Experimental measurements and CFD modelling of hydroxyapatite scaffolds in perfusion bioreactors for bone regeneration.

In the field of bone tissue engineering, particular interest is devoted to the development of 3D cultures to study bone cell proliferation under conditions similar to in vivo ones, e.g. by artificially producing mechanical stresses promoting a biological response (mechanotransduction). Of particular relevance in this context are the effects generated by the flow shear stress, which governs the nutrients delivery rate to the growing cells and which can be controlled in perfusion reactors. However, the introduction of 3D scaffolds complicates the direct measurement of the generated shear stress on the adhered cells inside the matrix, thus jeopardizing the potential of using multi-dimensional matrices. In this study, an anisotropic hydroxyapatite-based set of scaffolds is considered as a 3D biomimetic support for bone cells deposition and growth. Measurements of sample-specific flow resistance are carried out using a perfusion system, accompanied by a visual characterization of the material structure. From the obtained results, a subset of three samples is reproduced using 3D-Computational Fluid Dynamics (CFD) techniques and the models are validated by virtually replicating the flow resistance measurement. Once a good agreement is found, the analysis of flow-induced shear stress on the inner B-HA structure is carried out based on simulation results. Finally, a statistical analysis leads to a simplified expression to correlate the flow resistance with the entity and extensions of wall shear stress inside the scaffold. The study applies CFD to overcome the limitations of experiments, allowing for an advancement in multi-dimensional cell cultures by elucidating the flow conditions in 3D reactors.

Liquid flow in scaffold derived from natural source: experimental observations and biological outcome.

This study investigates the biological effects on a 3D scaffold based on hydroxyapatite cultured with MC3T3 osteoblasts in response to flow-induced shear stress (FSS). The scaffold adopted here (B-HA) derives from the biomorphic transformation of natural wood and its peculiar channel geometry mimics the porous structure of the bone. From the point of view of fluid dynamics, B-HA can be considered a network of micro-channels, intrinsically offering the advantages of a microfluidic system. This work, for the first time, offers a description of the fluid dynamic properties of the B-HA scaffold, which are strongly connected to its morphology. These features are necessary to determine the FSS ranges to be applied during in vitro studies to get physiologically relevant conditions. The selected ranges of FSS promoted the elongation of the attached cells along the flow direction and early osteogenic cell differentiation. These data confirmed the ability of B-HA to promote the differentiation process along osteogenic lineage. Hence, such a bioactive and naturally derived scaffold can be considered as a promising tool for bone regeneration applications.

Comparison of Outcomes Following EVAR Based on Aneurysm Diameter and Volume and Their Postoperative Variations.

PURPOSE: to evaluate the impact of bi- and 3-dimensional preoperative aortic morphological features and their immediate postoperative variations on the outcome of abdominal aortic aneurysms (AAA) treated by endovascular exclusion with standard devices (EVAR). MATERIALS AND METHODS: Double centre retrospective analysis of prospectively collected registry data of EVAR patients. For all patients, preoperative and 30-day computed tomographic angiography images (CTA) were reviewed. Preoperative maximum AAA diameter >59 mm and volume >159 cm3, and any 30-day postoperative increasing at CTA, were considered as potentially influencing the outcome. The outcome measures were: primary technical success; 30-day, 1-year, and mean follow-up reintervention, all-cause and AAA-related mortality rates, and also endoleak-related reinterventions. RESULTS: Three hundred and thrity-three patients were enrolled. Mean preoperative and 30-day AAA diameter and volume were 50.4 mm ± 11.8 vs. 49.1 mm ± 12.1, and 112.9 cm3 ± 79.5 vs. 112.1 cm3 ± 80.5, respectively. Primary technical success was achieved in all cases. At 34.9 months follow-up, cumulative reintervention rate was 12.0%, mortality rates 7.2%, without AAA-related deaths. Endoleak-related reintervention rate was 7.5%. At uni- and multi-variate analysis, preoperative AAA diameter >59 mm, and AAA volume >159 cm3 were significantly associated to reintervention (P = 0.012; P = 0.002), and reintervention and death (P = 0.002; P = 0.001) during follow-up. Additionally, any increase in postoperative AAA diameter or volume was significantly associated with reintervention (P = 0.001, P = 0.001) and reintervention and death (P = 0.006, P = 0.001). Endoleak-related reintervention were also significantly associated with all of the analysed morphological parameters (P = 0.019, P = 0.005, P = 0.005, and P = 0.002, respectively). CONCLUSIONS: Patients with larger baseline AAA size and volume as well as unfavourable early remodelling of the sac are associated to worse long-term EVAR outcome.

