Hypoxia inducible factor 1-alpha in the pathogenesis of abdominal aortic aneurysms in vivo: A narrative review.

Abdominal aortic aneurysms (AAAs) are relatively common, primarily among older men, and, in the case of rupture, are associated with high mortality. Although procedure-related morbidity and mortality have improved with the advent of endovascular repair, noninvasive treatment and improved assessment of AAA rupture risk should still be sought. Several cellular pathways seem contributory to the histopathologic changes that drive AAA growth and rupture. Hypoxia inducible factor 1-alpha (HIF-1α) is an oxygen-sensitive protein that accumulates in the cytoplasm under hypoxic conditions and regulates a wide array of downstream effectors to hypoxia. Examining the potential role of HIF-1α in the pathogenesis of AAAs is alluring, because local hypoxia is known to be present in the AAA vessel wall. A systematic scoping review was performed to review the current evidence regarding the role of HIF-1α in AAA disease in vivo. After screening, 17 studies were included in the analysis. Experimental animal studies and human studies show increased HIF-1α activity in AAA tissue compared with healthy aorta and a correlation of HIF-1α activity with key histopathologic features of AAA disease. In vivo HIF-1α inhibition in animals protects against AAA development and growth. One study reveals a positive correlation between HIF-1α-activating genetic polymorphisms and the risk of AAA disease in humans. The main findings suggest a causal role of HIF-1α in the pathogenesis of AAAs in vivo. Further research into the HIF-1α pathway in AAA disease might reveal clinically applicable pharmacologic targets or biomarkers relevant in the treatment and monitoring of AAA disease.

Open thrombectomy and retrograde mesenteric stenting as a treatment for acute in chronic occlusive mesenteric ischemia: A case report.

In this case report, we outline a tailored approach for a complex patient with acute in chronic proximal occlusive mesenteric disease complicated with fresh thrombosis and a heavily calcified aorta, where the standard treatment proved suboptimal. We outline the surgical considerations that ultimately led to performing a hybrid procedure of open thrombectomy combined with retrograde open mesenteric stenting of the superior mesenteric artery. The patient was a 75-year-old male, with a history of severe arteriosclerosis presenting with abdominal pain over 48 h. An initial diagnostic laparoscopy was performed at a local hospital showing signs of mesenteric ischemia. The patient was transferred to a major trauma hospital, where the patient underwent an open thrombectomy combined with retrograde open mesenteric stenting. The patient's intestines showed no signs of necrosis after surgery, and the patient was discharged nine days after surgery. The patient has experienced no complications and was alive at the 90-day follow-up. This case report outlines the clinical information available to the surgeons, leading to their decision of an infrequently used approach in emergency surgery. We believe that hybrid procedures utilizing the strengths of both open and endovascular surgery should be considered in complex patients where standard treatment options are suboptimal. European guidelines state that retrograde open mesenteric stenting should be performed when antegrade stenting fails, utilizing a through-and-through procedure. We believe that in some cases it is beneficial to the patient to use a hybrid approach including retrograde open mesenteric stenting as first line treatment.

Mapping the lack of public initiative against female genital mutilation in Denmark.

BACKGROUND: Female genital mutilation (FGM) is a harmful practice prevalent in 35 countries, mainly in Africa, as well as in some Middle Eastern countries and a few Asian countries. FGM comprises all procedures that involve partial or complete resection of, or other injury to, external female genitalia for non-medical reasons. The practice of FGM has spread to Western countries due to migration. The European Institute for Gender Equality recommend that FGM be combatted by nationally coordinated efforts through implementation of national action plans, guidelines for professionals as well as comprehensive research in the field. FGM was outlawed in Denmark 2003, but no national actions plan has been implemented. Instead, the task of combatting FGM is currently under the responsibility of local governments in the form of the 98 municipalities. The aim of this study is to investigate the Danish municipalities' efforts to prevent FGM on the local level, and whether these initiatives are in accordance with international recommendations and standards. METHODS: All 98 Danish municipalities were invited to respond to a questionnaire regarding FGM in their respective municipalities. The inclusion process and questionnaire was designed after a pilot study, which included 29 municipalities. The questionnaire consisted of four overall areas of focus: "action plan", "registration", "information material" and "preventive initiatives". Demographic data were gathered from the 2017 census by Statistics Denmark. Risk countries were defined as countries with a tradition for FGM, identified from the 2016 UNICEF definition. RESULTS: A total of 67 municipalities participated in the study. At the time of census, 1.8% of the Danish population was immigrants with origins in risk countries. A total of 10.4% of the responding municipalities indicated to have implemented a specific action plan against FGM. A total of 7,5% had implemented specific preventive initiatives against FGM. Registration of reported FGM cases were indicated to be performed in 73.1% of the responding municipalities; however, only 17.9% stated to perform registration of FGM specifically as such, and not as general child abuse. CONCLUSIONS: Our study shows that the current situation of FGM registration and prevention being under local administrative responsibility in the 98 Danish municipalities has led to a severe lack of coordinated public initiative against FGM.

