Transmural Inflammation Research Articles

Creeping fat formation and interaction with intestinal disease in Crohn's disease

Creeping fat (CrF), also known as fat wrapping, is a significant disease characteristic of Crohn's disease (CD). The transmural inflammation impairs intestinal integrity and facilitates bacteria translocation, aggravating immune response. CrF is a rich source of pro-inflammatory and pro-fibrotic cytokines with complex immune microenvironment. The inflamed and stricturing intestine is often wrapped by CrF, and CrF is associated with greater severity of CD. The large amount of innate and adaptive immune cells as well as adipocytes in CrF promote fibrosis in the affected intestine by secreting large amount of pro-fibrotic cytokines, adipokines, growth factors and fatty acids. CrF is a potential therapeutic target for CD treatment and a promising bio-marker for predicting response to drug therapy. This review aims to summarize and update the clinical manifestation and application of CrF and the underlying molecular mechanism involved in the pathogenesis of intestinal inflammation and fibrosis in CD.

Colorectal surgical management of colitis induced by vasculitis in the absence of inflammatory bowel disease: a case report and literature review.

Colitis caused by vasculitis is a rare and poorly understood pathology. Little evidence exists on its clinical presentation, path to diagnosis, and surgical management. In this report, we present a case report and literature review. A healthy 20-year-old male patient presented with hemorrhagic colitis requiring total colectomy with end ileostomy. Pathological examination showed pancolitis with multiple ulcers, transmural inflammation, hemorrhage, and microvascular thrombosis. Extensive serological testing revealed elevated cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and eosinophilia, leading to a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and vasculitis-induced colitis. A literature review was subsequently conducted. Nineteen studies were found documenting vasculitis-induced colitis in the absence of inflammatory bowel disease (IBD). Systemic signs of vasculitis, hemorrhagic colitis, and progression to fulminant colitis were present. Of all patients, 40.0% required colorectal surgery and 62.5% of those patients received a stoma; 25% underwent emergency surgery following failed immunosuppression. All cases relied on clinical correlation with serology and/or histopathology to reach a final diagnosis. We report a case of vasculitis-induced colitis caused by c-ANCA-positive EGPA. The review shows that vasculitis-induced colitis without IBD is an important differential that clinicians should be aware of in patients presenting with colitis.

Expression of 5-hydroxytryptamine 7 receptor in intestinal mucosa correlates with the degree of intestinal inflammation in Crohn’s disease

BackgroundCrohn’s disease (CD), an inflammatory bowel disease (IBD), is a complex and heterogeneous disease characterized by nonspecific transmural inflammation of the gastrointestinal tract. CD has a variety of potential causes with no effective treatment available yet. Current clinical laboratory findings from patients do not provide direct indication of the status of mucosal inflammation in the intestine. Recently, it has been found that intestinal inflammation is generally associated with increased levels of 5-hydroxytryptamine (5-HT), which acts as an important gastrointestinal signaling molecule in intestinal homeostasis by stimulating specific receptors. Most previous researches were carried out in vitro or with animal models, and there was a lack of authentic clinical research. In this study, clinical specimens from patients with Crohn’s disease were used to investigate the expression of 5-hydroxytryptamine 7 receptor (5-HT7R) in the induction and development of chronic non-specific inflammatory bowel disease.MethodsPatients with CD admitted to the Department of Gastroenterology in the First Affiliated Hospital of Anhui Medical University between June 2014 and January 2018 were recruited, among which 28 were in active disease and 32 were in remission. In addition, 20 patients who had no obvious abnormality by colonoscopy in the hospital during the same time period were recruited into the control group. Data of clinical disease activity (CDAI), CD endoscopic score (SES-CD) and magnetic resonance score (MaRIA) were collected from those two groups of patients. The expression and distribution of 5-HT7R were investigated and their correlations with clinical CDAI, MaRIA, and endoscopic SES-CD scores were analyzed.ResultsOur study demonstrated that 5-HT7R is expressed in intestinal neurons and CD11C-positive cells in human colon. In CD11c/CD86 double-positive cells in the bowel, 5-HT7R expression was significantly increased in the inflammatory area in the bowel of CD patients, and it was closely related to disease severity, MaRIA, and SES-CD scores.ConclusionThe expression of 5-HT7R was significantly correlated with the degree of gut inflammation in CD patients and could be a potential biomarker for disease activity and the therapeutic efficacy in patients with Crohn’s Disease.

