Explore the vast range of titles available.

ObjectivesPrimary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs).DesignNKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies.ResultsNKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo.ConclusionNKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL.

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8 + CD56 + (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαβ over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8 + cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

Background HIV-infection results in damage and dysfunction of the gastrointestinal system. HIV enteropathy includes pronounced CD4+ T-cell loss, increased intestinal permeability, and microbial translocation that promotes systemic immune activation, which is implicated in disease progression. A synbiotic is the combination of probiotics and prebiotics that could improve gut barrier function. Our study goal was to determine whether the use of a synbiotic, probiotics or a prebiotic can recover immunological parameters in HIV-infected subjects through of a reduction of microbial translocation and pro-inflammatory cytokine production. Methods A randomized, double-blind controlled study was performed; twenty Antiretroviral treatment-naïve HIV-infected subjects were subgrouped and assigned to receive a synbiotic, probiotics, a prebiotic, or a placebo throughout 16 weeks. Results We had no reports of serious adverse-events. From baseline to week 16, the synbiotic group showed a reduction in bacterial DNA concentrations in plasma ( p  = 0.048). Moreover, the probiotic and synbiotic groups demonstrated a decrease in total bacterial load in feces ( p  = 0.05). The probiotic group exhibited a significant increment of beneficial bacteria load (such as Bifidobacterium ; p  = 0.05) and a decrease in harmful bacteria load (such as Clostridium; p  = 0.063). In the synbiotic group, the CD4+ T-cells count increased (median: +102 cells/μL; p  = 0.05) and the level of Interleukin 6 cytokine decreased significantly ( p  = 0.016). Conclusions Our study showed a significant increase in CD4+ T lymphocyte levels in the synbiotic group, which could delay the initiation of antiretroviral therapy and decrease costs in countries with limited resources.

Enteropathy-associated T-cell lymphoma (EATL) is a rare, aggressive form of T-cell non-Hodgkin lymphoma, primarily affecting the small intestine. Due to its extremely low incidence and poor prognosis, studies on EATL are limited. This study aims to analyze the incidence trends, prognostic factors, and survival outcomes of EATL using the SEER database. We analyzed the incidence trends of EATL using SEER data from 2000 to 2021 and performed multivariate Cox regression to identify independent prognostic factors. Conditional survival (CS) analysis was performed to evaluate survival outcomes, and a CS-nomogram was developed to predict 1-, 3-, and 5-year overall survival (OS) and 5-year CS. The age-adjusted incidence rate of EATL was 0.014 per 100,000, showing a significant upward trend (APC 2.63). Multivariate analysis identified age, tumor site, tumor stage, surgery, and chemotherapy as independent OS risk factors. CS analysis showed that the 5-year survival probability progressively increased from 16% to 48%, 67%, 83%, and 93% after surviving 0, 1, 2, 3, and 4 years post-diagnosis. The dynamic nomogram showed excellent performance in predicting survival and stratifying patients into risk groups. This study provided valuable insights into the epidemiology, prognosis, and survival outcomes of EATL. The increasing incidence and CS outcomes highlighted the importance of early detection and intervention. The dynamic nomogram model developed here offered a more accurate prediction of individual survival outcomes and can aid in clinical decision-making.

Abstract Background Calprotectin is a marker of inflammation, but its clinical utility in dogs with chronic inflammatory enteropathies (CIE) is unknown. Objective Evaluation of fecal calprotectin in dogs with biopsy-confirmed CIE. Animals 127 dogs. Methods Prospective case-control study. Dogs were assigned a canine chronic enteropathy clinical activity index (CCECAI) score, and histologic lesions severity was assessed. Fecal calprotectin, fecal S100A12, and serum C-reactive protein (CRP) were measured. Food- or antibiotic-responsive cases (FRE/ARE, n = 13) were distinguished from steroid-/immunosuppressant-responsive or -refractory cases (SRE/IRE, n = 20). Clinical response to treatment in SRE/IRE dogs was classified as complete remission (CR), partial response (PR), or no response (NR). Results Fecal calprotectin correlated with CCECAI (ρ = 0.27, P = .0065) and fecal S100A12 (ρ = 0.90, P < .0001), some inflammatory criteria, and cumulative inflammation scores, but not serum CRP (ρ = 0.16, P = .12). Dogs with SRE/IRE had higher fecal calprotectin concentrations (median: 2.0 μg/g) than FRE/ARE dogs (median: 1.4 μg/g), and within the SRE/IRE group, dogs with PR/NR had higher fecal calprotectin (median: 37.0 μg/g) than dogs with CR (median: 1.6 μg/g). However, both differences did not reach statistical significance (both P = .10). A fecal calprotectin ≥15.2 μg/g separated both groups with 80% sensitivity (95% confidence interval [95%CI]: 28%-100%) and 75% specificity (95%CI: 43%-95%). Conclusions and Clinical Importance Fecal calprotectin could be a useful surrogate marker of disease severity in dogs with CIE, but larger longitudinal studies are needed to evaluate its utility in predicting the response to treatment.

