Association of Genetic Polymorphisms with Abdominal Aortic Aneurysm in the Processes of Apoptosis, Inflammation, and Cholesterol Metabolism.

Background and Objectives: This study aims to identify the minor allele of the single nucleotide polymorphisms (SNPs) DAB2IP rs7025486, IL6R rs2228145, CDKN2BAS rs10757278, LPA rs3798220, LRP1 rs1466535, and SORT1 rs599839 in order to assess the risk of abdominal aortic aneurysm (AAA) formation and define the linkage among these SNPs. Materials and Methods: A case-control study with AAA patients (AAA group) and non-AAA controls (control group) was carried out in a study population. DNA was isolated from whole blood samples; the SNPs were amplified using PCR and sequenced. Results: In the AAA group of 148 patients, 87.2% of the patients were male, 64.2% had a history of smoking, and 18.2% had relatives with AAA. The mean ± SD of age, BMI, and aneurysmal diameter in the AAA group were 74.8 ± 8.3 years, 27.6 ± 4.6 kg/m2, and 56.2 ± 11.8 mm, respectively. In comparison with 50 non-AAA patients, there was a significantly elevated presence of the SNPs DAB2IP rs7025486[A], CDKN2BAS rs10757278[G], and SORT1 rs599839[G] in the AAA group (p-values 0.040, 0.024, 0.035, respectively), while LPA rs3798220[C] was significantly higher in the control group (p = 0.049). A haplotype investigation showed that the SNPs DAB2IP, CDKN2BAS, and IL6R rs2228145[C] were significantly elevated in the AAA group (p = 0.037, 0.037, and 0.046) with minor allele frequencies (MAF) of 25.5%, 10.6%, and 15.4%, respectively. Only DAB2IP and CDKN2BAS showed significantly higher occurrences of a mutation (p = 0.028 and 0.047). Except for LPA, all SNPs were associated with a large aortic diameter in AAA (p < 0.001). Linkage disequilibrium detection showed that LPA to DAB2IP, to IL6R, to CDKN2BAS, and to LRP1 rs1466535[T] had D' values of 70.9%, 80.4%, 100%, and 100%, respectively. IL6R to LRP1 and to SORT1 had values for the coefficient of determination (r2) of 3.9% and 2.2%, respectively. Conclusions: In the investigated study population, the SNPs CDKN2BAS rs10757278, LPA rs3798220, SORT1 rs599839, DAB2IP rs7025486, and IL6R rs2228145 were associated with the development of abdominal aortic aneurysms. Individuals with risk factors for atherosclerosis and/or a family history of AAA should be evaluated using genetic analysis.

Safety and Feasibility of Robot-assisted Gait Training in Adults with Cerebral Palsy in an Inpatient Setting - an Observational Study.

BACKGROUND: To investigate the safety and feasibility of six sessions of Hybrid Assistive Limb (HAL) robot-assisted gait training (RAGT) integrated into an inpatient therapy concept and their influence on walking speed and gait parameters in adult CP patients. METHODS: Eleven subjects (male = 8, female = 3, mean age: 23 years and 2 months, ± 4.5 years) with spastic CP underwent six 20-minute RAGT sessions with the HAL during an 11-day hospital stay. Additionally, physiotherapy, physician-performed manual medicine, massage and exercise therapy were provided. Pre- (T1) and post- (T2) intervention assessments were: 10-metre walking test (10MWT), 6-minute walking test (6MWT), Gross Motor Function Measure (GMFM-88) and lower extremities passive range of motion (pROM). RESULTS: All subjects completed the study. No adverse events were noted. Walking speed in the 10MWT test increased from 32.5 s (± 24.5 s) at T1 to 27.5 s (± 21.4 s) at T2, without significance. Slight, but non-significant improvements were detected in the 6MWT, GMFM and pROM. Confounding factors did not significantly affect the results. Conclusion: Intensive therapy including HAL training leads to non-significant improvements. Further studies with more patients and longer intervention time could provide further insights into the RAGT therapy of adult patients with CP. Registration DRKS-ID: DRKS00020275.

Increased UHMWPE Particle-Induced Osteolysis in Fetuin-A-Deficient Mice.

