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The Journal of Allergy and Clinical... Jun 2024Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the... (Review)
Review
Eosinophilic gastrointestinal diseases (EGIDs) are a group of diseases characterized by selective eosinophil infiltration of the gastrointestinal (GI) tract in the absence of other causes of eosinophilia. These diseases are generally driven by type 2 inflammation, often in response to food allergen exposure. Among all EGIDs, the clinical presentation often includes a history of atopic disease with a variety of GI symptoms. EGIDs are traditionally separated into eosinophilic esophagitis (EoE) and non-EoE EGIDs. EoE is relatively better understood and now associated with clinical guidelines and 2 US Food and Drug Administration-approved treatments, whereas non-EoE EGIDs are rarer and less well-understood diseases without US Food and Drug Administration-approved treatments. Non-EoE EGIDs are further subclassified by the area of the GI tract that is involved; they comprise eosinophilic gastritis, eosinophilic enteritis (including eosinophilic duodenitis), and eosinophilic colitis. As with other GI disorders, the disease presentations and mechanisms differ depending on the involved segment of the GI tract; however, the differences between EoE and non-EoE EGIDs extend beyond which GI tract segment is involved. The aim of this article is to summarize the commonalities and differences between the clinical presentations and disease mechanisms for EoE and non-EoE EGIDs.
Topics: Humans; Eosinophilia; Enteritis; Gastritis; Eosinophilic Esophagitis; Animals; Eosinophils; Gastrointestinal Diseases
PubMed: 38555071
DOI: 10.1016/j.jaci.2024.03.013 -
Blood Oct 2023This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell...
This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, and follicular lymphoma. We report the results in cases of cHL. Adult patients with RR cHL who had received ≥1 prior lines of therapy and were ineligible for transplantation were treated in a dose-escalation cohort with 2 dose levels (DLs) and then on an expansion cohort at the recommended phase 2 dose (RP2D) in 21-day cycles. Vorinostat 100 mg twice a day (DL1) and 200 mg twice a day (DL2) was administered orally from days 1 to 5 and 8 to 12; all patients received pembrolizumab 200 mg IV every 3 weeks. The primary end point was safety and determination of RP2D. In total, 32 patients with cHL were enrolled, including 30 at DL2 (RP2D); 78% had received prior anti-programmed cell death 1 (anti-PD-1) therapy, and 56% were PD-1 refractory. Grade ≥3 adverse events (AEs) included hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Immune-related AEs included grade 1 or 2 thyroiditis (13%), grade 1 rash (6%), and grade 3 esophagitis/duodenitis (3%). The overall response rate (ORR) was 72% and complete response (CR) rate was 34%. Patients refractory to prior PD-1 blockade (n = 18) had ORR and CR rates of 56% and 11%, respectively. Pembrolizumab and vorinostat was well tolerated with a high ORR rate in RR cHL including in anti-PD-1-refractory disease. This trial was registered at www.clinicaltrials.gov as #NCT03150329.
Topics: Adult; Humans; Hodgkin Disease; Vorinostat; Programmed Cell Death 1 Receptor; Neoplasm Recurrence, Local; Antibodies, Monoclonal, Humanized
PubMed: 37339586
DOI: 10.1182/blood.2023020485 -
Biomaterials Nov 2023Duodenal ablation improves glycaemic control and weight loss, so it has been applied using hydrothermal catheters in obese and type 2 diabetes patients, indicating...
Duodenal ablation improves glycaemic control and weight loss, so it has been applied using hydrothermal catheters in obese and type 2 diabetes patients, indicating similar mechanisms and therapeutic effects as bariatric surgeries. Endoscopic photodynamic therapy is an innovative procedure that easily accessible to endocrine or gastrointestinal organs, so it is critical for the sprayed photosensitizer (PS) to long-term interact with target tissues for enhancing its effects. Surfactant-like PS was more stable in a wide range of pH and 2.8-fold more retained in the duodenum at 1 h than hydrophilic PS due to its amphiphilic property. Endoscopic duodenal ablation using surfactant-like PS was performed in high fat diet induced rat models, demonstrating body weight loss, enhanced insulin sensitivity, and modulation of incretin hormones. Locoregional ablation of duodenum could affect the profiles of overall intestinal cells secreting meal-stimulated hormones and further the systemic glucose and lipid metabolism, regarding gut-brain axis. Our strategy suggests a potential for a treatment of minimally invasive bariatric and metabolic therapy if accompanied by detailed clinical trials.
