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World Journal of Emergency Surgery :... 2019Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries... (Review)
Review
Duodeno-pancreatic and extrahepatic biliary tree injuries are rare in both adult and pediatric trauma patients, and due to their anatomical location, associated injuries are very common. Mortality is primarily related to associated injuries, but morbidity remains high even in isolated injuries. Optimal management of duodeno-bilio-pancreatic injuries is dictated primarily by hemodynamic stability, clinical presentation, and grade of injury. Endoscopic and percutaneous interventions have increased the ability to non-operatively manage these injuries. Late diagnosis and treatment are both associated to increased morbidity and mortality. Sequelae of late presentations of pancreatic injury and complications of severe pancreatic trauma are also increasingly addressed endoscopically and with interventional radiology procedures. However, for moderate and severe extrahepatic biliary and severe duodeno-pancreatic injuries, immediate operative intervention is preferred as associated injuries are frequent and commonly present with hemodynamic instability or peritonitis. The aim of this paper is to present the World Society of Emergency Surgery (WSES) and American Association for the Surgery of Trauma (AAST) duodenal, pancreatic, and extrahepatic biliary tree trauma management guidelines.
Topics: Abdominal Injuries; Bile Ducts, Extrahepatic; Duodenum; Focused Assessment with Sonography for Trauma; General Surgery; Guidelines as Topic; Humans; Pancreas; Tomography, X-Ray Computed; Trauma Centers; Triage; Ultrasonography
PubMed: 31867050
DOI: 10.1186/s13017-019-0278-6 -
European Journal of Pediatrics Jul 2022Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the... (Review)
Review
Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a complex and resource-limited solution associated with its own morbidity and mortality. We conducted a scoping review to present a contemporary summary of the epidemiology, aetiology, pathophysiology, diagnosis, management and complications of PIPO.Conclusion: PIPO represents a rare disorder that is difficult to diagnose and challenging to treat, with significant morbitity and mortality. The only known cure is intestinal transplantation. What is Known: • Paediatric intestinal pseudo-obstruction is a rare, heterogeneous disorder that confers a high rate of morbidity and mortality • Complications of paediatric intestinal pseudo-obstruction include chronic pain, small intestine bacterial overgrowth and malrotation. Other complications can occur related to its management, such as line infections with parenteral nutrition or cardiac side effects of prokinetic medications What is New: • Progress in medical and surgical therapy in recent years has led to improved patient outcomes • Enteral autonomy has been reported in most patients at as early as 1 month post-transplantation.
Topics: Child; Chronic Disease; Humans; Intestinal Pseudo-Obstruction; Intestine, Small; Intestines; Parenteral Nutrition
PubMed: 35482095
DOI: 10.1007/s00431-021-04365-9 -
World Journal of Emergency Surgery :... 2018Iatrogenic colonoscopy perforation (ICP) is a severe complication that can occur during both diagnostic and therapeutic procedures. Although 45-60% of ICPs are... (Review)
Review
Iatrogenic colonoscopy perforation (ICP) is a severe complication that can occur during both diagnostic and therapeutic procedures. Although 45-60% of ICPs are diagnosed by the endoscopist while performing the colonoscopy, many ICPs are not immediately recognized but are instead suspected on the basis of clinical signs and symptoms that occur after the endoscopic procedure. There are three main therapeutic options for ICPs: endoscopic repair, conservative therapy, and surgery. The therapeutic approach must vary based on the setting of the diagnosis (intra- or post-colonoscopy), the type of ICP, the characteristics and general status of the patient, the operator's level of experience, and surgical device availability. Although ICPs have been the focus of numerous publications, no guidelines have been created to standardize the management of ICPs. The aim of this article is to present the World Society of Emergency Surgery (WSES) guidelines for the management of ICP, which are intended to be used as a tool to promote global standards of care in case of ICP. These guidelines are not meant to substitute providers' clinical judgment for individual patients, and they may need to be modified based on the medical team's level of experience and the availability of local resources.
Topics: Aged; Aged, 80 and over; Colon; Colonoscopy; Disease Management; Female; Guidelines as Topic; Humans; Iatrogenic Disease; Intestinal Perforation; Male; Middle Aged
PubMed: 29416554
DOI: 10.1186/s13017-018-0162-9 -
Clinical Science (London, England :... Jan 2021Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell...
Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients' exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.
Topics: Adult; Animals; Cecum; Disease Models, Animal; Exosomes; Human Umbilical Vein Endothelial Cells; Humans; Ligation; Lipopolysaccharides; Male; Membrane Proteins; MicroRNAs; Middle Aged; RNA, Small Interfering; Rats; Sepsis
PubMed: 33416075
DOI: 10.1042/CS20200573 -
Theranostics 2020The dysfunctional gut-kidney axis forms a vicious circle, which eventually becomes a catalyst for the progression of chronic kidney disease (CKD) and occurrence of...