Particle-induced osteolysis is a major cause of aseptic prosthetic loosening. Implant wear particles stimulate tissue macrophages inducing an aseptic inflammatory reaction, which ultimately results in bone loss. Fetuin-A is a key regulator of calcified matrix metabolism and an acute phase protein. We studied the influence of fetuin-A on particle-induced osteolysis in an established mouse model using fetuin-A-deficient mice. Ten fetuin-A-deficient (Ahsg−/−) mice and ten wild-type animals (Ahsg+/+) were assigned to test group receiving ultra-high molecular weight polyethylene (UHMWPE) particle implantation or to control group (sham surgery). After 14 days, bone metabolism parameters RANKL, osteoprotegerin (OPG), osteocalcin (OC), alkaline phosphatase (ALP), calcium, phosphate, and desoxypyridinoline (DPD) were examined. Bone volume was determined by microcomputed tomography (µCT); osteolytic regions and osteoclasts were histomorphometrically analyzed. After particle treatment, bone resorption was significantly increased in Ahsg−/− mice compared with corresponding Ahsg+/+ wild-type mice (p = 0.007). Eroded surface areas in Ahsg−/− mice were significantly increased (p = 0.002) compared with Ahsg+/+ mice, as well as the number of osteoclasts compared with control (p = 0.039). Fetuin-A deficiency revealed increased OPG (p = 0.002), and decreased levels of DPD (p = 0.038), OC (p = 0.036), ALP (p < 0.001), and Ca (p = 0.001) compared with wild-type animals. Under osteolytic conditions in Ahsg−/− mice, OPG was increased (p = 0.013), ALP (p = 0.015) and DPD (p = 0.012) were decreased compared with the Ahsg+/+ group. Osteolytic conditions lead to greater bone loss in fetuin-A-deficient mice compared with wild-type mice. Reduced fetuin-A serum levels may be a risk factor for particle-induced osteolysis while the protective effect of fetuin-A might be a future pathway for prophylaxis and treatment.

Use of Robot-Assisted Gait Training in Pediatric Patients with Cerebral Palsy in an Inpatient Setting-A Randomized Controlled Trial.

Robot-assisted gait training (RAGT) provides a task-based support of walking using exoskeletons. Evidence shows moderate, but positive effects in the therapy of patients with cerebral palsy (CP). This study investigates the impact of RAGT on walking speed and gait parameters in pediatric CP patients. Thirty subjects (male = 23; female = 7), with a mean age of 13.0 ± 2.5 (9-17) years, and with spastic CP, were recruited. The intervention group (n = 15) underwent six 20-minute RAGT sessions with the Hybrid Assistive Limb (HAL) during an 11-day hospital stay. Additionally, a therapy concept including physiotherapy, physician-performed manual medicine, massage and exercise therapy was provided. The control group (n = 15) was treated with the therapy concept only. The outcome was based on a 10-Metre Walking Test (10MWT), 6-Minute Walking Test (6MWT), Gross Motor Function Measure (GMFM-88) and lower extremities passive range of motion. The intervention group achieved a mean increase in walking speed in the 10MWT (self-selected walking speed SSW) of 5.5 s (p = 0.378). There were no significant differences between the groups in the 10MWT (max) (p = 0.123) and the 6MWT (p = 0.8). Changes in the GMFM (total) and in the dimension standing and walking, running and jumping (D + E) showed clinically relevant significant results (p = 0.002 and p = 0.046). RAGT as a supplement to an inpatient therapy stay appears to have a positive, yet not significant impact on the gait parameters of pediatric CP patients as well as motivating them to practice walking. Further studies with adapted study designs are needed to evaluate different influencing factors.

Dexamethasone Does not Compensate for Local Anesthetic Cytotoxic Effects on Tenocytes: Morphine or Morphine Plus Dexamethasone May Be a Safe Alternative.

