Fibrin glue and coats compromise the integrity of colonic anastomosis: an experimental trial on rats.

Background: Anastomotic leak remains a dreaded complication in colorectal surgery. Identifying optimal techniques that minimize its incidence is an active area of investigation. The aim of this experimental study was to evaluate the effect of commonly used hemostatic products on the integrity of colonic anastomoses. Methods: Male Wistar rats were randomized into 4 groups. In the control group (A), the anastomosis was performed using the standard hand-sewn technique in the ascending colon. In group B the hand-sewn technique was reinforced with a collagen-fibrinogen patch, in group C with fibrin glue, and in group D with a polyethylene glycol (PEG)-coated oxidized cellulose patch. On the 7th postoperative day, anastomotic bursting pressure measurements were obtained. A specimen surrounding the anastomosis was retrieved for histopathologic evaluation. Results: Of the 19 rats, 17 survived and 15 were included in the analysis (5 in each of groups A, B and C). Testing in group D was discontinued following adverse events in the preliminary experiments. The mean bursting pressure of the anastomosis was significantly higher in the control group (A: 221±19.41 mmHg, B: 151±14.42 mmHg, and C: 112±13.57 mmHg; P=0.001). Anastomotic healing parameters were not different between groups. Conclusions: Although experimental data support the use of sealants in defective anastomoses, in this study the reinforcement of colonic anastomosis with fibrin or oxidized cellulose-PEG sealants did not improve either bursting pressure values or anastomotic healing. More data from robust anastomoses of animals and humans are needed before sealing becomes common clinical practice in colorectal surgery.

Potential impact of trained innate immunity on the pathophysiology of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) occurs in a low-grade inflammatory milieu dependent on highly complex networks that span well-beyond the hepatic tissue injury. Dysfunctional systemic metabolism that characterizes the disease, is further induced in response to environmental cues that modify energy and metabolic cellular demands, thereby altering the availability of specific substrates that profoundly regulate, through epigenetic mechanisms, the phenotypic heterogeneity of immune cells and influence hematopoietic stem cell differentiation fate. This immuno-metabolic signaling drives the initiation of downstream effector pathways and results in the decompensation of hepatic homeostasis that precedes pro-fibrotic events. Recent evidence suggests that innate immune cells reside in different tissues in a memory effector state, a phenomenon termed trained immunity, that may be activated by subsequent exogenous (e.g., microbial, dietary) or endogenous (e.g., metabolic, apoptotic) stmuli. This process leads to long-term modifications in the epigenetic landscape that ultimately precondition the cells towards enhanced transcription of inflammatory mediators that accelerates MAFLD development and/or progression. In this mini review we aimed to present current evidence on the potential impact of trained immunity on the pathophysiology of MAFLD, shedding light on the complex immunobiology of the disease and providing novel potential therapeutic strategies to restrain the burden of the disease.

Innate immunity and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), recently renamed as metabolic (dysfunction)-associated fatty liver disease (MAFLD), is a complex, multifactorial disease that progresses via nonalcoholic steatohepatitis (NASH) towards severe liver complications. MAFLD/NAFLD affects up to a third of the global population. It is connected with metabolic syndrome parameters and has been increasing in parallel with the rates of metabolic syndrome parameters worldwide. This disease entity exhibits a strong immune-inflammatory dimension. In MAFLD/NAFLD/NASH, a vast network of innate immune cells is mobilized that can provoke liver damage, leading to advanced fibrosis, cirrhosis and its complications, including hepatocellular carcinoma. However, our understanding of the inflammatory signals that drive the onset and progression of MAFLD/NAFLD/NASH is fragmented. Thus, further investigation is required to better understand the role of specific innate immune cell subsets in the disease, and to aid the design of innovative therapeutic agents to target MAFLD/NAFLD/NASH. In this review, we discuss current concepts regarding the role of innate immune system involvement in MAFLD/NAFLD/NASH onset and progression, along with presenting potential stress signals affecting immune tolerance that may trigger aberrant immune responses. A comprehensive understanding of the innate immune mechanisms involved in MAFLD/NAFLD/NASH pathophysiology will help the discovery of early interventions to prevent the disease, and lead to potential innovative therapeutic strategies that may limit its worldwide burden.