Abstract Chronic inflammatory enteropathies (CIE) in dogs are a group of disorders that are characterized by chronic persistent or recurrent signs of gastrointestinal disease and histologic evidence of mucosal inflammation. These CIEs are classified as either food-responsive, antibiotic-responsive, or immunosuppressant-responsive enteropathy. Patients not clinically responding to immunomodulatory treatment are grouped as nonresponsive enteropathy and dogs with intestinal protein loss as protein-losing enteropathy. Disease-independent clinical scoring systems were established in dogs for assessment of clinical disease severity and patient monitoring during treatment. Histopathologic and routine clinicopathologic findings are usually not able to distinguish the subgroups of CIE. Treatment trials are often lengthy and further diagnostic tests are usually at least minimally invasive. Biomarkers that can aid in defining the presence of disease, site of origin, severity of the disease process, response to treatment, or a combination of these would be clinically useful in dogs with CIE. This article summarizes the following biomarkers that have been evaluated in dogs with CIE during the last decade, and critically evaluates their potential clinical utility in dogs with CIE: functional biomarkers (cobalamin, methylmalonic acid, folate, α1-proteinase inhibitor, immunoglobulin A), biochemical biomarkers (C-reactive protein, perinuclear anti-neutrophilic cytoplasmic antibodies, 3-bromotyrosine, N-methylhistamine, calprotectin, S100A12, soluble receptor of advanced glycation end products, cytokines and chemokines, alkaline phosphatase), microbiomic biomarkers (microbiome changes, dysbiosis index), metabolomic biomarkers (serum metabolome), genetic biomarkers (genomic markers, gene expression changes), and cellular biomarkers (regulatory T cells). In addition, important performance criteria of diagnostic tests are briefly reviewed.

Abstract Background Protein-losing enteropathy (PLE) in dogs often carries a guarded prognosis, and it is unclear if survival differs among breeds. Hypothesis/Objectives Survival of pugs with PLE is shorter than that of other breeds of dogs with PLE. Animals Forty-seven pugs and 148 dogs of other breeds were diagnosed with PLE at seven United Kingdom (UK) referral hospitals. Methods Retrospective, multicenter observational study. Case records were reviewed to identify dogs diagnosed with PLE. Cox's proportional hazards regression was used to determine variables associated with survival. Results Median (interquartile range) survival in pugs with PLE and dogs of other breeds was 104 (22–719) days and 759 (61–1632) days, respectively (p = 0.002). The hazard of death was higher in pugs (hazard ratio [HR]: 1.961; 95% confidence interval [CI]: 1.108–3.741; p = 0.002) than in other dogs. Neutrophil counts in peripheral blood were associated with an increased hazard of death (HR change per 1 × 109/L: 1.045; 95% CI: 1.014–1.077; p = 0.004), whereas cobalamin concentration (HR: 0.995; 95% CI: 0.991–0.999) and cobalamin supplementation (HR: 0.517; 95% CI: 0.271–0.988) were positively associated with decreased hazard of death. A time-dependent effect on survival was identified for serum globulin concentrations, whereby globulin concentration was positively associated with hazard of death in dogs surviving 61–959 days (HR: 1.126; 95% CI: 1.040–1.219) and > 959 days (1.253; 95% CI: 1.048–1.497), but not 0–60 days (HR: 0.949; 95% CI: 0.891–1.011 days). Conclusions and Clinical Importance Results of our observational study suggest a worse prognosis for pugs with PLE compared to a selection of dogs of other breeds seen at UK referral centers.