Posttraumatic levels of liver enzymes can reduce the need for CT in children: a retrospective cohort study.

BACKGROUND: Computed tomography (CT) is the gold standard in the initial evaluation of the hemodynamically stable patient with suspected liver trauma. However, the adverse effects of radiation exposure are of specific concern in the pediatric population. It is therefore desirable to explore alternative diagnostic modalities. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are hepatic enzymes, which are elevated in peripheral blood in relation to liver injury. The aim of the present study was to investigate a potential role of normal liver transaminase levels in the decision algorithm in suspected pediatric blunt liver trauma. METHODS: Retrospective analysis of consecutively collected data from children (0-17 years) with blunt liver trauma, admitted to a single trauma centre in Denmark, between 2000 and 2013. Patients underwent abdominal CT during initial evaluation, and initial AST and/or ALT was measured. Based on local guidelines, we set the threshold for blood AST and ALT level to 50 IU/L. Nonparametric statistical tests were used. RESULTS: Sixty consecutive children with liver injury following blunt abdominal trauma were enrolled in the study. All patients with normal AST and/or ALT level were treated conservatively with success. Information on both AST and ALT was available in 47 children. Of these 47 children, three children had AST and ALT levels ≤50 IU/L. These children suffered from grade I liver injuries, and were treated conservatively with no complications. DISCUSSION: All children who presented with blunt liver injury and AST and ALT levels ≤50 IU/L did not require treatment. These findings indicate that AST and ALT could be included in an updated management algorithm as a screening method to avoid abdominal CT. Notable limitations to the study was the retrospective method of data collection, without inclusion of a control group. CONCLUSIONS: CT seems superfluous in the initial evaluation of hemodynamically stable children with suspected blunt liver injury and blood AST and ALT levels ≤50 IU/L.

Histone deactylase gene expression profiles are associated with outcomes in blunt trauma patients.

BACKGROUND: Treatment with histone deacetylase (HDAC) inhibitors, such as valproic acid, increases survival in animal models of trauma and sepsis. Valproic acid is a pan-inhibitor that blocks most of the known HDAC isoforms. Targeting individual HDAC isoforms may increase survival and reduce complications, but little is known of the natural history of HDAC gene expression following trauma. We hypothesized that distinct HDAC isoform gene expression patterns would be associated with differences in outcomes following trauma. METHODS: Twenty-eight-day longitudinal HDAC leukocyte gene expression profiles in 172 blunt trauma patients were extracted from the Inflammation and the Host Response to Injury (Glue Grant) data set. Outcome was classified as complicated (death or no recovery by Day 28, n = 51) or uncomplicated (n = 121). Mixed modeling was used to compare the HDAC expression trajectories between the groups, corrected for Injury Severity Score (ISS), base deficit, and volume of blood products transfused during the initial 12 hours following admission. Weighted gene correlation network analysis identified modules of genes with significant coexpression, and HDAC genes were mapped to these modules. Biologic function of these modules was investigated using the Gene Ontology database. RESULTS: Elevated longitudinal HDAC expression trajectories for HDAC1, HDAC3, HDAC6, and HDAC11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin 3 (SIRT3) was associated with adverse outcome (p < 0.01). Weighted gene correlation network analysis identified significant coexpression of HDAC and SIRT genes with genes involved in ribosomal function and down-regulation of protein translation in response to stress (HDAC1), T-cell signaling, and T-cell selection (HDAC3) as well as coagulation and hemostasis (SIRT3). No coexpression of HDAC11 was identified. CONCLUSION: Expression trajectories of HDAC1, HDAC3, HDAC6, HDAC11, and SIRT3 correlate with outcomes following trauma and may potentially serve as biomarkers. They may also be promising targets for pharmacologic intervention. The effects of HDAC and SIRT gene expression in trauma may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. LEVEL OF EVIDENCE: Prognostic study, level III.