Peri-procedural brain lesions prevention in CAS (3PCAS): Randomized trial comparing CGuard™ stent vs. Wallstent™.

BACKGROUND: Aim of this study was to evaluate peri-procedural incidence of new diffusion-weighted-magnetic-resonance-imaging (DWMRI) brain lesions in CAS patients treated by carotid mesh stent (CGuard™) or closed-cell stent (Wallstent™). METHODS: Consecutive patients with asymptomatic carotid stenosis ≥ 70% were submitted to preoperative DW-MRI scan, to exclude the presence of preoperative silent cerebral lesions. Patients were randomized to CGuard or Wallstent. DWMRI was performed immediately after the intervention and at 72-hour postoperatively. Moreover, pre and postoperative Mini-Mental-State-Examination Test (MMSE) and a Montreal-Cognitive-Assessment (MoCA) test were conducted, and S100ß and NSE neurobiomarkers were measured at 5-time points (preoperatively, 2, 12, 24, and 48 h postoperatively). RESULTS: From January 2015 to October 2016, sixty-one consecutive eligible patients were submitted to preoperative DWMRI scan. Three patients were excluded because of preoperative silent cerebral lesions. In 29 CGuard patients, 1 developed a minor stroke and 8 silent new lesions were observed in the 72 h-DWMRI (31%): 4 lesions were ipsilateral, and 4 lesions were contra or bilateral. In 29 Wallstent patients, 7 clinically-silent new lesions were found in the 72 h-DWMRI (24.1%; p = 0.38). In 4 cases lesions were ipsilateral and in 3 cases contra or bilateral. S100B values doubled at 48 h in 24 patients, and among them 12 presented new DWMRI lesions. 48-h S100B increase was significantly related to 72-h DWMRI lesions (p = 0.012). CONCLUSIONS: In our experience both stents showed an acceptable rate of subclinical neurological events with no significant differences at 72-hour DWMRI between groups. Bilateral/contralateral lesions suggest that periprocedural neurological damage may have extra-carotid sources.

Early Experience with a New Concept of Angioplasty Nitinol-Constrained Balloon Catheter (Chocolate®) in Severely Claudicant Patients.

BACKGROUND: To report our experience in treating severely claudicant patients, employing a "nitinol-constrained" balloon (Chocolate, TriReme Medical Inc., Pleasanton, CA-USA) before drug-coated balloon (DCB) in a standardized protocol. METHODS: Eighty-one (84 limbs) consecutive Rutherford category (RC) 3 patients treated between December 2014 and December 2016 for superficial femoral artery (SFA) and popliteal arterial (PA) disease by nitinol-constrained balloon followed by DCB were enrolled. Bailout stenting was performed by Zilver PTX implantation. Intraoperative technical success and bailout-stenting rates were assessed as well as clinical improvement, ankle-brachial index (ABI) modification, primary patency (PP), and secondary patency (SP) rates at follow-up. RESULTS: Sixty-eight patients (83.9%) were male and 31 (38.2%) diabetics. Fifty-five limbs (65.5%) presented occlusion (CTO); in 18 limbs CTO was longer than 150 mm. Bailout stenting rate was 9.5% (8/84). All patients completed 30-day follow-up: PP 100%, 61 patients completely asymptomatic (RC = 0). Mean follow-up was 12.3 ± 5.6 months; overall PP was 98.8%, and SP was 98.8%. At mid-term analysis, no differences in outcomes were recorded between stenosis and CTOs with a PP of 96.5 and 96%, respectively (p = 0.725). CTO length impacted early results: in cases of CTOs < 150 mm, PP was 100%, while in CTOs > 150 mm, it was 83.3% (p = 0031). ABI at 12-month was significantly higher with respect to preoperative values (p < 0.001). CONCLUSIONS: In this preliminary experience, our protocol seems to be safe and effective in treating SFA and PA lesions in claudicant patients with satisfactory early and 12-month results.

Aortic Bifurcation Morphology Alone is Not Able to Predict Outcome in Patients Submitted to Elective Endovascular Abdominal Aortic Aneurysm Repair.

