A Randomised Phase II Trial of Hippocampal Sparing Versus Conventional Whole Brain Radiotherapy After Surgical Resection or Radiosurgery in Favourable Prognosis Patients With 1-10 Brain Metastases.

AIMS: To assess in patients with 1-10 brain metastases, each of which has been treated by neurosurgery or stereotactic radiosurgery, whether hippocampal sparing whole brain radiotherapy (HS-WBRT) better spares neurocognitive function (NCF) than standard WBRT. Further, to assess whether a phase III randomised trial of HS-WBRT would be feasible in the UK. MATERIALS AND METHODS: A multicentre, randomised, open label phase II trial was undertaken, randomising patients to 30Gy in 10 fractions of WBRT or HS-WBRT. The primary endpoint was decline in Total recall using Hopkins Verbal Learning Test Revised (HVLT-R) at 4 months post treatment. To assess this, we aimed to recruit 84 patients over 3 years. Secondary endpoints included further measures of NCF, quality of life, duration of functional independence, local control of treated metastases, development of new metastases, disease control within the hippocampal regions, overall survival, steroid and antiepileptic medication requirements, and toxicity. RESULTS: The trial closed prematurely due to slower than anticipated recruitment. From April 2016 to January 2018, 23 patients were randomised. Follow up was a median of 25 months. Fifteen patients (6 WBRT, 9 HS-WBRT) were assessed for the primary endpoint; of these, 1 in each arm experienced significant decline in the 4-month HVLT-R Total recall score (p = 0.8). Patients in the HS-WBRT arm experienced less insomnia (p < 0.01) and drowsiness (p < 0.01). There were no differences in other secondary endpoints. CONCLUSION: A phase III randomised trial of HS-WBRT was shown not to be feasible at this time in the UK. As most randomised trials of HS-WBRT reported to date share common endpoints, including NCF, an individual patient data meta-analysis should be undertaken.

An analysis of iris pattern as a risk factor for skin cancer development in immunosuppressed renal transplant recipients.

INTRODUCTION: Renal transplant recipients are at increased risk of keratinocyte skin cancers with a tendency to have multiple, aggressive and difficult to treat tumours. The eye and the skin share the same embryological ectoderm. Iris pattern has recently been reported as a predictive risk factor for skin cancer in non-immunosuppressed Southern European (Grigore et al., J Eur Acad Dermatol Venereol, 2018, 1662) and Irish populations (Ridge et al., J Eur Acad Dermatol Venereol, 2022, e542). AIMS: To analyse if an individual's iris pattern is an independent risk factor for the development of keratinocyte skin cancers in renal transplant recipients. METHODS: Iris patterns of 110 renal transplant recipients were evaluated using the Simionescu visual three-step technique (iris periphery, colarette and iris freckling [Simionescu et al., Ann Res Rev Biol, 2014, 2525]). Established risk factors for skin cancer in transplant patients were recorded as confounding factors. RESULTS: Observational cross-sectional study including 110 renal transplant population. Thirty-one participants had skin cancer. In the skin cancer group, iris periphery was blue/grey in 74.3% (p = 0.053, OR 2.5), the colarette was light brown in 57.1% (p < 0.0043) and iris freckles were present in 55%(p = 0.044). Dark brown and blue colarettes were observed in controls. Binary Logistic Regression analysis showed light brown colarette is a significant independent risk factor for skin cancer (OR 4.54, p < 0.02, CI 1.56-10.57). CONCLUSION: Within this renal transplant population a blue iris periphery, light brown colarette and presence of freckling confers an independent risk for keratinocyte skin cancer. Iris pattern is a useful tool for identification of transplant patients at risk of keratinocyte skin cancer and an easy-to-use technique for risk evaluation in this cohort. This is the first study looking at iris pattern and keratinocyte skin cancer risk in renal transplant population.

Comparative assessment of radiation therapy-induced vasculitis using [18F]FDG-PET/CT in patients with non-small cell lung cancer treated with proton versus photon radiotherapy.

