Extraintestinal Disease Research Articles

The Impact of Inflammatory Bowel Diseases on Patients' Quality of Life and Work Functionality: An Observational Study.

This study aimed to assess the employment status, quality of life, and work functionality in patients affected by inflammatory bowel diseases (IBDs). Patients (N = 216) were enrolled between June 2020 and October 2021. Personal, clinical, and occupational features were investigated. The Short Inflammatory Bowel Disease Questionnaire and the Work Productivity and Activity Impairment questionnaire were administered. Among the enrolled patients, 114 (53%) were employed. The mean absenteeism and presenteeism percentages of 10% and 37% were determined, with 44% and 39% of daily and work activity impairment, respectively. A poor Health-Related Quality of Life (HRQoL) was retrieved (47 ± 12). Extraintestinal manifestations, disease activity, and HRQoL were associated with occupational outcomes. IBD can impact patients' work functionality. The association between clinical, psychological, and occupational issues suggests the relevance for a multidisciplinary management of the disease.

Acute Tuberculous Appendicitis, a Rare Entity

Tuberculous appendicitis is a rare disease, with an overall incidence of between 1.5-3.0% among tuberculosis patients. It was first described by Corbin et al in 1873 and since then has been rarely recorded in publications and case reports. In the USA, extrapulmonary disease is seen in around 20-30% of tuberculosis patients, with the most common extrapulmonary manifestations being bone (30%), urinary tract (24%) and lymph node (13%) involvement. A high index of suspicion is required to make the diagnosis of appendicular tuberculosis, although it can cause damage to the appendix without other signs of localized disease. We report a case of a woman diagnosed with primary tuberculous appendicitis in a patient with human immunodeficiency virus (HIV), with evidence of extra-intestinal disease.

Role of ArcA in the regulation of antibiotic sensitivity in avian pathogenic Escherichia coli

Avian pathogenic Escherichia coli (APEC) is one of the common extraintestinal infectious disease pathogens in chickens, geese, and other birds, inducing serious impediments to the development of the poultry industry. Hence, investigating how bacteria regulate themselves amidst different challenging conditions is immense essential in prevention and treatment for bacterial pathogen infections. The ArcA regulatory factor has been reported to regulate oxygen availability in strains, but its role in regulation of antibiotics resistance in APEC is unclear. This study delved into understanding how ArcA regulates antibiotic resistance in APEC. An E. coli APEC40 arcA knockout strain was constructed, and the regulatory mechanism of arcA on APEC antibiotic susceptibility was identified by drug sensitivity test, colony counting assay, real-time quantitative PCR, β-galactosidase assays and electrophoretic mobility shift assay (EMSA). The results showed that ArcA directly binds to the promoter region of the outer membrane protein OmpC/OmpW and regulates bacterial susceptibility to kanamycin and penicillin G. At the same time, the double knockout of ompW and ompW/arcA resulted in an increase in resistance to kanamycin compared to the deletion of the arcA gene. This outcome provided experimental proof suggesting that the outer membrane protein OmpW could serve as a crucial pathway for the ingress of kanamycin into cells. These results confirmed the important regulatory role of ArcA transcription factors under APEC antibiotic stress.

Molecular Detection of a Pathogenic Entamoeba among Symptomatic Children in Eastern Kurdistan of Iraq.

Entamoeba histolytica infects the large intestine of humans, causing a spectrum of clinical appearances ranging from asymptomatic colonization to severe intestinal and extra-intestinal disease. The parasite is identical microscopically to commensal nonpathogenic amoeba. To detect the pathogenic Entamoeba and estimate the precise prevalence of the parasite among the symptomatic pediatric population using molecular techniques. 323 fecal samples were collected from symptomatic children admitted to Sulaimani Pediatric Teaching Hospital, Sulaimaniyah Province, Iraq, from June to October 2021. A structured, validated questionnaire was prepared and used to report participants' gender, residency, and drinking water source. Then, stool samples were microscopically examined, and the positive samples were submitted to molecular analysis by amplifying the 18s rRNA gene using nested PCR to differentiate E. histolytica from other nonpathogenic Entamoeba. Finally, gene sequences were done to confirm the species. Microscopically, 58 positive samples represented Entamoeba species infection rate of 18% among symptomatic patients. However, only 18 samples were positive for E. histolytica based on molecular methods, which accounts for 31% of the positive by microscopy and 5.6% among the 323 symptomatic populations. NCBI, available in their database, gives the gene sequence and accession number. Patients' sociodemographic data and water sources were directly related to the infection rate. Classical microscopic examination provides a misleading profile about the prevalence of E. histolytica in an endemic region that might lead to unnecessary treatments and a lack of appropriate management for patients.

