Inflammation In Lamina Propria Research Articles

A case of Russell body gastritis associated with psychiatric disorder

Abstract Introduction/Objective Russell body gastritis is a benign and rare entity characterized by infiltration of lamina propria with plasma cells stuffed with spherical eosinophilic cytoplasmic inclusions known as Russell bodies which represent immunoglobulins. Russell bodies accumulate due to dysfunction in secretion pathway of plasma cells. Plasma cells with Russell bodies are also termed Mott cells. Although exact etiology is unknown, but it can be seen in association with other conditions like mucosa associated lymphoid tissue (MALT) lymphoma, multiple myeloma and plasmacytoma. This condition most commonly affects the antrum and may present as erythema or sometimes nodular lesion. Definitive diagnosis is based on histology. Methods/Case Report A middle-aged male with past medical history significant for polysubstance use disorder, bipolar disorder, and osteoarthritis was evaluated for bleeding per rectum and dyspepsia in the setting of chronic nonsteroidal anti-inflammatory drugs (NSAID) and ethanol use. Physical examination was remarkable for an external hemorrhoid and complete blood count showed anemia. Upper GI endoscopy and colonoscopy was performed. Patchy erythema was seen in antrum and duodenal bulb, and colonoscopy was unremarkable. Microscopic examination showed numerous plasma cells with Russell bodies (Mott cells) in the lamina propria and mild chronic inflammation in gastric mucosa. H. Pylori was negative by immunohistochemistry (IHC). Plasma cells were polyclonal and positive for CD138, and negative for cytokeratin which excluded plasmacytoma and signet-ring adenocarcinoma, respectively. Patient was placed on proton pump inhibitor therapy and discharged. Results (if a Case Study enter NA) Russell body gastritis can be seen in patients with and without H. Pylori infection. Cytokeratin, kappa and lambda immunohistochemistry stains, and gene rearrangement studies may be needed to exclude frequent lesions that may enter in the differential diagnosis. Long term effects and clinical significance of russell bodies accumulation is yet to be determined. Conclusion Russell body gastritis is a rare morphologic variant of chronic gastritis that may enter in the differential diagnosis with other more serious lesions. A careful morphologic examination and occasionally IHC stains / molecular studies are needed to make the correct diagnosis.

Lack of mTORC2 signaling in CD11c+ myeloid cells inhibits their migration and ameliorates experimental colitis.

The mammalian target of rapamycin (mTOR) pathway plays a key role in determining immune cells function through modulation of their metabolic status. By specific deletion of Rictor in CD11c+ myeloid cells (referred to here as CD11cRicΔ/Δ), we investigated the role of mTOR complex 2 (mTORC2) signaling in dendritic cells (DCs) function in mice. We showed that upon dextran sulfate sodium-induced colitis, the lack of mTORC2 signaling CD11c+ cells diminishes the colitis score and abrogates DC migration to the mesenteric lymph nodes, thereby diminishing the infiltration of T helper 17 cells in the lamina propria and subsequent inflammation. These findings corroborate with the abrogation of cytoskeleton organization and the decreased activation of Rac1 and Cdc42 GTPases observed in CD11c+-mTORC2-deficient cells. Meta-analysis on colonic samples from ulcerative colitis patients revealed increased gene expression of proinflammatory cytokines, which coincided with augmented expression of the mTOR pathway, a positive correlation between the DC marker ITGAX and interleukin-6, the expression of RICTOR, and CDC42. Together, this work proposes that targeting mTORC2 on DCs offers a key to hamper inflammatory responses, and this way, ameliorates the progression and severity of intestinal inflammatory diseases.

