Morphological Changes of the Ovarian Vein in Pelvic Venous Disorders.

OBJECTIVE: The management of pelvic venous disorders (PeVD) remains controversial. Open surgical and endovascular methods are currently used for treatment, but there are few data in the literature on the morphology and histology of the ectatic ovarian vein (OV). This study aimed to explore the histomorphological changes in a dilated OV in patients with PeVD and compare it with a normal OV obtained post-mortem and a normal great saphenous vein (GSV). METHODS: Histology of the OV was studied in 16 patients who underwent surgery for PeVD, 10 control cadavers from whom fragments of the OV without visible gross changes were taken at autopsy, and nine control patients in whom the GSV was resected to be used for coronary artery bypass. RESULTS: The OV wall in patients with PeVD consisted of three layers: intima, media, and adventitia. The OV looked very similar to the GSV wall because of a clearly developed layer of smooth muscle fibres. The thickness of the normal OV was significantly different to the OV wall in PeVD (475.3 µm, IQR 370.7, 607.6 vs. 776.3 µm, IQR 668.9, 879.6, p < .001) and did not differ significantly from the thickness of a normal GSV wall (784.3 µm, IQR 722.2, 898.2). The intima-media complex of the OV was significantly thinner than the GSV in PeVD (118.9 µm, IQR 75.6, 159.6 vs. 415 µm, IQR 399.5, 520.0, р < .001); however, the adventitia of the OV was significantly thicker than in normal OV and GSV (599.6 µm, IQR 444.3, 749.7 vs. 373.5 µm, IQR 323.8, 482.0 vs. 308.4 µm, IQR 275.9, 338.2, p < .001). CONCLUSION: Dilatation of the OV in patients with PeVD was accompanied by a significant increase in the overall thickness of the vein wall, which brings it closer in structure to the GSV. This implies that the OV may be used safely for transposition into the inferior vena cava or iliac vein.

An international, multispecialty, expert-based Delphi Consensus document on controversial issues in the management of patients with asymptomatic and symptomatic carotid stenosis.

OBJECTIVE: Despite the publication of various national/international guidelines, several questions concerning the management of patients with asymptomatic (AsxCS) and symptomatic (SxCS) carotid stenosis remain unanswered. The aim of this international, multi-specialty, expert-based Delphi Consensus document was to address these issues to help clinicians make decisions when guidelines are unclear. METHODS: Fourteen controversial topics were identified. A three-round Delphi Consensus process was performed including 61 experts. The aim of Round 1 was to investigate the differing views and opinions regarding these unresolved topics. In Round 2, clarifications were asked from each participant. In Round 3, the questionnaire was resent to all participants for their final vote. Consensus was reached when ≥75% of experts agreed on a specific response. RESULTS: Most experts agreed that: (1) the current periprocedural/in-hospital stroke/death thresholds for performing a carotid intervention should be lowered from 6% to 4% in patients with SxCS and from 3% to 2% in patients with AsxCS; (2) the time threshold for a patient being considered "recently symptomatic" should be reduced from the current definition of "6 months" to 3 months or less; (3) 80% to 99% AsxCS carries a higher risk of stroke compared with 60% to 79% AsxCS; (4) factors beyond the grade of stenosis and symptoms should be added to the indications for revascularization in AsxCS patients (eg, plaque features of vulnerability and silent infarctions on brain computed tomography scans); and (5) shunting should be used selectively, rather than always or never. Consensus could not be reached on the remaining topics due to conflicting, inadequate, or controversial evidence. CONCLUSIONS: The present international, multi-specialty expert-based Delphi Consensus document attempted to provide responses to several unanswered/unresolved issues. However, consensus could not be achieved on some topics, highlighting areas requiring future research.

Why do guidelines recommend screening for abdominal aortic aneurysms, but not for asymptomatic carotid stenosis? A plea for a randomized controlled trial.

BACKGROUND: Current guidelines do not recommend screening for asymptomatic carotid artery stenosis (AsxCS). The rationale behind this recommendation is that detection of AsxCS may lead to an unnecessary carotid intervention. In contrast, screening for abdominal aortic aneurysms is strongly recommended. METHODS: A critical analysis of the literature was performed to evaluate the implications of detecting AsxCS. RESULTS: Patients with AsxCS are at high risk for future stroke, myocardial infarction and vascular death. Population-wide screening for AsxCS should not be recommended. Additionally, screening of high-risk individuals for AsxCS with the purpose of identifying candidates for a carotid intervention is inappropriate. Instead, selective screening for AsxCS should be considered and should be viewed as an opportunity to identify individuals at high risk for atherosclerotic cardiovascular disease and future cardiovascular events for the timely initiation of intensive medical therapy and risk factor modification. CONCLUSIONS: Although mass screening should not be recommended, there are several arguments suggesting that selective screening for AsxCS should be considered. The rationale supporting such selective screening is to optimize risk factor control and to initiate intensive medical therapy for prevention of future cardiovascular events, rather than to identify candidates for an intervention.