DOP25 Antibodies against Neutrophil Extracellular Traps (ANETAs) are associated with more severe disease course in Ulcerative Colitis

Abstract Background Antibodies against Neutrophil Extracellular Traps (ANETAs) have emerged as markers in multiple autoimmune disorders (i.e. rheumatoid arthritis and systemic lupus) associated with disease activity. We investigated the presence of ANETAs and their influence on disease course in Inflammatory Bowel Disease (IBD). Methods Serum samples from UC (n=33), Crohn's Disease (CD; n=28), and healthy controls (HC; n=8) underwent incubation with non-lytic Neutrophil Extracellular Traps (NETs) for immunofluorescence microscopy. For clinical relevance, these patients were followed over ten years to track treatment resistance, extraintestinal manifestations, surgeries, and disease recurrence (Table 1). For functional relevance, in vitro generated NETs were exposed to ANETAs, followed by quantifying macrophage-mediated clearance of these ANETA pre-treated NETs by real-time microscopy via pHrodo for 24 hours, as well as assessing pro-inflammatory cytokine (IL-6, TNF-α, IL-8, and IL-23) genetic expression levels in these macrophages. Results Among UC patients, ANETA positivity correlated with high rates of treatment resistance, extraintestinal manifestations, colorectal surgeries, and recurrence of disease like pouchitis (93.3% vs. 6.7%, 61.5% vs. 38.5%; 71.4% vs. 28.6%; 87.5% vs. 12.5%, for ANETA+ and ANETA- UC patients, respectively). CD patients with ANETAs exhibited high rates of resistance to treatment (75% vs 25%) and lower rates of extraintestinal manifestations, colectomy, and disease recurrence (38.1% vs 61.9%, 40% vs 60%, 33.3% vs 66.7%) (Fig 1A). Macrophages displayed robust engulfment of untreated NETs and those treated with healthy control sera, while ANETA-coated NETs exhibited reduced susceptibility to macrophage phagocytosis (Fig 1B). Gene expression analysis revealed a significant upregulation of pro-inflammatory cytokines (IL-6, TNF-α, IL-8, and IL-23) when NETs were incubated with serum from ANETA-positive individuals compared to sera from healthy controls (p<0.05). Conclusion ANETAs may serve as markers for a distinct subgroup of UC patients characterized by aggressive disease and poorer prognosis. The potential mechanism might involve impaired NETs clearance by, and inducing a proinflammatory response in macrophages. Discrepancies observed between UC and CD suggest diverse pathophysiological mechanisms in both diseases. Further research is imperative to comprehensively understand the underlying pathophysiology, function, and potential clinical applications of ANETAs in IBD.

Interleukin-9 production by type 2 innate lymphoid cells induces Paneth cell metaplasia and small intestinal remodeling

Paneth cell metaplasia (PCM) typically arises in pre-existing gastrointestinal (GI) diseases; however, the mechanistic pathway that induces metaplasia and whether PCM is initiated exclusively by disorders intrinsic to the GI tract is not well known. Here, we describe the development of PCM in a murine model of chronic myelogenous leukemia (CML) that is driven by an inducible bcr-abl oncogene. Mechanistically, CML induces a proinflammatory state within the GI tract that results in the production of epithelial-derived IL-33. The binding of IL-33 to the decoy receptor ST2 leads to IL-9 production by type 2 innate lymphoid cells (ILC2) which is directly responsible for the induction of PCM in the colon and tissue remodeling in the small intestines, characterized by goblet and tuft cell hyperplasia along with expansion of mucosal mast cells. Thus, we demonstrate that an extra-intestinal disease can trigger an ILC2/IL-9 immune circuit, which induces PCM and regulates epithelial cell fate decisions in the GI tract.

