Minimally-invasive versus open pancreatoduodenectomies with vascular resection: A 1:1 propensity-matched comparison study.

Background: Minimally invasive pancreatic pancreatoduodenectomy (MIPD) is increasingly adopted worldwide and its potential advantages include reduced hospital stay and decrease pain. However, evidence supporting the role of MIPD for tumours requiring vascular reconstruction remains limited and requires further evaluation. This study aims to investigate the safety and efficacy of MIPD with vascular resection (MIPDV) by performing a 1:1 propensity-score matched (PSM) comparison with open pancreatoduodenectomy with vascular resection (OPDV) based on a single surgeon's experience. Methods: This is a retrospective review of 41 patients who underwent PDV between 2011 and 2020 by a single surgeon. After PSM, the comparison was made between 13 MIPDV and 13 OPDV. Results: Thirty-six patients underwent venous reconstruction (VR) only and 5 underwent arterial reconstruction of which 4 had concomitant VR. The types of VR included 22 wedge resections with primary repair, 8 segmental resections with primary anastomosis and 11 requiring interposition grafts. Post-operative pancreatic fistula (POPF) occurred in 3 (7.3%) patients. Major complications (>Grade 2) occurred in 16 (39%) patients, of which 7 were due to delayed gastric emptying requiring nasojejunal tube placement. There was 1 (2.4%) 30-day mortality (OPDV). Of the 13 MIPDV, there were 3 (23.1%) open conversions. PSM comparison demonstrated that MIPDV was associated with longer median operative time (720 min vs. 485 min (P = 0.018). There was no statistically significant difference in other key perioperative outcomes such as intra-operative blood loss, overall morbidity, major morbidity rate, POPF and length of stay. Conclusion: Our initial experience with the adoption MIPDV has demonstrated it to be safe with comparable outcomes to OPDV despite the longer operation time.

Persistent changes in liver methylation and microbiome composition following reversal of diet-induced non-alcoholic-fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a metabolic liver disease that is thought to be reversible by changing the diet. To examine the impact of dietary changes on progression and cure of NAFLD, we fed mice a high-fat diet (HFD) or high-fructose diet (HFrD) for 9 weeks, followed by an additional 9 weeks, where mice were given normal chow diet. As predicted, the diet-induced NAFLD elicited changes in glucose tolerance, serum cholesterol, and triglyceride levels in both diet groups. Moreover, the diet-induced NAFLD phenotype was reversed, as measured by the recovery of glucose intolerance and high cholesterol levels when mice were given normal chow diet. However, surprisingly, the elevated serum triglyceride levels persisted. Metagenomic analysis revealed dietary-induced changes of microbiome composition, some of which remained altered even after reversing the diet to normal chow, as illustrated by species of the Odoribacter genus. Genome-wide DNA methylation analysis revealed a "priming effect" through changes in DNA methylation in key liver genes. For example, the lipid-regulating gene Apoa4 remained hypomethylated in both groups even after introduction to normal chow diet. Our results support that dietary change, in part, reverses the NAFLD phenotype. However, some diet-induced effects remain, such as changes in microbiome composition, elevated serum triglyceride levels, and hypomethylation of key liver genes. While the results are correlative in nature, it is tempting to speculate that the dietary-induced changes in microbiome composition may in part contribute to the persistent epigenetic modifications in the liver.

Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis.

Complications of acute respiratory distress syndrome (ARDS) are common among critically ill patients infected with highly pathogenic influenza viruses. Macrophages and neutrophils constitute the majority of cells recruited into infected lungs, and are associated with immunopathology in influenza pneumonia. We examined pathological manifestations in models of macrophage- or neutrophil-depleted mice challenged with sublethal doses of influenza A virus H1N1 strain PR8. Infected mice depleted of macrophages displayed excessive neutrophilic infiltration, alveolar damage, and increased viral load, later progressing into ARDS-like pathological signs with diffuse alveolar damage, pulmonary edema, hemorrhage, and hypoxemia. In contrast, neutrophil-depleted animals showed mild pathology in lungs. The brochoalveolar lavage fluid of infected macrophage-depleted mice exhibited elevated protein content, T1-α, thrombomodulin, matrix metalloproteinase-9, and myeloperoxidase activities indicating augmented alveolar-capillary damage, compared to neutrophil-depleted animals. We provide evidence for the formation of neutrophil extracellular traps (NETs), entangled with alveoli in areas of tissue injury, suggesting their potential link with lung damage. When co-incubated with infected alveolar epithelial cells in vitro, neutrophils from infected lungs strongly induced NETs generation, and augmented endothelial damage. NETs induction was abrogated by anti-myeloperoxidase antibody and an inhibitor of superoxide dismutase, thus implying that NETs generation is induced by redox enzymes in influenza pneumonia. These findings support the pathogenic effects of excessive neutrophils in acute lung injury of influenza pneumonia by instigating alveolar-capillary damage.