Purpose: The purposes of this in vitro study were to investigate whether the addition of dexamethasone can compensate for any cytotoxic effects of the amide-type local anesthetics (LA) bupivacaine and ropivacaine and whether morphine and morphine-6-glucuronide (M6G) may be a safe alternative for peritendinous application. Methods: Biopsies of human biceps tendons (n = 6) were dissected and cultivated. Cells were characterized by the expression for tenocyte markers, collagen I, biglycan, tenascin C, scleraxis, and RUNX via reverse transcriptase-polymerase chain reaction and immunohistochemistry. Tenocytes were incubated with bupivacaine, ropivacaine, morphine, M6G, or a saline control with and without addition of dexamethasone for 15, 60, or 240 min. Cell viability was determined by quantifying the presence of adenosine-triphosphate. Results: Significant time-dependent cytotoxic effects were observed for LA after all exposure times. After 15, 60, and 240 minutes, cell viability decreased to 81.1%, 49.4% and 0% (P < .001) for bupivacaine and to 81.4%, 69.6%, and 9.3% (P < .001) for ropivacaine compared to saline control. Dexamethasone did not compensate for these cytotoxic effects. Cell viability was not affected after 15, 60-min exposures to morphine and M6G but decreased significantly (P < .001) after 240 minutes compared to saline control. However, in combination with dexamethasone, tenocyte viability was significantly increased at all times for morphine (P < .01) and at 15 and 60 minutes for M6G (P < .01). Conclusions: The results showed that amide-type LA have a time-dependent cytotoxic effect on human tenocytes in vitro, which could not be compensated for by dexamethasone, whereas morphine and M6G had no cytotoxic effects on tenocytes after 15 and 60 minutes. The addition of dexamethasone to morphine and M6G had a positive effect on viability, which increased significantly compared to the opioids. Clinical Relevance: It is known that amide-type local anesthetics used for local joint analgesia have chondrotoxic side-effects. The combined application of morphine and dexamethasone may be a safe alternative.

The Implant Proteome-The Right Surgical Glue to Fix Titanium Implants In Situ.

Titanium implants are frequently applied to the bone in orthopedic and trauma surgery. Although these biomaterials are characterized by excellent implant survivorship and clinical outcomes, there are almost no data available on the initial protein layer binding to the implant surface in situ. This study aims to investigate the composition of the initial protein layer on endoprosthetic surfaces as a key initiating step in osseointegration. In patients qualified for total hip arthroplasty, the implants are inserted into the femoral canal, fixed and subsequently explanted after 2 and 5 min. The proteins adsorbed to the surface (the implant proteome) are analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A statistical analysis of the proteins' alteration with longer incubation times reveals a slight change in their abundance according to the Vroman effect. The pathways involved in the extracellular matrix organization of bone, sterile inflammation and the beginning of an immunogenic response governed by neutrophils are significantly enriched based on the analysis of the implant proteome. Those are generally not changed with longer incubation times. In summary, proteins relevant for osseointegration are already adsorbed within 2 min in situ. A deeper understanding of the in situ protein-implant interactions in patients may contribute to optimizing implant surfaces in orthopedic and trauma surgery.

Therapeutic Treatments for Osteoporosis-Which Combination of Pills Is the Best among the Bad?

Osteoporosis is a chronical, systemic skeletal disorder characterized by an increase in bone resorption, which leads to reduced bone density. The reduction in bone mineral density and therefore low bone mass results in an increased risk of fractures. Osteoporosis is caused by an imbalance in the normally strictly regulated bone homeostasis. This imbalance is caused by overactive bone-resorbing osteoclasts, while bone-synthesizing osteoblasts do not compensate for this. In this review, the mechanism is presented, underlined by in vitro and animal models to investigate this imbalance as well as the current status of clinical trials. Furthermore, new therapeutic strategies for osteoporosis are presented, such as anabolic treatments and catabolic treatments and treatments using biomaterials and biomolecules. Another focus is on new combination therapies with multiple drugs which are currently considered more beneficial for the treatment of osteoporosis than monotherapies. Taken together, this review starts with an overview and ends with the newest approaches for osteoporosis therapies and a future perspective not presented so far.

Geriatric Proximal Femur Fractures During the Covid-19 Pandemic - Fewer Cases, But More Comorbidities.

