Altered Genome-Wide DNA Methylation in the Duodenum of Common Variable Immunodeficiency Patients.

Purpose: A large proportion of Common variable immunodeficiency (CVID) patients has duodenal inflammation with increased intraepithelial lymphocytes (IEL) of unknown aetiology. The histologic similarities to celiac disease, lead to confusion regarding treatment (gluten-free diet) of these patients. We aimed to elucidate the role of epigenetic DNA methylation in the aetiology of duodenal inflammation in CVID and differentiate it from true celiac disease.

Multiregional transcriptomics identifies congruent consensus subtypes with prognostic value beyond tumor heterogeneity of colorectal cancer.

Intra-tumor heterogeneity compromises the clinical value of transcriptomic classifications of colorectal cancer. We investigated the prognostic effect of transcriptomic heterogeneity and the potential for classifications less vulnerable to heterogeneity in a single-hospital series of 1093 tumor samples from 692 patients, including multiregional samples from 98 primary tumors and 35 primary-metastasis sets. We show that intra-tumor heterogeneity of the consensus molecular subtypes (CMS) is frequent and has poor-prognostic associations independently of tumor microenvironment markers.

Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease.

Background & Aims: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment.

Allogeneic bone marrow transplantation for patients with treatment-refractory Crohn's Disease.

Background & Aims: Durable remissions of Crohn's Disease (CD) have followed myeloablative conditioning therapy and allogeneic marrow transplantation. For patients with treatment-refractory disease, we used reduced-intensity conditioning to minimize toxicity, marrow from donors with low Polygenic Risk Scores for CD as cell sources, and protracted immune suppression to lower the risk of graft-versus-host disease (GVHD). Our aim was to achieve durable CD remissions while minimizing transplant-related complications.

Navigation-Assisted Surgery for Locally Advanced Primary and Recurrent Rectal Cancer.

Background: In some surgical disciplines, navigation-assisted surgery has become standard of care, but in rectal cancer, indications for navigation and the utility of different technologies remain undetermined.

Methods: The NAVI-LARRC prospective study (NCT04512937; IDEAL Stage 2a) evaluated feasibility of navigation in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC). Included patients had advanced tumours with high risk of incomplete (R1/R2) resection, and navigation was considered likely to improve the probability of complete resection (R0).

Clinical and biochemical impact of vitamin B6 deficiency in primary sclerosing cholangitis before and after liver transplantation.

Background And Aims: We previously demonstrated that people with primary sclerosing cholangitis (PSC) had reduced gut microbial capacity to produce active vitamin B6 (pyridoxal 5'-phosphate [PLP]), which corresponded to lower circulating PLP levels and poor outcomes. Here, we define the extent and biochemical and clinical impact of vitamin B6 deficiency in people with PSC from several centers before and after liver transplantation (LT).

Methods: We used targeted liquid chromatography-tandem mass spectrometry to measure B6 vitamers and B6-related metabolic changes in blood from geographically distinct cross-sectional cohorts totaling 373 people with PSC and 100 healthy controls to expand on our earlier findings.

Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

Background: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy.

Methods: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010.

Clinical Variables as Indicative Factors for Endoscopy in Adolescents with Esophageal Atresia.

Introduction: Gastro-esophageal reflux disease (GERD) occurs frequently in patients operated for esophageal atresia (EA). Longstanding esophagitis may lead to dysphagia, strictures, columnar metaplasia, and dysplasia with an increased risk of adenocarcinoma. Are clinical factors and non-invasive assessments reliable indicators for follow-up with endoscopy?

Material And Method: A follow-up study with inclusion of EA adolescents in Norway born between 1996 and 2002 was conducted.

Duodenal inflammation in common variable immunodeficiency has altered transcriptional response to viruses.

Background: A substantial proportion of common variable immunodeficiency (CVID) patients has duodenal inflammation of largely unknown etiology. However, because of its histologic similarities with celiac disease, gluten sensitivity has been proposed as a potential mechanism.

Objective: We aimed to elucidate the role of the duodenal microenvironment in the pathogenesis of duodenal inflammation in CVID by investigating the transcriptional, proteomic, and microbial signatures of duodenal biopsy samples in CVID.

Spatial transcriptomics identifies enriched gene expression and cell types in human liver fibrosis.