Using source-associated mobile genetic elements to identify zoonotic extraintestinal E. coli infections

A one-health perspective may provide new and actionable information about Escherichia coli transmission. E. coli colonizes a broad range of vertebrates, including humans and food-production animals, and is a leading cause of bladder, kidney, and bloodstream infections in humans. Substantial evidence supports foodborne transmission of pathogenic E. coli strains from food animals to humans. However, the relative contribution of foodborne zoonotic E. coli (FZEC) to the human extraintestinal disease burden and the distinguishing characteristics of such strains remain undefined. Using a comparative genomic analysis of a large collection of contemporaneous, geographically-matched clinical and meat-source E. coli isolates (n = 3111), we identified 17 source-associated mobile genetic elements – predominantly plasmids and bacteriophages – and integrated them into a novel Bayesian latent class model to predict the origins of clinical E. coli isolates. We estimated that approximately 8 % of human extraintestinal E. coli infections (mostly urinary tract infections) in our study population were caused by FZEC. FZEC strains were equally likely to cause symptomatic disease as non-FZEC strains. Two FZEC lineages, ST131-H22 and ST58, appeared to have particularly high virulence potential. Our findings imply that FZEC strains collectively cause more urinary tract infections than does any single non-E. coli uropathogenic species (e.g., Klebsiella pneumoniae). Our novel approach can be applied in other settings to identify the highest-risk FZEC strains, determine their sources, and inform new one-health strategies to decrease the heavy public health burden imposed by extraintestinal E. coli infections.

A review on aeromoniasis in poultry: A bacterial disease of zoonotic nature

Aeromonas spp. are widely distributed in surface water, sewage, untreated and chlorinated, drinking water, as well as meats, fish, shellfish, poultry, and their products. A disease caused by Aeromonas spp. is designated as aeromoniasis. It can affect different aquatic animals, mammals, and birds in different geographic regions. Moreover, gastrointestinal and extra-intestinal disease conditions may be provoked in humans as a result of food poising with Aeromonas spp. Some Aeromonas spp. have been identified, however, Aeromonas hydrophila (A. hydrophila), A. caviae, and A. veronii bv sobria may be of public health significance. Aeromonas spp. are members of family Aeromonadaceae and genus Aeromonas. They are Gram-negative rod-shaped, facultative anaerobic, and oxidase and catalase-positive bacteria. The pathogenicity of Aeromonas in different hosts is mediated by several virulence factors such as endotoxins, cytotoxic enterotoxin, cytotoxins, hemolysins, adhesins, and extracellular enzymes such as proteases, amylases, lipases, ADP-ribosyltransferases, and DNases. Most avian species are susceptible to either natural or experimental infections with Aeromonas spp. Infection usually arises through feacal-oral route. Traveler's diarrhea as well as other systemic and local infections are the clinical picture of food poisoning associated with aeromoniasis in humans. Despite Aeromonas spp. being sensitive to various antimicrobials, multiple drug resistance has been commonly reported worldwide. Accordingly, this review highlights aeromoniasis in poultry regarding Aeromonas virulence factors epidemiology, pathogenicity, zoonosis, and antimicrobial resistance.

P530 The Burden on Cohabitants of Patients with Inflammatory Bowel Disease: A Cross-Sectional Study

