BACKGROUND: Pediatric patients with Inflammatory Bowel Disease (IBD) undergo costly and invasive investigations to diagnose and treat their chronic disease. To that end, it is important for researchers and physicians to continue to work to find novel tools to improve diagnosis and treatment processes. One of the main challenges is differentiating between the two main forms of IBD, Crohn disease (CD) and ulcerative colitis (UC). Physicians currently rely on a combination of endoscopic evaluations, mucosal biopsies, radiology studies, and biochemical testing to assess for the presence and extent of inflammation in the gastrointestinal (GI) tract. Serologic biomarkers can be useful to some extent, but changes in these markers do not typically reflect disease specific to the GI tract, or the state of inflammation related to a patient's IBD. In contrast, fecal biomarkers have the unique potential to provide specific information about inflammation in the GI tract. While serum antibody levels have been well studied for use in the diagnosis of patients with IBD, fecal antibody levels and anti-saccharomyces cerevisiae antibody (ASCA) in particular, have not been extensively evaluated. In this study, we will assess the dynamic range of fecal ASCA levels in acute and convalescent fecal samples collected from children and adolescents with CD and UC. METHODS: We recruited pediatric patients from inpatient and ambulatory settings at the Gastroenterology Program at Boston Children's Hospital. Patients had a diagnosis of either CD or UC. We collected baseline stool samples during a point of active disease, and follow-up samples three to six months later during a point of inactive disease. Samples were analyzed for fecal ASCA as well as lactoferrin (FLA), another marker of inflammation that can be measured in the stool. RESULTS: In patients with CD, fecal ASCA levels were significantly higher during active disease than during inactive disease. Additionally, fecal ASCA levels were higher in patients with CD than in patients with UC, regardless of disease activity. When compared to FLA, ASCA was shown to differentiate between CD and UC, with greater changes in the level of fecal ASCA (active - inactive) correlating with a diagnosis of CD. In patients with CD, FLA levels were significantly higher in the context of active disease than in inactive disease. However, FLA did not differentiate between CD and UC. CONCLUSIONS: Our results suggest that fecal ASCA may be a new marker of inflammation in the GI tract. Unlike FLA, changes in fecal ASCA levels appear more dynamic in patients with CD. Future studies are required to further demonstrate both how changes in fecal ASCA may help physicians distinguish between different forms of IBD as well as how measurement of fecal ASCA may help assess disease activity and response to therapy in patients with CD.

INTRODUCTION: The inflammation observed in patients with IBD can negatively impact the intake or absorption of vitamin D. This can increase the risk of disease relapse, impact patients’ quality of life, and increase the risk of IBD related surgeries. In addition to the traditional observation that vitamin D deficiency may be a comorbid manifestation of IBD, there is now growing evidence pointing to serum vitamin D levels as a pathogenic factor contributing to the initiation and propagation of mucosal inflammation in patients with IBD. It is well-established that variation in clinical practice leads to less optimal outcomes in any clinical setting. The relative scarcity of clinical and translational studies is even more pronounced in the pediatric population. OBJECTIVES: The primary objective of this study is to quantify the prevalence of clinician assessment of vitamin D levels in pediatric patients with IBD. We will also look at this behavior in subpopulations and compare their vitamin D status. It is secondary for this study to also describe variations in physician practices with respect to the testing and treatment of vitamin D deficiency at a single tertiary care IBD Center. METHODS: We conducted a retrospective cohort study on consecutive patients with UC, CD, and ID, that were followed in the ambulatory program in the Center for Inflammatory Bowel Disease at Boston Children’s Hospital from 1/1/2014 to 12/31/2014. We identified 498 patients and collected their demographic information, serologic testing, and physician prescribing behavior. RESULTS: Out of the entire population, 64% of the patients were vitamin D deficient (vitamin D level below 32 ng/ml). 24% of the patients received vitamin D supplementation. Vitamin D deficiency was less prevalent in patients with UC than those with CD, with an OR of 0.64 (95% CI 0.43-0.94). Out of the ones receiving supplementation, 37% of them were deficient. In terms of physician practice trends, 62% of the patients were not formally prescribed supplementation. 14.5% of those who were prescribed supplementation were receiving 50,000 IU weekly, and the rest receiving 400 – 2,000 IU daily. Patients with vitamin D levels below 20 ng/ml were more likely to receive the high dose vitamin D prescription (OR 11.5) than those with levels between 20 and 30 ng/ml (OR 5.7). CONCLUSIONS: Our study suggests that despite high prevalence of vitamin D deficiency in pediatric patients with IBD, there is a lack of consensus with respect to the assessment of vitamin D levels and consistency in prescribing vitamin D supplementation. With the potential role that vitamin D plays in IBD pathology and suggestions of the therapeutic effects of vitamin D supplementation, further studies are needed to explore this area.