DOP81 Rosnilimab, a novel PD-1 agonist monoclonal antibody, reduces T cell proliferation, inflammatory cytokine secretion, and PD-1high expressing CD4 and CD8 T cells: Results from a Phase 1 healthy volunteer clinical trial

Abstract Background Programmed cell death protein 1 (PD-1) is expressed on activated T cells and is a key co-inhibitory node in immune regulation. By targeting regulatory mechanisms to modulate immune cells driving disease, there is an opportunity to restore immune balance. Rosnilimab is a PD-1 agonist antibody designed to reduce T cell proliferation and inflammatory cytokine secretion and deplete PD-1high T follicular helper, T peripheral helper, and T effector cells. It is being studied for ulcerative colitis (UC), where PD-1+ T cells are prevalent in inflamed lamina propria (>40%) and the periphery. The primary objective of this healthy volunteer Phase 1 study was to assess the safety and tolerability of single ascending doses (SAD) and multiple ascending doses (MAD) of rosnilimab. Findings from pharmacokinetic (PK) and pharmacodynamic (PD) assessments are summarized. Methods This single-centre study included 14 cohorts in SAD and 3 cohorts in MAD. Each cohort had 8 participants (6 active, 2 placebo [PBO]). Cohorts were enrolled sequentially in each phase. Intravenous (IV) and subcutaneous (SC) administration were assessed in SAD; SC route was assessed in MAD. Results A total of 144 participants were enrolled; 90 to active SAD cohorts, 18 to active MAD cohorts, and 30 and 6 to SAD and MAD PBO cohorts, respectively. Rosnilimab was well tolerated with no dose-limiting toxicities or deaths. Two serious adverse events were reported in SAD (deemed unrelated to treatment) and 0 in MAD. PD-1 expressing cells were reduced by ~50% in both CD4+ and CD8+ subsets, in a dose-dependent manner and in correlation with full receptor occupancy (RO) through Day 30 in SAD. PD activity was rapid with sustained reduction in PD-1+ T cells, and ex-vivo stimulation resulted in reduced T cell functional activity. This reduction was maximized on PD-1high expressing T cells: ~90% reduction vs baseline. There was no significant impact on the overall total T cell or regulatory T (Treg) cell numbers, resulting in restoration of T cell composition to a less activated state and a positive shift in the Treg:Teff ratio. An antigen-specific functional T cell assay measuring ex vivo interferon-gamma release in response to antigen challenge was inhibited up to ~90% vs baseline and the response lasted for more than 30 days following a single dose. Rosnilimab had a favourable PK profile consistent with full RO, a 2-week half-life, and dose-proportional exposure in IV and SC dosing. Conclusion Rosnilimab demonstrated favourable safety, PK, and PD activity. The role of PD-1 in UC pathophysiology coupled with these results and translational data, demonstrate proof of mechanism and support progression into a Phase 2 study of rosnilimab in UC. (NCT06127043)

THU437 Oral Ulcers As A Clue To Bone Fragility

Abstract Disclosure: S. Sridhar: None. E.I. Krug: None. Introduction: Metabolic bone disease is common in celiac disease (CD) and can occur in patients without gastrointestinal symptoms. Successful treatment of malabsorption is associated with amelioration of bone loss. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of CD (1). According to American College of Gastroenterology Guidelines, tissue transglutaminase (tTG)-IgA antibody and total IgA level is the single preferred test for detection of CD in adults due to reported sensitivity of 90-98% and specificity of 95-97%. No additional testing is typically recommended for patients without IgA deficiency (2). Case: The patient is a 58 year old woman with past medical history of RAS treated with prednisone, 5 mg daily for 10 years, facial and ocular rosacea, menopause at age 49, asthma, chronic back and neck pain, history of spontaneous rib fracture and L4 compression fractures during chiropractic manipulation, who had progressive bone loss despite ongoing treatment with oral bisphosphonates, calcium and vitamin D supplementation for 4 years with good adherence, and was referred for endocrine evaluation. Laboratory studies revealed TSH 1.94 mIU/L (0.4-4.5), 25(OH)vit D 41 ng/mL (30-100 ng/mL), PTH 31 pg/mL (14-64), Ca 9. mg/dL (8.6-10.4), albumin 4.1 mg/dL (3.6-5.1), Mg 2.1 mg/dL (1.5-2.5), tTG-IgA 1 U/mL (<4), total IgA 190 mg/dL (47-310), Gliadin deamidated peptide IgA Ab 11 Units (<20), Gliadin deamidated peptide IgG Ab (DGP-IgG) 44 Units (<20). Duodenal biopsy revealed diffuse increase in intraepithelial lymphocytes, acute and chronic inflammation of lamina propria, focally marked villous blunting consistent with CD. The patient reported complete resolution of RAS and rosacea symptoms within one month of starting a strict gluten free diet. She also noted marked improvement in neck and back pain. After 6 months repeat DGP-IgG was 13 Units. Treatment with teriparatide of 12 months duration resulted in 12.1% and 5.4% gain in bone density of lumbar spine and total hip respectively. Conclusion: CD should be suspected in patients with osteoporosis and extraintestinal conditions including RAS and, possibly, rosacea. CD has been reported in 2.83% of 247 patients with RAS screened for (tTG)-IgA and anti-endomysial IgA Abs (2). Rosacea has also been linked to CD in one study (3). Our case suggests that patients presenting with RAS may need to be tested for DGP-IgG reported to have a sensitivity of 92% and specificity of 100%, regardless of total IgA level.