Topics: Humans; Animals; Rats; Diabetes Mellitus, Type 2; Incretins; Photosensitizing Agents; Surface-Active Agents; Obesity; Duodenum; Blood Glucose
PubMed: 37778055
DOI: 10.1016/j.biomaterials.2023.122336 -
European Journal of Internal Medicine Mar 2024Whipple's disease, an extremely rare, chronic infection caused by Tropheryma whipplei, an actinobacterium ubiquitously present in the environment, is a multisystemic... (Review)
Review
Whipple's disease, an extremely rare, chronic infection caused by Tropheryma whipplei, an actinobacterium ubiquitously present in the environment, is a multisystemic condition that can affect several organs. Therefore, Whipple's disease should always be considered by physicians working across various branches of medicine, including internal medicine, rheumatology, infectious diseases, gastroenterology, haematology, and neurology. Initially, Whipple's disease is challenging to diagnose due to both its rarity and non-specific clinical features, almost indistinguishable from rheumatological conditions. A few years later, the onset of gastrointestinal symptoms increases the specificity of its clinical picture and helps in reaching the correct diagnosis. Diagnosis is typically made by finding PAS-positive macrophages in the lamina propria at duodenal biopsy. PCR for Tropheryma whipplei is nowadays also increasingly available, and represents an undeniable help in diagnosing this condition. However, it may also be misleading as false positives can occur. If not promptly recognized and treated, central nervous system involvement may develop, which can be fatal. The therapeutic gold standard has not yet been fully established, particularly in cases of recurrent disease, neurological involvement, and an immune reconstitution inflammatory syndrome that may arise following the initiation of antibiotic therapy.
Topics: Humans; Whipple Disease; Rare Diseases; Anti-Bacterial Agents; Biopsy; Tropheryma; Physicians
PubMed: 38105122
DOI: 10.1016/j.ejim.2023.12.009 -
American Journal of Veterinary Research Sep 2023The objectives of this study were to quantify lymphocytes and eosinophils in the mucosa of the duodenum and rectum in asthmatic horses.
OBJECTIVE
The objectives of this study were to quantify lymphocytes and eosinophils in the mucosa of the duodenum and rectum in asthmatic horses.
ANIMALS
8 healthy and 10 asthmatic horses.
PROCEDURES
Asthmatic horses were evaluated in a symptomatic (after 6 weeks of exposure to moldy hay) and asymptomatic status (3 and 7 months after being fed alfalfa pellets [n = 4] or treated with inhaled fluticasone [6]). Duodenal and rectal biopsies were endoscopically (n = 4 to 6) taken in each horse. Eosinophils were counted on slides stained with hematoxylin, eosin, phloxine, and saffron, and immunohistochemistry was used to evaluate T and B lymphocytes using CD3 and CD20, respectively.
RESULTS
The duodenal and rectal epithelium of asthmatic and control horses contained exclusively T lymphocytes (CD3). Symptomatic asthmatic horses, compared to controls, had a significantly higher number of T lymphocytes (CD3) in the duodenal epithelium (P = .016) and the adjacent lamina propria of the villi (P = .04). Compared to symptomatic asthmatic horses, the fluticasone-treated group had significantly fewer T lymphocytes in the total lamina propria of the rectal mucosa (P < .01).
CLINICAL RELEVANCE
Taken together, these results suggest that asthmatic horses have greater infiltration of T lymphocytes in the duodenal and rectal mucosa, indicating a certain degree of inflammation, which could be due to a systemic inflammatory effect and/or a local effect of ingested hay allergens in asthmatic horses. Systemic markers of inflammation have not been investigated to better qualify if the infiltration noted is due to a local and/or systemic effect.
Topics: Horses; Animals; T-Lymphocytes; Rectum; Duodenum; Lymphocytes; Asthma; Intestinal Mucosa; Inflammation; Fluticasone; Horse Diseases
PubMed: 37532235
DOI: 10.2460/ajvr.23.04.0083 -
Environmental Toxicology Nov 2023Exosomes are applied as biomarkers in several diseases according to their disease-specific profiles. However, the exosomes effects in functional dyspepsia (FD) are still...
BACKGROUND
Exosomes are applied as biomarkers in several diseases according to their disease-specific profiles. However, the exosomes effects in functional dyspepsia (FD) are still fragmentary. Here we examined the role of Eosinophil and mast cell derived-exosomes in FD progression.
METHODS
Fifty FD subjects and age- and sex-matched healthy controls were included in this retrospective cohort study. Duodenal mucosa and gastric juice were collected to analyze molecular difference. Eosinophil and mast cell were evaluated by immunofluorescence and microarray was subjected to examine the expression levels of NEAT1, miR-211-5p, and glial cell line-derived neurotrophic factor (GDNF), which were subsequently were tested by quantitative reverse transcription PCR (RT-qPCR) validation cohorts. CCK-8 assays, and wound healing assays were used to evaluate integrity of intestinal mucosal barrier in vitro. Rats' weights and gastric emptying rates were used as evaluation of FD severity in vivo.
