Chimney parallel grafts and thoracic endovascular aortic repair for blunt traumatic thoracic aortic injuries: A systematic review.

BACKGROUND: Whilst the management of blunt traumatic thoracic aortic injury has seen a paradigm shift to an 'endovascular first' approach, the limitations of thoracic endovascular aortic repair remain. An inadequate proximal landing zone limits the use of thoracic aortic stent grafts and in an emergent polytrauma setting, aortic arch debranching via open surgery may not be practical or feasible. A wholly endovascular approach to debranching utilising 'off-the-shelf' stents and parallel graft techniques may represent a possible solution. Hence, we sought to perform a systematic review investigating the use of chimney graft techniques alongside thoracic aortic stenting in blunt traumatic thoracic aortic injury. METHODS: We performed the systematic review in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Searches were performed on Medline (PubMed), Web of Science and Scopus to identify articles describing the use of chimney grafts in traumatic aortic transection (PROSPERO: CRD42017082549). RESULTS: The systematic search revealed 172 papers, of which 88 duplicates were removed resulting in 84 papers to screen. Based on title, abstract and full text review, six articles were included for final analysis. There were nine patients in total with an average age of 41 (three females, five males, one unspecified), all with significant polytrauma, secondary to the mechanism of injury. A variety of stents were used between centres, with techniques showing a predominance to stenting of the left subclavian artery (77%, n = 7). The technical success rate was 82%, with two (18%) cases of type 1 endoleaks, of which one resolved spontaneously. CONCLUSIONS: Despite the encouraging results, this by no means provides for a firm conclusion given the small sample size. Patients should still be judiciously selected on a case-by-case basis when employing the chimney graft technique. Larger cohort studies are needed to establish these findings.

Hepatic rhythmicity of endoplasmic reticulum stress is disrupted in perinatal and adult mice models of high-fat diet-induced obesity.

We investigated the regulation of hepatic ER stress in healthy liver and adult or perinatally programmed diet-induced non-alcoholic fatty liver disease (NAFLD). Female mice were fed either obesogenic or control diet before mating, during pregnancy and lactation. Post-weaning, offspring from each maternal group were divided into either obesogenic or control diet. At six months, offspring were sacrificed at 4-h intervals over 24 h. Offspring fed obesogenic diets developed NAFLD phenotype, and the combination of maternal and offspring obesogenic diets exacerbated this phenotype. UPR signalling pathways (IREα, PERK, ATF6) and their downstream regulators showed different basal rhythmicity, which was modified in offspring exposed to obesogenic diet and maternal programming. The double obesogenic hit increased liver apoptosis measured by TUNEL staining, active caspase-3 and phospho-JNK and GRP78 promoter methylation levels. This study demonstrates that hepatic UPR is rhythmically activated. The combination of maternal obesity (MO) and obesogenic diets in offspring triggered altered UPR rhythmicity, DNA methylation and cellular apoptosis.

Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas

The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults (AU)

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Maternal obesity alters endoplasmic reticulum homeostasis in offspring pancreas.

The prevalence of non-alcoholic fatty pancreas disease (NAFPD) is increasing in parallel with obesity rates. Stress-related alterations in endoplasmic reticulum (ER), such as the unfolded protein response (UPR), are associated with obesity. The aim of this study was to investigate ER imbalance in the pancreas of a mice model of adult and perinatal diet-induced obesity. Twenty female C57BL/6J mice were assigned to control (Con) or obesogenic (Ob) diets prior to and during pregnancy and lactation. Their offspring were weaned onto Con or Ob diets up to 6 months post-partum. Then, after sacrifice, plasma biochemical analyses, gene expression, and protein concentrations were measured in pancreata. Offspring of Ob-fed mice had significantly increased body weight (p < 0.001) and plasma leptin (p < 0.001) and decreased insulin (p < 0.01) levels. Maternal obesogenic diet decreased the total and phosphorylated Eif2α and increased spliced X-box binding protein 1 (XBP1). Pancreatic gene expression of downstream regulators of UPR (EDEM, homocysteine-responsive endoplasmic reticulum-resident (HERP), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP)) and autophagy-related proteins (LC3BI/LC3BII) were differently disrupted by obesogenic feeding in both mothers and offspring (from p < 0.1 to p < 0.001). Maternal obesity and Ob feeding in their offspring alter UPR in NAFPD, with involvement of proapoptotic and autophagy-related markers. Upstream and downstream regulators of PERK, IRE1α, and ATF6 pathways were affected differently following the obesogenic insults.

