Background
Hepatosteatosis is the earliest stage in the pathogenesis of nonalcoholic fatty (NAFLD) and alcoholic liver disease (ALD). As NAFLD is affecting 10–24% of the general population and ...approximately 70% of obese patients, it carries a large economic burden and is becoming a major reason for liver transplantation worldwide. ALD is a major cause of morbidity and mortality causing 50% of liver cirrhosis and 10% of liver cancer related death. Increasing evidence has accumulated that gut-derived factors play a crucial role in the development and progression of chronic liver diseases.
Methods
A selective literature search was conducted in Medline and PubMed, using the terms “nonalcoholic fatty liver disease,” “alcoholic liver disease,” “lipopolysaccharide,” “gut barrier,” and “microbiome.”
Results
Gut dysbiosis and gut barrier dysfunction both contribute to chronic liver disease by abnormal regulation of the gut-liver axis. Thereby, gut-derived lipopolysaccharides (LPS) are a key factor in inducing the inflammatory response of liver tissue. The review further underlines that endotoxemia is observed in both NAFLD and ALD patients. LPS plays an important role in conducting liver damage through the LPS-TLR4 signaling pathway. Treatments targeting the gut microbiome and the gut barrier such as fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, and intestinal alkaline phosphatase (IAP) represent potential treatment modalities for NAFLD and ALD.
Conclusions
The gut-liver axis plays an important role in the development of liver disease. Treatments targeting the gut microbiome and the gut barrier have shown beneficial effects in attenuating liver inflammation and need to be further investigated.
Background
Anastomotic leakage after rectal resection represents a severe complication for the patient and requires an early and appropriate management. Endoscopic vacuum therapy (EVT) has become the ...treatment of choice for anastomotic leakage after rectal resection in several institutions in Germany, and commercially available systems are currently distributed in approximately 30 countries worldwide. However, there is no evidence that EVT is superior to any other treatment for anastomotic leakage after rectal resection.
Methods
Twenty-one patients treated with EVT for anastomotic leakage after rectal resection were retrospectively compared to a historical cohort of 41 patients that received conventional treatment. Primary endpoints were death, treatment success and long-term preservation of intestinal continuity. Secondary endpoints were length of hospital stay and duration of treatment.
Results
There was no difference in mortality (
p
= 0.624). The intention-to-treat analysis showed a significantly higher success rate of EVT compared to conventional treatment (95.2% vs. 65.9%,
p
= 0.011). EVT was associated with preservation of intestinal continuity in a significant higher percentage of patients than patients undergoing conventional treatment (86.7% vs. 37.5%,
p
= 0.001). Conventional treatment tended to a shorter length of hospital stay (31.1 vs. 42.2 days,
p
= 0.066) but with no difference in overall duration of treatment. Time until closing of a diverting stoma did not differ between groups (10.2 months in the EVT group vs. 9.4 months in the conventional treatment group,
p
= 0.721).
Conclusion
According to this retrospective study, conventional therapy and EVT are both options for the treatment of anastomotic leakage after rectal resection. EVT might be more effective in terms of definite healing and preservation of intestinal continuity.
The development of animal models reflecting the pathologies of ulcerative colitis (UC) and Crohn's disease (CD) remains a major challenge. The NOD/SCID/IL2rγ
(NSG) mouse strain, which is ...immune-compromised, tolerates the engraftment of human peripheral blood mononuclear cells (PBMC) derived from patients with UC (NSG-UC) or CD (NSG-CD). This offers the opportunity to examine the impact of individual immunological background on the development of pathophysiological manifestations. When challenged with ethanol, NSG-UC mice exhibited a strong pro-inflammatory response, including the development of edemas, influx of human T cells, B cells and monocytes into the mucosa and submucosa, and elevated expression of the inflammatory markers CRP and CCL-7. Fibrotic alterations were characterized by an influx of fibroblasts and a thickening of the muscularis mucosae. In contrast, the development of pathological manifestations in NSG-CD mice developed without challenge and was signified by extensive collagen deposition between the muscularis propria and muscularis mucosae, as observed in the areas of strictures in CD patients. Vimentin-expressing fibroblasts supplanting colonic crypts and elevated expression of HGF and TGFß corroborated the remodeling phenotype. In summary, the NSG-UC and NSG-CD models partially reflect these human diseases and are powerful tools to examine the mechanism underlying the inflammatory processes in UC and CD.