BACKGROUND: The COVID-19 pandemic is challenging healthcare systems worldwide. This study examines geriatric patients with proximal femur fractures during the COVID-19 pandemic, shifts in secondary disease profile, the impact of the pandemic on hospitalization and further treatment. METHODS: In a retrospective monocentric study, geriatric proximal femur fractures treated in the first six months of 2020 were analyzed and compared with the same period of 2019. Pre-traumatic status (living in a care home, under supervision of a legal guardian), type of trauma, accident mechanism, geriatric risk factors, associated comorbidities, time between hospitalization and surgery, inpatient time and post-operative further treatment of 2 groups of patients, aged 65-80 years (Group 1) and 80+ years (Group 2) were investigated. RESULTS: The total number of patients decreased (70 in 2019 vs. 58 in 2020), mostly in Group 1 (25 vs. 16) while the numbers in Group 2 remained almost constant (45 vs. 42). The percentage of patients with pre-existing neurological conditions rose in 2020. This corresponded to an increase in patients under legal supervision (29.3%) and receiving pre-traumatic care in a nursing home (14.7%). Fractures were mostly caused by minor trauma in a home environment. In 2020, total number of inpatient days for Group 2 was lower compared to Group 1 (p = 0.008). Further care differed between the years: fewer Group 1 patients were discharged to geriatric therapy (69.6% vs. 25.0%), whereas in Group 2 the number of patients discharged to a nursing home increased. CONCLUSIONS: Falling by elderly patients is correlated to geriatric comorbidities, consequently there was no change in the case numbers in this age group. Strategic measures to avoid COVID-19 infection in hospital setting could include reducing the length of hospital stays by transferring elderly patients to a nursing home as soon as possible and discharging independent, mobile patients to return home.

Does Needle Design Affect the Regenerative Potential of Bone Marrow Aspirate? An In Vitro Study.

While autologous bone is still the gold standard for treatment of bone defects, its availability is limited. Sufficient numbers of mesenchymal stroma cells (MSC) may be an alternative. Small volumes of bone marrow aspirate (BMA) were harvested with two different needle systems comparing the yield and regenerative potency of the MSCs. BMA (10 mL) was aspirated from the posterior iliac crest of 12 patients with degenerative spinal disc disease using both needle systems in each patient: the Jamshidi needle (JAM) and on the contralateral side the Marrow Cellution® Needle (AMC). Number of mononuclear cells (MNCs) and regeneration capacity (colony-forming unit/CFU) were determined. MSCs were characterized for surface markers and their differentiation into trilineages. There was no significant difference between the two harvesting needles regarding the quantity of MNCs in BMA: 5.2 ± 1.8 × 109 MNC/mL for AMC vs. 4.8 ± 2.5 × 109 MNC/mL for JAM, p = 0.182. The quantity of CFUs per ml BMA was similar for both groups: 3717 ± 5556 for AMC and 4305 ± 5507 for JAM (p = 0.695). The potency of MSCs expressed as colony-forming potential per 106 MNC resulted in 0.98 ± 1.51 for AMC and 1.00 ± 0.96 for JAM (p = 0.666). Regardless of the needle design, 10 mL bone marrow aspirate contains a sufficient number of about 40,000 MSCs that can be used to enhance bone healing.

In-vivo comparison of the Ni-free steel X13CrMnMoN18-14-3 and titanium alloy implants in rabbit femora - A promising steel for orthopedic surgery.

A variety of metallic biomaterials is used for fracture fixation. Allergic reactions towards nickel-containing steels urge the need for alternatives. The present study investigated the suitability of the nickel-free stainless steel P2000 in comparison to titanium alloy implants for bone surgical applications in a rabbit femora defect model. Thirty-six rabbits received two different cylindrical implants press-fit inserted into the distal femoral metaphysis. At day 0, 28, and 56, implant ingrowth was monitored by radiography; implant stability was assessed by pull-out torque measurements while bone-to-implant contact (BIC) was determined histomorphometrically. Radiography revealed comparable implant ingrowth after 1 and 2 months for both implant materials. The pull-out force of P2000 tended to be higher than that for titanium at day 28 (p = .076) but the values were comparable at day 56 (p = .905). At day 56, implant fixation was significantly increased compared to the day of surgery for both, P2000 (p = .030) and for titanium alloy (p = .026). Microscopic examination revealed that both implant types appeared to be well integrated and firmly anchored in the bone. BIC ratio of titanium alloy tended to be higher at day 28 (p = .079) but they did not differ significantly at day 56 (p = .711). In the present rabbit femora defect model, the nickel-free stainless steel P2000 provides primary stability and osseointegration comparable to that of titanium alloy implants.

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment.

During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell-tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, ß-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC‱ of MNC with 9.8 ± 10.7‱ for the TCP and 12.8 ± 10.2‱ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration.

Comparison of the Biomechanical Properties of the Advanta V12/iCast and Viabahn Stent-Grafts as Bridging Devices in Fenestrated Endografts: An In Vitro Study.