PURPOSE: The aim of the present study was to evaluate the impact of the aortic bifurcation (AB) morphological characteristics, analyzed on computed tomography angiography (CTA), on outcomes of patients with abdominal aortic aneurysms (AAAs), treated by endovascular aneurysm repair (EVAR) in a single-center experience. MATERIALS AND METHODS: A retrospective analysis was conducted using a prospectively collected database. Morphological features considered as potentially impacting outcomes were maximum AB diameter (ABmax), minimum diameter (ABmin), mean diameter (ABaverage), AB area (ABarea), and AB calcification (ABcalcification) and thrombosis (ABthrombosis). Outcome measures were perioperative, 30-day, and midterm AAA-related reinterventions and all-cause mortalities. RESULTS: Investigators reviewed 306 preoperative CTA scans. Maximum aortic diameter was 51.4 ± 12.4 mm (range 40-110), and mean ABmax was 24.2 ± 8.8 mm (range 10-60), ABmin 17.0 ± 5.4 mm (range 4-40), ABaverage 20.6 ± 6.5 mm (range 9-47.5), and ABarea 35.2 ± 24.2 mm2 (range 6-176). ABcalcification ≥ 50% was present in 63 patients (20.6%), and ABthrombosis ≥ 50% in 102 patients (33.3%). Technical success was obtained in all cases, without perioperative reintervention or death. At 30-day follow-up, the reintervention rate was 3.3%, and mortality rate was 1.3%. At a mean follow-up period of 35 ± 28.6 (range, 1-72) months, reintervention and mortality rates were 6.5 and 4.9%, respectively. None of the analyzed thresholds were predictive of adverse outcomes. At multivariate analysis, association of a narrowed AB with severe calcification of the distal aorta showed a significant differences in terms of reinterventions (p = 0.009). CONCLUSIONS: Our limited experience seems to reveal that a cutoff of ≤ 20 mm for AB diameter, as in current guidelines, is ineffective in predicting outcomes after EVAR.

Genetic influence on femoral plaque and its relationship with carotid plaque: an international twin study.

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.

Real-Life Experience with Ovation Stent Graft: Lesson Learned from the First One Hundred Fifty Treated Patients.

BACKGROUND: The objective of the study was to report immediate and midterm results of an unselected population of patients treated for abdominal aortic aneurysms (AAAs) by endovascular aneurysm repair (EVAR) using the Ovation stent graft. METHODS: A double-center retrospective study was conducted on a prospectively collected database between 2012 and 2015. One hundred fifty-six elective patients were included. The outcome measures considered for analysis were primary technical success, 30-day and midterm reinterventions, and all-cause and AAA-related mortality rates. The presence of an aortic neck ≤10 mm, and of a noncylindrical aortic neck, as well as a narrowed aortic bifurcation was defined as an aortic bifurcation average diameter (ABaverage) ≤ 18 mm or an ABarea ≤ 20 mm2, and an external iliac artery diameter ≤5 mm was considered as independent factors potentially influencing the outcome. RESULTS: Male patients totaled 128 (82.1%), and mean age was 74.83 ± 6.76 years (range: 56-91). Mean aortic diameter was 57.15 ± 8.77 mm, mean diameter at inferior renal artery level + 13 was 24.44 ± 3.31 mm, and mean aortic neck length was 18.77 ± 8.45 mm. Fifty-four patients (34.6%) had an aortic neck ≤10 mm, and cylindrical aortic neck shape was present in 34 patients (21.8%). Regarding the aortic bifurcation (AB), 31 patients (19.9%) presented ABaverage ≤ 18 mm, and 35 (22.4%) an ABarea ≤ 20 mm2. Technical success was achieved in all cases. At 30-day follow-up, 2 type I endoleaks (1.3%) were detected. One patient was successfully treated endovascularly by proximal aortic cuff implantation, while the other patient refused further treatment. Three-month unscheduled computed tomographic angiography shows endoleak resolution and complete aneurysm seal. One patient suffered from a limb graft occlusion, managed by medical treatment. At a mean follow-up time of 20.4 ± 8.8 (1-60) months, 6 reinterventions were reported, including 2 embolizations for type II endoleak and 4 for iliac and femoral vessel occlusive disease. Log-rank test on preoperative anatomical features showed no significant differences in terms of freedom from reinterventions, and P values were 0.653 for aortic neck length ≤10 mm, 0.309 for noncylindrical aortic neck length shape, 0.520 for ABaverage ≤ 18 mm, 0.604 for ABarea ≤ 20 mm2, and 0.421 for external iliac artery diameter ≤5 mm. CONCLUSIONS: Our initial experience suggests that in an unselected patient population undergoing AAA repair, EVAR by Ovation stent graft can be performed safely with satisfactory immediate and midterm outcomes.

Endovascular Solution of Acute Limb Ischemia Engendered by Persistent Sciatic Artery Pseudoaneurysm due to Stent Fracture.

