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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 :... 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 -
Theranostics 2020Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD...
Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. : To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. : The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. : PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.
Topics: Animals; Colonoscopy; Dextran Sulfate; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gastrointestinal Microbiome; Inflammation; Inflammatory Bowel Diseases; Male; Mice; Mice, Inbred C57BL; RNA, Ribosomal, 16S; Sesquiterpenes; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 32373209
DOI: 10.7150/thno.43716 -
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 -
World Journal of Emergency Surgery :... Jul 2023Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure... (Review)
Review
Laparotomy incisions provide easy and rapid access to the peritoneal cavity in case of emergency surgery. Incisional hernia (IH) is a late manifestation of the failure of abdominal wall closure and represents frequent complication of any abdominal incision: IHs can cause pain and discomfort to the patients but also clinical serious sequelae like bowel obstruction, incarceration, strangulation, and necessity of reoperation. Previous guidelines and indications in the literature consider elective settings and evidence about laparotomy closure in emergency settings is lacking. This paper aims to present the World Society of Emergency Surgery (WSES) project called ECLAPTE (Effective Closure of LAParoTomy in Emergency): the final manuscript includes guidelines on the closure of emergency laparotomy.
Topics: Humans; Laparotomy; Abdominal Wound Closure Techniques; Suture Techniques; Incisional Hernia; Reoperation
PubMed: 37496068
DOI: 10.1186/s13017-023-00511-w -
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 -
Journal of Neuroinflammation Nov 2021Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many...
BACKGROUND
Inflammatory bowel disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined.
METHODS
Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% dextran sodium sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB.
RESULTS
DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation.
CONCLUSIONS
Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9.
Topics: Animals; Biomarkers; Brain; Calgranulin B; Caspase 1; Chemokines; Colitis; Cytokines; Dextran Sulfate; Humans; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neuroinflammatory Diseases; Quinolines
PubMed: 34758843
DOI: 10.1186/s12974-021-02317-6