Abstract Background Inflammatory bowel disease is a chronic disease characterized by digestive symptoms with an increasing incidence and prevalence. It is well established its impact on the quality of life of patients and their main caregivers but no study has yet considered the consequences of IBD on cohabitants with no direct involvement in patient`s care. Our aims were to analyze quality of life in cohabitants of people with IBD and identify potential related factors. Methods We conducted a cross-sectional study that included patients with IBD and their house-hold members. Participants were recruited from a period of two months from patients attending the IBD unit of our hospital. Inclusion criteria were a definite diagnosis of IBD and household members living in the same house for a period of 1 year or more. Exclusion criteria were an age <18, refusal to participate or subjects unable to fulfill the questionnaires. Demographic data was obtained for patients and household members. IBD activity was assessed by using the Partial Mayo Score and the Harvey-Bradshaw score. Other relevant information regarding the prior and current state of the disease was collected. Quality of life was assessed in the case of the patients with the Inflammatory Bowel Disease Questionnaire (IBDQ-32) and for the household members we used the Household Members Quality of Life-Inflammatory Bowel Disease (HHMQoL-IBD) questionnaire. Results We included 22 patients with UC, 32 patients with CD and 2 patients with indeterminate colitis and 82 household members. Both groups had similar sociodemographic characteristics. The univariate analysis of the quality of life of cohabitants showed a significant association of HHMQoL-IBD and IBDQ-32 score in their relatives (p<0.0001) (Figure 1), last CRP (p=0.043), number of disease flares in the last year (p=0.04), extraintestinal diseases (p=0.01) and particularly articular disease (p=0.04). Cohabitants of patients with CD had significantly lower HHMQoL-IBD than UC ones (53 ± 18 vs. 62 ± 23; p=0.049). Among cohabitants of patients with UC and CD, patient’s CRP in the last control was related to HHMQoL-IBD score (p=0.043 and p=0.04 respectively). In a linear multiple regression analysis, IBDQ-32 score (p<0.0001) in patients and the presence of extraintestinal disease (p=0.048) were independent predictors of cohabitant’s quality of life, and particularly articular disease. Conclusion Quality of life in household members of patients with IBD is related to patient’s quality of life and extraintestinal conditions related to the disease. Our study shows how important is to analyze and act in the patient’s whole environment, taking into consideration not only clinical variables but also the relational conditions and impact of the disease.

The Two-Component System CpxRA Affects Antibiotic Susceptibility and Biofilm Formation in Avian Pathogenic Escherichia coli.

Avian pathogenic Escherichia coli (APEC) is one of the common extraintestinal infectious disease pathogens in chickens, geese, and other birds. It can cause a variety of infections, and even the death of poultry, causing enormous economic losses. However, the misuse and abuse of antibiotics in the poultry industry have led to the development of drug resistance in the gut microbes, posing a challenge for the treatment of APEC infections. It has been reported that the CpxRA two-component system has an effect on bacterial drug resistance, but the specific regulatory mechanism remains unclear. In this study, the regulatory mechanism of CpxRA on APEC biofilm formation and EmrKY efflux pump was investigated. The cpxRA knockout strain of E. coli APEC40 was constructed, and the molecular regulatory mechanism of CpxR on biofilms and efflux pump-coding genes were identified by biofilm formation assays, drug susceptibility test, real-time reverse transcription quantitative PCR, and electrophoretic mobility shift assay (EMSA). The results indicated that CpxR can directly bind to the promoter region of emrKY and negatively regulate the sensitivity of bacteria to ofloxacin and erythromycin. These results confirm the important regulatory role of the CpxRA two-component system under antibiotic stress in APEC.

Microbiota in the Natural History of Pancreatic Cancer: From Predisposition to Therapy.

Early microbiome insights came from gut microbes and their role among intestinal and extraintestinal disease. The latest evidence suggests that the microbiota is a true organ, capable of several interactions throughout the digestive system, attracting specific interest in the biliopancreatic district. Despite advances in diagnostics over the last few decades and improvements in the management of this disease, pancreatic cancer is still a common cause of cancer death. Microbiota can influence the development of precancerous disease predisposing to pancreatic cancer (PC). At the same time, neoplastic tissue shows specific characteristics in terms of diversity and phenotype, determining the short- and long-term prognosis. Considering the above information, a role for microbiota has also been hypothesized in the different phases of the PC approach, providing future revolutionary therapeutic insights. Microbiota-modulating therapies could open new issues in the therapeutic landscape. The aim of this narrative review is to assess the most updated evidence on microbiome in all the steps regarding pancreatic adenocarcinoma, from early development to response to antineoplastic therapy and long-term prognosis.