Optimal periprocedural antithrombotic treatment in carotid interventions: An international, multispecialty, expert review and position statement.

BACKGROUND: The optimal antithrombotic (antiplatelet or anticoagulant) treatment of patients undergoing extracranial carotid artery interventions is a subject of debate. The aim of this multidisciplinary document was to critically review the recommendations of current guidelines, taking into consideration the results of recently published studies. METHODS: The various antithrombotic strategies reported were evaluated for asymptomatic and symptomatic patients undergoing extracranial carotid artery interventions (endarterectomy, transfemoral carotid artery stenting [CAS] or transcarotid artery revascularization [TCAR]). Based on a critical review, a series of recommendations were formulated by an international expert panel. RESULTS: For asymptomatic patients, we recommend low-dose aspirin (75-100 mg/day) or clopidogrel (75 mg/day) with the primary goal to reduce the risk of myocardial infarction and cardiovascular event rates rather than to reduce the risk of stroke. For symptomatic patients, we recommend dual antiplatelet treatment (DAPT) initiated within 24 h of the index event to reduce the risk of recurrent events. We suggest that following transfemoral CAS or TCAR, patients continue DAPT for 1 month after which a single antiplatelet agent is used. High level of evidence to support anticoagulant treatment for patients with carotid artery disease is lacking. CONCLUSIONS: The antithrombotic treatment offered to carotid patients should be individualized, taking into account the presence of symptoms, the type of intervention and the goal of the treatment. The duration and type of DAPT (ticagrelor instead of clopidogrel) should be evaluated in future trials.

Benefits and drawbacks of statins and non-statin lipid lowering agents in carotid artery disease.

International guidelines strongly recommend statins alone or in combination with other lipid-lowering agents to lower low-density lipoprotein cholesterol (LDL-C) levels for patients with asymptomatic/symptomatic carotid stenosis (AsxCS/SCS). Lowering LDL-C levels is associated with significant reductions in transient ischemic attack, stroke, cardiovascular (CV) event and death rates. The aim of this multi-disciplinary overview is to summarize the benefits and risks associated with lowering LDL-C with statins or non-statin medications for Asx/SCS patients. The cerebrovascular and CV beneficial effects associated with statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and other non-statin lipid-lowering agents (e.g. fibrates, ezetimibe) are reviewed. The use of statins and PCSK9 inhibitors is associated with several beneficial effects for Asx/SCS patients, including carotid plaque stabilization and reduction of stroke rates. Ezetimibe and fibrates are associated with smaller reductions in stroke rates. The side-effects resulting from statin and PCSK9 inhibitor use are also highlighted. The benefits associated with lowering LDL-C with statins or non-statin lipid lowering agents (e.g. PCSK9 inhibitors) outweigh the risks and potential side-effects. Irrespective of their LDL-C levels, all Asx/SCS patients should receive high-dose statin treatment±ezetimibe or PCSK9 inhibitors for reduction not only of LDL-C levels, but also of stroke, cardiovascular mortality and coronary event rates.

Comparison of Recent Practice Guidelines for the Management of Patients With Asymptomatic Carotid Stenosis.

Despite the publication of several national/international guidelines, the optimal management of patients with asymptomatic carotid stenosis (AsxCS) remains controversial. This article compares 3 recently released guidelines (the 2020 German-Austrian, the 2021 European Stroke Organization [ESO], and the 2021 Society for Vascular Surgery [SVS] guidelines) vs the 2017 European Society for Vascular Surgery (ESVS) guidelines regarding the optimal management of AsxCS patients.The 2017 ESVS guidelines defined specific imaging/clinical parameters that may identify patient subgroups at high future stroke risk and recommended that carotid endarterectomy (CEA) should or carotid artery stenting (CAS) may be considered for these individuals. The 2020 German-Austrian guidelines provided similar recommendations with the 2017 ESVS Guidelines. The 2021 ESO Guidelines also recommended CEA for AsxCS patients at high risk for stroke on best medical treatment (BMT), but recommended against routine use of CAS in these patients. Finally, the SVS guidelines provided a strong recommendation for CEA+BMT vs BMT alone for low-surgical risk patients with >70% AsxCS. Thus, the ESVS, German-Austrian, and ESO guidelines concurred that all AsxCS patients should receive risk factor modification and BMT, but CEA should or CAS may also be considered for certain AsxCS patient subgroups at high risk for future ipsilateral ischemic stroke.