INTRODUCTION: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The inflammation observed in IBD negatively impact absorption of iron. This could lead to increased hospitalizations, affect growth and development, and decrease overall quality of life. This is especially pronounced in the pediatric population. The screening and treatment of iron deficiency anemia (IDA) varies between centers, and as a result, roughly 40-60% of pediatric IBD patients are iron deficient. OBJECTIVES: The objective of this study is to assess the efficacy and safety profile of intravenous and enteral iron therapy in a population of iron deficient patients with IBD. The secondary aim of this study is to determine if oral or intravenous iron therapy can improve hematologic and iron parameters. We will also examine the longitudinal changes in gastrointestinal (GI) symptoms and quality of life in patients receiving oral and intravenous iron supplementation. METHODS: We conducted a prospective cohort study in pediatric patients with IBD admitted to the inpatient GI service at Boston Children’s Hospital from 09/05/2017 to 03/05/2018. Forty-six IBD patients were screened, and twenty-nine (63%) were identified as iron deficient and were consented for data collection through chart review and administration of the IMPACT-III quality of life questionnaire. RESULTS: Out of the twenty-nine IBD patients, eighteen (62%) received intravenous iron, seven (24%) received oral iron, and four (14%) were untreated and served as controls. The mean change in hemoglobin in patients receiving parenteral, oral, or no iron therapy was 1.6g/dl±0.5, 1.1g/dl±0.4, and 0.2g/dl±0.5, respectively. The change in hemoglobin was significant between the parenteral and oral iron group (P<0.05). The mean change in health-related quality of life scores in patients receiving parenteral or oral iron therapy was 11.6±11.4 and 3.8l±7.5, respectively. CONCLUSION: Our study demonstrates that intravenous iron therapy was more efficacious than oral iron in improving hematologic and iron parameters in IBD patients. This improvement was concomitant with higher scores on the IMPACT-III quality of life questionnaire, suggesting that iron supplementation improves health-related quality of life in IBD patients with iron deficiency anemia.

Bakgrund: Irritable Bowel Syndrome är en långvarig och återkommande sjukdom karakteriserad av abdominell smärta och förändrat tarmtömningsmönster. Patofysiologin anses vara komplex och multifaktorell. Viktigaste komponenten i etiologin är en störning i tarm-hjärna-axeln. Sjukdomsincidensen är i väst 7-30% och globalt 12%. Sjuksköterskan bör ha kunskap om både patofysiologin, etiologin och patienters erfarenheter av att leva med IBS för att kunna erbjuda personcentrerad vård. Syfte: Syftet var att belysa patienters erfarenheter av att leva med Irritable Bowel Syndrome. Metod: En litteraturstudie som baserades på 12 kvalitativa vetenskapliga artiklar. Artiklarna kvalitetgranskades och en dataanalys utfördes genom innehållsanalys. Resultat: Från innehållsanalysen framkom fyra kategorier och nio subkategorier; fysiska symptom (smärta, fatigue, och påverkat sex- och samliv), emotionell påverkan (rädsla, skuld och skam), mötet med sjukvården (bristande stöd, givande vårdmöten) och hantering av sjukdomen (egenvård, anpassningar). Konklusion: Förutom fysiska symtom och en emotionell påverkan framkom patienterfarenheter av en kamp för respekt från sjukvården. Sjuksköterskan bör vara medveten om problematiken, lyssna på patienters erfarenheter och använda kunskapen för att förmedla en personcentrerad omvårdnad. Sjuksköterskan har ett ansvar att vara ajour med den senaste forskningen för att kunna undervisa och informera patienter som en del av evidensbaserad omvårdnad. Nyckelord: Egenvård, IBS, Irritable Bowel Syndrome, långvarig sjukdom, omvårdnad, patienterfarenheter, personcentrerad vård. / Background: Irritable Bowel Syndrome is a long-standing periodical disorder characterized by abdominal pain and altered bowel habits. The pathophysiology is considered to be complex and due to a multitude of factors. The most important component in the etiology is a dysfunction in the gut-brain-axis communication. The incidence of the disorder is 7-30% in the West and 12% globally. A nurse should have knowledge about both pathophysiology, etiology and patients’ experiences from living with IBS in order to offer a person centered care. Aim: The aim was to illuminate patients’ experiences from living with Irritable Bowel Syndrome. Method: A literature review based on 12 qualitative scientific articles. The articles underwent a quality audit and data analysis was carried out through content analysis. Results: The content analysis generated four categories and nine sub-categories; physical symptoms (pain, fatigue, and altered sex life), emotional effects (fear, guilt and shame), The encounter with Healthcare Services (lack of support, rewarding healthcare encounters) and management of the disorder (self-care, adaptations). Conclusion: Except from physical symptoms and emotional effects, patient experiences revealed a struggle to obtain respect from the Healthcare Services. The nurse should be aware about these experiences, be able to listen to patients’ experiences and use this knowledge to mediate a person centered care. The nurse has a responsibility to stay updated with the latest scientific research in order to teach and inform patients as part of evidence based nursing practice.Keywords: IBS, Irritable Bowel Syndrome, longstanding disorder, nursing, person centered care, patient experiences, self-care.