Hematopoietic Stem Cell Transplantation in Refractory Crohn's Disease: Should It Be Considered?

Hematopoietic stem cell transplantation (HSCT) is widely used in benign and malignant hematological diseases. During the last decade, HSCT, mainly autologous, also gained increasing attention in the treatment of refractory autoimmune diseases. Crohn's disease (CD) is an inflammatory bowel disease leading to transmural inflammation potentially affecting all parts of the luminal gastrointestinal tract. Despite improving therapeutic options, including various biologics, some patients are refractory to all lines of available conservative therapy, leading to increased morbidity and reduced quality of life. Apart from surgery, HSCT might be a reasonable treatment alternative for refractory CD patients. This review aims to describe the current role of HSCT in CD and discusses the procedure, the correct patient selection, the clinical efficacy from initial remission to following relapse rates, and complications of this treatment.

S500 Long-Term Follow-Up of Esophageal Strictures in Eosinophilic Esophagitis Using Structured Esophagram Protocol

Introduction: Reversal of transmural fibrostenosis in eosinophilic esophagitis (EoE) is not well studied. Our aim was to determine the effect of medical therapy, dilation and initial diameter on esophageal lumen diameter using serial structured esophagrams over a period of years. Methods: Retrospective study of 78 patients who completed two EoE protocol esophagrams at an academic tertiary referral center 2003 to 2021. Maximum and minimum esophageal diameters were measured on images during rapid swallowing in the RAO recumbent position. EoE was diagnosed by consensus definition and classified as active using ≥15 eosinophils per high power field (hpf). Demographics, medical therapies, and endoscopic data were obtained by chart review. Change in esophageal diameter was analyzed with Wilcoxon signed rank test and reported as median, 25th percentile (Q1), and 75th percentile (Q3) values. Results: Median age at first esophagram was 36.2 and 60.3% were male. Medical therapies during last esophagram were PPI (39.5%), swallowed topical steroids (31.6%), diet elimination (13.2%), biologic therapies (1.3%), and clinical trials (1.3%). Eleven patients had dilation before the first esophagram and 33 between esophagrams without significant effect on results. Median years between esophagrams was 2.6 (Table). Median maximum diameter significantly increased by 1.0 mm (Q1: -1.0 mm, Q3: 3.0 mm) (P=0.034) independent of dilation (P=0.744). Median maximum diameter change per year significantly increased by 0.4 mm (Q1: -0.4 mm, Q3: 1.3 mm, P=0.010). The increase appeared most profound in patients starting in the lowest maximum diameter group (9-15 mm) with median increase of 3.0 mm while the highest starting maximum diameter group ( >21 mm) had further narrowing by 2.0 mm (Figure). There was no difference in maximum diameter change for patients on medical therapy compared to no therapy at second esophagram at 1.0 mm (Q1: -1.0 mm Q3: 3.0 mm) and 1.0 mm (Q1: 0.0 mm Q3: 2.0 mm) respectively (P=0.640); however, for patients in disease remission at second esophagram, there was a significant increase in maximum diameter per year compared to active disease at 0.8 mm (Q1: 0.0 mm Q3: 5.3 mm) and 0.0 mm (Q1: -0.4 mm Q3: 0.6 mm) respectively (P=0.019). Conclusion: Long term medical therapy leads to a small, but significant improvement in esophageal diameter in EoE. Whether this improvement is due to reversal of fibrosis or transmural inflammation is unclear.Figure 1.: Maximum Diameter Change Between Esophagram 1 and 2 based on starting maximum esophageal diameter. Table 1. - Esophagram Characteristics No Dilation (n=43) Dilation (n=34) P-Value Total (n=78) P-Value Median Years Between Esophagrams (Range) 2.7 (0.1-11.6) 2.4 (0.1-12.4) 2.6 (0.1-12.4) Median Maximum Diameter Change, mm 1.0 1.0 0.744 1.0 0.034 Q1, mm -1.0 0.0 -1.0 Q3, mm 2.5 3.0 3.0 Median Maximum Diameter Change Per Year, mm 0.3 0.4 0.961 0.4 0.010 Q1, mm -0.4 0.0 -0.4 Q3, mm 1.5 1.3 1.3 Median Minimum Diameter Change, mm 0.0 1.0 0.317 0.0 0.277 Q1, mm -2.0 -1.0 -1.5 Q3, mm 2.0 3.0 2.0 Median Minimum Diameter Change Per Year, mm 0.0 0.4 0.249 0.0 0.059 Q1, mm -0.7 -0.3 -0.5 Q3, mm 0.9 1.5 1.1 mm, millimeters; Q1, 25th percentile; Q3, 75th percentile