Regional differences in the incidence of lymphocytic and collagenous colitis over time

Background In microscopic colitis (MC), the incidence has increased over the last decades. The aim of the present study was to determine the incidence of lymphocytic (LC) and collagenous colitis (CC) in the county Skåne (Scania), southern Sweden, during the period 2010–20 with focus both on the temporal and spatial variations. Methods The MC diagnosis was retrieved from the biopsy registries at the Departments of Pathology. Established diagnostic criteria (increased lymphocyte count, inflammation in lamina propria and in CC a collagen band) were used for diagnosis. Age, gender, date for diagnosis and municipality of residence were retrieved for all patients. Results In total 1985 patients could be identified with a mean age of 62.9 years (SD 15.7) whereof 1415 were women. The incidence for CC was stable with a total age-standardized rate (ASR) per 100 000 person-years of 6.34, (range 4.6–8.1). In LC the ASR was 7.90 (range 1.7–15.2) but increased markedly 2015–20 reaching 15.2 in 2019. Also, the northwest part of the region showed significantly higher ASR:s of LC during the last part of the decade in comparation to the whole region. Conclusions The incidence of CC was stable during the period while LC differed substantially in a way that indicates that it most probably must be two different disease entities. In LC, in view of the marked and rapid increase, although no definitive explanation could be found, causative environmental factors could be contemplated, why further studies are indicated.

Assessment of efficacy and safety of advanced endoscopic irreversible electroporation catheter in the esophagus

Nonthermal irreversible electroporation (NTIRE) is emerging as a promising tissue ablation technique. However, maintaining irreversible electroporation (IRE) electrodes against displacement during strong esophageal spasms remains an obstacle. The present study aimed to evaluate the efficacy and safety of newly designed balloon-type endoscopic IRE catheters. Six pigs were randomly allocated to each catheter group, and each pig was subjected to four ablations at alternating voltages of 1500 V and 2000 V. Esophagogastroscopy was performed during the IRE. The ability of balloon-type catheters to execute complete IRE with 40 pulses was assessed. The success rate was higher for the balloon-type catheter than that for the basket-type (12/12 [100%] vs. 2/12 [16.7%], p < 0.001). Following gross inspection and histologic analysis of the 1500-V vs. 2000-V balloon-type catheter revealed a larger mucosal damage area (105.3 mm2 vs. 140.8 mm2, p = 0.004) and greater damage depth (476 μm vs. 900 μm, p = 0.02). Histopathology of the ablated tissue revealed separated epithelium, inflamed lamina propria, congested muscularis mucosa, necrotized submucosa, and disorganized muscularis propria. Balloon-type catheters demonstrated efficacy, achieving full electrical pulse sequences under NTIRE conditions, and a safe histological profile below 2000 V (1274 V/cm). Optimal electrical conditions and electrode arrays pose ongoing challenges.

Destroyed bladders: Characterization of progressive inflammatory cystitis.