Case Report: Krukenberg tumor is a metastatic adenocarcinoma of the ovary that classically arises from the gastrointestinal tract, most often as a metastasis from the stomach as the primary origin, followed by colon. Krukenberg tumors are very rare malignant tumors of the ovary, only accounting for 1-2% of all ovarian malignancies. They tend to present with bilateral involvement. The most common presenting symptoms are abdominal pain, distention, and ascites, secondary to the large ovarian masses. Postmenopausal vaginal bleeding is a rare presenting symptom of a Krukenberg tumor. The diagnosis is commonly delayed until late in the disease progression. We present a case of a 77-year-old woman with stage IV metastatic adenocarcinoma of lower GI with mesenteric involvement and pulmonary nodules. Her disease was confirmed by mesenteric mass biopsy and was histologically CK20 positive, CDX positive, and CK7 negative. She underwent eighteen rounds of palliative chemotherapy with oral capecitabine (Xeloda) over the course of fifteen months. Sixteen months after the initial diagnosis, imaging uncovered a new cystic pelvic mass measuring 15x13x12 cm, decreased mesenteric mass, increasing liver lesion, metastasis to the left adrenal gland, and minimal ascites. She has had vaginal bleeding. Patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy and small bowel resection by gynecological oncologist. The left ovary was involved by metastatic adenocarcinoma, 15 cm, consistent with small bowel origin. The small bowel resection showed adenocarcinoma, 3.3 cm in size with serosal invasion arising in an adenoma. Patient is planned for chemotherapy with irinotecan in palliation. Our case demonstrates a rare case of small bowel adenocarcinoma later presenting as a Krukenburg tumor.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22329号 / 医博第4570号 / 新制||医||1041(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 坂井 義治, 教授 斎藤 通紀, 教授 岩田 想 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Risk factors of manifestation and course of treatment of inflammatory bowel disease in children Typical Crohn's disease (CD), Crohn's colitis, typical and atypical ulcerative colitis (UC) are currently perceived as different forms of inflammatory bowel disease (IBD). The incidence of IBD is increasing worldwide in both the adult and paediatric populations. Although the role of genetic background and environmental factors in the development of these diseases is known to some extent, the exact cause of IBD has still not been determined. Comprehensive care requires a precise and data-driven approach to minimize the risk of complicated disease course and the development of disease-related and/or treatment-associated complications. The main goal of this work is to identify new predictive factors affecting individual areas of care of paediatric patients with IBD. The range of clinical situations addressed in this work includes the possibility of predicting the diagnosis, the generally complicated disease course, the response to a particular therapeutic regimen, the development of side effects associated with the therapeutic procedure and the patient's adherence to the treatment. Part of the original works was done in a retrospective design, part as prospective observational studies and two of the original works...

