Hyperbaric oxygen therapy ameliorates TNBS-induced acute distal colitis in rats

Abstract\ud \ud Background\ud This study investigated the therapeutic effects of hyperbaric oxygen in experimental acute distal colitis focusing on its effect on the production of pro-inflammatory cytokines, nitric oxide and hypoxia-inducible factor 1alpha.\ud \ud \ud Methods\ud Colitis was induced with a rectal infusion of 150 mg/kg of TNBS under anesthesia with Ketamine (50 mg/kg) and Xylazine (10 mg/kg). Control animals received only rectal saline. After colitis induction, animals were subjected to two sessions of hyperbaric oxygen and were then euthanized. The distal intestine was resected for macroscopic analysis, determination of myeloperoxidase activity, western-blotting analyses of inducible nitric oxide synthase and cyclooxygenase-2 expression and immunohistochemical analysis of hypoxia-inducible factor 1alpha and cyclooxygenase-2. Cytokines levels in the distal intestine were measured using an enzyme-linked immunosorbent assay.\ud \ud \ud Results\ud Hyperbaric oxygen therapy attenuated the severity of acute distal colitis, with reduced macroscopic damage score. This effect was associated with prevention in the increase of pro-inflammatory cytokine production; myeloperoxidase activity, in the expression of inducible nitric oxide synthase and cyclooxygenase-2. Finally, hyperbaric oxygen inhibited the acute distal colitis-induced up-regulation of hypoxia-inducible factor 1alpha.\ud \ud \ud Conclusions\ud The results indicate that hyperbaric oxygen attenuates the severity of acute distal colitis through the down-regulation of pro-inflammatory events.This work was supported by FAEPA\ud (Fundação de Apoio ao Ensino, Pesquisa e Assistência), Ribeirão Preto\ud Medical School University of Sao Paulo, Brazil and Grant 2011/19670-0 from\ud São Paulo Research Foundation (FAPESP)

Infliximab Trough Levels and Quality of Life in Patients with Inflammatory Bowel Disease in Maintenance Therapy

Objective. Investigate the association between infliximab trough levels and quality of life in inflammatory bowel disease patients in maintenance therapy. Methods. We carried out a transversal study with inflammatory bowel disease patients in infliximab maintenance therapy. Infliximab trough levels were determined using a quantitative rapid test. Disease activity indices (partial Mayo Score and Harvey-Bradshaw Index) and endoscopic scores (endoscopic Mayo Score or Simple Endoscopic Score in Crohn’s disease) were obtained. Quality of life was assessed using the Inflammatory Bowel Disease Questionnaire (IBDQ). Results. Seventy-one consecutive subjects were included in the study (55 with Crohn’s disease and 16 with ulcerative colitis). Drug levels were considered satisfactory (≥3 μg/mL) in 28 patients (39.4%) and unsatisfactory (<3 μg/mL) in 43 (60.6%). Satisfactory trough levels were associated with higher rates of clinical remission and mucosal healing. Higher trough levels were also associated with improved IBDQ scores, particularly regarding bowel symptoms, systemic function, and social function. Conclusion. Satisfactory trough levels of infliximab were associated with higher rates of clinical remission, mucosal healing, and improved quality of life in inflammatory bowel disease patients on maintenance therapy

A Novel Severity Score Index for Febrile Neutropenic Patients with Colorectal Diseases

Introduction. Abdominal and anorectal disorders may be the cause of clinical decompensation in neutropenic febrile patients, particularly those with hematologic diseases. Infection is a cause for concern for the colorectal surgeon. Some conditions have few manifestations and can lead to death within a short period of time. This study presents the novel colorectal disorder severity score for febrile neutropenic patients. Materials and Methods. This was a case series study analyzing the medical records of 897 patients admitted to the Hematology and Hematopoietic Stem Cell Transplant Unit in a university hospital between the years 2008 and 2013. Seventy-four episodes of febrile neutropenia in 69 patients diagnosed with an abdominal or anorectal infection site were eligible for the study. The new scoring system proposed here is based on the author’s clinical experience and an extensive literature review. In addition to the extensive literature review, effect measures were calculated, and a statistical analysis was performed. Based on an evaluation of common biological plausibility criteria, five factors were selected as the main predictors of hospital mortality in febrile neutropenic patients with colorectal disease. Results. The proposed score demonstrated increased mortality as the condition worsened as reflected by an increasing score (Fisher’s exact test: 0.001). When considering the logistic model for the probability of death by score level, the AUC value was 0.82 (0.72-0.925), and the Hosmer-Lemeshow statistic value was 2.3, p=0.806. Conclusion. The proposed scoring system allows prediction of the likelihood of death during hospitalization for febrile neutropenic patients with an abdominal and anorectal focus. New studies on the subject are required, and the proposed scoring scale must be validated on a larger and different sample of patients

Adjunctive Hyperbaric Oxygen Therapy in Refractory Crohn’s Disease: An Observational Study

Background and Aims. Patients may experience complications of Crohn’s disease (CD) even when treated with optimal medical therapy strategies. Previous data have shown the efficacy of hyperbaric oxygen therapy (HBOT) in the management of complicated CD. However, there is no consensus regarding the optimal number of sessions or duration of treatment regimens. The aim of the present study was to investigate the efficacy of HBOT in CD patients who were refractory to conventional medical management. Methods. This study included patients who underwent HBOT for the treatment of the following complications: perianal fistulizing Crohn’s disease (pCD), enterocutaneous fistulas (ECF), or pyoderma gangrenosum (PG). Complete healing was defined as the closure of external orifice and the absence of active draining (in pCD), complete wound healing (in PG), and granulation or complete wound epithelialization with no enteric draining (in ECF). The persistence of draining and the absence of wound granulation were defined as incomplete healing. Results. Forty patients were included. The mean CD duration was 10.6±5.8 years. pCD comprised most of the included patients (25/62.5%), followed by ECF (n=13/32.5%) and PG (n=6/15%). In two patients (5%), a combination of ECF and PG was diagnosed, and in one patient (2.5%), all three complications were observed. A total of 32 patients (82.5%) had complete healing. Patients with PG had the highest healing rates (100%), followed by those with ECF (84.6%) and pCD (80%). Conclusions. Adjunctive HBO was associated with significant healing rates for CD-associated complications such as pCD, ECF, and PG

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course

sTREM-1 Predicts Disease Severity and Mortality in COVID-19 Patients: Involvement of Peripheral Blood Leukocytes and MMP-8 Activity

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients (n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19