Biochemical study for Amoebic dysentery in patients with Entamoeba histolytica in Thi-Qar province/southern Iraq

Entamoeba histolytica is a parasitic protozoan that caused amoebiasis or amoebic dysentery, it is an intestinal disease which infects colon and liver Amoebic dysentery is spread all over the world. E. histolytica is causing the death of human cells and leading to develop invasion, and ulceration of the intestine. However, amebic liver abscess (ALA) considers as major common extraintestinal disease caused by E. histolytica. The current study was designed to estimate the effect of E. histolytica trophozoite on liver functions through the evaluation of some bio-chemical parameters for patients with amebiasis. Blood sample were collected from patients with amoebic dysentery after diagnosed about 100 from stool sample from them microscopically and detected by PCR technique to confirm the infection with am-amebiasis, all sample with amoebiasis were subjected to biochemical study after the separation of serum. Biochemical parameters that included during this study were AST, ALT and ALP. Lipid profile included Triglyceride and Cholesterol as well as some minerals like Iron, Zinc, and Potassium. The results for the level of AST and ALT were showed a high significant difference (P<0.01) where AST was (22.84+/-7.83) in patients’ compared with (55.36+/-16.8) in control groups and ALT level Was (20.4+/- 9.37) in patients compared with (47+/-20.1) in control groups. Additionally, there is no significant difference (p>0.05) in ALP level where it was (351.7+/-235.2) in patients with amoebic dysentery compared with (336. 13+/-204.08) in controls group. Triglyceride were also checked in patients with amoebic dysentery and the results showed that a significant difference (p<0.05) between (166.72+/-62.4) in patients and (135. 43+/-45.2) in control groups. Cholesterol level was also checked in patients and the results showed there is no significant difference (P>0.05) between (185.8+/-77.2) in patients and (160.19+/-51.3) in controls groups. In addition, some minerals were studied during the following study like Iron, Zinc, and Potassium for patients with and the results were not showed a significant difference (P>0.05) in zinc, potassium and iron where the level of iron were ( 85.24+/-16.58) in patients compared with ( 81.22+/-15.5) in control groups, while the level of zinc were (108.09+/-24.4) in patients and ( 101.76+/-24.4) in control groups , the level of potassium were (3.73+/-1.89) in patients and compared with ( 3.84+/-1.14) in control groups.

Prevalence and Antimicrobial Resistance of Campylobacter jejuni and Campylobacter coli in Wild Birds from a Wildlife Rescue Centre.

Simple SummaryWildlife may be zoonotic carriers of pathogens. The aim of this paper was to investigate the presence of Campylobacter (C.) jejuni and C. coli, which are responsible for enteric syndromes and sometimes extraintestinal diseases in humans, in wild birds housed at a wildlife rescue centre. Sensitivity to antibiotics was also investigated in the detected strains. Two hundred and nine birds belonging to 33 different species were considered in the study. Campylobacter was found in 52 birds (24.88%), mainly in omnivorous species. In terms of housing conditions, the infection rate was higher in birds housed in indoor (57.14%) than in outdoor aviaries (31.74%). Interestingly, Campylobacter was not detected in some species whose mean temperature body was below 40 °C or higher than 42.2 °C. All detected strains were C. jejuni except for three C. coli that were identified in Long-eared Owls. The most commonly found antibiotic resistance was against drugs such as trimethoprim/sulfamethoxazole, ciprofloxacin and enrofloxacin. Multi-drug resistance against two or more antibiotics was also detected. The findings of the study highlight the relevance of increasing biosecurity measures at the wildlife rescue centres to reduce health risks to staff involved in wildlife management.Climate change, excessive exploitation of agricultural land which reduces natural habitats, wildlife shooting, and the use of pesticides all cause difficulties for wildlife, with considerable numbers of animals being brought to wildlife rescue centres. Although the efforts of staff involved in wildlife management at these centres usually focus on therapeutic treatments to reintroduce them into the wild, the monitoring of pathogens that may be transmitted to humans is of relevance. Campylobacter (C.) jejuni and C. coli are frequently carried by animals without inducing clinical signs and are responsible for enteric disorders and more rarely extra-intestinal disease in humans. Farm species and poultry, in particular, are the main reservoirs of C. jejuni and C. coli, but wild animals may also be carriers. The aim of this paper was to investigate the presence of C. jejuni and C. coli in wild birds housed at a wildlife rescue centre and to evaluate the sensitivity of the detected strains to antibiotics. Campylobacter was found in 52 out of 209 (24.88%) birds from 33 different species. C. jejuni was more prevalent, while C. coli was only detected in three Long-eared Owls (Asio otus). The incidence of the infection was particularly high (72.22%) among omnivorous species. Infection rates were higher in birds housed indoors (57.14%) than outdoors (31.74%). Moreover, Campylobacter was not detected in species whose mean temperature body is below 40 °C or higher than 42.2 °C. The most common antibiotic resistance in the tested strains was against trimethoprim/sulfamethoxazole, ciprofloxacin and enrofloxacin. In addition, multi-drug resistance was also found. The results highlight the need to increase biosecurity measures at rescue centres so as to reduce health-related risks to workers involved in wildlife management.