Purpose: To compare experimentally the biomechanical properties of the Viabahn Balloon-Expandable Stent Graft (VBX) with the widely used Advanta V12/iCast in the role of bridging stent-grafts for fenestrated endovascular aortic repair. Materials and Methods: Test sheets made of polyester having 2 rows of 5 fenestrations in 6-mm and 8-mm diameters were used to simulate a commercially made fenestrated aortic endograft. In total, 40 stent-grafts measuring 6×39 mm and 8×39 mm (10 of each size for each stent-graft) were implanted in fenestration sheets immersed in a 37°C water bath. After flaring, all stent-grafts were evaluated using microscopy and radiography. Biomechanical evaluation included pullout and the shear stress force testing; results are reported in Newtons (N) as the median (minimum-maximum). Results: After flaring, no damage or fracture to the stent-graft structures were detected. Pullout forces for the 6-mm stent-grafts were 27.1 N (20.0-28.9) for the VBX and 16.6 N (14.7-19.2) for the Advanta (p=0.008). Pullout forces for the 8-mm stent-grafts were 20.1 N (14.8-21.5) for the VBX and 15.8 N (12.4-17.5) for the Advanta (p=0.095). The shear stress forces necessary to dislocate the device at 150% stent diameter displacement was 12.5 N (VBX) vs 14.7 N (Advanta) for the 6-mm devices and 23.3 N (VBX) vs 20.2 N (Advanta) for the 8-mm stents (p>0.99 and p=0.222, respectively). Conclusion: In vitro tests simulating external pull and shear forces on bridging stent-grafts implanted in fenestrations showed that the VBX had resistance to dislocation equivalent to a well-known control device.

Comparative in vitro activity of bacteriophage endolysin HY-133 against Staphylococcus aureus attached to vascular graft surface.

Novel strategies are needed for combating Staphylococcus aureus biofilm in vascular graft infections. We investigated the in vitro activity of bacteriophage endolysin HY-133, daptomycin and rifampin against S. aureus attached to vascular graft surface. Daptomycin showed rapid bactericidal effect on surface-associated S. aureus, while the activity of HY-133 on graft surface-adherent cells was moderate and rifampin did not achieve bactericidal effect. Even in the highest concentrations, all antimicrobials used failed in a complete eradication of the surface-adherent bacteria.

Surgical vacuum filter-derived stromal cells are superior in proliferation to human bone marrow aspirate.

BACKGROUND: During joint replacement, surgical vacuum suction guarantees a sufficient overview on the situs. We assume high concentrations of mesenchymal stromal cells (MSCs) on surgical vacuum filters. We compared the in vitro proliferative and differentiation potency of cells from the following: (i) bone marrow (BM), (ii) cancellous bone (CB), (iii) vacuum filter (VF), and (iv) cell saver filtrate reservoir (SF) in 32 patients undergoing elective total hip replacement. METHODS: Mononuclear cells (MNC) were isolated, and cell proliferation and colony-forming units (CFU) were measured. Adherent cells were characterized by flow cytometry for MSC surface markers. Cells were incubated with osteogenic, adipogenic, and chondrogenic stimuli. Cells were cytochemically stained and osteoblastic expression (RUNX-2, ALP, and BMP-2) investigated via qPCR. RESULTS: Dependent on the source, initial MNC amount as well as CFU number was significantly different whereas generation time did not vary significantly. CFU numbers from VF were superior to those from SR, BM, and CB. The resulting amount of MSC from the respective source was highest in the vacuum filter followed by reservoir, aspirate, and cancellous bone. Cells from all groups could be differentiated into the three mesenchymal lines demonstrating their stemness nature. However, gene expression of osteoblastic markers did not differ significantly between the groups. CONCLUSION: We conclude that surgical vacuum filters are able to concentrate tissue with relevant amounts of MSCs. A new potent source of autologous regeneration material with clinical significance is identified. Further clinical studies have to elucidate the regenerative potential of this material in an autologous setting.

Performance of BeGraft and BeGraft+ Stent-Grafts as Bridging Devices for Fenestrated Endovascular Aneurysm Repair: An In Vitro Study.