We identified a subset of patients with noninfectious cystitis who develop refractory symptoms marked by diffuse inflammatory changes, reduced bladder capacity, and vesicoureteral reflux (VUR), termed here as "progressive inflammatory cystitis" (PIC). Our objective was to describe the phenotype, disease outcomes, and pathologic findings of PIC. A single institution retrospective cohort study of patients with PIC. Patients with a history of pelvic radiation, urologic malignancy, or neurogenic bladder were excluded. We describe cohort characteristics and use bivariate analyses to compare subgroups. Kaplan-Meier methods estimate time to urinary diversion. From 2008 to 2020, 46 patients with PIC were identified. The median age of symptom onset was 63 years old (interquartile range [IQR]: 56, 70) and the most common presenting symptoms were urinary urgency/frequency (54%) and incontinence (48%). Urodynamics showed a median maximum bladder capacity of 80 mL (IQR: 34, 152), commonly with VUR (68%) and hydronephrosis (59%). Ultimately 36 patients (78%) underwent urinary diversion at a median of 4.5 years (IQR: 2, 6.5) after symptom onset. Significant pathologic findings include presence of ulceration (52%), acute and chronic inflammation (68%), including eosinophils (80%), lymphoid follicles (56%), and mast cells in both lamina and muscularis propria (76%). PIC is a newly defined entity characterized by significantly diminished bladder capacity, upper tract changes, and relatively quick progression to urinary diversion. Larger prospective cohort studies are required to further characterize this severe phenotype of chronic noninfectious cystitis, aid earlier diagnosis, and guide management decisions.

Cronkhite-Canada Syndrome Presenting with life-threatening protein-losing enteropathy: a case report

Background: Cronkhite Canada Syndrome (CCS) is a rare gastrointestinal polyposis syndrome. The diagnosis of CCS is made by clinical, endoscopic and histopathological findings. Chronic diarrhea, malnutrition, alopecia, skin hyperpigmentation, onychodystrophy, hypogeusia, protein loss due to chronic inflammatory changes in the intestinal mucosa are common findings.Nutritional support, high protein diet, antibiotics, correction of electrolyte imbalance, and corticosteroids are frequently used in CCS treatment. Aim of the study: Here we present a newly diagnosed Cronkhite Canada Syndrome patient who has suffered life-threatening protein loss. Material and methods: Medical documentation was used. Case report: A 62-year-old male patient presented with bloodless diarrhea, happening 8-10 times a day for 4 months, and general condition disorder. On admission, arterial blood pressure was 80/50 mm/hg, pulse was 110 per minute and body temperature was 38.8°C. In laboratory tests, total protein: 38 mg/dl and albumin: 20 g/L.Upper and lower gastrointestinal system (GIS) endoscopy revealed 2-20 mm polyps in the stomach, duodenum, colon, and a small amount in the distal esophagus. Pathological examination of polypectomy materials revealed edematous and inflamed lamina propria consisting of plasma cells, neutrophils and eosinophils.The patient benefited from total parenteral nutrition, high protein dietary supplementation, antibiotic therapy and was followed with upper and lower GIS endoscopy. Conclusions: CCS is a rare disease that can cause life-threatening hypoalbuminemia and requires close follow-up.

Dysphonia in Polymyositis/Dermatomyositis in Adults.

The purpose of this study was to examine clinical dysphonia in patients with polymyositis (PM)/dermatomyositis (DM). The subjects were 21 Japanese patients with PM/DM (11 females, 10 males; mean age ± SD, 61.4 ± 16.2 years) who visited our department between April 2009 and March 2020. Dysphonia was evaluated by laryngoscopy and histopathological examination. Eight (38.1%) patients were aware of dysphonia. These patients included one with PM and 7 with DM, 5 were male and 3 were female, and the mean age at diagnosis was 62.0 (range 48 to 72) years. White lesions on the vocal cords were found in 7 of the patients with dysphonia. The patient without these white lesions had regurgitation into the nasal cavity. Histopathological examination revealed inflammation of lamina propria in the laryngeal white lesions. White lesions on the vocal cords were found in patients with dysphonia in patients with polymyositis (PM)/dermatomyositis (DM). Histopathological examination revealed fiber necrosis and inflammatory cell infiltration in lamina propria of the laryngeal lesions. White lesions on the vocal cords were relieved by treatment. Level of Evidence 2b (Individual retrospective cohort study).

