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.

3-D Contrast-Enhanced Fusion Ultrasound for Accurate Volume Assessment of Vessel Lumen and Plaque in Carotid Artery Disease as Compared With Computed Tomography Angiography.

OBJECTIVE: Three-dimensional contrast-enhanced fusion ultrasound (CEFUS) of atherosclerotic carotid arteries provides spatial visualization of the vessel lumen, creating a lumenography. As in 3-D computed tomography angiography (CTA), 3-D CEFUS outlines the contrast-filled lumen. Plaque and vessel contours are distinguished in 3-D CEFUS, allowing plaque volume quantification as a valid estimate of carotid plaque burden. Three-dimensional CEFUS is unproven in intermodality studies, vindicating the assessment of 3-D CEFUS applicability and comparing 3-D CEFUS and 3-D CTA lumenography as a proof-of-concept study. METHODS: Using an ultrasound system with magnetic tracking, a linear array transducer and SonoVue contrast agent, 3-D CEFUS acquisitions were generated by spatial stitching of serial 2-D images. From 3-D CEFUS and 3-D CTA imaging, the atherosclerotic carotid arteries were reconstructed with lumenography in an offline software program for lumen and plaque volume quantification. Bland-Altman analysis was used for inter-image modality agreement. RESULTS: The study included 39 carotid arteries. Mean lumen and plaque volume in 3-D CEFUS were 0.63 cm3 (standard deviation [SD]: 0.26) and 0.62 cm3 (SD: 0.26), respectively. Lumen volume differences between 3-D CEFUS and 3-D CTA were non-significant, with a mean difference of 0.01 cm3 (SD: 0.02, p = 0.26) and limits of agreement (LoA) range of ±0.11 cm3. Mean plaque volume difference was -0.12 cm3 (SD: 0.19, p = 0.006) with a LoA range of ±0.39 cm3. CONCLUSION: There was strong agreement in lumenography between 3-D CEFUS and 3-D CTA. The interimage modality difference in plaque volumes was substantial because of challenging vessel wall definition in 3-D CTA. Three-dimensional CEFUS is viable in quantifying carotid plaque volume burden and can potentially monitor plaque development over time.

Surgical techniques for repair of abdominal rectus diastasis: a scoping review.

Rectus diastasis is characterized by widening and laxity of the linea alba, causing the abdominal content to bulge. Rectus diastasis is treated either conservatively with physiotherapy, or surgically, surgical treatment showing especially convincing results. The primary aim of this study was to describe surgical techniques used to correct abdominal rectus diastasis. Secondary, we wished to assess postoperative complications in relation to the various techniques. A systematic scoping review was conducted and reported according to the PRISMA-ScR statement. PubMed, Embase, and Cochrane Library were searched systematically. Studies were included if they described a surgical technique used to repair abdominal rectus diastasis, with or without concomitant ventral hernia. Secondary outcomes were recurrence rate and other complications. A total of 61 studies were included: 46 used an open approach and 15 used a laparoscopic approach for repair of the abdominal rectus diastasis. All the included studies used some sort of plication, but various technical modifications were used. The most common surgical technique was classic low abdominoplasty. The plication was done as either a single or a double layer, most commonly with permanent sutures. There were overall low recurrence rates and other complication rates after both the open and the laparoscopic techniques. We identified many techniques for repair of abdominal rectus diastasis. Recurrence rate and other complication rates were in general low. However, there is a lack of high-level evidence and it is not possible to recommend one method over another. Thus, further randomized controlled trials are needed in this area.

Technical details and findings during a second Lichtenstein repair or a second laparoscopic repair in the same groin: a study based on medical records.