RESULTS
Eosinophil and mast cell were enriched and secreted more exosomes in duodenal mucosa of FD patients. We identified differential lncRNAs that were consistently and significantly up regulated in FD cases. Of these, NEAT1 was further validated by RT-qPCR and had closely relationship with GDNF. MiR-211-5p level was found to be reduced in FD and negatively related with NEAT1 and GDNF. Furthermore, NEAT1and GDNF relived FD while miR-211-5p made symptoms worse. The NEAT1/miR-211-5p/GDNF axis had a good predictive ability for FD.
CONCLUSIONS
The NEAT1/miR-211-5p/GDNF could be a potential FD biomarker.
Topics: Humans; Rats; Animals; MicroRNAs; Retrospective Studies; Glial Cell Line-Derived Neurotrophic Factor; Eosinophils; Mast Cells; Exosomes; Duodenum; Intestinal Mucosa; RNA, Long Noncoding
PubMed: 37466184
DOI: 10.1002/tox.23895 -
Annals of Surgical Oncology Feb 2024The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current... (Review)
Review
BACKGROUND
The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current evidence supporting the use of neoadjuvant therapy (NAT) in AA and DA.
METHODS
The study searched PubMed, Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCO), and ClinicalTrials.gov databases for observational or randomized studies published between 2002 and 2022 evaluating survival outcomes for patients with non-metastatic AA or DA who received systemic therapy and surgical resection. The data extracted included overall survival, progression-free survival, and pathologic response (PR) rate.
RESULTS
From the 347 abstracts identified in this study, 29 reports were reviewed in full, and 15 were included in the final review. The selected studies published from 2007 to 2022 were retrospective. Eight were single-center studies; five used the National Cancer Database (NCDB); and two were European multicenter/national studies. Overall, no studies identified survival differences between NAT and upfront surgery (with or without adjuvant therapy). Two NCDB studies reported longer survival with NAT/AT than with surgery. Five single-center studies reported a significant portion of NAT patients who achieved PR, and one study identified major PR as an independent predictor of survival. Other outcomes associated with NAT included conversion from unresectable to resectable disease, reduced lymph node positivity, and decreased local recurrence rate.
CONCLUSION
Evidence supporting the use of NAT in AA and DA is weak. No randomized studies exist, and observational data show mixed results. For patients with DA and AA, NAT appears safe, but better evidence is needed to understand the preferred multidisciplinary management of DA and AA periampullary malignancies.
Topics: Humans; Adenocarcinoma; Combined Modality Therapy; Common Bile Duct Neoplasms; Multicenter Studies as Topic; Neoadjuvant Therapy; Pancreatic Neoplasms; Retrospective Studies; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 37952021
DOI: 10.1245/s10434-023-14531-y -
The Journal of Allergy and Clinical... Sep 2023Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An...
BACKGROUND
Eosinophilic gastritis/gastroenteritis (EoG/EoGE) are rare disorders with pathologic gastric and/or small intestinal eosinophilia lacking an approved therapy. An allergic mechanism is postulated but underexplored mechanistically and therapeutically.
OBJECTIVE
We evaluated the effectiveness of a food allergen-free diet (elemental formula) in controlling gastrointestinal eosinophilia in adult EoG/EoGE.
METHODS
Adults aged 18 to 65 years with histologically active EoG/EoGE (≥30 eosinophils per high-power field) in the stomach and/or duodenum and gastrointestinal symptoms within the month preceding enrollment were prospectively enrolled onto a single-arm clinical trial to receive elemental formula for 6 consecutive weeks. The primary end point was percentage of participants with complete histologic remission (<30 eosinophils per high-power field in both stomach and duodenum). Exploratory outcomes were improvement in symptoms, endoscopy results, blood eosinophilia, quality of life, Physician Global Assessment score, and EoG-relevant gastric transcriptome and microbiome.
RESULTS
Fifteen adults (47% male, average age 37.7 years, average symptom duration 8.8 years) completed the trial. Multi-gastrointestinal segment involvement affected 87%. All subjects had complete histologic remission in the stomach (P = .002) and duodenum (P = .001). Scores improved in overall PhGA (P = .002); EGREFS (P = .003); EGDP (P = .002); SODA pain intensity (P = .044), non-pain (P = .039), and satisfaction (P = .0024); and PROMIS depression (P = .0078) and fatigue (P = .04). Food reintroduction reversed these improvements. The intervention was well tolerated in 14 subjects, with 1 serious adverse event reported in 1 subject.
CONCLUSION
An amino acid-based elemental diet improves histologic, endoscopic, symptomatic, quality-of-life, and molecular parameters of EoG/EoGE; these findings and disease recurrence with food trigger reintroduction support a dominant role for food allergens in disease pathogenesis.
CLINICALTRIALS
gov Identifier: NCT03320369.
Topics: Adult; Male; Humans; Female; Prospective Studies; Amino Acids; Quality of Life; Enteritis; Eosinophilia; Gastroenteritis; Food Hypersensitivity; Allergens; Food, Formulated; Eosinophilic Esophagitis
PubMed: 37462600
DOI: 10.1016/j.jaci.2023.05.024