We report a case of acute limb ischemia (ALI) due to a thromboembolism from a persistent sciatic artery (PSA) pseudoaneurysm precipitated by a fractured stent. Patient, previously treated for ALI by fibrinolysis and stent implantation, presented with a PSA pseudoaneurysm (undetected during first hospitalization), stent fracture (SF), and occlusion of vessels below the knee. Fibrinolysis was performed, restoring direct flow to the foot. A week later, an endovascular procedure was attempted to reline SF and exclude the PSA pseudoaneurysm by deployment of two 13 × 100-mm peripheral endografts (Viabahn; W.L. Gore & Associates, Flagstaff, AZ). At 1-year follow-up, patient was asymptomatic without further clinical events.

Femoral Artery Ultrasound Examination.

We compared intima-media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment.

Angioseal VIP® vs. StarClose SE® closure devices: a comparative analysis in non-cardiological procedures.

BACKGROUND: The aim of this paper was to compare the use of two different commercially available vascular closure devices (VCD), Angioseal VIP® (St. Jude Medical, St. Paul, MN, USA) and StarClose SE (Abbott Laboratories, Abbott Park, IL, USA). METHODS: From January 2010 to January 2012, 347 patient underwent retrograde femoral arterial puncture for different interventional procedures (angioplasty, stenting, embolization for bleeding, fibrinolysis for ischemia and chemoembolization). Hemostasis was achieved by deployment of an Angioseal VIP® (N.=184) or StarClose SE® (N.=163). In 94 cases, the retrograde femoral access was bilateral and managed with two StarClose SE devices (N.=53) or an Angioseal VIP® plus a StarClose SE® (N.=41). RESULTS: Technical success was obtained in 95.1% (330/347) of patients. Overall time to hemostasis (TTH) and time to ambulation (TTA) were 5,5±1,5 min (range 3-8 min) and 6±2.5 hr (range 2-9 hours) respectively. No statistical significative difference (P>0.05) were appreciable between to groups for both TTH and TTA: Angioseal VIP® TTH was 5.3±1.4 min and StarClose SE® TTH was 5.6±1.6 min; Angioseal VIP® TTA was 5.9±1.8 hr and StarClose SE® TTA was 6.1±1.9 hr. VAS scores result underline a mild difference between two devices. Angioseal VIP® patients experience a mild to moderate pain within the first 3 minutes from the deployment. Whereas StarClose SE® patients still experience pain at 5 minutes from deployment. The device failure rate was 4.9% (17 cases) and included 13 minor complications and 4 major complications. Minor complications (3.75%) occurred during the initial phase and consisted in recurrent wound bleeding (N.=5 StarClose SE®; N.=4 Angioseal VIP®) treated with manual compression, and hematoma (N.=2 StarClose SE®; N.=2 Angioseal VIP®) that solved spontaneously. The 4 major complications (1,15%) were: 1 Angioseal-related common femoral artery (CFA) obstruction treated with surgical bypass from the CFA to the superficial femoral artery; 1 Angioseal-related CFA dissection solved with surgery; 1 Angioseal-related embolization of the deep femoral artery partially treated with localized fibrinolysis; 1 StarClose-related pseudoaneurysm treated with manual compression. CONCLUSIONS: Both Angioseal VIP® and StarClose SE® systems can be considered safe and effective in providing hemostasis following a variety of interventional vascular procedures.

Non-vascular interventional procedures: effective dose to patient and equivalent dose to abdominal organs by means of DICOM images and Monte Carlo simulation.

This study evaluates X-ray exposure in patient undergoing abdominal extra-vascular interventional procedures by means of Digital Imaging and COmmunications in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to assess the effective and equivalent doses, under the hypothesis of their correlation with the dose area product (DAP) measured during each examination. This allows to collect dosimetric information about each patient and to evaluate associated risks without resorting to in vivo dosimetry. The dose calculation was performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based Monte Carlo program for calculating patient doses in medical X-ray examinations), by using the real geometrical and dosimetric irradiation conditions, automatically extracted from DICOM headers. The DAP measurements were also validated by using thermoluminescent dosemeters on an anthropomorphic phantom. The expected linear correlation between effective doses and DAP was confirmed with an R(2) of 0.974. Moreover, in order to easily calculate patient doses, conversion coefficients that relate equivalent doses to measurable quantities, such as DAP, were obtained.

CT angiography and magnetic resonance angiography findings after surgical and interventional radiology treatment of peripheral arterial obstructive disease.