Controlling the Impact of Helicobacter pylori-Related Hyperhomocysteinemia on Neurodegeneration.

Helicobacter pylori infection consists a high global burden affecting more than 50% of the world's population. It is implicated, beyond substantiated local gastric pathologies, i.e., peptic ulcers and gastric cancer, in the pathophysiology of several neurodegenerative disorders, mainly by inducing hyperhomocysteinemia-related brain cortical thinning (BCT). BCT has been advocated as a possible biomarker associated with neurodegenerative central nervous system disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and/or glaucoma, termed as "ocular Alzheimer's disease". According to the infection hypothesis in relation to neurodegeneration, Helicobacter pylori as non-commensal gut microbiome has been advocated as trigger and/or mediator of neurodegenerative diseases, such as the development of Alzheimer's disease. Among others, Helicobacter pylori-related inflammatory mediators, defensins, autophagy, vitamin D, dietary factors, role of probiotics, and some pathogenetic considerations including relevant involved genes are discussed within this opinion article. In conclusion, by controlling the impact of Helicobacter pylori-related hyperhomocysteinemia on neurodegenerative disorders might offer benefits, and additional research is warranted to clarify this crucial topic currently representing a major worldwide burden.

Helicobacter pylori infection as a potential risk factor for multiple sclerosis.

Helicobacter pylori infection (Hp-I) has been associated with a wide spectrum of gastrointestinal and extra-digestive manifestations, including neurodegenerative diseases. Contradictory data have been published on Hp-I and multiple sclerosis (MS) association, with studies mainly using serology for Hp-I detection that cannot distinguish between active and past infections. We herein hypothesize that humoral and cellular immune responses induced by active Hp-I, beyond damaging locally the gastric mucosa, they may shape the character of systemic autoimmune responses, contributing to MS pathogenesis. To investigate our hypothesis, active Hp-I has been diagnosed in two small MS Greek cohorts by using primarily gastric mucosa histology. A higher prevalence of active Hp-I was documented in MS patients vs. controls (86.4 vs. 50%, P = 0.002)accompanied by exclusive existence of duodenal ulcer and autoimmune diseases with endoscopic and histological findings of chronic active gastritis for the MS group. Our preliminary data suggested that active Hp-Iunlike other studies, may not protect, but contribute to MS and we proposed possibleHp-relating mechanisms involved in MS pathophysiology, that merit further evaluation.

Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis.

Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48-2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17-9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09-27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.

A fully covered self-expandable metal stent anchored by a 10-Fr double pigtail plastic stent: an effective anti-migration technique.

BACKGROUND: Fully covered self-expandable metal stents (FCSEMS) have been used successfully in the treatment of malignant and benign biliary strictures. However, stent migration is a major complication. We investigated the efficacy of anchoring FCSEMS with a 10-Fr double-pigtail plastic stent to prevent migration in patients with biliary strictures. METHODS: Between January 2012 and May 2013, 10 patients with malignant biliary strictures and one patient with a suprapapillary benign biliary stenosis were enrolled in the study. The primary endpoint of the study was to record the migration rate of FCSEMS. RESULTS: The placement of FCSEMSs and the anchoring with a 10-Fr double-pigtail plastic stent were successful in all patients. During a median follow-up period of eight months, proximal or distal migration of FCSEMS was not observed. No procedural complications related to the placement of FCSEMS and/or the anchoring plastic stent were recorded. CONCLUSIONS: The placement of an anchoring 10-Fr double-pigtail stent is a simple and effective anti-migration technique for FCSEMS in patients with malignant biliary strictures.