Inflammation induces pro-NETotic neutrophils via TNFR2 signaling.

Cytokines released during chronic inflammatory diseases induce pro-inflammatory properties in polymorphonuclear neutrophils (PMNs). Here, we describe the development of a subgroup of human PMNs expressing CCR5, termed CCR5+ PMNs. Auto- and paracrine tumor necrosis factor (TNF) signaling increases intracellular neutrophil elastase (ELANE) abundance and induces neutrophil extracellular traps formation (NETosis) in CCR5+ PMNs, and triggering of CCR5 amplifies NETosis. Membranous TNF (mTNF) outside-in signaling induces the formation of reactive oxygen species, known activators of NETosis. Invivo, we find an increased number of CCR5+ PMNs in the peripheral blood and inflamed lamina propria of patients with ulcerative colitis (UC). Notably, failure of anti-TNF therapy is associated with higher frequencies of CCR5+ PMNs. In conclusion, we identify a phenotype of pro-NETotic, CCR5+ PMNs present in inflamed tissue invivo and inducible invitro. These cells may reflect an important component of tissue damage during chronic inflammation and could be of diagnostic value.

Epithelial Abnormalities in the Small Intestine of Zambian Children With Stunting.

BackgroundEnvironmental enteropathy (EE) contributes to impaired linear growth (stunting), in millions of children worldwide. We have previously reported that confocal laser endomicroscopy (CLE) shows fluorescein leaking from blood to gut lumen in vivo in adults and children with EE. We set out to identify epithelial lesions which might explain this phenomenon in Zambian children with stunting non-responsive to nutritional support.MethodsWe performed confocal laser endomicroscopy (CLE) in 75 children and collected intestinal biopsies for histology in 91 children. CLE videos were evaluated, employing the Watson score to determine severity of leakiness. Morphometry was carried out on well-orientated mucosa and 3 biopsies were examined by electron microscopy.ResultsConfocal laser endomicroscopy demonstrated substantial leakage from circulation to gut lumen in 73 (97%) children. Histology consistently showed characteristic changes of EE: villus blunting, lamina propria and epithelial inflammation, and depletion of secretory cells (Paneth cells and goblet cells). Epithelial abnormalities included marked variability in epithelial height, disorganised and shortened microvilli, dilated intercellular spaces, pseudostratification, formation of synechiae between epithelium on adjacent villi, crypt destruction, and abundant destructive lesions which may correspond to the microerosions identified on CLE.ConclusionEpithelial abnormalities were almost universal in Zambian children with non-responsive stunting, including epithelial microerosions, cell-cell adhesion anomalies, and defects in secretory cells which may all contribute to impairment of mucosal barrier function and microbial translocation.

Intestinal schistosomiasis with colonic polyps

Schistosomiasis is a parasitic infection which commonly affects the intestine. Colonic polyps associated with intestinal schistosomiasis are not commonly reported in young people. Our case report describes a 20-year-old man from North-Central Nigeria who presented with recurrent passage of loose, mucoid, bloody stool, and weight loss. His biochemical profile and stool tests were unremarkable. A colonoscopy showed multiple ulcers and polyps with ulcerated surfaces in the transverse and sigmoid colon. Histopathology revealed islands of colonic-type mucosa containing numerous benign colonic glands in a densely inflamed lamina propria containing lymphocytes, eosinophils, and histiocytes, with numerous ova and calcified parasite bodies of Schistosoma. The patient was treated with praziquantel and showed marked clinical improvement.