Purpose: To investigate 2 generations of balloon-expandable covered stents as potential bridging devices using an in vitro model of stent-graft fenestrations. Materials and Methods: Twenty BeGraft and 20 BeGraft+ cobalt-chromium stents covered in expanded polytetrafluoroethylene (ePTFE) in 6- and 8-mm diameters were tested in sheets mimicking stent-graft fenestrations. Microscopy and radiography were employed to evaluate stent morphology after flaring. In vitro bench tests measured maximum pullout (perpendicular displacement) and the shear stress (axial displacement) forces needed to dislocate the stents. Results: No alteration of ePTFE coverage was detected in the flared stents. Digital radiography and computed tomography showed marked alteration of the stent geometry, which was more pronounced in the BeGraft group. No fractures were detected. Median (minimum-maximum) pullout forces for the 6-mm stent-grafts were 17.1 N (15.8-19.6) for the BeGraft device and 30.4 N (20.2-31.9) for the BeGraft+ device (p=0.006). Median (minimum-maximum) pullout forces for the 8-mm stent-grafts were 11.3 N (11-12.1) for the BeGraft device and 21.8 N (18.2-25.5) for the BeGraft+ device (p<0.001). The shear stress test showed median forces of 10.5 vs 15.28 N at 150% of the stent diameter for the 6-mm BeGraft and BeGraft+ stent-grafts, respectively, and 15.23 vs 20.72 N at 150% stent diameter for the 8-mm models (p=0.016 and 0.017, respectively). Conclusion: Flaring changed the stent geometry but did not provoke stent fractures. The BeGraft+ is superior to the BeGraft in terms of pullout and shear stress forces, demonstrating greater resilience.

In Vitro Evaluation of the Gore Viabahn Balloon-Expandable Stent-Graft for Fenestrated Endovascular Aortic Repair.

PURPOSE: To evaluate the safety and integrity of a new stent-graft as a potential bridging device in fenestrated stent-grafts using an in vitro fenestrated model. MATERIALS AND METHODS: Polyester test sheets with ten 6-mm- or 8-mm-diameter fenestrations were used to simulate a fenestrated main body endoprosthesis. In total, 50 Viabahn balloon-expandable (VBX) stent-grafts of varying lengths (29 and 39 mm) and diameters (6, 7, and 8 mm) were implanted in the fitting fenestrations. After release, the 6- and 7-mm-diameter stent-grafts were flared with a 10×20-mm angioplasty balloon; a 12×20-mm balloon was used in the 8-mm-diameter devices. Safety of the devices was defined as absence of fractures detected on radiography or computed tomography (CT), as well as material failure detected by microscopy and water permeability testing. The forces (in Newtons, N) needed for perpendicular dislocation (pullout force) and axial dislocation (shear stress force) were also evaluated. RESULTS: Forty VBX stent-grafts were subjected to digital radiographic imaging and multiplanar CT. None showed any stent fracture. Subsequent microscopy indicated no damage to the fabric or separation of the graft after flaring. Ten VBX stent-grafts underwent water permeability testing after flaring; no water passed through the graft wall during a 10-minute period under an intraluminal pressure at 120 mm Hg. Testing of 25 VBX stent-grafts revealed initial pullout forces between 11.3 and 31 N. Shear stress tests showed that the average force needed to dislocate the stent-grafts by 50% of their diameter ranged between 5.75 and 6.91 N (mean 6.1±0.5 N) for the 6-mm stents and between 3.31 and 5.4 N (mean 4.4±0.8) for the 8-mm stents. CONCLUSION: This preliminary study demonstrated the applicability of the VBX as a bridging stent-graft in a simulated fenestration model. A comparison with other stent-grafts and clinical assessment are required.

Effectiveness of Intra-Arterial Aneurysm Sac Embolization for Type Ia Endoleak after Endovascular Aneurysm Repair.