S3481 Small Bowel Obstruction Caused by Neurofibromatosis

Introduction: We report an unusual case of acute small bowel obstruction in a woman with Neurofibromatosis type 1 (NF1) caused by numerous gastrointestinal neurofibromas. NF1 is an autosomal dominant genetic disorder that is classically characterized by the development of cutaneous neurofibromas, but less commonly, it is associated with a variety of gastrointestinal tumors including plexiform neurofibromas, mucosal ganglioneuromas, and gastrointestinal stromal tumors [1]. Up to 25% of patients with NF1 are reported to have a gastrointestinal tumor of some kind, but it is estimated that only 5% develop gastrointestinal symptoms including bleeding, abdominal pain, abdominal distention, constipation, and very rarely small bowel obstruction (SBO) [2]. Case Description/Methods: Patient is a 26-year-old female with a past medical history significant for poorly controlled Crohn’s disease who presented due to abdominal pain and hematochezia. Physical exam was notable for pain in the right upper quadrant. CT abdomen and pelvis with contrast showed high-grade small bowel obstruction with tethering of small bowel centrally concerning for active Crohn’s disease. Colorectal surgery was consulted and performed laparotomy with ileocecectomy and end ileostomy formation. The terminal ileum and cecum were sent to pathology for further analysis. The pathology report showed “wall thickening with extensive neural hyperplasia (ganglioneuromatosis) and plexiform neurofibromas. The features seen in the resection favor intestinal neurofibromatous proliferations with secondary chronic mucosal changes. There is no transmural inflammation, granulomas or other features typically seen in Crohn's disease.” (Figure) Discussion: This patient was initially thought to have SBO due to Crohn’s disease flare, but pathology report showed that the underlying cause was secondary to plexiform neurofibromas. A systematic review of the literature shows that this is a rare finding as only 25 cases were identified from 1972 to 2013 of NF1 patients who underwent laparotomy for SBO [2]. SBO is a rare but possible manifestation of NF1.Figure 1.: CT Abdomen / Pelvis showing high grade small bowel obstruction.

S771 Impact of Early Biologic Therapy in Real-World Cohort of Crohn’s Disease Patients

Introduction: Crohn’s disease (CD) is characterized by transmural inflammation and ongoing inflammatory activity, which over time results in the accumulation of bowel damage, which may lead to complications such as strictures, fistulas/fissures, and abscesses, as well as disability. Optimally controlling inflammation early in the disease course of CD, during the ‘window of opportunity,’ may be the best way to change disease course. Recent evidence and clinical practice guidelines suggest that early biologic therapy is preferred in treating moderate to severe CD. Early use of biologic therapy and achievement of mucosal healing can contribute to disease course modification. We hypothesize that significantly more CD patients treated within 2 years of diagnosis will achieve clinical remission and have less CD-related complications than those treated 2 or more years after diagnosis. Methods: We conducted a retrospective cohort study of CD patients treated within the Military Health System to assess the relationship of timing of initiation of biologic therapy with the control of CD. Data was collected from January 1, 2013 to December 30, 2020 to measure the course of patients’ disease as determined by clinical, biochemical, radiologic, and endoscopic/histologic findings, with an assessment of clinical outcomes and complications to include CD-related emergency room visits, steroid use, hospitalizations, and surgeries. Results: 343 patients with CD were identified, of which 184 were started on biologic therapy within 2 years of diagnosis, while 159 were started on biologic therapy 2 or more years after diagnosis. Patients who initiated biologic therapy within 2 years of diagnosis had significantly fewer CD-related complications (p< 0.0001) (Figure 1a). Evidence of perianal disease at diagnosis was predictive of an increased likelihood of CD-related complications (Figure 1b). Patients on monotherapy with thiopurines prior to biologic therapy were also more likely to experience CD-related complications (Figure 1c). Conclusion: These findings demonstrate that earlier initiation of biologics (within 2 years of diagnosis) results in a lower probability of CD-related complications, including emergency room visits, steroid use, hospitalizations, and surgeries. This real-world study is one of the first to confirm prior clinical trial data on decreased complications in early initiation of biologic therapy in CD patients.Figure 1.: Survival curves for complications with respect to timing of biologic start (1a), presence of perianal disease (1b) and thiopurine therapy prior to biologic stat (1c).