Differential diagnosis of pulmonary Sarcoidosis in an elderly patient: case report/ Diagnóstico diferencial de Sarcoidose pulmonar em um paciente idoso: relato de caso

INTRODUCTION: Sarcoidosis is a worldwide disease with a lifetime incidence rate of 0.85–2.4%, generally affecting people between 25 and 40 years of age. The clinical phenotype of sarcoidosis can be extremely diverse in terms of presentation, involved organs, duration and severity, however, pulmonary involvement is present in 86–92% of cases according to chest radiography, alone or in association with locations extrapulmonary in about 50% of cases. PURPOSE: to demonstrate a clinical case, by differential diagnosis, of pulmonary sarcoidosis. METHODOLOGY: this is a clinical case study with a qualitative and descriptive perspective, which consists of research that, in general, takes place with direct data collection, whose researcher is the indispensable instrument. CASE REPORT: elderly patient, who, after admission to the emergency room, had symptoms such as mental confusion, wasting syndrome, with previous imaging exams without alterations. The results of transbronchial biopsy showed foci of fibrosis in the lamina propria and non-caseating epithelioid granulomatous inflammation in the lung parenchyma, as well as negative Baar and fungus tests. From this perspective, the differential diagnosis was found, closing the clinical case for pulmonary sarcoidosis. DISCUSSION: The diversity of the sarcoidosis phenotype is often linked to epidemiological factors and, interestingly, as shown by recent studies, to the genotype. FINAL CONSIDERATIONS: sarcoidosis is a frequent but multifaceted disease that still poses diagnostic and therapeutic challenges.

Utility of colon allograft biopsies in surveillance of patients with small intestinal transplantation – A systematic study of 129 biopsies

Abstract Introduction/Objective A segment of right colon is sometimes included with small intestinal allografts to preserve the ileocecal valve and maintain water reabsorption. We correlated pathological findings of colon allograft biopsies obtained during surveillance colonoscopies with clinical, endoscopic, and microbiologic findings. Methods/Case Report All colon allograft biopsies from surveillance colonoscopies over a 3-year period were reviewed for crypt apoptotic activity, cryptitis, lamina propria inflammation, ulceration, and crypt architectural distortion. Clinical and endoscopic findings, and positive cultures a week before and after the biopsies were recorded. Results (if a Case Study enter NA) There were 129 colon biopsies from 29 patients; 98 were histologically normal, whereas 28 showed rare apoptoses (n=14), focal cryptitis (n=8), increased intraepithelial lymphocytes (n=2), moderate acute rejection (n=1), and crypt architectural distortion (n=2). Of these 29 patients, 8 had abnormal endoscopic findings, 21 were normal. Out of 8 patients with abnormal endoscopic exams, 50% had normal histology on biopsy. Twenty-one biopsies were associated with positive cultures in the blood (n=5), urine (n=16) or wound, peritoneal, stool (n=6); 3 had abnormal endoscopies, and 4, abnormal histology. One patient with C.difficle toxin had normal endoscopy and focal cryptitis, whereas another with CMV DNA in blood showed endoscopically congested mucosa and rare apoptoses on biopsy. Of 12 biopsies (7 patients) with abnormal endoscopic findings, (erythema, congestion, ulceration), 4 biopsies had no pathologic findings, 8 had rare apoptosis, and one each had focal cryptitis and chronic colitis. Paired small intestinal biopsies were present with 59 biopsies; 10 showed rare apoptosis and 2, focal cryptitis. Of 70 without paired small intestinal biopsies, there were 5 with rare apoptotic bodies, 5 with focal cryptitis, and 2 with crypt architectural distortion. Conclusion The correlation of histologic, endoscopic, and microbiologic findings in colonic allograft surveillance biopsies is inconsistent. Colon allograft biopsies have limited utility in the follow-up of patients, particularly in absence of paired small intestinal biopsies.

