Angiotensin Receptor-Neprilysin Inhibition (Sacubitril/Valsartan) Reduces Structural Arterial Stiffness in Middle-Aged Mice.

BACKGROUND: Increasing arterial stiffness is a prominent feature of the aging cardiovascular system. Arterial stiffening leads to fundamental alterations in central hemodynamics with widespread detrimental implications for organ function resulting in significant morbidity and death, and specific therapies to address the underlying age-related structural arterial remodeling remain elusive. The present study investigates the potential of the recently clinically available dual angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan (LCZ696) to counteract age-related arterial fibrotic remodeling and stiffening in 1-year-old mice. METHODS AND RESULTS: Treatment of in 1-year-old mice with ARNI (sacubitril/valsartan), in contrast to angiotensin receptor blocker monotherapy (valsartan) and vehicle treatment (controls), significantly decreases structural aortic stiffness (as measured by in vivo pulse-wave velocity and ex vivo aortic pressure myography). This phenomenon appears, at least partly, independent of (indirect) blood pressure effects and may be related to a direct antifibrotic interference with aortic smooth muscle cell collagen production. Furthermore, we find aortic remodeling and destiffening due to ARNI treatment to be associated with improved parameters of cardiac diastolic function in aged mice. CONCLUSIONS: This study provides preclinical mechanistic evidence indicating that ARNI-based interventions may counteract age-related arterial stiffening and may therefore be further investigated as a promising strategy to improve cardiovascular outcomes in the elderly.

Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening, and osteopontin release in abdominal aortic aneurysm.

AIMS: Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling of the vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their role in AAA is poorly understood. METHODS AND RESULTS: The present study revealed that platelets play a crucial role in promoting AAA through modulation of inflammation and degradation of the extracellular matrix (ECM). They are responsible for the up-regulation of SPP1 (osteopontin, OPN) gene expression in macrophages and aortic tissue, which triggers inflammation and remodelling and also platelet adhesion and migration into the abdominal aortic wall and the intraluminal thrombus (ILT). Further, enhanced platelet activation and pro-coagulant activity result in elevated gene expression of various cytokines, Mmp9 and Col1a1 in macrophages and Il-6 and Mmp9 in fibroblasts. Enhanced platelet activation and pro-coagulant activity were also detected in AAA patients. Further, we detected platelets and OPN in the vessel wall and in the ILT of patients who underwent open repair of AAA. Platelet depletion in experimental murine AAA reduced inflammation and ECM remodelling, with reduced elastin fragmentation and aortic diameter expansion. Of note, OPN co-localized with platelets, suggesting a potential role of OPN for the recruitment of platelets into the ILT and the aortic wall. CONCLUSION: In conclusion, our data strongly support the potential relevance of anti-platelet therapy to reduce AAA progression and rupture in AAA patients.

Abdominal Aortic Endograft Implantation Immediately Induces Vascular Stiffness Gradients That May Promote Adverse Aortic Neck Dilatation: Results of A Porcine Ex Vivo Study.