PURPOSE: There are cases where surgeons repair a recurrent inguinal hernia using a second Lichtenstein repair (Lichtenstein-Lichtenstein) or a second laparoscopic repair (Laparoscopy-Laparoscopy) in the same groin even though this contradicts current guideline recommendations. The aim of this study was to provide an overview of surgical modifications and findings during these reoperations. METHODS: Patients in this observational study were identified in the nationwide Danish Hernia Database during a 6-year period. Outcomes were identified in medical records. The primary outcome was the prevalence of tailored reoperations and standard reoperations for Lichtenstein-Lichtenstein and Laparoscopy-Laparoscopy, respectively. The secondary outcomes were findings during the reoperation such as inguinal hernia type and size, fibrosis, and difficulty to identify anatomical landmarks. RESULTS: Of the 102 Lichtenstein reoperations, 43 (42%) were tailored repairs and 59 (58%) were standard repairs. The most common modifications were posterior wall reinforcement with permanent sutures, dividing a structure to enable sufficient hernioplasty, and a modification of the new mesh size and/or shape. There were no differences in the findings during tailored- and standard Lichtenstein reoperations. Of the 58 laparoscopic reoperations, 35 (60%) were tailored repairs and 23 (40%) were standard repairs. The most common modifications were necessitation of a coated mesh due to insufficient peritoneal coverage and use of unusual mesh sizes and/or shapes. Fibrosis was more commonly described during the tailored laparoscopic reoperations. CONCLUSIONS: A substantial part of the Lichtenstein- and the laparoscopic reoperations was tailored approaches, and various modifications were used. Fibrosis was more commonly described during tailored laparoscopic reoperations.

Pharmacokinetics and Safety of Intravenous, Intravesical, Rectal, Transdermal, and Vaginal Melatonin in Healthy Female Volunteers: A Cross-Over Study.

INTRODUCTION: We aimed to investigate the pharmacokinetic properties and safety of melatonin administered by alternative routes of administration. METHODS: This study employed a cross-over design in healthy female volunteers. Twenty-five milligrams of melatonin was administered intravenously, intravesically, rectally, transdermally, and vaginally. Blood samples were collected at specified time points up to 24 h following intravenous, intravesical, rectal, and vaginal administration, and up to 48 h following transdermal administration. Plasma melatonin concentrations were determined by radioimmunoassay. Sedation was evaluated by a simple reaction-time test, and sleepiness was assessed by the Karolinska Sleepiness Scale. Adverse events were registered for each route of administration. RESULTS: Ten participants were included. We documented a mean (SD) time to maximal concentration of 51 (29) min for intravesical, 24 (20) min for rectal, 21 (8) h for transdermal, and 147 (56) min for vaginal administration. The mean (SD) elimination half-life was 47 (6) min for intravenous, 58 (7) min for intravesical, 60 (18) min for rectal, 14.6 (11.1) h for transdermal, and 129 (17) min for vaginal administration. The mean (SD) bioavailability was 3.6 (1.9)% for intravesical, 36.0 (28.6)% for rectal, 10.0 (5.7)% for transdermal, and 97.8 (31.7)% for vaginal administration. No significant changes in reaction times were observed following administration of melatonin by any of the administration routes. Increased tiredness was documented following transdermal administration only. No serious adverse effects were documented. CONCLUSION: Rectally and vaginally administered melatonin may serve as relevant alternatives to standard oral melatonin therapy. Transdermal delivery of melatonin displayed an extended absorption and can be applied if prolonged effects are intended. Intravesical administration displayed, as expected, a very limited bioavailability. Melatonin administered by these routes of administration was safe.

Treatment Options for Abdominal Rectus Diastasis.

Background: Abdominal rectus diastasis is a condition where the abdominal muscles are separated by an abnormal distance due to widening of the linea alba causing the abdominal content to bulge. It is commonly acquired in pregnancies and with larger weight gains. Even though many patients suffer from the condition, treatment options are poorly investigated including the effect of physiotherapy and surgical treatment. The symptoms include pain and discomfort in the abdomen, musculoskeletal and urogynecological problems in addition to negative body image and impaired quality of life. The purpose of this review was to give an overview of treatment options for abdominal rectus diastasis. Results: The first treatment step is physiotherapy. However, evidence is lacking on which regimen to use and success rates are not stated. The next step is surgery, either open or laparoscopic, and both surgical approaches have high success rates. The surgical approach includes different plication techniques. The recurrence and complication rates are low, complications are minor, and repair improves low back pain, urinary incontinence, and quality of life. Robotic assisted surgery might become a possibility in the near future, but data are still lacking. Conclusions: Evidence on what conservatory treatment to use is sparse, and more research needs to be done. Both open and laparoscopic surgery have shown positive results. Innovative treatment by robotic assisted laparoscopic surgery has potential, however, more research needs to be done in this area as well. An international guideline for the treatment of rectus diastasis could be beneficial for patients and clinicians.