S2418 Crohn’s Colitis Mimicking Ischemic Colitis: A Case Report

Introduction: Crohn’s disease (CD) can mimic ischemic colitis (IC) in the elderly. Here we present an elderly male diagnosed with CD when IC was initially suspected, and further evaluation revealed that CD was the primary diagnosis. Case description/methods: A 69-year-old male with a history of coronary artery disease with recent percutaneous coronary angioplasty & stent placement on aspirin and clopidogrel presented with hematochezia. He had an acute onset of a large amount of rectal bleeding and denied any other symptoms or having prior hematochezia or chronic diarrhea. Exam noted for hemodynamic stability with no tenderness to palpation of abdomen. Hemoglobin was 10.3 from 17 (Normal [N]: 13.5-17.5 gm/dl). Clinically suspected to have IC. Esophagogastroduodenoscopy (EGD) showed a small superficial non-bleeding gastric ulcer, gastritis, and duodenitis, and no stigmata of recent bleeding. Colonoscopy revealed three large deep ulcers in the proximal descending colon, splenic flexure, and distal transverse colon, with the largest ulcer measuring 50 mm. These ulcers were characterized by heaped up margins with some reactive granulation tissue, suggestive of chronicity. Biopsies showed focal acute cryptitis and diffuse lymphoplasmacytic inflammation in lamina propria without architectural distortion. CT angiography abdomen and pelvis showed widely patent arterial vasculature. Clopidogrel was held for 2 weeks to check healing of ulceration. Repeat colonoscopy showed similar findings, without improvement of ulcerations. Repeat colonic biopsies showed chronic moderately active colitis with ulceration, cytomegalovirus staining was negative. Fecal calprotectin was >3000 [N: < 49 ug/g]. C-reactive protein was 63 [N: < 9 mg/L]. MR Enterography with no small bowel disease but noted hyperenhancement and thickening in the ascending and transverse colon. The initial findings, work up and lack of resolution, was most consistent with CD. Discussion: It is critical to distinguish IC from CD for appropriate management of patients. Differentiating between IC and CD can be challenging in the elderly. Endoscopy and histologic evaluation can aid correct diagnosis. Repeat endoscopy to assess progression or resolution is of utmost importance in differentiating CD from IC, but data is limited on appropriate timing. Lack of follow up endoscopy will most likely lead to misdiagnosis and incorrect management of the underlying pathology. Thus, a high index of suspicion must be maintained when discerning CD from IC.Figure 1.: A: Initial colonoscopy showing heaping upped margins of the splenic flexure ulcerations. B: Repeat colonoscopy showing deep colonic ulceration with heaped up margins at the area of splenic flexure without any resolution.

Dietary Microencapsulated Blend of Organic Acids and Plant Essential Oils Affects Intestinal Morphology and Microbiome of Rainbow Trout (Oncorhynchus mykiss).

A study was conducted on 500 juvenile rainbow trout (122 ± 4 g) fed either a control diet or a treatment diet containing 300 mg/kg of a microencapsulated blend of organic acids and essential oils to elucidate effects on intestinal morphology and microbiome. Proximal intestinal villi length was significantly increased in fish fed the treatment diet. Despite no differences in gut inflammation scores, edema, lamina propria inflammation and apoptosis were completely absent in the distal intestine of fish fed the treatment diet. Next-generation sequencing of the 16S rDNA showed no differences in alpha and beta diversity, and gut bacteria were mainly composed of Firmicutes, Bacteroidetes and Proteobacteria. On the genus level, LefSe analysis of indicator OTUs showed Bacteroides, Sporosarcina, Veillonella, Aeromonas and Acinetobacter were associated with the control diet whereas Streptococcus, Fusobacterium and Escherichia were associated with the treatment diet. Aeromonas hydrophila and Acinetobacter spp. are opportunistic pathogens and several strains have been found to be resistant to antibiotics. The increase in villi length and reduction of specific pathogens indicates that feeding a microencapsulated blend of organic acids and essential oils improves gut health and may serve as a part of an effective strategy to reduce antibiotic use in aquaculture.

Oral administration of D-serine prevents the onset and progression of colitis in mice.