Elevation of CD40/CD40L Inflammatory Pathway Molecules in Carotid Plaques from Moderate-and-Severe Obstructive Sleep Apnea Patients.

A chronic inflammatory process characteristic of obstructive sleep apnea promotes vascular endothelial dysfunction and atherogenesis. This process can lead to destabilization and rupture of cardiovascular plaques, which clinically manifests as an acute coronary syndrome or stroke. The aim of this study was to investigate the inflammatory pathway leading to plaque destabilization in non-to-mild and moderate-to-severe groups of OSA patients. This prospective study involved enrollment of patients scheduled for endarterectomy. A sleep study was performed prior to surgery. Immunohistochemistry was performed on atherosclerotic plaques from carotid arteries obtained during standard open endarterectomy to determine levels of CD40, CD40L receptors, MCP-1, and MMP-9. The 46 patients included 14 controls, 13 with mild, 11 with moderate, and 8 with severe OSA. Increased expression of CD40, CD40L receptors, MCP-1, and MMP-9 were found to be proportionate with OSA severity. However, significant differences among groups were observed only for MCP-1 (p = 0.014). Increased expression of inflammatory markers (CD40, CD40L, MCP-1, MMP-9) is associated with increasing OSA severity. This suggests the CD40-CD4-L inflammatory pathway may contribute to plaque instability and rupture in OSA patients.

Provisional focal stenting of complex femoropopliteal lesions using the Multi-LOC multiple stent delivery system - 12-month results from the LOCOMOTIVE EXTENDED study.

Background: This study aimed to evaluate a Multiple Stent Delivery System for provisional focal stenting of the femoropopliteal artery. Patient and methods: The LOCOMOTIVE EXTENDED study (Multi-LOC for flOw liMiting Outcomes after plain old balloon angioplasty and/or drug-coated balloon Treatment in the infrainguinal position with the objectIVE to implant multiple stent segments) is a prospective, single-arm, multicentre observational study. The Multi-LOC Multiple Stent Delivery System (B.Braun, Melsungen, Germany) was used for provisional focal stenting of the femoropopliteal artery. We enrolled 357 patients with 449 femoropopliteal lesions; all had flow-limiting dissections or recoil following angioplasty. Eligibility included Rutherford classification 2 to 5 with a de novo or non-stented restenotic femoropopliteal lesion undergoing plain balloon or drug-coated balloon angioplasty. The 6- and 12-month efficacy endpoints encompassed target lesion revascularisation and primary patency rates. Results: The mean patient age was 71 ± 10 years. The mean lesion length was 16.0 ± 9.7 cm; 44.5% were TASC II C/D lesions and 31.4% were chronic total occlusions. By operator choice, 45% of the patients underwent drug-coated balloon angioplasty. On average, 4.0 stents (each 13 mm long) were placed in each lesion, resulting in a scaffolding proportion of 56% of the total lesion length with a technical success rate of 98.3%. At 6 and 12 months, the freedom from clinically driven target lesion revascularisation was 95.5% and 88.7% and the primary patency rates were 88.7% and 82.3%, respectively. At 12 months, significant improvements were noted in Rutherford categories and ankle-brachial indices. In multiple regression analyses, both diabetes mellitus and no distal run-off vessel showed a trend toward worse TLR, while other factors such as DCB predilation or the lesion length were not predictive. Conclusions: The LOCOMOTIVE EXTENDED study demonstrated the safety and efficacy of the Multi-LOC stent system for focal provisional stenting of complex femoropopliteal lesions.

TLRs and RAGE are elevated in carotid plaques from patients with moderate-to-severe obstructive sleep apnea syndrome.