The dysfunctional gut-kidney axis forms a vicious circle, which eventually becomes a catalyst for the progression of chronic kidney disease (CKD) and occurrence of related complications. However, the pathogenic factors of CKD-associated intestinal dysfunction and its mechanism remain elusive. We first identified the protein-bound uremic toxin indoxyl sulfate (IS) as a possible contributor to intestinal barrier injury. Transepithelial electrical resistance, permeability assay and transmission electron microscopy were carried out to evaluate the damaging effect of IS on intestinal barrier in intestinal epithelial cells, IS-injected mice and CKD mice. In vitro and in vivo experiments were performed to investigate the role of IS in intestinal barrier injury and the underlying mechanism. Finally, CKD mice treated with AST-120 (an oral adsorbent for IS) and gene knockout mice were used to verify the mechanism and to explore possible interventions for IS-induced intestinal barrier injury. Transepithelial electrical resistance and the expressions of tight junction-related genes were significantly suppressed by IS in intestinal epithelial cells. In vitro experiments demonstrated that IS inhibited the expression of dynamin-related protein 1 (DRP1) and mitophagic flux, whereas DRP1 overexpression attenuated IS-induced mitophagic inhibition and intestinal epithelial cell damage. Furthermore, IS suppressed DRP1 by upregulating the expression of interferon regulatory factor 1 (IRF1), and IRF1 could directly bind to the promoter region of DRP1. Additionally, the decreased expression of DRP1 and autophagosome-encapsulated mitochondria were observed in the intestinal tissues of CKD patients. Administration of AST-120 or genetic knockout of IRF1 attenuated IS-induced DRP1 reduction, mitophagic impairment and intestinal barrier injury in mice. These findings suggest that reducing IS accumulation or targeting the IRF1-DRP1 axis may be a promising therapeutic strategy for alleviating CKD-associated intestinal dysfunction.
Topics: Adsorption; Animals; Carbon; Disease Models, Animal; Dynamins; Epithelial Cells; Gastrointestinal Agents; Humans; Indican; Interferon Regulatory Factor-1; Intestinal Diseases; Intestinal Mucosa; Kidney; Male; Mice; Mitophagy; Oxides; Permeability; Renal Elimination; Renal Insufficiency, Chronic; Tight Junctions
PubMed: 32641998
DOI: 10.7150/thno.45455 -
Redox Biology Feb 2023Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can...
Mucus forms the first line of defence of the intestinal mucosa barrier, and mucin is its core component. Glutamine is a vital energy substance for goblet cells; it can promote mucus synthesis and alleviate damage to the intestinal mucus barrier after burn injury, but its mechanism is not fully understood. This study focused on the molecular mechanisms underlying the effects of glutamine on the synthesis and modification of mucin 2 (MUC2) by using animal and cellular models of burn sepsis. We found that anterior gradient-2 (AGR2) plays a key role in the posttranslational modification of MUC2. Oxidative stress induced by burn sepsis enhanced the S-glutathionylation of AGR2, interfered with the processing and modification of MUC2 precursors by AGR2 and blocked the synthesis of mature MUC2. Further studies revealed that NADPH, catalysed by glucose-6-phosphate dehydrogenase (G6PD), is a key molecule in inhibiting oxidative stress and regulating AGR2 activity. Glutamine promotes O-linked N-acetylglucosamine (O-GlcNAc) modification of G6PD via the hexosamine pathway, which facilitates G6PD homodimer formation and increases NADPH synthesis, thereby inhibiting AGR2 S-glutathionylation and promoting MUC2 maturation, ultimately reducing damage to the intestinal mucus barrier after burn sepsis. Overall, we have demonstrated that the central mechanisms of glutamine in promoting MUC2 maturation and maintaining the intestinal mucus barrier are the enhancement of G6PD glycosylation and inhibition of AGR2 S-glutathionylation.
Topics: Animals; Mice; Glucosephosphate Dehydrogenase; Glutamine; Goblet Cells; Mucus; NADP
PubMed: 36565645
DOI: 10.1016/j.redox.2022.102581 -
Microbiome Jun 2022Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel...
BACKGROUND
Well-balanced interactions between gut microbiota and the immune system are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). Toll-like receptor 4 (TLR4) functions as a sensor mediating the crosstalk between the intestinal commensal microbiome and host immunity, but the influence of TLR4 on the shaping of intestinal microbiota and immune responses during colon inflammation remains poorly characterized. We investigated whether the different susceptibilities to colitis between wild-type (WT) and TLR4 mice were gut microbiota-dependent and aimed to identify the potential immunity modulation mechanism.
METHODS
We performed antibiotic depletion of the microbiota, cohousing experiments, and faecal microbiota transplantation (FMT) in WT and TLR4 mice to assess the influence of TLR4 on intestinal microbial ecology. 16S rRNA sequencing was performed to dissect microbial discrepancies, and dysbiosis-associated immune perturbation was investigated by flow cytometry. Akkermansia muciniphila (A. muciniphila)-mediated immune modulation was confirmed through the T-cell transfer colitis model and bone marrow chimaera construction.
RESULTS
TLR4 mice experienced enhanced susceptibility to DSS-induced colitis. 16S rRNA sequencing showed notable discrepancy in the gut microbiota between WT and TLR4 mice. In particular, A. muciniphila contributed most to distinguishing the two groups. The T-cell transfer colitis model and bone marrow transplantation (BMT) consistently demonstrated that A. muciniphila ameliorated colitis by upregulating RORγt Treg cell-mediated immune responses. Mucosal biopsies from human manifested parallel outcomes with colon tissue from WT mice, as evidenced by the positive correlation between TLR4 expression and intestinal A. muciniphila colonization during homeostasis.
CONCLUSIONS
Our results demonstrate a novel protective role of TLR4 against intestinal inflammation, wherein it can modulate A. muciniphila-associated immune responses. These findings provide a new perspective on host-commensal symbiosis, which may be beneficial for developing potential therapeutic strategies. Video abstract.
Topics: Akkermansia; Animals; Colitis; Colon; Dextran Sulfate; Inflammation; Mice; Mice, Inbred C57BL; Nuclear Receptor Subfamily 1, Group F, Member 3; RNA, Ribosomal, 16S; T-Lymphocytes, Regulatory; Toll-Like Receptor 4
PubMed: 35761415
DOI: 10.1186/s40168-022-01296-x