L-amino acids are the predominant forms of organic molecules on the planet, but recent studies have revealed that various foods contain D-amino acids, the enantiomers of L-amino acids. Though diet plays important roles in both the development and progression of inflammatory bowel disease (IBD), to our best knowledge, there has been no report on any potential interactions between D-amino acids and IBD. In this report, we aim to assess the effects of D-serine in a murine model of IBD. To induce chronic colitis, naïve CD4 T cells (CD4+ CD62+ CD44low) from wild-type mice were adoptively transferred into Rag2-/- mice, after or before the mice were orally administered with D-serine. In vitro proliferation assays were performed to assess naïve CD4 T cell activation under the Th-skewing conditions in the presence of D-serine. Mice treated with D-serine prior to the induction of colitis exhibited a reduction in T-cell infiltration into the lamina propria and colonic inflammation that were not seen in mice fed with water alone or L-serine. Moreover, D-serine suppressed the progression of chronic colitis when administered after the disease induction. Under in vitro conditions, D-serine suppressed the proliferation of activated CD4 T cells and limited their ability to differentiate to Th1 and Th17 cells. Our results suggest that D-serine not only can prevent, but also has efficacious effects as a treatment for IBD.

Histologic Features of Tacrolimus-induced Colonic Injury.

Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.

Molecular pathways underlying tissue injuries in the bladder with ketamine cystitis.

Ketamine cystitis (KC) is a chronic bladder inflammation leading to urinary urgency, frequency, and pain. The pathogenesis of KC is complicated and involves multiple tissue injuries in the bladder. Recent studies indicated that urothelium disruption, lamina propria fibrosis and inflammation, microvascular injury, neuropathological alterations, and bladder smooth muscle (BSM) abnormalities all contribute to the pathogenesis of KC. Ketamine has been shown to induce these tissue injuries by regulating different signaling pathways. Ketamine can stimulate antiproliferative factor, adenosine triphosphate, and oxidative stress to disrupt urothelium. Lamina propria fibrosis and inflammation are associated with the activation of cyclooxygenase-2, nitric oxide synthase, immunoglobulin E, and transforming growth factor β1. Ketamine contributes to microvascular injury via the N-methyl-D aspartic receptor (NMDAR), and multiple inflammatory and angiogenic factors such as tumor necrosis factor α and vascular endothelial growth factor. For BSM abnormalities, ketamine can depress the protein kinase B, extracellular signal-regulated kinase, Cav1.2, and muscarinic receptor signaling. Elevated purinergic signaling also plays a role in BSM abnormalities. In addition, ketamine affects neuropathological alterations in the bladder by regulating NMDAR- and brain-derived neurotrophic factor-dependent signaling. Inflammatory cells also contribute to neuropathological changes via the secretion of chemical mediators. Clarifying the role and function of these signaling underlying tissue injuries in the bladder with KC can contribute to a better understanding of the pathophysiology of this disease and to the design of effective treatments for KC.

Giardia duodenalis pathogenicity on immunosuppressed animal model.

Giardiasis is the major water-borne diarrheal disease present worldwide caused by the common intestinal parasite, Giardia duodenalis. This work aims to investigate the effect of G. duodenalis infection pathogenicity in immunosuppressed animals through histopathological examination. A total of 45 BALB/c mice were divided into four groups; G1 (negative control), G2 (healthy animals exposed to Giardia); G3 (immunosuppressed animals exposed to Giardia), and G4 (non-exposed immunosuppressed animals). Our study revealed that G3 was the most affected group with an infection rate of 100%. The animals showed general weakness, soft stool, and high death rate with severe histopathological changes in the duodenum and mild degenerative changes in hepatic tissues. In G2, the maximal lesions in both duodenum and liver were on the 11th day. We spotted damage in the villi, edema in the central core, and submucosa, in addition to increased cellular infiltration with inflammation in lamina propria. The presence of the parasites within the villi and the lumen was clear. Most of the hepatocytes revealed hydropic and fatty changes, also dilated congested central veins and edema were observed. G3 changes were more intense than G2 with massive Giardia trophozoites between the intestinal villi, lumen, and extensive fatty liver degeneration. Immune suppression plays a significant role in the severity of injury with the Giardia parasites in duodenum and liver cells.