PURPOSE: Endovascular aortic repair (EVAR) is the method of choice for most abdominal aortic aneurysm (AAA) patients requiring intervention. However, chronic aortic neck dilatation (AND) following EVAR progressively weakens the structural seal between vessel and endograft and compromises long-term results of the therapy. This experimental ex vivo study seeks to investigate mechanisms of AND. MATERIALS AND METHODS: Porcine abdominal aortas (n=20) were harvested from slaughterhouse pigs and connected to a mock circulation. A commercially available endograft was implanted (n=10) or aortas were left untreated as controls (n=10). Vascular circumferential strain was assessed via ultrasound in defined aortic segments as a parameter of aortic stiffness. Histology and aortic gene expression analysis were performed to investigate potential changes of aortic wall structure and molecular differences due to endograft implantation. RESULTS: We found that endograft implantation acutely induces a significant stiffness gradient directly at the interface between stented and unstented aortic segments under pulsatile pressure. Comparing stented aortas with unstented controls, we detected increased aortic expression levels of inflammatory cytokines (Il6 and Ccl2) and matrix metalloproteinases (Mmp2 and Mmp9) after 6 hours of pulsatile pressurization. This effect, however, was abolished when repeating the same experiment under 6 hours of static pressure. CONCLUSIONS: We identified endograft-induced aortic stiffness gradients as an early trigger of inflammatory aortic remodeling processes that might promote AND. These results highlight the importance of adequate endograft designs to minimize vascular stiffness gradients and forestall late complications, such as AND. CLINICAL IMPACT: AND may compromise the long-term results following endovascular aortic repair. However, the mechanisms behind the underlying detrimental aortic remodeling are still unclear. In this study we find that endograft-induced aortic stiffness gradients induce an inflammatory aortic remodeling response consistent with AND. This novel pathomechanistic insight may guide the design of new aortic endografts that minimize vascular stiffness gradients and forestall late complications such as AND.

Time-dependent effects of cellulose and gelatin-based hemostats on cellular processes of wound healing.

Introduction: Oxidized regenerated cellulose-based (ORC - TABOTAMP), oxidized non-regenerated cellulose-based (ONRC - RESORBA CELL), and gelatin-based (GELA - GELITA TUFT-IT) hemostats are commonly used in surgery. However, their impact on the wound healing process remains largely unexplored. We here assess time-dependent effects of exposure to these hemostats on fibroblast-related wound healing processes. Material and methods: Hemostats were applied to fibroblast cell cultures for 5-10 (short-), 30 and 60 min (intermediate-) and 24 h (long-term). Representative images of the hemostat degradation process were obtained, and the pH value was measured. Cell viability, apoptosis and migration were analyzed after the above exposure times at 3, 6 and 24 h follow-up. Protein levels for tumor necrosis factor α (TNF-α) and transforming-growth factor ß (TGF-ß) were assessed. Results: ORC and ONRC reduced pH values during degradation, while GELA proved to be pH-neutral. Hemostat structural integrity was prolonged for GELA (vs. ORC and ONRC). TGF-ß and TNF-α levels were reduced for ORC and ONRC (vs. GELA and control) (p < 0.05). Further, exposure of ORC and ONRC for longer than 5-10 min reduced cell viability vs. GELA and control at 3 h post-exposure (p < 0.05). Similarly, cell migration was impaired with ORC and ONRC exposure longer than 60 min at 24 h follow-up (p < 0.05). Conclusions: Short-term exposure to ORC and ONRC impairs relevant wound healing-related processes in fibroblasts, and alters protein levels of key mediating cytokines. GELA does not show similar effects. We conclude that GELA may be preferred over ORC and ONRC over short-, intermediate- and long-term exposures. Future validation of the clinical relevance is warranted.

Nicotine Affects Murine Aortic Stiffness and Fatigue Response During Supraphysiological Cycling.

Nicotine exposure is a major risk factor for several cardiovascular diseases. Although the deleterious effects of nicotine on aortic remodeling processes have been studied to some extent, the biophysical consequences are not fully elucidated. In this investigation, we applied quasi-static and dynamic loading to quantify ways in which exposure to nicotine affects the mechanical behavior of murine arterial tissue. Segments of thoracic aortas from C57BL/6 mice exposed to 25 mg/kg/day of subcutaneous nicotine for 28 days were subjected to uniaxial tensile loading in an open-circumferential configuration. Comparing aorta segments from nicotine-treated mice relative to an equal number of control counterparts, stiffness in the circumferential direction was nearly twofold higher (377 kPa ± 165 kPa versus 191 kPa ± 65 kPa, n = 5, p = 0.03) at 50% strain. Using a degradative power-law fit to fatigue data at supraphysiological loading, we observed that nicotine-treated aortas exhibited significantly higher peak stress, greater loss of tension, and wider oscillation band than control aortas (p ≤ 0.01 for all three variables). Compared to simple stress relaxation tests, fatigue cycling is shown to be more sensitive and versatile in discerning nicotine-induced changes in mechanical behavior over many cycles. Supraphysiological fatigue cycling thus may have broader potential to reveal subtle changes in vascular mechanics caused by other exogenous toxins or pathological conditions.