Molecular diversity for Entamoeba histolytica virulence factor genes isolated from patients with amoebic dysentery

Entamoebahistolytica is a parasitic protozoan that caused amoebiasis, a diseases which infects the liver and colon and spread all over the world. E.histolytica is causing the death of human cells and leading to develop invasion, and ulceration of the intestine. However, amoebic liver abscess(ALA) considers as major common extraintestinal disease caused by E.histolytica.The aims of this study, was to detect E. histolytica by polymerase chain reaction (PCR), and to differentiate it from other amoeba species in a stool samples of human. Study the pathogenicity of E. histolytica in human through determining the presence of virulence factors like cysteine protease, amoebapore and Gal/lectin. A total of 100 stool samples were collected from patients with amoebic dysentery and then examined microscopically to confirm the presence of E. histolytica and other Entamoeba species, 72 ( 72%) out of 100 examined samples with E.histolytica were positive by PCR and 28(28%) were negative. The positive samples with PCR have been submitted to detect the virulence factors of E.histolytica by PCR and the results showed that the total of 72(100%)were positive with cysteine proteases gene, shown 62(86.11%) were positive with amoebapore and 65(90.27) were positive with lectin. Gene sequence for cysteine protease, amoebapore and lectin in local E. histolytica human isolates showed the nucleotide alignment similarity and substitution mutations in all of cysteine protease, amoebapore and Gal/GalNAc lectin. Phylogenetic tree analysis based on cysteine protease gene partial sequence in local E.histolytica human isolates that used for genetic variation analysis showed genetic closed related to NCBI-BLAST E.histolytica Japan strain (AK421547.1) at total genetic changes (0.0060-0.0010%), while Phylogenetic tree analysis based on amoebapore B gene partial sequence in local E.histolytica human isolates that used for genetic variation analysis showed genetic closed related to NCBI-BLAST E.histolytica, Germany strain (X76904.1) at total genetic changes (0.0060-0.0010%). Phylogenetic tree analysis based on Gal/GalNAc lectin gene partial sequence in local E. histolytica human isolates that used for genetic variation analysis showed genetic closed related to NCBI-BLAST E.histolytica Bangladesh strain (AF501280.1) at total genetic changes (0.0060-0.0020.

Multi-omics analysis to characterize molecular adaptation of Entamoeba histolytica during serum stress.

Entamoeba histolytica is responsible for dysentery and extraintestinal disease in humans. To establish successful infection, it must generate adaptive response against stress due to host defense mechanisms. We have developed a robust proteomics workflow by combining miniaturized sample preparation, low flow-rate chromatography, and ultra-high sensitivity mass spectrometry, achieving increased proteome coverage, and further integrated proteomics and RNA-seq data to decipher regulation at translational and transcriptional levels. Label-free quantitative proteomics led to identification of 2344 proteins, an improvement over the maximum number identified in E. histolytica proteomic studies. In serum-starved cells, 127 proteins were differentially abundant and were associated with functions including antioxidant activity, cytoskeleton, translation, catalysis, and transport. The virulence factor, Gal/GalNAc-inhibitable lectin subunits, was significantly altered. Integration of transcriptomic and proteomic data revealed that only 30% genes were coordinately regulated at both transcriptional and translational levels. Some highly expressed transcripts did not change in protein abundance. Conversely, genes with no transcriptional change showed enhanced protein abundance, indicating post-transcriptional regulation. This multi-omics approach enables more refined gene expression analysis to understand the adaptive response of E. histolytica during growth stress.