Background
Evidence for endoscopic vacuum therapy (EVT) for colorectal defects is still based on small patient series from various institutions, employing different treatment algorithms and methods. ...As EVT was invented at our institution 20 years ago, the aim was to report the efficacy and safety of EVT for colorectal defects as well as to analyze factors associated with efficacy, therapy duration, and outpatient treatment.
Methods
Cohort study with analysis of prospectively collected data of patients receiving EVT for colorectal defects at a tertiary referral center in Germany (
n
= 281).
Results
The majority of patients had malignant disease (83%) and an American Society of Anesthesiologists classification of III/IV (81%). Most frequent indications for EVT were anastomotic leakage after sigmoid or rectal resection (67%) followed by rectal stump leakage (20%). EVT was successful in 256 out of 281 patients (91%). EVT following multi-visceral resection (
P
= 0.037) and recent surgical revision after primary surgery (
P
= 0.009) were risk factors for EVT failure. EVT-associated adverse events occurred in 27 patients (10%). Median treatment duration was 25 days. Previous chemo-radiation (
P
= 0.006) was associated with a significant longer duration of EVT. Outpatient treatment was conducted in 49% of patients with a median hospital stay reduction of 15 days and 98% treatment success. Younger patient age (
P
= 0.044) was associated with the possibility of outpatient treatment. Restoration of intestinal continuity was achieved in 60% of patients where technically possible with a 12-month rate of 52%.
Conclusions
In patients with colorectal defects, EVT appears to be a safe and effective, minimally invasive option for in- and outpatient treatment.
The quality of mesorectal resection is crucial for resection in rectal cancer, which should be performed by laparoscopy for better outcome. The use of indocyanine green (ICG) fluorescence is now ...routinely used in some centers to evaluate bowel perfusion. Previous studies have demonstrated in animal models that selective intra-arterial ICG staining can be used to define and visualize resection margins in rectal cancer. In this animal study, we investigate if laparoscopic intra-arterial catheterization is feasible and the staining of resection margins when performing total mesorectal excision with a laparoscopic medial to lateral approach is possible. In 4 pigs, laparoscopic catheterization of the inferior mesenteric artery (IMA) is performed using a seldinger technique. After a bolus injection of 10 ml ICG with a concentration of 0.25 mg/ml, a continuous intra-arterial perfusion was established at a rate of 2 ml/min. The quality of the staining was evaluated qualitatively. Laparoscopic catheterization was possible in all cases, and the average time for this was 30.25 ± 3.54 min. We observed a significant fluorescent signal in all areas of the IMA supplied, but not in other parts of the abdominal cavity or organs. In addition, the mesorectum showed a sharp border between stained and unstained tissue. Intraoperative isolated fluorescence augmentation of the rectum, including the mesorectum by laparoscopic catheterization, is feasible. Inferior mesenteric artery catheterization and ICG perfusion can provide a fluorescence-guided roadmap to identify the correct plane in total mesorectal excision, which should be investigated in further studies.
'Resilience' has quickly risen to prominence in international security and development circles. In recent years it has found its way into political discourse on state building and state fragility, ...triggering a vast but often conceptually indistinct examination of the subject. Given its meaning in policy publications and guidelines, 'resilience' tends to eschew a static conceptualisation of statehood, turning instead to a more dynamic, complex and process-oriented rendering of state-society relations. This illustrates a conceptual shift from 'failed states' to 'fragile states and situations'. It also transforms the concept of 'failed state' as a mere threat perception - with 'stability' as its logical other - into 'fragility' as a particular form of social and political risk. This paper analyses the concepts in 43 policy papers, focusing on the nexus of 'resilience' and 'fragility' in international state building, and assesses potential consequences. What does 'resilience' - as the opposite vision to 'fragility' - in fact mean? What is the practice derived from this chimerical state of states?