An IVF pregnancy, a neck lump and shortness of breath.

We present the case of a young primigravida, conceived with in vitro fertilisation, referred with unilateral neck swelling and pleuritic chest pain. Our case highlights the potential complexity of the management of the complications of assisted conception techniques. The discussion explores important considerations in the management of such patients.

Non-alcoholic fatty pancreas disease pathogenesis: a role for developmental programming and altered circadian rhythms.

OBJECTIVES: Emerging evidence suggests that maternal obesity (MO) predisposes offspring to obesity and the recently described non-alcoholic fatty pancreas disease (NAFPD) but involved mechanisms remain unclear. Using a pathophysiologically relevant murine model, we here investigated a role for the biological clock--molecular core circadian genes (CCG) in the generation of NAFPD. DESIGN: Female C57BL6 mice were fed an obesogenic diet (OD) or standard chow (SC) for 6 weeks, prior to pregnancy and throughout gestation and lactation: resulting offspring were subsequently weaned onto either OD (Ob_Ob and Con_Ob) or standard chow (Ob_Con and Con_Con) for 6 months. Biochemical, pro-inflammatory and pro-fibrogenic markers associated with NAFPD were then evaluated and CCG mRNA expression in the pancreas determined. RESULTS: Offspring of obese dams weaned on to OD (Ob_Ob) had significantly increased (p≤0.05): bodyweight, pancreatic triglycerides, macrovesicular pancreatic fatty-infiltration, and pancreatic mRNA expression of TNF-α, IL-6, α-SMA, TGF-ß and increased collagen compared to offspring of control dams weaned on to control chow (Con_Con). Analyses of CCG expression demonstrated a phase shift in CLOCK (-4.818, p<0.01), REV-ERB-α (-1.4,p<0.05) and Per2 (3.27,p<0.05) in association with decreased amplitude in BMAL-1 (-0.914,p<0.05) and PER2 (1.18,p<0.005) in Ob_Ob compared to Con_Con. 2-way ANOVA revealed significant interaction between MO and post-weaning OD in expression of CLOCK (p<0.005), PER1 (p<0.005) and PER2 (p<0.05) whilst MO alone influenced the observed rhythmic variance in expression of all 5 measured CCG. CONCLUSIONS: Fetal and neonatal exposure to a maternal obesogenic environment interacts with a post-natal hyper-calorific environment to induce offspring NAFPD through mechanisms involving perturbations in CCG expression.

Recent advancements in drug treatment of obesity.

The prevalence of obesity is rising worldwide, with the U.K. having the highest prevalence in Europe. Obesity is associated with significant morbidity and has substantial healthcare implications, with current projections estimating that by 2030 obesity will cost the NHS approximately pounds 2 billion each year. Lifestyle modification remains the cornerstone of anti-obesity treatment, but drugs can be introduced as adjuncts to assist and maintain weight loss. Some 1.45 million obesity-related prescriptions were dispensed in 2009, highlighting the high demand for obesity pharmacotherapy. At present, the lipase inhibitor orlistat (Xenical) is the only UK-approved long-term medical therapy for obesity. Double-blind clinical trials have shown that orlistat significantly increases weight loss compared to placebo, but the array of adverse side effects associated with orlistat limits its tolerability. The need for more effective and better-tolerated anti-obesity medications is clear and six therapies have reached phase-III trials.