Translating mouse models of abdominal aortic aneurysm to the translational needs of vascular surgery.

INTRODUCTION: Abdominal aortic aneurysm (AAA) is a condition that has considerable socioeconomic impact and an eventual rupture is associated with high mortality and morbidity. Despite decades of research, surgical repair remains the treatment of choice and no medical therapy is currently available. Animal models and, in particular, murine models, of AAA are a vital tool for experimental in vivo research. However, each of the different models has individual limitations and provide only partial mimicry of human disease. This narrative review addresses the translational potential of the available mouse models, highlighting unanswered questions from a clinical perspective. It is based on a thorough presentation of the available literature and more than a decade of personal experience, with most of the available models in experimental and translational AAA research. RESULTS: From all the models published, only the four inducible models, namely the angiotensin II model (AngII), the porcine pancreatic elastase perfusion model (PPE), the external periadventitial elastase application (ePPE), and the CaCl2 model have been widely used by different independent research groups. Although the angiotensin II model provides features of dissection and aneurysm formation, the PPE model shows reliable features of human AAA, especially beyond day 7 after induction, but remains technically challenging. The translational value of ePPE as a model and the combination with ß-aminopropionitrile to induce rupture and intraluminal thrombus formation is promising, but warrants further mechanistic insights. Finally, the external CaCl2 application is known to produce inflammatory vascular wall thickening. Unmet translational research questions include the origin of AAA development, monitoring aneurysm growth, gender issues, and novel surgical therapies as well as novel nonsurgical therapies. CONCLUSION: New imaging techniques, experimental therapeutic alternatives, and endovascular treatment options provide a plethora of research topics to strengthen the individual features of currently available mouse models, creating the possibility of shedding new light on translational research questions.

Outflow Through Aortic Side Branches Drives False Lumen Patency in Type B Aortic Dissection.

Objective: Thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD) aims to induce false lumen (FL) thrombosis by sealing intimal tears between the true (TL) and the FL, and blocking the inflow into the FL. Incomplete thrombosis of the FL is correlated with poor clinical outcome. We hypothesize that the number of major and minor branches arising from the FL affects FL patency and may negatively influence TEVAR induced FL thrombosis. Methods: Computed tomography (CT)-scans from 89 patients diagnosed with TBAD [best medical treatment (BMT) n = 52, TEVAR n = 37] from two high-volume vascular surgery centers were analyzed retrospectively. Analysis included evaluation of the FL patency status, the number, location and size of intimal tears, and the presence of minor and major side branches originating from the FL. Multiple regression analysis was conducted to evaluate obtained parameters as predictors for FL thrombosis status. Results: In univariate analysis, the strongest correlation for FL patency was found for the number of major (R = 0.79) and minor (R = 0.86) side branches originating from the FL. When applying a multiple linear regression model, the number of major (normalized beta 0.37; P < 0.001) and minor (normalized beta 0.41; P < 0.01) side branches arising from the FL were valid predictors for the axial length of the patent and non-patent FL, and additionally determined the length of the patent FL at 12-month follow-up in patients that underwent TEVAR. Conclusions: Our data suggest that the number of minor side branches that originate from the FL in TBAD is an important determinant of FL patency, to a greater degree than previously assumed.

Exosome miR-501-3p Elevation Contributes to Progression of Vascular Stiffness.