PURPOSE: To evaluate the effectiveness and durability of intra-arterial aneurysm sac embolization for the treatment of type Ia endoleak after endovascular aneurysm repair (EVAR). MATERIALS AND METHODS: From February 2011 to December 2016, 22 patients underwent embolization of a type Ia endoleak after EVAR. Four patients (18%) were treated during the index EVAR and 18 (82%) in follow-up. Five patients (23%) were treated urgently and 17 (77%) electively. The embolization was performed with the use of liquid embolic agent, coils, and/or plugs. Adjunctive neck procedures were performed in 55% (n = 12) of the patients. The primary endpoint of this study was freedom from sac enlargement. Key secondary endpoints were technical success and freedom from endoleak-related reinterventions. RESULTS: Technical success was 100%. The 30-day mortality was 5% (n = 1; acute coronary syndrome). At a mean follow-up of 15.4 months (range 0.1-65.4) the freedom from sac enlargement rate was 76% (16 out of 21). Reintervention-free survival rates at 6, 12, and 24 months were 80%, 68% and 68%, respectively. CONCLUSIONS: In patients with persistent type Ia endoleak the embolization of the aneurysm sac with or without adjunctive neck procedures can be safely performed, leading to acceptable clinical and radiologic outcomes.

Intrasurgical Protein Layer on Titanium Arthroplasty Explants: From the Big Twelve to the Implant Proteome.

PURPOSE: Aseptic loosening in total joint replacement due to insufficient osteointegration is an unsolved problem in orthopaedics. The purpose of the study is to obtain a picture of the initial protein adsorption layer on femoral endoprosthetic surfaces as the key to the initiation of osseointegration. EXPERIMENTAL DESIGN: The paper describes the first study of femoral stem explants from patients for proteome analysis of the primary protein layer. After 2 min in situ, the stems are explanted and frozen in liquid nitrogen. Proteins are eluted under reducing conditions and analyzed by LC-MS/MS. RESULTS: After exclusion of proteins identified by a single peptide, the implant proteome is found to consist of 2802 unique proteins. Of these, 77% are of intracellular origin, 9% are derived from the plasma proteome, 8% from the bone proteome, and four proteins with highest specificity score could be assigned to the bone marrow proteome (transcriptome). The most abundant protein in the adsorbed total protein layer is hemoglobin (8-11%) followed by serum albumin (3.6-6%). CONCLUSIONS: A detailed knowledge of the initial protein film deposited onto the implants, as demonstrated here for the first time, may help to understand and predict the response of the osseous microenvironment to implant surfaces.

Biomechanical Stability and Osteogenesis in a Tibial Bone Defect Treated by Autologous Ovine Cord Blood Cells-A Pilot Study.

The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA.

Rapid in Vitro Quantification of S. aureus Biofilms on Vascular Graft Surfaces.

Objectives: Increasing resistance of microorganisms and particularly tolerance of bacterial biofilms against antibiotics require the need for alternative antimicrobial substances. S. aureus is the most frequent pathogen causing vascular graft infections. In order to evaluate the antimicrobial efficacy, quantification of the bacterial biofilms is necessary. Aim of the present study was the validation of an in vitro model for quantification of bacterial biofilm on vascular graft surfaces using three different assays. Methods: Standardized discs of vascular graft material (Dacron or PTFE) or polystyrene (PS) as control surface with 0.25 cm2 surface area were inoculated with 10-3 diluted overnight culture of three biofilm-producing S. aureus isolates (BEB-029, BEB-295, SH1000) in 96-well PS culture plates. After incubation for 4 and 18 h, the biofilm was determined by three different methods: (a) mitochondrial ATP concentration as measure of bacterial viability (ATP), (b) crystal violet staining (Cry), and (c) vital cell count by calculation of colony-forming units (CFU). The experiments were performed three times. Quadruplicates were used for each isolate, time point, and method. In parallel, bacterial biofilms were documented via scanning electron microscopy. Results: All three methods could quantify biofilms on the PS control. Time needed was 0:40, 13:10, and 14:30 h for ATP, Cry, and CFU, respectively. The Cry assay could not be used for vascular graft surfaces due to high unspecific background staining. However, ATP assay and CFU count showed comparable results on vascular graft material and control. The correlations between ATP and CFU assay differed according to the surface and incubation time and were significant only after 4 h on Dacron (BEB-029, p = 0.013) and on PS (BEB-029, p < 0.001). Between ATP and Cry assay on PS, a significant correlation could be detected after 4 h (BEB-295, p = 0.027) and after 18 h (all three strains, p < 0.026). The reproducibility of the ATP-assay presented as inter-assay-variance of 2.1 and as intra-assay variance of 8.1 on polystyrene. Conclusion: The in-vitro model reproducibly quantifies biofilm on standardized vascular graft surfaces with ATP assay as detection system. The ATP assay allows accelerated microbial quantification, however the correlation with the CFU assay may be strain- and surface-dependent.