In the last years, technical innovations in the field of CT angiography (CTA) and magnetic resonance angiography (MRA) have allowed accurate and highly detailed evaluation of peripheral vascular pathologies. This has dramatically changed the diagnostic approach in treatment planning of peripheral arterial obstructive disease and also enabling early identification of treatment failure or treatment-related complications after surgical or endovascular procedures. Although Doppler Ultrasound is the first-line imaging modality during follow-up after treatment, its role is currently diminishing in importance mostly because of the proliferation of high-end CT and MR scanners capable of fast, reproducible, and highly reliable vascular imaging. The aim of this study is to review the various surgical and endovascular procedures for peripheral arterial obstructive disease and to provide CTA and MRA samples of common and uncommon complications related to treatment.

Use of ultrasound in the insertion of a vascular closure device: a comparative retrospective study with the standard blind technique.

PURPOSE: To evaluate whether ultrasound (US) assistance can decrease the rate of complications related to the use of vascular closure devices (VCDs). MATERIALS AND METHODS: A retrospective comparative study was done on 150 consecutive patients who had a VCD inserted under US guidance after retrograde common-femoral-artery (CFA) puncture. This group was compared to a historical control group of 150 consecutive patients who had the same VCDs inserted with the standard blind technique. After the procedures, patients were placed at bedrest for at least 6 h. Technical success, defined as correct deployment without adjunctive manual compression, blood count and US evaluation of the arterial puncture site was done at 24 h and at 3 months. Differences in terms of efficacy and safety were statistically evaluated using US guidance as a predictor for a lower complication rate. RESULTS: Technical success was achieved in 147/150 patients (98 %) in the study group vs. 141/150 cases (94 %) of the control group (p = 0.038). In three cases (2 %) adjunctive manual compression (≤5 min) was required. One pseudoaneurysm (0.65 %) occurred after 24 h, solved with manual compression. Six minor complications (4 %)--haematoma (n = 5; 3.35 %), recurrent wound bleeding (n = 1; 0.65 %)--were reported. In the control group four (2.65 %) major complications occurred: CFA occlusion managed with surgical bypass, CFA dissection solved by surgical bypass, two pseudoaneurysms solved with manual compression. Thirteen (8.65 %) minor complications were observed with haematoma (n = 10; 6.65 %), and recurrent wound bleeding (n = 3; 2.0 %). The comparative analysis of the total complication rate and major complication rate between the study group and the control group was statistically significant (p = 0.016 and p = 0.049, respectively). A 24-h evaluation showed a triphasic flow within the CFA in 150/150 patients (100 %) of the study group and in 146/150 cases (97.35 %) of the control group. CONCLUSION: VCD inserted under US guidance increases the success rate reducing the number of complications.

Percutaneous vertebroplasty with the rotational fluoroscopy imaging technique.

OBJECTIVE: To evaluate the feasibility of the rotational angiography unit (RAU) as a single technique to guide percutaneous vertebroplasty (PVP). MATERIALS AND METHODS: Twenty-five consecutive patients (35 vertebral bodies, 20 lumbar and 15 thoracic) were treated using RA fluoroscopy. Using a state-of-the-art flat-panel angiographer (Artis zee, Siemens, Erlangen, Germany), rotational acquisitions were obtained in all patients for immediate post-procedure 2D/3D reconstructions. Pre- and postoperative back pain was assessed with the visual analog scale (VAS). Fluoroscopy time, patient radiation dose exposure, technical success, mean procedure time, mean number of rotational acquisitions and procedural complications were recorded. All features were compared with a historical cohort of patients (N = 25) who underwent PVP under CT and mobile C-arm fluoroscopy guidance. RESULTS: In all cases, safe and accurate control of the needle insertion and bone-cement injection was successfully obtained with high-quality fluoroscopy images. One cement leakage was detected in the RAU group, and two leakages were detected in the CT and C-arm fluoroscopy group. Technical features were significantly different between the two groups (RAU vs. CT): mean procedure time: 38.2 min vs. 60.2 min (p = 0.02); median fluoroscopy time: 14.58 and 4.58 min (p = 0.02); median number of rotational acquisitions: 5 vs. 10 (p = 0.02); mean patient dose: 6 ± 1.3 mSv vs. 23 ± 1.3 mSv (p = 0.02). There were minor complications (pain, small hematoma) in two patients (8%) in the study group and three cases (12%) in the control group. CONCLUSION: RAU guidance is an effective and safe technique for performing PVP because it reduces the procedural time and radiation exposure.