Background: Tight junction (TJ) disruption and dysfunction are involved in the progression of arteriosclerosis. miR-501-3p regulates endothelial TJ protein-1, resulting in TJ disruption. Because exosomal microRNAs can travel to distant tissues and influence cell behavior, patients with elevated miR-501-3p may experience accelerated vascular disease progression secondary to miR-501-3p-induced reductions in TJ. This study investigated whether plasma exosome miR-501-3p levels are associated with vascular stiffness, an indicator for arteriosclerotic changes. Methods and Results: Fifty-one subjects (mean [±SD] age 70±8 years, 37% male) enrolled in a medical checkup program were recruited to the study. Brachial-ankle arterial pulse wave velocity (baPWV) and plasma exosome miR-501-3p expression were measured. Patients were divided into 2 groups depending on whether their miR-501-3p ∆Ct values were above ("High"; n=24) or below ("Low"; n=27) the cut-off levels determined by receiver operating characteristic (ROC) curve analysis. Median (interquartile range) baPWV levels were significantly higher in the miR-501-3p High than Low group (1,664 [1,496-1,859] vs. 1,450 [1,353-1,686] cm/s, respectively; P<0.05). Multivariate logistic regression analysis showed a significant association between increased baPWV and High miR-501-3p expression (odds ratio 4.66). At follow-up visits (mean 62 months later), baPWV remained significantly higher in the miR-501-3p High than Low group (1,830 [1,624-2,056] vs. 1,620 [1,377-1,816] cm/s, respectively; P<0.05). Conclusions: High expression levels of exosome miR-501-3p contribute to arteriosclerotic changes.

Controlled isoflurane anesthesia exposure is required for reliable behavioral testing in murine surgical models.

We investigated the effects of variations in anesthesia exposure time prior to conducting anxiety response behavioral testing in sham controls from an experimental murine model. The staying time in the center area of the Open Field test in the "long exposure" group was significantly decreased compared to that of the "short exposure" group. Significant correlation was found between anesthesia time and the duration of staying time in the center area. We conclude that anesthesia time may have a significant impact on behavioral anxiety testing in this context, and advise careful control of this parameter in protocol optimization in related surgical animal models.

Clinical outcomes after direct and indirect surgical venous thrombectomy for inferior vena cava thrombosis.

OBJECTIVE: Inferior vena cava thrombosis is rare, but patients are at high risk for development of a post-thrombotic syndrome (PTS) in the long term. Surgical approaches include indirect transfemoral venous thrombectomy (iTFVT) and direct open venous thrombectomy (dOVT). This study reports patient outcomes after iTFVT and dOVT for inferior vena cava thrombosis covering a 25-year follow-up period. METHODS: The study period was from January 1, 1982, to December 31, 2013. Data were retrieved from archived medical records, and patients were invited for a detailed phlebologic follow-up examination (DPFE). Health-related quality of life was assessed with the 36-Item Short Form Health Survey questionnaire. Patient survival, patency rates, and freedom from PTS were calculated using Kaplan-Meier estimation with log-rank testing. The χ2 test with Yates continuity correction and logistic regression analysis were applied to identify associations between risk factors or coagulation disorders, mortality, and PTS. RESULTS: Complete medical records were available for 152 patients. Patients' 5-year survival was 91% ± 3%, and 5-year primary and secondary patency rates were 80% ± 3% and 94% ± 2%. Freedom from PTS after 25 years was 84% ± 6%. No differences for patient survival, patency rates, or freedom from PTS were identified between iTFVT, dOVT, and a combination of both procedures. Antithrombin III deficiency was the most common coagulation disorder, and patients' physical function and social function were impaired compared with those found in German normative data (P < .05). No risk factor or coagulation disorder was associated with survival or PTS. CONCLUSIONS: Open surgical venous thrombectomy is safe and delivers satisfying short- and long-term outcomes compared with endovascular approaches. It remains valuable for patients who are not eligible for other interventional therapies.

The JOTEC iliac branch device for exclusion of hypogastric artery aneurysms: ABRAHAM study.