Isolated Crohn's Colitis: Is Localization Crucial? Characteristics of Pediatric Patients From the CEDATA-GPGE Registry.

IntroductionPediatric patients with inflammatory bowel disease (IBD) are classified into Crohn's disease (CD), ulcerative colitis (UC), and unclassifiable (IBD-U). However, data provide evidence that ileal CD (L1) is distinct from colonic CD (L2). The aim of this study was to investigate the clinical features of isolated Crohn's colitis in a pediatric population.Material and MethodsChildren who were prospectively included in the CEDATA–GPGE registry on diagnosis were compared according to the diagnosis of CD with L2 vs. L1 and ileocolonic (L3) involvement pattern as well as IBD-U and UC. The clinical significance of L2 was investigated with regard to extraintestinal manifestations, treatment, surgery, and disease activity.ResultsFifty-two patients with L2 CD at a median age of 13.4 years (±3.8 SD) were compared with 182 L1 (13.8 ± 2.9 SD), 782 with L3 (12.8 ± 3.3 SD), 653 with UC (12.7 ± 3.8 SD), and 111 patients with IBD-U (11.9 ± 4.7 SD). Bloody stools at diagnosis were more common in L2 (44%) than in L1 (19.7%) and L3 (28.8%), but not as common as in UC (66.5%) and IBD-U (61.3%). Fewer CD patients with L2 (10.2%) received exclusive enteral nutrition therapy (EEN) as induction than patients with L1 (34.3%) and L3 (33.3%). After induction therapy, 42.3% of patients with L2 received immunosuppressants and 21% biologicals during follow-up (L1 56.5/10.5%; L3 59/21%; CU 43.5/11.9%; IBD-U 26.1/12.6%). Extraintestinal manifestations were more frequent in L2 (23.1%) vs. L1 (18.7%), L3 (20.2%), CU (15.8%), and IBD-U (11.7%). The number of patients requiring surgery did not differ within the CD subgroups and was significantly lower in UC and IBD-U. Perianal fistula surgery was significantly more common in L2 (44%) than in L1 (4.8%) or L3 (21.7%). In addition, the frequency of surgery for perianal abscesses was also more frequent in L2 (55.6%) than in L1 (12.7%) or L3 (38.4%).ConclusionsThe consideration of pediatric Crohn's colitis as a distinct disease seems necessary as it is characterized by extraintestinal manifestations (EIMs) with mainly joint involvement and perianal fistulas or abscesses requiring surgery and biologic therapy. Thus, colonic Crohn's disease may have an influence on the therapeutic stratification and should be addressed in further studies.

A PROSPECTIVE STUDY OF ROLE OF MDCT IN EVALUATION OF COLORECTAL LESIONS WITH HISTOPATHOLOGICAL CORRELATION

Introduction: Multidetector computed tomography (MDCT) is increasingly useful technique in evaluation of the intestinal diseases, which allows evaluation of bowel diseases as well as extra-intestinal disease [1]. Thickening of the bowel wall is the commonly identied abnormality on CT in case of colorectal lesions [2]. Colorectal lesions can present as a mass or focal/diffuse bowel wall thickening, which may be associated with perienteric abnormalities. MDCTprovides images of the bowel wall and extra colonic tissues in one setting. MDCTprovides rapid acquisition with thinner collimation, allowing for multiphase studies with improved resolution [3]. Purpose: Present study aimed to characterize wall thickening in patients with colorectal lesions as either benign or malignant based on criteria specic to CTimaging using histopathology as gold standard. Material and methods: This prospective, correlative study consisted of people who were suspected to have large bowel lesions and referred to radiodiagnosis department at apollo hospital, hyderabad. Once a bowel wall thickening was detected, their radiologic features were analyzed by using criteria specic to CT imaging and characterized as either benign or malignant. Finally, the radiological diagnosis was correlated with histopathology. Results:Atotal of 75 participants were included (mean age: 61-70; 42[56%] men; 33[44%] women).Of these, all 56 malignant lesions and 17 of 19 benign lesions were correctly diagnosed in CT with a sensitivity of 96.43% and 78.95% respectively (P= .0001). Except 2 cases with inammatory lesions, who were diagnosed as malignant in CT. Conclusion: MDCThas a high predictive value in the diagnosis and differentiation of benign and malignant lesions of the large bowel.

