietary framework for most patients with IBD, though supporting evidence remains largely observational and randomized controlled trial data are limited. We propose a paradigm shift from dietary exclusion toward inclusion, diversity, and nutritional adequacy, with registered dietitians as essential partners in IBD care. When elimination is clinically indicated, it should be time-limited, goal-directed, and followed by structured food reintroduction. Moving beyond restriction represents not a retreat from dietary focus, but its maturation, aligning nutritional guidance with the principles of patient-centered, evidence-based disease management.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13589753/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149008016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Diet to Dysbiosis: The Microbiome's Relationship to Eosinophilic Esophagitis.","authors":"Eunjae J Yoo, Yecheskel Schneider, Matthew Bechtold, Amiko M Uchida","doi":"10.1007/s11894-026-01058-x","DOIUrl":"10.1007/s11894-026-01058-x","url":null,"abstract":"<p><strong>Purpose of the review: </strong>Eosinophilic esophagitis is a chronic, type 2 inflammatory disease of the esophagus. Diet elimination trials suggest that EoE is triggered by food antigens, however, incomplete response rates present gaps in our understanding. This review aims to synthesize current evidence surrounding the diet-microbiome-immune axis in EoE and propose a conceptual framework for how dietary interventions may influence disease beyond antigen elimination.</p><p><strong>Recent findings: </strong>Many studies on the EoE microbiome highlight descriptive differences in cross-sectional cohorts, although findings remain inconsistent and lack a unifying disease signature. We highlight evidence from broader mucosal and gastrointestinal microbiome research and discuss the importance of microbial metabolic function and their role in regulating epithelial barrier integrity and immune responses. We present the case that in EoE, elimination diets may unintentionally alter microbial substrates and metabolic activity, leading to heterogeneity in treatment response independent of dietary antigen removal. We review early and limited experimental data that suggest microbial metabolites such as short-chain fatty acids may influence esophageal barrier function and identify gaps in understanding mechanistic and longitudinal implications for patients. The interactions and implications of the diet-microbiome-immune axis is ripe for exploration. We explore reframing elimination diets to think beyond the antigens being removed, and probe what microbially active foods may be introduced (or not) and thus have clinically relevant microbiome-modulating properties. Future work should prioritize longitudinal, diet-controlled, and multi-omic approaches to elucidate causal relationships and support the development of microbiome-informed, precision dietary strategies in EoE.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13622940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do Multi-Omics Approaches Improve the Diagnosis of Microbial Overgrowth Syndromes?","authors":"Juliana de Freitas Germano, Gabriela Leite, Mark Pimentel","doi":"10.1007/s11894-026-01057-y","DOIUrl":"10.1007/s11894-026-01057-y","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review investigates how advances in breath testing (BT), small bowel (SB) culture, metagenomics, metatranscriptomics, transcriptomics and proteomics are reshaping the definition and diagnosis of small intestinal bacterial overgrowth (SIBO). It also discusses whether SIBO should be redefined as part of a larger group of microbial overgrowth syndromes.</p><p><strong>Recent findings: </strong>Recent studies identify distinct hydrogen-, methane-, and hydrogen sulfide-associated overgrowth phenotypes, termed SIBO, intestinal methanogen overgrowth (IMO), and intestinal sulfide overproduction (ISO). SB sampling shows that these conditions involve different microbial patterns and functional activity, symptoms, and host responses. Quantitative shotgun metagenomics provides greater taxonomic and functional resolution than culture, while metatranscriptomics reveals active microbial pathways. On top of that, host transcriptomics and proteomics contribute to the better understanding of the predominant microbial effects in host cellular mechanisms in each of the distinct small bowel overgrowth types. SIBO has been increasingly identified as a disorder of microbial ecology and function rather than bacterial quantity alone. Integrating BT with SB sampling and multi-omics approaches may improve classification, clarify symptom mechanisms, and support a more individualized treatment, although standardized methods and further clinical validation remain necessary.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13550075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic Dysfunction-Associated Steatotic Liver Disease in the Aging Population: A Narrative Review of Pathophysiological Synergy, Diagnostic Challenges, and Tailored Management.","authors":"Koji Takahashi, Nana Yamada, Terunao Iwanaga, Takafumi Sakuma, Hidehiro Kamezaki","doi":"10.1007/s11894-026-01055-0","DOIUrl":"10.1007/s11894-026-01055-0","url":null,"abstract":"<p><strong>Purpose of review: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition in older adults, yet its management in the geriatric context remains poorly characterized. This review examines the unique pathophysiology, diagnostic challenges, and tailored therapeutic strategies for MASLD in the aging population.</p><p><strong>Recent findings: </strong>The convergence of inflammaging, mitochondrial senescence, and the deteriorating liver-muscle axis drives distinct geriatric MASLD phenotypes, including \"Lean MASLD\" and post-menopausal sex-reversal. These processes promote progression to metabolic dysfunction-associated steatohepatitis (MASH), the inflammatory stage of the disease. Chronodisruption-potentially mediated by melatonin deficiency and nuclear factor-kappa B activation-has been proposed as a novel driver. Advanced liver fibrosis has been associated with systemic biological aging. Diagnostically, standard Fibrosis-4 index thresholds are unreliable in patients over 65, and \"silent cirrhosis\" with normal aminotransferases is common. Carbon-ion radiotherapy has emerged as a potentially sarcopenia-friendly treatment option for MASLD-related hepatocellular carcinoma. Managing geriatric MASLD requires a paradigm shift from liver-centric histological targets toward functional longevity. Avoiding the \"Sarcopenia Trap,\" recalibrating non-invasive fibrosis tests with age-adjusted thresholds, promoting alcohol abstinence, and addressing chronodisruption are essential components of a holistic, individualized care framework.