OBJECTIVE: Hypogastric artery aneurysms (HAAs) are rare but life-threatening in cases of rupture. Open or endovascular techniques traditionally aimed at occluding the hypogastric artery (HA) have considerable risk of pelvic ischemia. Iliac branch devices (IBDs) are indicated for aortoiliac aneurysms; however, they have also been used lately for HAAs. Currently, there are no reports about patient outcomes focusing on HAA therapy using IBDs. We retrospectively analyzed early and midterm outcomes using IBDs for HAAs. METHODS: Patients who received IBDs for HAAs at our department from January 1, 2012, through March 1, 2018, were included. Exclusion criteria were as follows: no HA involvement, emergency procedures, and HA stent grafting without IBD. Perioperative and follow-up data were collected from medical records. RESULTS: There were 18 IBDs (only IBD, n = 4; IBD + endovascular aneurysm repair [EVAR], n = 7; IBD ± EVAR + side branch occlusion, n = 7) implanted into 14 male patients (76 ± 4 [70-83] years). There were no intraoperative complications, and the technical success rate was 100%. After 19 ± 11 (2-39) months of follow-up, two hybrid (external iliac artery occlusion, n = 1; EVAR graft kinking, n = 1) and four endovascular reinterventions due to two type IB (side branch coiling + stent graft extension) and two type IIIB (stent grafting) endoleaks were required. One IBD-related type II endoleak revealed constant aneurysm diameters during follow-up. One small type IB endoleak was self-limited. Estimated freedom from reintervention was 31% ± 23% at 2.7 years. The clinical success and patency rate was 100%. The IBD-related mortality was 0%. CONCLUSIONS: The IBD for HAA shows good early and midterm results. Adequate sealing of HA landing zones and side branch occlusion are technically challenging but crucial to prevent type IB and type II endoleaks.

An Automated Algorithm to Quantify Collagen Distribution in Aortic Wall.

Arterial diseases including abdominal aortic aneurysm and atherosclerosis are biomechanical diseases characterized by significant changes in the structure and strength of the vessel wall. It is now established that local variations in fibrillar collagen and elastin matrix turnover is critical to arterial stiffening and progression of the disease. The collagen content in the aortic wall has nominally been quantified by biochemical assays and immunohistochemical analysis as the total amount because of the difficulty in separating the media and adventitia. In this work, we have developed an algorithm for automatic quantification of layer-specific collagen content from bright-field and polarized microscopic images of histological sections of mouse aorta stained with Picrosirius red (PSR) stain. The images were processed sequentially including separation of layers, erosion, segregation of regions, binarization, and quantification of pixel intensities to obtain collagen content in the media and adventitia separately. We observed that the automated algorithm rapidly and accurately quantified collagen content from a wide range of image quality compared with manual measurements particularly when the medial and adventitial layers overlap. Together, our algorithm will be of significant impact in the rapid, reliable, and accurate analyses of collagen distribution in histological sections of connective tissues.

Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility.

Aim: Arterial stiffness is a significant risk factor for many cardiovascular diseases, including abdominal aortic aneurysms (AAA). Nicotine, the major active ingredient of e-cigarettes and tobacco smoke, induces acute vasomotor effects that may temporarily increase arterial stiffness. Here, we investigated the effects of long-term nicotine exposure on structural aortic stiffness. Methods: Mice (C57BL/6) were infused with nicotine for 40 days (20 mg/kg/day). Arterial stiffness of the thoracic (TS) and abdominal (AS) aortic segments was analyzed using ultrasound (PWV, pulse wave velocity) and ex vivo pressure myograph measurements. For mechanistic studies, aortic matrix-metalloproteinase (MMP) expression and activity as well as medial elastin architecture were analyzed. Results: Global aortic stiffness increased with nicotine. In particular, local stiffening of the abdominal segment occurred after 10 days, while thoracic aortic stiffness was only increased after 40 days, resulting in aortic stiffness segmentation. Mechanistically, nicotine exposure enhanced expression of MMP-2/-9 and elastolytic activity in both aortic segments. Elastin degradation occurred in both segments; however, basal elastin levels were higher in the thoracic aorta. Finally, MMP-inhibition significantly reduced nicotine-induced MMP activity, elastin destruction, and aortic stiffening. Conclusion: Chronic nicotine exposure induces aortic MMP expression and structural aortic damage (elastin fragmentation), irreversibly increasing aortic stiffness. This process predominantly affects the abdominal aortic segment, presumably due in part to a lower basal elastin content. This novel phenomenon may help to explain the role of nicotine as a major risk factor for AAA formation and has health implications for ECIGs and other modes of nicotine delivery.