S2720 Crohn’s Disease Manifesting as a Jejunal Obstruction at Diagnosis

Introduction: Crohn’s disease is an inflammatory bowel disease caused by transmural inflammation and may affect any portion of the luminal gastrointestinal tract. It is commonly associated with abdominal pain, fatigue, weight loss and diarrhea as the initial presentation. It is vastly uncommon that Crohn’s disease is diagnosed as a bowel obstruction as it initial presentation. We present a gentleman whose initial presentation of Crohn’s disease was a small bowel obstruction from an inflammatory mass. Case Description/Methods: Patient is a 21-year-old male with no significant past medical history who presented to the ED with myalgias, abdominal pain, nausea, and vomiting for one month. He was recently seen at a different hospital for similar symptoms. He underwent EGD which showed Mallory Weiss tears in the esophagus and a gastric emptying study which showed abnormal transit of solids and liquids. He was treated at that time for gastroparesis. On this admission, he had a normal gastric emptying study. He continued to have large amounts of emesis in amounts over one liter in volume. A CT abdomen and pelvis with oral contrast showed marked distention and dilation of the duodenum to the level of the superior mesenteric artery to where there was relative obstruction and moderate narrowing and a stricture in the proximal to mid jejunum with mesenteric nodal prominence. A small bowel series with gastrograffin had similar findings. Patient underwent a laparoscopic small bowel resection where a small bowel mass at the level of the mid jejunum was found, causing focal narrowing and partial obstruction. The mass pathology revealed a central structure with mural thickening and features suggestive of Crohn’s disease. His post operative course was unremarkable, and he followed up with gastroenterology outpatient for evaluation and treatment of his new diagnosis of Crohn’s disease. (Figure) Discussion: Crohn’s disease includes a wide collection of clinical presentations. Small bowel obstruction progresses in moderate to severe cases of Crohn’s, which typically is a chronic issue. To our knowledge, one other case report has been published with the initial presentation of Crohn’s disease manifesting as an obstruction. Our patient had misleading initial work up and isolated jejunal involvement without other intestinal involvement which may have contributed to the delay in his diagnosis.Figure 1.: Left and middle panels reveal the small bowel series with small intestine narrowing and dilatation. Right similarly reveals small bowel dilation and mesenteric nodal prominence.

S2228 A Segmental Colitis Associated With Diverticulosis versus Inflammatory Bowel Disease: A Diagnostic Dilemma Despite Total Proctocolectomy

Introduction: Patients with diverticular disease can develop segmental colitis associated with diverticulosis (SCAD). It can range from mild inflammatory changes to chronic active inflammation that mimics inflammatory bowel disease (IBD). SCAD usually presents a more benign outcome, with a low rate of complications. Here, we present a complex case in which a diagnosis was still unclear till the final stage of the management. Case Description/Methods: A 60-year-old female was admitted for hypovolemic shock. She was resuscitated, and the GI was consulted for the management of IBD. She was recently diagnosed with ulcerative colitis about 2 months ago. She has abdominal pain in the right lower side, and examination revealed mild abdominal tenderness. She was already on prednisone 60 mg daily for 2 weeks and infliximab maintenance dose (completed 2 doses) and mesalamine from the last admission. She has had 3 colonoscopies in the past. The first colonoscopy 6 months ago showed a normal rectum, unable to traverse the sigmoid colon due to stricture and diverticulosis. The biopsy showed a normal rectum and a very focal area of cryptitis. The last colonoscopy 2 months ago showed a severely inflamed ulcerated mucosa in the sigmoid colon (Figure, left). Colon biopsy showed mild acute cryptitis and distorted and branched crypts. No crypt abscesses or granulomas were seen. On this admission, CT enterography showed pancolitis. Serology for Crohn's disease (CD) was negative, including ASCA IgA and ASCA IgG. The strong differential diagnosis was SCAD vs.IBD. The decision was to continue with the medical treatment (i.e., completion of steroid course, infliximab, and follow the response) and was discharged. The patient again presented with a shock one month after this admission. Unfortunately, she had colonic perforation and had total proctocolectomy with ileostomy creation. Pathology of surgical specimens revealed mild chronic active colitis and severe diverticular disease with associated transmural inflammation (Figure, right). Ileum excision showed no significant pathologic changes unlikely to be CD. The patient was doing well till the last follow-up. Discussion: This is a unique case where the diagnosis of SCAD vs. IBD was unclear regardless of the availability of serology, endoscopic, surgery, and histopathological examinations. In this complex case, we suggest a multidisciplinary team approach to improve patient-centered care.Figure 1.: Left: colonoscopy showing inflamed ulcerated mucosa in the sigmoid colon. Right: Pathology shows mild chronic active colitis and severe diverticular disease.