Abstract Background Immune system abnormalities including hypogammaglobulinemia and T-cell deficiency occur in humans with protein-losing enteropathy (PLE). It is unknown whether similar abnormalities occur in dogs with PLE. Objective To evaluate serum immunoglobulin (Ig) concentrations and immune cell populations in dogs with PLE (with histologic evidence of chronic inflammatory enteropathy, intestinal lymphangiectasia (IL), or both) compared to healthy controls (HC). Animals Eighteen dogs with PLE and 18 HC dogs. Methods Prospective study. Serum IgA, IgG, and IgM concentrations were measured via ELISA in treatment-naïve dogs with PLE and compared to concentrations in HC dogs. RNA gene expression of specific immune cell surface markers in peripheral blood mononuclear cells (PBMCs) was measured in both groups by quantitative PCR. Results Dogs with PLE had lower concentrations of serum IgG compared to HC dogs (4.5 mg/mL, range 0.67–22.4 mg/mL vs. 19 mg/mL, range 1.8–80.3 mg/mL; p < 0.001). Serum IgM concentrations were also lower in dogs with PLE versus HC (2.4 mg/mL, range 0.0009–53.1 mg/mL vs. 14.2 mg/mL, range 2.1–172.8 mg/mL; p = 0.002). Expression of CD3e (0.24, range 0.003–1.1 vs. 0.92, range 0.41–3.2; p < 0.001), CD5 (0.17, range 0.01–0.46 vs. 0.94, range 0.23–5; p < 0.001), and CD8 (0.47, range 0.06–1.7 vs. 0.92, range 0.32–2.4; p = 0.007) were reduced in dogs with PLE compared to their mean absolute expression in HC dogs. Conclusions and Clinical Importance Dogs with PLE have quantitative reductions in immune system components, similar to humans with IL. These abnormalities in immune system components might be considered in the management and monitoring of dogs with PLE.

Abstract Background More than 50% of dogs with protein-losing enteropathy (PLE) fail to respond to standard therapies. Octreotide, a somatostatin analogue, is used in cases of intestinal lymphangiectasia (IL) in humans with some success. Objectives Describe the use of octreotide in dogs with PLE including reason for and details of prescription, adverse effects, and apparent response. Animals Eighteen dogs with PLE, 13 with histopathology available. Ninety-two percent (12/13) had IL diagnosed on biopsy. All 13 dogs had intestinal inflammatory infiltrates noted. Methods Multicenter, retrospective, descriptive study. Cases were volunteered for inclusion by individual attending veterinarians who reported the use of octreotide in cases of PLE. Results In 16/18 (89%) cases octreotide was prescribed to PLE dogs with a clinical suspicion or confirmed diagnosis of IL that were refractory to standard therapies. Median serum albumin at the time of octreotide prescription was 1.7 g/dL (range, 1.0-3.1 g/dL). The median dose of octreotide prescribed was 20 μg/kg, SQ, daily with a range of 4-39 μg/kg, SQ, daily. Adverse effects were noted in 3/18 (17%, 95% CI [4%, 41%]) of dogs; discontinuation of the drug was necessary in 1 dog. Improvement in clinical signs was noted in 6/12 (50%, 95% CI [21%, 79%]). Conclusions and Clinical Importance Octreotide was most commonly prescribed to dogs with PLE and suspected or confirmed IL that had failed to respond to standard therapies. Though a benefit to PLE dogs cannot be confirmed, octreotide was well tolerated by the majority of dogs at the doses prescribed in this study.

Abstract Background The relationship between the development of SHPT and ionized magnesium (iMg) concentrations in blood of dogs with chronic gastrointestinal (GI) disease and abnormally low 25(OH)D is undefined. Objectives Evaluate relationships between ionized magnesium (iMg), PTH, ionized calcium (iCa), and 25(OH)D in dogs with chronic enteropathy (CE) with or without protein-losing enteropathy (PLE) and abnormal 25(OH)D. Determine whether dogs with CE or PLE, decreased 25(OH)D and SHPT have differences in iMg, iCa, or 25(OH)D when compared to dogs that do not have SHPT. Animals Fifty dogs with CE +/− PLE and abnormally low serum 25(OH)D. Methods Retrospective search of submissions database at a veterinary diagnostic laboratory for vitamin D profiles submitted in years 2017 to 2020. Cases were excluded if supplemented with Ca, Mg, or vitamin D. Spearman correlation was performed to evaluate relationships between iMg, PTH, 25(OH)D, and iCa. Ionized Mg, iCa, and 25(OH)D concentrations were compared between dogs with SHPT and those with normal PTH concentrations. Results Concentrations of iMg were weakly negatively correlated with PTH (rho, −.31; P = .03), and weakly positively correlated with serum 25(OH)D (rho, .34, P = .02) and iCa (rho, .42, P = .003). Ionized magnesium concentrations were lower in dogs with abnormally low 25(OH)D and SHPT compared to dogs with abnormally low 25(OH)D and normal parathyroid hormone concentrations (P = .01). Conclusions and Clinical Importance Hypomagnesemia might contribute to alterations in iCa and parathyroid hormone in dogs with CE +/− PLE and abnormally low 25(OH)D.