Systemic Upregulation of IL-10 (Interleukin-10) Using a Nonimmunogenic Vector Reduces Growth and Rate of Dissecting Abdominal Aortic Aneurysm.

Objective- Recruitment of immunologic competent cells to the vessel wall is a crucial step in formation of abdominal aortic aneurysms (AAA). Innate immunity effectors (eg, macrophages), as well as mediators of adaptive immunity (eg, T cells), orchestrate a local vascular inflammatory response. IL-10 (interleukin-10) is an immune-regulatory cytokine with a crucial role in suppression of inflammatory processes. We hypothesized that an increase in systemic IL-10-levels would mitigate AAA progression. Approach and Results- Using a single intravenous injection protocol, we transfected an IL-10 transcribing nonimmunogenic minicircle vector into the Ang II (angiotensin II)-ApoE-/- infusion mouse model of AAA. IL-10 minicircle transfection significantly reduced average aortic diameter measured via ultrasound at day 28 from 166.1±10.8% (control) to 131.0±5.8% (IL-10 transfected). Rates of dissecting AAA were reduced by IL-10 treatment, with an increase in freedom from dissecting AAA from 21.5% to 62.3%. Using flow cytometry of aortic tissue from minicircle IL-10-treated animals, we found a significantly higher percentage of CD4+/CD25+/Foxp3 (forkhead box P3)+ regulatory T cells, with fewer CD8+/GZMB+ (granzyme B) cytotoxic T cells. Furthermore, isolated aortic macrophages produced less TNF-α (tumor necrosis factor-α), more IL-10, and were more likely to be MRC1 (mannose receptor, C type 1)-positive alternatively activated macrophages. These results concurred with gene expression analysis of lipopolysaccharide-stimulated and Ang II-primed human peripheral blood mononuclear cells. Conclusions- Taken together, we provide an effective gene therapy approach to AAA in mice by enhancing antiinflammatory and dampening proinflammatory pathways through minicircle-induced augmentation of systemic IL-10 expression.

MicroRNA-Mediated Therapy Modulating Blood-Brain Barrier Disruption Improves Vascular Cognitive Impairment.

OBJECTIVE: There are currently no effective treatments for the prevention of dementia associated with vascular cognitive impairment. MicroRNAs regulate gene expression at the post-transcriptional level and play key roles in vascular disorders. TNFα (tumor necrosis factor-α) regulates blood-brain barrier breakdown through modification of cerebral tight junctions. Here, we sought key TNFα-responsive microRNAs that might influence blood-brain barrier breakdown via cerebral tight junction disruption in vascular cognitive impairment. APPROACH AND RESULTS: Using a mouse model of vascular cognitive impairment, chronic cerebral hypoperfusion within the white matter was induced with bilateral common carotid artery stenosis (BCAS) surgery. TNFα gene expression was increased in white matter post-BCAS surgery, and TNFα stimulation decreased claudin-5, ZO-1 (tight-junction protein 1), and occludin gene expression in murine brain endothelial cells. In silico analysis predicted 8 candidate microRNAs as regulators of claudin-5, ZO-1, and occludin gene expression. Of these, only miR-501-3p was upregulated by TNFα in vitro and was upregulated in the white matter after BCAS surgery. Further, miR-501-3p directly bound to the 3'-untranslated region of human ZO-1 and downregulated transendothelial electric resistance. In vivo administration of a locked nucleic acid -modified antisense oligonucleotide versus miR-501-3p suppressed BCAS-induced reduction of ZO-1 gene expression and blood-brain barrier disruption within the white matter and significantly ameliorated working memory deficits after BCAS surgery. CONCLUSIONS: We here provide the first evidence that the TNFα-miR-501-3p-ZO-1 axis plays an important role in the pathogenesis of cerebral hypoperfusion-induced working memory deficits and white matter lesions, as a result of blood-brain barrier breakdown via tight junction disruption. Therapeutic manipulation of miR-501-3p holds promise for limiting vascular cognitive impairment progression.