BACKGROUND: There is growing evidence that obstructive sleep apnea (OSA) promotes vascular endothelial dysfunction and atherogenesis. Pathways that mediate this pathology may include Toll-like receptors (TLRs) and receptor for advanced glycation end products (RAGE) which play a significant role in proinflammatory processes. The aim of this study was to measure the expression of the above-mentioned receptors in relation to OSA severity in carotid plaques obtained during open endarterectomy. METHODS: This prospective study included patients with a sleep study prior to surgery and a plaque specimen obtained during standard open endarterectomy. Immunohistochemistry of TLR2, TLR4, TLR7, TLR9, RAGE, HMGB1, and NF-κB was performed on atherosclerotic plaques from carotid arteries of patients with and without OSA. RESULTS: There were 46 patients (22 women, mean age 73.2 ± 1.3 years): 14 control patients, 13 with mild, 11 with moderate, and 8 with severe OSA. The expression of all TLRs and RAGE increased proportionately with increasing OSA severity. The largest differences between patients with severe OSA and no OSA were found for TLR2 (2.88 ± 0.35 vs. 1.27 ± 0.47, p < 0.001), TLR4 (2.88 ± 0.35 vs. 1.64 ± 0.5, p < 0.001), TLR9 (2.38 ± 0.52 vs. 1.45 ± 0.52, p < 0.01), and RAGE (2.5 ± 0.53 vs. 1.82 ± 0.6, p < 0.05). CONCLUSION: TLR2, TLR4, TLR9, and RAGE expression was significantly increased in carotid plaques of patients with moderate-to-severe OSA when compared with control patients with no OSA and those with mild OSA. TLR and RAGE-mediated pathways may play a significant role in OSA-dependent atherogenesis.

Clinical significance of mirror lesions in lower extremity arterial disease.

OBJECTIVE: The aim of this study was to investigate the clinical relevance of bilateral peripheral arterial disease (PAD) patterns. BACKGROUND: No prior study has evaluated the clinical significance of symmetrical lesion patterns, particularly the coexistence of same-level significant plaques in both lower extremities ("mirror lesions"). METHODS: We conducted a single-facility, primary data analysis involving 225 patients with symptomatic PAD. RESULTS: Eighty-two percent of the patients had bilateral lesions: 14.2% had femoropopliteal, 38.7% had infrapopliteal, and 27.1% had both femoropopliteal and infrapopliteal lesions. The lesions were found in the exact same arteries bilaterally in 24.9% of the patients, while 26.7% had a local mirror pattern limited to the femoropopliteal (13.7%) or infrapopliteal (12.9%) arteries. Having a lesion in an artery was a risk factor for occlusive disease of the corresponding artery on the other side. Patients presenting with critical limb ischemia (CLI) had a history of resting pain (17%), ulceration/gangrene (13%), or prior amputation (26%) of the contralateral limb. Patients with significant bilateral disease had unilateral false-negative ABI results in 11.6% of the cases. The arterial Doppler study results were unilaterally false-negative in 19.6% and bilaterally false-negative in 2.8% of the patients. CONCLUSIONS: Patients with known peripheral arterial disease need to have both limbs fully evaluated and monitored, even in cases with negative screening results. Mirror angiographic imaging is common and often accompanied by symptoms of claudication. Unilateral ischemia is a strong risk factor for contralateral disease. Patients with CLI are at high risk for occlusive lesions of the nonindex limb.

Obstructive sleep apnea in patients scheduled for endarterectomy - preliminary study.

Introduction The association between obstructive sleep apnea and atherosclerosis is confirmed for long time, but the pathomechanism is still not known. The aim of this study was to investigate the prevalence of OSA in patients scheduled for endarterectomy and the influence of this procedure on the sleep study parameters and sleepiness. Materials and methods 46 patients scheduled for open carotid endarterectomy were enrolled in the study. Sleep study and Epworth Sleepiness Scale (ESS) was performed preoperatively. In 11 out of 46 patients, sleep study was performed both before and after the surgery. Results The mean age of the group was 69,9 years (± 8,6), 21 patients (45,7%) were female. For 46 patients mean pAHI, ODI, pRDI and %snoring were 16,2 (± SD=15,2), 10,4 (± SD=12,2) and 18,9 (± SD=14,9), respectively. Normal pAHI was noticed in 14 patients (30%), while mild (pAHI 5-15), moderate (pAHI 15-30) and severe (pAHI>30) OSA was observed in 13 (38%), 11 (24%) and 8 (18%) subjects, respectively. The mean ESS score for 27 out of 46 patients was 6,3 (± SD=5,6). The postoperative results of sleep study in 11 patients showed no significant change. Conclusions This study revealed the prevalence of moderate to severe OSA in 42% of patients scheduled for endarterectomy, while no excessive daytime sleepiness was observed in this group. The results of the study show that patients with carotid atherosclerosis should undergo sleep diagnosis in order to rule out obstructive sleep apnea.

