Publications by authors named "Ben Raude"

5 Publications

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The Role of Mitochondrial Function in Peripheral Arterial Disease: Insights from Translational Studies.

Int J Mol Sci 2021 Aug 6;22(16). Epub 2021 Aug 6.

German Aerospace Center (DLR), Institute of Aerospace Medicine, D-51147 Cologne, Germany.

Recent evidence demonstrates an involvement of impaired mitochondrial function in peripheral arterial disease (PAD) development. Specific impairments have been assessed by different methodological in-vivo (near-infrared spectroscopy, P magnetic resonance spectroscopy), as well as in-vitro approaches (Western blotting of mitochondrial proteins and enzymes, assays of mitochondrial function and content). While effects differ with regard to disease severity, chronic malperfusion impacts subcellular energy homeostasis, and repeating cycles of ischemia and reperfusion contribute to PAD disease progression by increasing mitochondrial reactive oxygen species production and impairing mitochondrial function. With the leading clinical symptom of decreased walking capacity due to intermittent claudication, PAD patients suffer from a subsequent reduction of quality of life. Different treatment modalities, such as physical activity and revascularization procedures, can aid mitochondrial recovery. While the relevance of these modalities for mitochondrial functional recovery is still a matter of debate, recent research indicates the importance of revascularization procedures, with increased physical activity levels being a subordinate contributor, at least during mild stages of PAD. With an additional focus on the role of revascularization procedures on mitochondria and the identification of suitable mitochondrial markers in PAD, this review aims to critically evaluate the relevance of mitochondrial function in PAD development and progression.
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August 2021

The effect of revascularization on recovery of mitochondrial respiration in peripheral artery disease: a case control study.

J Transl Med 2021 06 4;19(1):244. Epub 2021 Jun 4.

Department of Vascular Surgery, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.

Background: Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle.

Methods: Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB).

Results: Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010).

Conclusions: Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.
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June 2021

Giant saccular aneurysm of the internal carotid artery with adhesion to the vagus nerve: A Case Report.

Int J Surg Case Rep 2021 Apr 27;81:105845. Epub 2021 Mar 27.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of vascular surgery, Berlin, Germany. Electronic address:

Introduction And Importance: Aneurysms of the carotid artery are rare and potentially a risk factor for developing neurological events. This case report describes the treatment of a giant saccular aneurysm of the right extracranial internal carotid artery (ICA) with adhesion to the vagus verve.

Case Presentation: An 85-year-old female presented with an asymptomatic pulsating mass on the right neck. Ultrasonography and MR angiography revealed a giant aneurysm of the right internal carotid artery with a massive tortuosity. Intraoperatively, a massive adhesion of the vagus nerve to the aneurysm was found. A resection of the aneurysm followed by a spatulated end-to-end anastomosis was performed. Postprocedural neurological symptoms included a transient paralysis of the vagus nerve that recovered within six weeks.

Clinical Discussion: The treatment options of ICA aneurysms include open surgical and endovascular interventions. Endovascular treatment may be a good option for aneurysms with a particular morphology. However, open surgery is the favorable option for immense ICA aneurysms with a tortuous anatomical path.

Conclusion: Aneurysm resection with end-to-end anastomosis is a possible surgical option in the case of tortuous extracranial ICA aneurysms. Leaving parts of the aneurysmal wall prevented occurring persisting damage of the adhesive vagus nerve.
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April 2021

Aortoduodenal fistulas after endovascular abdominal aortic aneurysm repair and open aortic repair.

J Vasc Surg 2021 09 5;74(3):711-719.e1. Epub 2021 Mar 5.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of vascular surgery, Berlin, Germany.

Objective: In the present study, we have reported and compared aortoduodenal fistulas (ADFs) after endovascular abdominal aortic aneurysm repair (EVAR) vs after open aortic repair (OAR).

Methods: We retrospectively analyzed the data from patients treated for ADFs from January 2015 to May 2020 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated. The primary endpoints of the present study were 30-day and 1-year mortality. The secondary endpoints were major postoperative complications.

Results: A total of 24 patients (20 men; median age, 69 years; range, 53-82 years) were admitted with ADFs after EVAR (n = 9) or OAR (n = 15). These patients accounted for ∼4.3% of all abdominal aortic aneurysm repairs in our hospital. The median interval from the initial aortic repair and the diagnosis of ADF was 68 months (range, 6-83 months) for the ADF-EVAR group and 80 months (range, 1-479 months) for the ADF-OAR group. Three patients in the ADF-EVAR group had refused surgical treatment owing to their high surgical risk. One patient in the ADF-OAR group had undergone removal of the aortic prosthesis without replacement. Of the remaining 20 patients, 12 (ADF-EVAR group, n = 4; ADF-OAR group, n = 8) had undergone in situ replacement of the aorta and 8 (ADF-EVAR group, n = 2; ADF-OAR group, n = 6) had undergone extra-anatomic reconstruction with aortic ligation. After a mean follow-up of 26 months, no patient had experienced early limb loss. However, one case of rupture of the venous graft (ADF-EVAR), one case of aortic stump blowout (ADF-OAR), and one case of a ureteroarterial fistula with a homograft (ADF-OAR) had occurred. Overall, the incidence of postoperative complications was significantly greater after ADF-OAR (93% vs 33%; P = .036). The most frequent bacteria involved in the blood cultures were Escherichia coli (25% of patients), and Candida spp. (61%) were the predominant pathogens found on intra-abdominal smears. The in-hospital mortality rates for the ADF-EVAR and ADF-OAR group were 22% and 13%, respectively. The corresponding 1 -year mortality rates were 22% and 33%.

Conclusions: Patients with ADFs after EVAR or OAR have limited overall survival. In addition to the similar therapeutic approaches, we found no significant differences in postoperative mortality between these two uncommon pathologic entities. In our study, the overall postoperative morbidity seemed greater for the ADF-OAR group.
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September 2021

Vascular surveillance by haptotactic blood platelets in inflammation and infection.

Nat Commun 2020 11 13;11(1):5778. Epub 2020 Nov 13.

DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 80802, Munich, Germany.

Breakdown of vascular barriers is a major complication of inflammatory diseases. Anucleate platelets form blood-clots during thrombosis, but also play a crucial role in inflammation. While spatio-temporal dynamics of clot formation are well characterized, the cell-biological mechanisms of platelet recruitment to inflammatory micro-environments remain incompletely understood. Here we identify Arp2/3-dependent lamellipodia formation as a prominent morphological feature of immune-responsive platelets. Platelets use lamellipodia to scan for fibrin(ogen) deposited on the inflamed vasculature and to directionally spread, to polarize and to govern haptotactic migration along gradients of the adhesive ligand. Platelet-specific abrogation of Arp2/3 interferes with haptotactic repositioning of platelets to microlesions, thus impairing vascular sealing and provoking inflammatory microbleeding. During infection, haptotaxis promotes capture of bacteria and prevents hematogenic dissemination, rendering platelets gate-keepers of the inflamed microvasculature. Consequently, these findings identify haptotaxis as a key effector function of immune-responsive platelets.
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November 2020