Liver fibrosis and cirrhosis have limited therapeutic options and represent a serious unmet patient need. Recent use of single-cell RNA sequencing (scRNAseq) has identified enriched cell types infiltrating cirrhotic livers but without defining the microanatomical location of these lineages thoroughly. To assess whether fibrotic liver regions specifically harbor enriched cell types, we explored whether whole-tissue spatial transcriptomics combined with scRNAseq and gene deconvolution analysis could be used to localize cell types in cirrhotic explants of patients with end-stage liver disease (total n = 8; primary sclerosing cholangitis, n = 4; primary biliary cholangitis, n = 2, alcohol-related liver disease, n = 2).

Biliary Adenofibroma: A Rare Liver Tumor with Transition to Invasive Carcinoma.

Biliary adenofibroma is a rare benign liver tumor with potential for malignant transition. It has a bile duct origin characterized by a complex tubulocystic biliary epithelium with fibrous stroma. MRI features may suggest this uncommon entity, and histological findings can be diagnostic.

Calprotectin Expressing Donor-Derived Macrophages Increase in Acute Gastrointestinal Graft-Versus-Host Disease.

Acute graft versus host disease (GVHD) is a major cause of morbidity and mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD is therefore the main obstacle for a more widespread use of this highly effective and potentially curative therapy. Although donor T cells are believed to be key mediators in the pathogenesis of acute GVHD, recent reports have suggested that monocyte-derived macrophages also contribute.

Evaluation of diagnostic factors used to refer children with constipation for rectal biopsies.

Purpose: Children with constipation and suspected Hirschsprung's disease are referred for rectal biopsy. Since this is an invasive procedure, appropriate indications should be applied to minimize the number of "unnecessary" biopsies.

Methods: We reviewed all constipated children who underwent a rectal biopsy to diagnose a possible Hirschsprung's disease at a tertiary referral hospital over a 6-year period (2013-2018).

Fatal Cholestatic Liver Injury during Treatment with PD1 Immune Checkpoint Inhibitor for Malignant Melanoma: A Case Report.

The use of immune checkpoint inhibitors has dramatically improved the chance of surviving malignant melanomas; however, the effect comes at the cost of toxicities that are difficult to predict. Immune-mediated hepatitis is the most common form of liver toxicity, but fatal outcome is uncommon. We report the case of a 70-year-old female with metastatic malignant melanoma who developed severe liver toxicity characterized by bile duct injury and cholestasis.

Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD.

Can we ablate liver lesions close to large portal and hepatic veins with MR-guided HIFU? An experimental study in a porcine model.

Objectives: Invasive treatment of tumors adjacent to large hepatic vessels is a continuous clinical challenge. The primary aim of this study was to examine the feasibility of ablating liver tissue adjacent to large hepatic and portal veins with magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU). The secondary aim was to compare sonication data for ablations performed adjacent to hepatic veins (HV) versus portal veins (PV).

Machine learning for intraoperative prediction of viability in ischemic small intestine.

Objective: Evaluation of intestinal viability is essential in surgical decision-making in patients with acute intestinal ischemia. There has been no substantial change in the mortality rate (30%-93%) of patients with acute mesenteric ischemia (AMI) since the 1980s. As the accuracy from the first laparotomy alone is 50%, the gold standard is a second-look laparotomy, increasing the accuracy to 87%-89%.

Ischemia/reperfusion injury in porcine intestine - Viability assessment.

Aim: To investigate viability assessment of segmental small bowel ischemia/reperfusion in a porcine model.

Methods: In 15 pigs, five or six 30-cm segments of jejunum were simultaneously made ischemic by clamping the mesenteric arteries and veins for 1 to 16 h. Reperfusion was initiated after different intervals of ischemia (1-8 h) and subsequently monitored for 5-15 h.

Establishment of a surgical bile duct injection technique giving direct access to the bile ducts for studies of the murine biliary tree.

Cholangiopathies are progressive disorders with largely unknown pathoetiology and limited treatment options. We aimed to develop a novel surgical technique with direct access to the bile ducts that would complement existing mouse models of cholestasis, biliary inflammation, and fibrosis and present a new route of administration for testing of potential treatment strategies. We developed a surgical technique to access the murine biliary tree by injection of different solvents through catheterization of the gall bladder with simultaneous clamping of the common bile duct.

HLA-DQ:gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge.

Objective: Initiation of a gluten-free diet without proper diagnostic work-up of coeliac disease is a frequent and demanding problem. Recent diagnostic guidelines suggest a gluten challenge of at least 14 days followed by duodenal biopsy in such patients. The rate of false-negative outcome of this approach remains unclear.