Pyogenic infection of the hip joint as a complication of a femoral artery vascular access for percutaneous coronary intervention.

A rare case of clinical complication following a percutaneous coronary intervention is presented. A femoral vascular access was chosen to treat a coronary lesion with a stent implantation. This femoral vascular access, however, resulted in a pyogenic infection of the ipsilateral hip joint that was not properly diagnosed for an extended post-interventional period. The hip joint completely deteriorated before its underlying cause was identified. This case report illustrates the importance of recognizing potential endovascular complications independently of their frequency.

Surgery for retrohepatic caval thrombus in patients with advanced renal cell carcinoma: a case series.

BACKGROUND: Thrombotic involvement of the inferior vena cava (IVC) occurs in about 10% of all patients with renal cell carcinoma (RCC). It is treated with radical resection of tumor and thrombus. We present the results of a recent case series of 20 patients with retrohepatic IVC thrombus. METHODS: Our cohort of 20 patients included 16 primary resections (radical nephrectomy and thrombectomy with and without vascular graft), three recurrences primarily operated on elsewhere (thrombectomy and vascular graft), and one recurrence due to a new liver metastasis. RESULTS: All surviving patients were discharged with a patent IVC. The overall mortality rate was 10%, and the overall complication rate was 35%. Both are in keeping with results presented worldwide. CONCLUSIONS: Our series provides a corroborating extension to the existing dataset on RCC-related IVC thrombus removal. It confirms that the radical surgical approach can be performed safely and successfully with respect to venous patency.

Study of angiogenic gene ointments designed for skin neovascularization.

AIM: In this study attention was focused on gene preparations that stimulate angiogenesis in the skin. Angiogenesis was stimulated by gene preparations encoding angiogenic factors introduced into the skin by injection, and applied as ointments. MATERIAL AND METHODS: The appropriate angiogenic formulations containing angiogenic nonviral vectors (pVEGF, pFGF, pSDF, pVIF), or viral vectors (rAAV/VEGF, rAAV/SDF) were prepared for the test. Cholesterol ointment was used as the vehicle for viral and non-viral vectors. The new vessels in the mouse skin were counted according to the criteria suggested by Sidky and Auerbach. RESULTS: Studies indicate that all non-viral (pVEGF, pFGF, pSDF, pVIF) and viral (rAAV/VEGF, rAAV/SDF) vectors strongly stimulate new vessel formation when administered into mouse skin as injections. The impact of angiogenic gene ointments for skin angiogenesis was about 3-4 times weaker than that observed for injection preparations. CONCLUSIONS: Angiogenic injection gene preparations strongly stimulate skin neovascularization. The clinical usefulness of gene ointments should stimulate further laboratory studies in the field of experimental skin gene therapy.

Recombinant adeno-associated viruses (rAAV2) facilitate the intraperitoneal gene delivery to cancer cells.

Peritoneal dissemination of cancer cells is characteristic of advanced stages of ovarian, breast and lung cancers, and is associated with poor patient survival. The presence of cancer cells in effusions complicates treatment protocols, while cell eradication is seriously limited. One of the novel options available is cancer gene therapy with recombinant adeno-associated viruses. This combination represents the most promising gene delivery vehicles to neoplasmatic cells within serosal cavities due to their unique properties that include the ability to infect proliferating cells of broad host range, as well as the potential of long-term expression. Recombinant infectious adeno-associated virus serotype 2 particles (rAAV2) were produced in a helper-free system using an AAV-293 packaging cell line, and quantitatively analyzed by real-time PCR. Balb/c mice intraperitoneally pre-injected with L1 cancer cells were treated with different doses of rAAV2. Subsequently, the mice were sacrificed and intraperitoneal effusions were analyzed for rAAV presence and rAAV/ß-galactosidase (LacZ) vector efficiency in order to infect cancer cells within the peritoneal cavity. We reported an efficient infection of L1 cancer cells disseminated into the peritoneal cavity by rAAV2. The expression of reporter genes (GFP and LacZ) attributable to the rAAV cell uptake was closely dependent on an applied multiplicity of infection ratio (MOI). The highest infection efficiency was observed at a MOI of 50 and 200. Our study confirmed the ability of adeno-associated viruses to facilitate gene transferability to cancer cells disseminated in the serosal cavity, as well as the potential usefulness of these viruses as a new approach in cancer gene therapy.