Les maladies inflammatoires chroniques de l’intestin (MICI), qui comprennent les deux principales formes, la maladie de Crohn (MC) et la rectocolite hémorragique (RCH), sont caractérisées par une inflammation chronique et récurrente de la muqueuse intestinale, ayant un impact considérable sur la qualité de vie. À l'heure actuelle, la prise en charge thérapeutique de la MC n'est pas curative et un tiers des patients ne réagissent pas aux traitements biologiques et aux immunosuppresseurs. Par conséquent, de nouvelles stratégies pour traiter cette maladie sont fortement attendues. La dérégulation de l'interaction entre d'une part les facteurs génétiques et le système immunitaire de l'hôte, et d'autre part le microbiote intestinal et les facteurs environnementaux, est impliquée dans le développement des MICI. Cette perturbation entraîne effectivement une augmentation de la perméabilité intestinale et une inflammation persistante. Restaurer le microbiote «dysbiotique» et les fonctions intestinales altérées représentent donc une thérapeutique alternative intéressante. De ce fait, les probiotiques sont une option intéressante et ont été utilisés avec succès chez des patients souffrant de pouchite et de RCH. Cependant, leur effet protecteur est clairement souche-dépendant et plusieurs souches probiotiques bien connues n’ont pu conduire à un résultat clinique probant, en particulier chez les patients souffrant de MC. Le décryptage des mécanismes moléculaires sera donc la clé pour permettre une recommandation efficace des probiotiques dans le traitement ou la prévention des MICI. La sélection de souches basée sur des critères de sélection bien définis et en utilisant des modèles bien maitrisés est indispensable à ce processus. L'objectif principal de cette thèse était de sélectionner des lactobacilles et des bifidobactéries parmi une collection de souches françaises et libanaises, capables de présenter des propriétés protectrices contre les MICI, en se concentrant sur leurs capacités immuno-régulatrices et leurs capacités à renforcer la barrière épithéliale. Des approches in vitro ont été utilisées pour sélectionner des souches ayant une activité anti-inflammatoire et également capables d'améliorer la fonction de la barrière intestinale. Cinq souches ont été identifiées présentant des caractéristiques différentes, mais avec un potentiel thérapeutique élevé. Deux souches se sont révélées hautement protectrices dans deux modèles différents de colite aiguë et de colite de bas grade. Nos résultats ont confirmé en outre l'hypothèse selon laquelle la capacité des souches à atténuer l'inflammation est en partie due à l'amélioration de la barrière intestinale et à la restauration des protéines de jonction serrés.Un nombre croissant d’études génétiques ont prouvé que l’autophagie peut affecter plusieurs aspects de la réponse immunitaire des muqueuses, notamment via l’élimination de bactéries intracellulaires, la sécrétion de peptides antimicrobiens, la production de cytokines pro-inflammatoires et la présentation des antigènes. Par conséquent, l'autophagie peut être considérée comme un mécanisme de régulation clé impliqué dans la physiopathologie de la MC. Nous avons donc évalué la capacité des souches à activer cette voie et montré que les souches sélectionnées étaient en effet capables d’induire une activation de l’autophagie dans des cellules dendritiques murines. Nous avons démontré in vitro que le blocage de l'autophagie pouvait diminuer la capacité des souches à induire la sécrétion d'IL-10, cytokine anti-inflammatoire et, inversement, à exacerber la sécrétion d'IL-1β, cytokine pro-inflammatoire. Nous avons pu confirmer, à l'aide d'un modèle murin de colite, que la capacité protectrice d’une souche impliquait la machinerie autophagique, et nous avons pu mettre en évidence le rôle des cellules dendritiques dans ce processus [...] / Inflammatory bowel disease (IBD), including the two main types, Crohn’s disease (CD) and ulcerative colitis (UC), is characterized by chronic, relapsing inflammation of the gut mucosa with considerable impact on the quality of life. At present, the therapeutic management of CD is not curative and one third of patients fails to respond to current biologicals and immunosuppressive drugs. Therefore new strategies for treating this disease are imperative.The deregulation of the normal interplay between the genetics and immune system of the host on the one hand, and the gut microbiota and environmental factors on the other hand, is known to be associated with the development of IBD, as this disturbance is leading to increased intestinal permeability and persistent inflammation. Restoring the “dysbiotic” microbiota and the impaired intestinal functions represent an attractive therapeutic alternative. Probiotics represent therefore an interesting option and have been used quite successfully in patients suffering from pouchitis and UC. However, their protective effect is clearly strain-dependent and several well-known probiotic strains failed to fulfill the expected clinical outcome, especially when applied in CD. Deciphering the molecular mechanisms will be the key to the recommendation of probiotics for the treatment or prevention of IBD. Selecting strains on well-defined selection criteria and using well-studied models is indispensable to this process.The main objective of this thesis was first to select lactobacilli and bifidobacteria from a collection of French and Lebanese strains that exhibited protective properties against IBD, focusing on their immunoregulatory capacities and their capacities to strengthen the epithelial barrier.In vitro approaches were used to select strains with anti-inflammatory activity and also able to enhance intestinal barrier function. Five strains were identified with different characteristics, but entailing a high potential for the management of IBD. Two strains, e.g. were found to be highly protective in two different models of acute and low grade colitis. Our results furthermore support the hypothesis that the capacity of the strains to alleviate inflammation is in part mediated by the improvement of the intestinal barrier and the restoration of tight junction proteins.A growing number of genetic studies provided strong evidence that autophagy machinery can affect several aspects of the mucosal immune response, including intracellular bacterial killing, antimicrobial peptide secretion, pro-inflammatory cytokine production and antigen presentation. Therefore, autophagy can be considered as a key regulator mechanism most likely involved in the physio-pathogenesis of CD.We therefore evaluated the capacity of the strains to activate this pathway and showed that the selected strains were indeed able to induce autophagy activation in dendritic cells. We demonstrated in vitro that blocking the autophagy machinery can abolish the capacity to induce the secretion of the anti-inflammatory cytokine IL-10 after immune cell stimulation, while exacerbating the secretion of the pro-inflammatory cytokine IL-1β. We could confirm, using a murine model of colitis, that the protective capacity of the selected strains indeed involves autophagy mechanisms, and we could highlight the role of dendritic cells in this process. We therefore propose here that autophagy is a novel mechanism through which probiotics can exhibit their immunoregulatory capacities.