The Primary Stability of a Bioabsorbable Poly-L-Lactic Acid Suture Anchor for Rotator Cuff Repair Is Not Improved with Polymethylmethacrylate or Bioabsorbable Bone Cement Augmentation.

BACKGROUND: The incidence of osteoporosis and rotator cuff tears increases with age. Cement augmentation of bones is an established method in orthopedic and trauma surgery. QUESTIONS/PURPOSES: This study analyses if polymethylmethacrylate or bioabsorbable cement can improve the primary stability of a bioabsorbable suture anchor in vitro in comparison to a non-augmented suture anchor in osteoporotic human humeri. METHODS: The trabecular bone mineral density was measured to ensure osteopenic human specimens. Then the poly-l-lactic acid Bio-Corkscrew® FT was implanted in the greater tuberosity footprint with polymethylmethacrylate Refobacin® cement augmentation (n = 8), with Cerament™ Bone Void Filler augmentation (n = 8) and without augmentation (n = 8). Using a cyclic testing protocol, the failure loads, system displacement, and failure modes were recorded. RESULTS: The Cerament™ augmented Bio-Corkscrew® FT yielded the highest failure loads (206.7 N), followed by polymethylmethacrylate Refobacin® augmentation (206.1 N) and without augmentation (160.0 N). The system displacement was lowest for Cerament™ augmentation (0.72 mm), followed by polymethylmethacrylate (0.82 mm) and without augmentation (1.50 mm). Statistical analysis showed no significant differences regarding the maximum failure loads (p = 0.1644) or system displacement (p = 0.4199). The main mode of failure for all three groups was suture slippage. CONCLUSION: The primary stability of the Bio-Corkscrew® FT is not influenced by bone cement augmentation with polymethylmethacrylate Refobacin® or with bioabsorbable Cerament™ in comparison to the non-cemented anchors. The cement augmentation of rotator cuff suture anchors in osteoporotic bones remains questionable since biomechanical tests show no significant advantage.

Open surgery for iliofemoral deep vein thrombosis with temporary arteriovenous fistula remains valuable.

Objective We assessed outcomes of open surgical venous thrombectomy with temporary arteriovenous fistula, and the procedure's effect on health-related quality of life. Method We retrospectively analyzed 48 (26 at long-term) patient medical records. Mortality rates, patency, and risk of post-thrombotic syndrome were analyzed using Kaplan-Meier estimation. The association between risk factors/coagulation disorders and patency/post-thrombotic syndrome along with patient health-related quality of life at long-term was analyzed employing various statistical methods. Results Patient one-year survival rate was 93 ± 4% and primary one-year patency rate was 89 ± 5% (secondary one-year patency rate 97 ± 3%). Freedom from post-thrombotic syndrome after eight years was 80 ± 12% (post-thrombotic syndrome rate 20 ± 12%). Health-related quality of life was impaired vs. normative data in the physical and social subscales, and in the mental component score ( p < .05). Conclusions Open surgical venous thrombectomy appears safe compared with literature-reported outcomes in similar patients using alternative approaches. Iliofemoral deep vein thrombosis impairs physical, social, and mental health-related quality of life.