Similar to Crohn’s Disease, but Diagnosed with Stenotic Ischemic Enteritis or Ischemic Colitis: Case Series and a Systematic Review

Background and Study Aims: Stenotic ischemic enteritis or ischemic colitis, along with transmural inflammation, ulcers and strictures, is extremely similar to Crohn’s disease. We aimed to report relevant cases and perform a systematic review to help distinguish two diseases. Patients and Methods: We reviewed our institutional experience with stenotic ischemic enteritis or ischemic colitis. Besides, we performed a comprehensive literature review using Medline (OvidSP), Web of Science, PubMed, Cochrane Library, and Embase from inception to March 2022. Demographic parameters, serological indexes, imaging markers, histological features and treatment were abstracted from our cases and included literatures. Results: We reported four cases of stenotic ischemic enteritis and one stenotic is chemic colitis in our centre, and they were all male, aging 22-65 years old. Characteristics of the five patients were presented and histological examination played an essential role in discriminating them from CD. Besides, 35 patients of stenotic IE from 17 publications were included in the systematic review and the characteristics of included patients were also presented. Conclusions: The treatment to stenotic ischemic enteritis or ischemic colitis and CD was different. Although they are very similar, but they can be distinguished from each other according to demographic features, radiographic and endoscopic imaging, especially histological evaluation.

Fibrosis in fat: From other diseases to Crohn's disease.

Creeping fat is a specific feature of Crohn’s disease (CD) and is characterized by mesenteric fat wrapping around the intestine. It highly correlates with intestinal transmural inflammation, muscular hypertrophy, fibrosis, and stricture formation. However, the pathogenesis of creeping fat remains unclear. Molecular crosstalk exists between mesenteric fat and the intestine. Indeed, creeping fat contains different types of cells, including adipocytes and immune cells. These cell types can produce various cytokines, fatty acids, and growth factors, which affect the mesenteric fat function and modulate intestinal inflammation and immunity. Moreover, adipocyte progenitors can produce extracellular matrix to adapt to fat expansion. Previous studies have shown that fat fibrosis is an important feature of adipose tissue malfunction and exists in other diseases, including metabolic disorders, cancer, atrial fibrillation, and osteoarthritis. Furthermore, histological sections of CD showed fibrosis in the creeping fat. However, the role of fibrosis in the mesenteric fat of CD is not well understood. In this review, we summarized the possible mechanisms of fat fibrosis and its impact on other diseases. More specifically, we illustrated the role of various cells (adipocyte progenitors, macrophages, mast cells, and group 1 innate lymphoid cells) and molecules (including hypoxia-inducible factor 1-alpha, transforming growth factor-beta, platelet-derived growth factor, and peroxisome proliferator-activated receptor-gamma) in the pathogenesis of fat fibrosis in other diseases to understand the role of creeping fat fibrosis in CD pathogenesis. Future research will provide key information to decipher the role of fat fibrosis in creeping fat formation and intestinal damage, thereby helping us identify novel targets for the diagnosis and treatment of CD.

1052 Intussusception of the Appendix in a Young Adult with Cystic Fibrosis: An Important Differential Diagnosis of Abdominal Pain in Cystic Fibrosis Patients?

Abstract Background Cystic fibrosis (CF) is commonly associated with gastrointestinal manifestations from infancy to adulthood. Intussusception in the paediatric CF population is widely reported, whereas in the adult, distal intestinal obstruction syndrome (DIOS) is common affecting 20%, of which, intussusception is rare and appendiceal intussusception is rarer, affecting 1%. Case-Description A 20-year-old male with CF presented with 3 days of right iliac fossa pain and diarrhoea. On admission, he was hypotensive and afebrile. Clinical examination revealed tenderness of the right flank with a palpable mass in the right iliac fossa. Serum investigations showed mildly raised inflammatory markers. Contrast CT of the abdomen-pelvis confirmed intussusception of the appendix into the ascending colon. Histological analysis of the appendix further demonstrated intussusception, with intraluminal mucinous material. Fascinatingly, no transmural inflammation was present. The patient underwent a laparotomy-open appendicectomy. Interestingly, intraoperative findings showed the intussusception resolved, no longer requiring surgical reduction. Patient postoperative recovery was complicated by pneumonia for which he was transferred for specialist CF respiratory care and thereafter, discharged. Discussion Literature review highlighted a paucity of data, with 10 reported cases of appendiceal intussusception in adult CF patients. Interestingly, we report the intussusception had reduced by the time of operation. This is in-keeping with previous case reports of transient intussusception which spontaneously resolved. Conclusion From this rare case presentation, we have learnt it is imperative to carry a high index of suspicion for gastrointestinal manifestations in CF patients where acute appendicitis is seen less often and differential diagnoses like DIOS and intussusception should be considered.