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One Patient, Two Problems: Applying Short Bowel Syndrome Management Principles in Inflammatory Bowel Disease patients.","authors":"Adeeti J Chiplunker, James Burton, Bryn Koehler, Matthew L Bechtold","doi":"10.1007/s11894-026-01054-1","DOIUrl":"10.1007/s11894-026-01054-1","url":null,"abstract":"<p><strong>Purpose of review: </strong>Surgery for inflammatory bowel disease (IBD) often results in alterations in gut function beyond the anatomical changes. While some patients develop short bowel syndrome (SBS), a significant proportion of IBD patients benefit from pharmacologic and dietary interventions for SBS even in the absence of true SBS or IF.</p><p><strong>Recent findings: </strong>While no formal criteria exist to clearly define the presence of SBS in IBD patients, the presence of specific features in the surgical and clinical history are crucial to the rapid identification of SBS or IF in IBD patients. Anatomy specific dietary considerations and interventions provide significant benefits and lay the foundation for a structured approach to optimizing anti-motility and adjunctive therapies. IBD patients with post-surgical anatomy benefit from management strategies used in patients in SBS. Optimal dosing of anti-motility agents and oral rehydration solution form the foundations of management in all practice settings.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gastrointestinal Manifestations and Nutrition Support in Hypermobile Ehlers-Danlos, Postural Orthostatic Tachycardia, and Mast Cell Activation Syndromes.","authors":"Jennifer Katz, Allison M Angeli, Apeksha Alicea, Kerstin Austin","doi":"10.1007/s11894-026-01050-5","DOIUrl":"10.1007/s11894-026-01050-5","url":null,"abstract":"<p><strong>Purpose of review: </strong>Gastrointestinal symptoms are common and often severe in patients with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders (hEDS/HSD), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS). This review provides a structured, practical framework for evaluation of gastrointestinal symptoms and appropriate use of nutrition support in this population, where clinical practice remains variable and escalation to non-oral nutrition support may occur prematurely.</p><p><strong>Recent findings: </strong>Emerging data highlight the high prevalence of disorders of gut-brain interaction, avoidant/restrictive food intake disorder, and malnutrition in these overlapping conditions. Evidence suggests that enteral and parenteral nutrition are frequently initiated without adequate trials of conservative and behavioral interventions, and that de-escalation once advanced nutrition support is established remains challenging. A coordinated evaluation integrating validated tools should precede escalation to non-oral nutrition support. Enteral nutrition is preferred when oral strategies fail, and parenteral nutrition should be reserved for intestinal failure. A multidisciplinary, biopsychosocial care model is essential to optimize outcomes and reduce unnecessary harm in this complex population.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers in Irritable Bowel Syndrome: Bridging Gut-Brain Mechanisms to Precision Care.","authors":"Manjeet Kumar Goyal, Omesh Goyal, Rishi Chowdhary, Tanisha Sehgal, Gayatri Brahmandam, Anushri Parikh, Insiya Rampurawala, Ashita Rukmini Vuthaluru, Prerna Goyal, Abdulfattah Issak","doi":"10.1007/s11894-026-01053-2","DOIUrl":"10.1007/s11894-026-01053-2","url":null,"abstract":"<p><strong>Purpose of review: </strong>Irritable bowel syndrome is a common disorder of gut-brain interaction characterized by chronic abdominal pain and altered bowel habits in the absence of structural pathology. Its pathophysiology reflects a complex interplay between the central nervous system, enteric nervous system, microbiota, immune signaling, epithelial barrier dysfunction etc. Despite advances in the understanding of the mechanisms causing IBS, the diagnosis of IBS remains primarily symptom-based, necessitating the use of objective tools to improve diagnostic precision and personalized management. This review synthesizes highlights existing literature on IBS biomarkers, including inflammatory markers (cytokines, C-reactive protein), microbial signatures (gut microbiota composition, anti-CdtB and anti-vinculin antibodies), metabolic indicators (bile acids, short-chain fatty acids), and markers of intestinal permeability (zonulin) to assess their applications in the diagnosis and management of IBS. We also examined emerging multi-omics technologies that identify the complex patterns linking the gut, the brain and the microbiota. Early research focusing on single biomarkers demonstrated limited diagnostic utility due to the heterogeneous and multifactorial nature of IBS. Recent advances support the development of composite, mechanism-based biomarker panels that integrate multiple biological domains, offering improved representation of underlying pathophysiological processes. These developments mark a shift from a single-marker approach toward multidimensional biomarker strategies. This narrative review synthesizes current evidence and proposes a framework for integrating biomarkers into clinical practice. Biomarkers are best utilized following a positive symptom-based diagnosis and exclusion of alarm features, to stratify patients into biologically relevant subtypes and guide targeted therapy. This supports a transition from exclusion-based diagnosis of IBS towards a positive and more precise one.</p>","PeriodicalId":10776,"journal":{"name":"Current Gastroenterology Reports","volume":"28 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13477457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}