Updates on the diagnosis and management of celiac disease.

Celiac disease is a chronic autoimmune enteropathy affecting about 1% of the population. Gluten ingestion triggers an immune response in genetically susceptible patients, resulting in intestinal and extraintestinal disease manifestations. Current recommendations for diagnosis include serology for celiac-specific antibodies to transglutaminase, endomysium, and deamidated gliadin, and IgA serology. New highly accurate point-of-care tests can efficiently screen for celiac disease and improve the diagnostic timeframe. Definitive diagnosis is most commonly made via biopsy of the small bowel showing villous atrophy. A gluten-free diet with micronutrient supplementation is the only recommended treatment for celiac disease. Primary care providers must be able to recognize screening indications, refer patients appropriately, and provide proper patient education and follow-up.

Fatigue is a systemic extraintestinal disease manifestation largely independent of disease activity, chronicity, and nutritional deficiencies in inflammatory bowel disease on biologics

Background Fatigue is a common symptom reported by patients with chronic immunoinflammatory diseases and with profound negative implications on health-related quality of life. This study aimed to delineate underlying components contributing to fatigue in patients with inflammatory bowel disease (IBD) receiving biologic therapy. Methods Cross-sectional questionnaire study of all patients with IBD receiving any biologic therapy at a tertiary IBD center. Fatigue was assessed by Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F). Disease activity and quality of life were evaluated by generic questionnaires. Principal component analysis (PCA) was used to identify components of variables explaining fatigue. Results Three hundred patients with IBD were included. Moderate-to-severe fatigue defined as FACIT-F ≤ 39 was present in half of the included patients. PCA condensed variables associated with fatigue into three main components contributing to 49% of observed fatigue. The first component, explaining 21% of fatigue, included factors related to disease chronicity, e.g., long disease duration, high number of previously used biologic therapies, presence of previous intestinal surgery, and increasing age. The second component explained 14% of fatigue and comprised disease activity-related aspects, e.g., disease activity indices and C-reactive protein. The third explained 14% of fatigue and comprised various nutritional deficiencies. Conclusion Fatigue can partly be explained by chronicity, disease activity, and nutritional deficits. However, the cause of fatigue is unexplained in approximately half of the patients with IBD supporting that fatigue can be an independent, systemic extraintestinal disease manifestation in IBD.

Relationship between CRISPR sequence type and antimicrobial resistance in avian pathogenic Escherichia coli

Avian pathogenic Escherichia coli (APEC) is a primary cause of extraintestinal disease and respiratory infections in chickens; therefore, various antimicrobials applied via mass medication in farms to control APEC in Korea. In this study, we analyzed the relationship between CRISPR sequence type and antimicrobial resistance (AMR) in APEC isolates. Based on spacer distribution, a total of 103 CRISPR-positive APEC isolates were classified into 25 E. coli sequence types (ESTs), largely into two clusters that were correlated with phylogenetic groups: isolates appearing to have CRISPR 1 and/or 2 (93.2 %) and those having CRISPR 3 and 4 (6.8 %). Moreover, ESTs were divided into three AMR pattern-based groups: cephems-resistant group, non-cephems-resistant group, and antimicrobial sensitive group. There were significant differences among the groups (p < 0.05). Sixteen of the 25 ESTs had a significantly higher distribution of multidrug-resistant (MDR) isolates than the other ESTs (p < 0.05), and the ratio of MDR isolates was significantly higher than that of non-MDR isolates in the CRISPR 1 and 2 arrays (p < 0.05). A total of 9 protospacers were identified with protospacer, with protospacer 1 in CRISPR 1 being the most prevalent among the isolates (41.7 %). The protospacers of CRISPR 1 and 2 loci were associated with protection against external invaders such as bacteriophage or endogenous gene regulation. However, each protospacer of the CRISPR 3 and 4 loci originated from genes associated with AMR plasmids. These results indicate that CRISPR sequence type can improve AMR bacteria and enhance strategies for tackling the complexity of AMR in bacterial pathogens.