Chronic Mesenteric Ischemia: Patient Outcomes Using Open Surgical Revascularization.

BACKGROUND: Chronic mesenteric ischemia (CMI) is a rare disease. Open treatment (OT) remains a valuable treatment option. We analyzed patient outcomes after OT and investigated health-related quality of life (HRQoL). METHODS: Data were analyzed retrospectively. The investigation period was from January 1, 2001, to December 31, 2014. We investigated mortality and patency rates using Kaplan-Meier analysis. HRQoL was measured using a 36-item health survey. Various statistical methods were employed. RESULTS: A total of 100 patients (celiac trunk [TC: n = 23], superior mesenteric artery [SMA: n = 26], or both [n = 51]) were included. Median follow-up was 5 ± 35 months. One-year survival rate for TC was 75 ± 11%, for SMA: 79 ± 10%, and for both: 96 ± 3%. TC 5-year survival was 75 ± 11% (SMA: 57 ± 16%: both: 80 ± 8%). Obesity and the length of hospital stay were independently associated with patient survival (p < 0.05). Primary 1-year patency rate was 60 ± 13% for TC (SMA: 86 ± 10%; both: 71 ± 8%) and secondary 1-year patency rate was 84 ± 9% for TC (SMA: 100%; both: 79 ± 7%). HRQoL was inferior compared to the German normative data (p < 0.05). CONCLUSION: CMI overlaps between gastrointestinal and vascular surgery. OT is safe, and simultaneous revascularization of the TC and the SMA does not affect mortality. Patients would not necessarily benefit from OT in terms of HRQoL.

Elevated risk of thrombophilia in agenesis of the vena cava as a factor for deep vein thrombosis.

BACKGROUND: Congenital absence of the inferior vena cava (AIVC) is a rare malformation which may be associated with an increased risk for deep vein thrombosis (DVT). However, the role of thrombophilia in AIVC and DVT is unknown. METHODS: Between 1982 and 2013 41 patients (12 female, 29 male, mean age 28 S.D. 11 years) were detected at the University of Düsseldorf, Germany, with AIVC. Based on medical history, clinical examination, imaging and coagulation studies, we performed on this collective a risk characterisation. Extensive literature research added further 123 published cases during 1993 and 2013. AIVC-patients were compared with iliocaval DVT-patients without AIVC (n = 168) treated during the same period in our clinic (90 female, 78 male, mean age 38 S.D. 17 years). RESULTS: In contrast to classical DVT younger men were more often affected. Factor-V-Leiden-mutation, 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism and hyperhomocysteinemia individually are associated with an increased risk of DVT in patients with AIVC. Aplasia/hypoplasia of the right or left kidney is also associated with IVCA. CONCLUSIONS: AIVC should be considered in young patients who present with DVT involving the vena cava. Analysis of publications with AIVC and our patients yielded a typical spectrum of AIVC-associated DVT characteristics: AIVC occurs in young male adults, is revealed by proximal DVT, not necessarily accused by precipitating factors like immobilisation, and is mostly located bilateral. Hereditary coagulation abnormalities seem to be more often a contributing factor for DVT in AIVC.

Spontaneous rupture of an isolated iliac artery dissection in a young man because of cystic medial degeneration Erdheim-Gsell.

BACKGROUND: Rupture of isolated iliac artery dissections is a life-threatening event and has not been associated with cystic medial degeneration (CMD) Erdheim-Gsell. METHODS: A young man presented to our emergency unit in a critical hemodynamic condition. Computed tomography scan feigned the rupture of an internal iliac artery. RESULTS: Surprisingly, we found a ruptured dissection of the common iliac artery during open surgery. Reconstruction was done by Dacron graft interposition between common and internal iliac artery and external iliac artery implantation into the graft. Histology revealed CMD. CONCLUSIONS: Spontaneous iliac artery dissection and rupture can be caused by CMD and requires immediate surgical intervention.