Role of Multiparametric Intestinal Ultrasound in the Evaluation of Response to Biologic Therapy in Adults with Crohn’s Disease

Crohn’s disease is one of the two most common types of inflammatory bowel disease. Current medical therapies are based on the use of glucocorticoids, exclusive enteral nutrition, immunosuppressors such as azathioprine and methotrexate, and biological agents such as infliximab, adalimumab, vedolizumab, or ustekinumab. International guidelines suggest regular disease assessment and surveillance through objective instruments to adjust and personalize the therapy, reducing the overall rates of hospitalization and surgery. Although endoscopy represents the gold-standard for surveillance, its frequent use is strongly bordered by associated risks and costs. Consequently, alternative non-invasive tools to objectify disease activity and rule active inflammation out are emerging. Alongside laboratory exams and computed tomography or magnetic resonance enterography, intestinal ultrasonography (IUS) shows to be a valid choice to assess transmural inflammation and to detect transmural healing, defined as bowel wall thickness normalization, no hypervascularization, normal stratification, and no creeping fat. Compared to magnetic resonance imaging (MRI) or computed tomography, CT scan, IUS is cheaper and more widespread, with very similar accuracy. Furthermore, share wave elastography, color Doppler, and contrast-enhanced ultrasonography (CEUS) succeed in amplifying the capacity to determine the disease location, disease activity, and complications. This review aimed to discuss the role of standard and novel ultrasound techniques such as CEUS, SICUS, or share wave elastography in adults with Crohn’s disease, mainly for therapeutic monitoring and follow-up.

Dual energy computed tomography in Crohn’s disease: a targeted review

ABSTRACT Introduction Crohn’s disease (CD) is a common chronic inflammatory bowel disease characterized by transmural inflammation and extra-intestinal complications. The diagnosis of CD is made using a combination of clinical, biochemical, endoscopic, imaging and histological features. Among imaging methods, computed tomography enterography (CTE) is the most commonly used. Dual-energy CTE allows objective evaluation of patients with CD. Along with the findings seen in conventional CTE, dual-energy CTE can generate iodine density maps and quantify the iodine content in the involved segments of the bowel, thus providing a measure of the perfusion of the affected bowel. In addition, the virtual monochromatic images generated from dual-energy CTE allow better qualitative evaluation of the mural and extramural findings. Areas covered We performed a targeted systemic review of all the studies in the literature to understand the role of dual-energy CT in the diagnosis and assessment of the severity of CD. Expert opinion Dual-energy CTE is superior to conventional CTE in the evaluation of CD. Besides quantifying iodine in the pathological segments, other quantitative parameters like the mural thickness of affected bowel segments, the number of segments involved, ulcerations, comb sign, lymphadenopathy, and the mural heterogeneity can also be assessed in dual-energy CTE.

Improved comprehensive evaluation of Crohn’s disease activity by intestinal computed tomography enterography combined with endoscopy and biochemical indicators

Background and study aimsThe treatment approach for Crohn’s disease (CD) is focused on mucosal healing and resolution of transmural inflammation. The aim of this study is to evaluate the correlation between computed tomography enterography (CTE) and other treatments, in particular, endoscopy and biochemical indicators, in newly diagnosed patients with CD. Patients and methodsOne hundred twenty-three patients with CD who received CTE in Xiangya Hospital, Central South University, China, from April 2017 to April 2019 were included. The clinical case data and imaging results were retrospectively reviewed. The clinical activity of CD was determined by the Crohn’s disease activity index (CDAI) score and biochemical indicators. The relationships between CTE and endoscopy, CDAI score, and inflammatory markers were evaluated. ResultsThe diagnostic rate of CTE of the 123CD patients was 68.3% (84/123). Logistic regression analysis showed that the specific CTE manifestations related to CD activity were intestinal wall stratification, comb sign, and abdominal abscesses (P < 0.05). Spearman’s rank correlation analysis showed that inflammatory markers positively correlated with different CTE imaging manifestations. ConclusionIntestinal CTE combined with endoscopy and biochemical indicators is both comprehensive and effective in evaluating the condition of CD patients.