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Bakgrund: Inflammatorisk tarmsjukdom (IBD) är ett samlingsnamn för de kroniska tarmsjukdomarna Crohns sjukdom (CD) och Ulcerös kolit (UK). Det gemensamma för de två sjukdomarna är att de löper i skov med försämringsperioder och långa besvärsfria perioder samt att de drabbar relativt unga personer. Det är viktigt att sjuksköterskan kan stödja dessa individer genom evidensbaserad och personcentrerad vård för att kunna ge en så god omvårdnad som möjligt.  Syfte: Beskriva individers upplevelse av att leva med inflammatorisk tarmsjukdom Metod: En litteraturöversikt valdes som metod. Artikelsökningen genomfördes i databaserna CINAHL Complete och PubMed. De begränsningar som gjordes i databassökningarna var vetenskapliga originalartiklar, skrivna på engelska, genomgått peer-review och publicerade mellan 2009-2019. Totalt inkluderades elva artiklar i resultatet, av dessa var tio artiklar kvalitativa och en var kvantitativ. Resultat: Resultatet visade att individerna upplevde att sjukdomen påverkade deras arbetsliv, sociala liv, känslor och identitet. Deras möte med hälso- och sjukvården påverkade personernas förtroende för vården samt deras vilja att söka vård framöver. Det visades även att personer med inflammatorisk tarmsjukdom genomgick en transitionsperiod efter deras diagnos. Hur personerna upplevde att leva med IBD påverkades av om de för tillfället befann sig i ett skov eller nyligen fått diagnosen. De personer som befann sig i ett skov eller nyligen fått diagnosen hade en övervägande negativ syn.  Diskussion: Resultatet diskuterades utifrån Katie Erikssons teori om lidande och hälsa. Författarna resonerade om individernas negativa påverkan kunde kopplas till stigman av sjukdomen. De diskuterade även angående den långsiktiga påverkan av frånvaron från arbetet och sociala sammanhang. Författarna fann i resultatet att individer med IBD upplevde sjukdomen olika i sin vardag beroende på hur länge de haft sjukdomen och vilken inställning de har gentemot sin IBD. Därmed bör vården anpassas efter de individuella behoven för att säkerställa att insatserna främjar hälsan. / Background: Inflammatory bowel disease (IBD) is a chronic illness that includes Crohn´s disease (CD) and ulcerative colitis (UK). Both diseases have in common that they have relapse and periods with improvement. The diseases effects relatively young people. It is important that the nurse can support these individuals through evidence based and person-centred care in order to provide the best possible care. Aim: Describe individuals experiences of living with inflammatory bowel disease  Method: A literature review was chosen as the method. The article search was carried out in the databases CINAHL complete and PubMed. The limitations made in the database searches were scientific original articles, written in English, peer-reviewed and published over the last ten years. A total of eleven articles was included in the result, of which ten were of qualitative design and one was quantitative design. Results: The results showed that the individuals experienced that the disease affected their working life, social life, feelings and identity. Their meeting with healthcare services affected their trust in the care and their willingness to seek care in the future. It was also shown that people with inflammatory bowel disease underwent a transition period after the diagnosis. How the individuals experienced living with IBD was affected by whether they were relapsing or in remission. People currently in a relapse had a more negative view of the disease.  Discussion: The result was discussed based on Katie Eriksson´s theory of suffering and health. The authors reasoned if the negative impact of the individuals could be linked to the stigma and shame of the disease. They also discussed the long-term impact of the absence from work and social activities. The authors found in the results that individuals with IBD experienced the disease differently in their daily lives depending on how long they had the disease and what attitude they had towards their IBD. The care should be adapted to the individual needs to ensure that the efforts promotes health.