Background
During the last two decades, vacuum-assisted wound therapy has been successfully transferred to an endoscopic treatment approach of various upper and lower gastrointestinal leaks called ...endoscopic vacuum therapy (EVT). As mostly small case series are published in this field, the aim of our systematic review and meta-analysis was to evaluate the efficacy and safety of EVT in the treatment of colorectal leaks.
Methods
A systematic search of MEDLINE/PubMed and Cochrane databases was performed using search terms related to EVT and colorectal defects (anastomotic leakage, rectal stump insufficiency) according to the PRISMA guidelines. Randomized controlled trials (RCTs), observational studies, and case series published by December 2020 were eligible for inclusion. A meta-analysis was conducted on the success of EVT, stoma reversal rate after EVT as well as procedure-related complications. Statistical interferences were based on pooled estimates from random effects models using DerSimonian-Laird estimator.
Results
Only data from observational studies and case series were available. Twenty-four studies reporting on 690 patients with colorectal defects undergoing EVT were included. The mean rate of success was 81.4% (95% CI: 74.0%–87.1%). The proportion of diverted patients was 76.4% (95% CI: 64.9%–85.0%). The mean rate of ostomy reversal across the studies was 66.7% (95% CI: 58.0%–74.4%). Sixty-four patients were reported with EVT-associated complications, the weighted mean complication rate across the studies was 12.1% (95% CI: 9.7%–15.2%).
Conclusions
Current medical evidence on EVT in patients with colorectal leaks lacks high quality data from RCTs. Based on the data available, EVT can be seen as a feasible treatment option with manageable risks for selected patients with colorectal leaks.
Widely used distinctions between national and international, between external and local, direct our view away from the political economy of classed interests guiding interventions. In Western and ...authoritarian interventions alike, such interests align across borders, calling into question the separateness of profiteers groups. Critiques of the liberal peace have overlooked how (capitalist) interests alloy the practice of interventions beyond norms, legitimation claims and international order; unless researchers turn to mapping the cross-connections of the global 'interventionist class', interventionism will not be fully understood.
Purpose
To evaluate the role of the nucleotide oligomerization domain 2 (NOD2) mutation status and other risk factors for the incidence of postoperative complications after ileocolic resection for ...Crohn’s disease (CD).
Methods
Data of 138 patients consecutively undergoing ileocolic resection for CD at a tertiary academic referral center were retrospectively analyzed including single nucleotide polymorphism (SNP) data of the NOD2 gene. Uni- and multivariate regression analysis was performed to identify factors associated with increased risk of severe postoperative complications.
Results
From 114 patients (83%), the NOD2 mutation status was available. Of these, 60 (53%) had a NOD2 wildtype, whereas eleven (10%) were homozygous for the high risk p.Leu1007fsX1008 (rs2066847) variant. Major postoperative complications occurred in 28 patients (20%). Twenty-seven of these (96%) were intraabdominal septic complications such as anastomotic leakage or abscess. Male gender (
P
= 0.029; OR 3.052, the duration of CD (time months from initial diagnosis of CD to surgery;
P
= 0.001; OR 1.009), previous abdominal surgery for CD (
P
= 0.017; OR 3.49), and the presence of enteric fistulas (
P
= 0.023; OR 3.21) were identified as independent risk factors for major postoperative complications. Homozygosity for the NOD2 high-risk variant p.Leu1007fsX1008 did not show increased postoperative morbidity in the short and long-term outcome.
Conclusions
We could detect independent risk factors for major postoperative complications after ileocolic resection for Crohn’s disease. However, patients with the high-risk variant p.Leu1007fsX1008 of the NOD2 gene did not show increased postoperative morbidity.
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