Surgical strategies for intestinal Crohn's disease.

As a type of inflammatory bowel disease, Crohn's disease (CD) is characterized by jumping lesions and transmural inflammation. The treatment goal is to control the development of inflammation with drugs such as 5-Amino Salicylic Acid, azathioprine and hormones, but most patients still need surgical treatment eventually. The surgical treatment of CD requires exquisite surgical design and solid surgical procedures to minimize the progression of intestinal lesions and preserve the normal bowel segment as much as possible. This study aims to summarize and discuss the surgical treatments for intestinal CD, and to provide references for the surgical treatment of intestinal CD. Clinical data of 122 patients with CD were analyzed retrospectively. They all received surgical treatments in the Second Xiangya Hospital of Central South University between Jan. 1, 2015 and Jan. 1, 2021. The data included general information, clinical manifestations, preoperative examination, preoperative preparation, surgical methods, pathological examination, complications, and follow-up data. Except 1 case of emergency surgery, all the other patients met the surgical indications of intestinal CD after multi-disciplinary discussion (MDT) and they were transferred to surgery for elective surgery, and received high-quality intestinal preparation before surgery. Among them, 99 cases underwent one-stage abdominal operation and 23 cases underwent the second abdominal operation. All patients underwent successful surgery with good surgical results, with significantly alleviated clinical symptoms and the BMI significantly increased compared with those before surgery. There were 14 cases (11.5%) of postoperative complications. One case of delayed anastomotic fistula and one case of small intestinal cutaneous fistula which were successfully treated by conservative treatment, the other 12 cases were successfully treated by reoperation, and there were no complications with follow-up operation. The postoperative pathological diagnosis for all patients was clear. All patients received regular follow-up with 5-70 (median 36) months and no clinical recurrence was found. As the surgical treatment of intestinal CD, surgeons should strictly grasp the surgical indications based on the MDT. During the operation of small intestinal CD, it is advisable to preserve bowel segment as much as possible. For patients with short remaining normal bowel segment, the intestinal canal should be preserved as far as possible, even for the mildly diseased bowel, so as to avoid the occurrence of short bowel syndrome and leave room for possible reoperation. In the treatment of secondary duodenal CD, it is necessary to carefully identify the nature of the local lesions. Different surgical treatments should be performed according to whether there is an internal fistula and the size of this fistula. Meanwhile, duodenectomy or pancreaticoduodenectomy should be considered as the final surgical method in the treatment of primary duodenal CD.

Development, Validation, and Evaluation of the Pediatric Inflammatory Crohn’s Magnetic Resonance Enterography Index From the ImageKids Study

Cross-sectional imaging is important in the assessment of transmural inflammation in Crohn's disease (CD). Small bowel involvement is often more extensive in pediatric CD, requiring a panentering measuring tool. We undertook to develop a magnetic resonance enterography (MRE)-based index that would measure inflammation in all segments of the intestine, without rectal contrast. Children with CD underwent ileocolonoscopy and MRE and half were prospectively followed for 18 months when MRE was repeated. Item generation and reduction were performed by a Delphi panel of pediatric radiologists, a systematic literature review, a cross-sectional study of 48 MREs, and a steering committee. Formatting and weighting were performed using multivariate modeling adjusted by a steering committee. MREs were read locally and centrally. Reliability, validity, and responsiveness were determined using several clinimetric and psychometric approaches. Thirty items were initially generated and reduced to 5 using regression analysis on 159 MREs: wall thickness, wall diffusion weighted imaging, ulcerations, mesenteric edema, and comb sign. In the validation cohort of 81 MREs, the weighted global PICMI correlated well with the radiologist global assessment (r= 0.85; P < .001) and with the simple endoscopic score in a subsample with ileocolonic disease (r= 0.63; P < .001). Interobserver and test-retest reliability were high (interclass correlation coefficients, 0.84; 95% confidence interval [CI], 0.79-0.87; and 0.81, 95% CI, 0.65-0.90, respectively; both P < .001). Excellent responsiveness was found at repeated visits (n= 116 MREs; area under the receiver operating characteristic curve 0.96; 95% CI, 0.93-0.99). Transmural healing was defined as PICMI ≤10 and response as a change of >20 points with excellent discriminative validity (area under the receiver operating characteristic curve= 0.96; 95% CI, 0.93-0.99). The PICMI is a valid, reliable, and responsive index for assessing transmural inflammation in pediatric CD. It scores the entire bowel length and does not require intravenous contrast or rectal enema and, therefore, is suitable for use in children. (ClinicalTrials.gov, Number: NCT01881490.).

Diagnosis of giant cell arteritis using clinical, laboratory, and histopathological findings in patients undergoing temporal artery biopsy

ObjectiveTo identify the clinical, laboratory, and histopathological features that may predict the diagnosis of giant cell arteritis (GCA). MethodsA retrospective chart review was performed on patients who underwent temporal artery biopsy (TAB) between January 1, 2011 and March 31, 2019. Patient demographics, clinical characteristics, laboratory features, histopathological features, and biopsy results were collected. GCA status was determined by a neuro-ophthalmologist (OOA). Stepwise logistic regression analysis was performed to identify features that predict GCA status. ResultsOf 101 patients who underwent TAB, 31 (31%) were diagnosed with GCA. Age was found to be statistically significant for the diagnosis of GCA (P = 0.009), with an average age of 74.4 years ( ± 8.1) in those with GCA vs. 68.9 years ( ± 10.0) in those without. The incidence of transient vision loss was higher in GCA than non-GCA patients (P = 0.005). Anterior arteritic ischemic optic neuropathy (n = 3), ophthalmic artery occlusion (n = 2), and posterior ischemic optic neuropathy (n = 1) were seen only in the GCA group. Of the 31 GCA patients, 15 had active GCA (48%), 3 (10%) had healed temporal arteritis (HTA), 8 (26%) had suggested HTA, and 5 (16%) had false negative biopsies. Of the 70 non-GCA patients, 63 (90%) had negative biopsies, 2 (3%) had HTA, and 5 (7%) had suggested HTA. Histopathological analysis revealed that CD68 staining had a sensitivity of 69% and specificity of 86%. Both presence of multinucleated giant cells (MNGC) and transmural inflammation had 100% specificity; however, sensitivity was ≤ 50%. In patients with negative TABs and complete risk factor data available (n = 66), the odds of GCA increased 2.16-fold every 5 years of age, and 1.08-fold every mg/day of oral steroid use. A biopsy result of HTA had an odds ratio of 84.7 and suggested HTA of 49.2 against a negative TAB for diagnosis of GCA. ConclusionAge at time of biopsy, HTA, and suggested HTA are predictive for the diagnosis of GCA. Transient vision loss is more commonly seen in GCA, and anterior arteritic ischemic optic neuropathy, ophthalmic artery occlusion, and posterior ischemic optic neuropathy are important ophthalmic manifestations of GCA. CD68 staining is more sensitive but less specific for diagnosing GCA in comparison to other histopathologic findings such as presence of MNGC and transmural inflammation. Further work is recommended to investigate the importance of the specific histopathologic finding of CD68 staining in the diagnosis of GCA.

Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease

In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ= 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value= 73%). In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. gov number: NCT03107793.

Расширенная резекция брыжейки тонкой кишки при болезни Крона (обзор литературы)

INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel disease characterized by intermittent lesions of the gut wall and transmural inflammation. The disease affects the gastrointestinal tract along the whole length from the mouth to the anus. More than 50% of patients with CD within the first 10 years following established diagnosis develop strictures or fistulas. These complications lead to intestinal obstruction which is a common indication for surgery in the volume of resection of the affected bowel. Surgery for CD complications does not rid the patient of the disease. Endoscopic and clinical recurrence of CD is a common phenomenon after surgical resection of the gut. The surgical approach to treatment of CD have not gained a wide spread since the first description of the disease. It is evident that to reduce the frequency of recurrences, it is necessary to improve surgical tactics. Clarification and better understanding of the anatomy and function of mesentery in recent years has led to the suggestion of its probable role in the pathogenesis of CD. Extended mesenteric resection may improve the outcomes of surgery in CD. Rather than to mobilize and excise the mesentery as in colorectal cancer, the mesentery is usually transected at the level of the intestine and remains in an organism. This review provides the data of recent studies of the role of mesentery in the pathogenesis of CD, which permit to suggest that extended resection of mesentery can significantly improve surgical results in CD and to reduce the frequency of endoscopic and clinical recurrences and reoperations. CONCLUSION: Mesentery is involved in the pathogenesis of Crohns disease and the development of relapse. Further study of its role will lead to a decrease in the frequency of relapses and repeated surgical interventions in Crohns disease.