PURPOSE: To assess radiation therapy (RT)-induced vasculitis in patients with non-small cell lung cancer (NSCLC) by examining changes in the uptake of 18F-fluoro-D-deoxyglucose ([18F]FDG) by positron emission tomography/computed tomography (PET/CT) images of the ascending aorta (AA), descending aorta (DA), and aortic arch (AoA) before and after proton and photon RT. METHOD: Thirty-five consecutive locally advanced NSCLC patients were definitively treated with proton (n = 27) or photon (n = 8) RT and concurrent chemotherapy. The patients were prospectively enrolled to undergo [18F]FDG-PET/CT imaging before and 3 months after RT. An adaptive contrast-oriented thresholding algorithm was applied to generate mean standardized uptake values (SUVmean) for regions of interest (ROIs) 3 mm outside and 3 mm inside the outer perimeter of the AA, DA, and AoA. These ROIs were employed to exclusively select the aortic wall and remove the influence of blood pool activity. SUVmeans before and after RT were compared using two-tailed paired t-tests. RESULTS: RT treatments were associated with increased SUVmeans in the AA, DA, and AoA-1.9%, 0.3%, and 1.3% for proton and 15.8%, 9.5%, and 15.5% for photon, respectively. There was a statistically significant difference in the ∆SUVmean (post-RT SUVmean - pre-RT SUVmean) in patients treated with photon RT when compared to ∆SUVmean in patients treated with proton RT in the AA (p = 0.043) and AoA (p = 0.015). There was an average increase in SUVmean that was related to dose for photon patients (across structures), but that was not seen for proton patients, although the increase was not statistically significant. CONCLUSION: Our results suggest that patients treated with photon RT for NSCLC may exhibit significantly more RT-induced inflammation (measured as ∆SUVmean) in the AA and AoA when compared to patients who received proton RT. Knowledge gained from further analyses in larger cohorts could aid in treatment planning and help prevent the significant morbidity and mortality associated with RT-induced vascular complications. TRIAL REGISTRATION: NCT02135679.

The power of partnership: Exploring collaboration dynamics in U.S. transplant research.

INTRODUCTION: Collaboration is one of the hallmarks of academic research. This study analyzes collaboration patterns in U.S. transplant research, examining publication trends, productive institutions, co-authorship networks, and citation patterns in high-impact transplant journals. METHODS: 4,265 articles published between 2012 and 2021 were analyzed using scientometric tools, logistic regression, VantagePoint software, and Gephi software for network visualization. RESULTS: 16,003 authors from 1,011 institutions and 59 countries were identified, with Harvard, Johns Hopkins, and University of Pennsylvania contributing the most papers. Odds of international collaboration significantly increased over time (OR 1.03; p â€‹= â€‹0.040), while odds of citation in single-institution collaborations decreased (OR 0.99; p â€‹= â€‹0.016). Five major scientific communities and central institutions (Harvard University and University of Pittsburgh) connecting them were identified, revealing interconnected research clusters. CONCLUSIONS: Collaboration enhances knowledge exchange and research productivity, with an increasing trend of institutional and international collaboration in U.S. transplant research. Understanding this community is essential for promoting research impact and forming strategic partnerships.

A broadly applicable approach to enrich electronic-health-record cohorts by identifying patients with complete data: a multisite evaluation.

OBJECTIVE: Patients who receive most care within a single healthcare system (colloquially called a "loyalty cohort" since they typically return to the same providers) have mostly complete data within that organization's electronic health record (EHR). Loyalty cohorts have low data missingness, which can unintentionally bias research results. Using proxies of routine care and healthcare utilization metrics, we compute a per-patient score that identifies a loyalty cohort. MATERIALS AND METHODS: We implemented a computable program for the widely adopted i2b2 platform that identifies loyalty cohorts in EHRs based on a machine-learning model, which was previously validated using linked claims data. We developed a novel validation approach, which tests, using only EHR data, whether patients returned to the same healthcare system after the training period. We evaluated these tools at 3 institutions using data from 2017 to 2019. RESULTS: Loyalty cohort calculations to identify patients who returned during a 1-year follow-up yielded a mean area under the receiver operating characteristic curve of 0.77 using the original model and 0.80 after calibrating the model at individual sites. Factors such as multiple medications or visits contributed significantly at all sites. Screening tests' contributions (eg, colonoscopy) varied across sites, likely due to coding and population differences. DISCUSSION: This open-source implementation of a "loyalty score" algorithm had good predictive power. Enriching research cohorts by utilizing these low-missingness patients is a way to obtain the data completeness necessary for accurate causal analysis. CONCLUSION: i2b2 sites can use this approach to select cohorts with mostly complete EHR data.

Generate Analysis-Ready Data for Real-world Evidence: Tutorial for Harnessing Electronic Health Records With Advanced Informatic Technologies.

Although randomized controlled trials (RCTs) are the gold standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data has been vital in postapproval monitoring and is being promoted for the regulatory process of experimental therapies. An emerging source of real-world data is electronic health records (EHRs), which contain detailed information on patient care in both structured (eg, diagnosis codes) and unstructured (eg, clinical notes and images) forms. Despite the granularity of the data available in EHRs, the critical variables required to reliably assess the relationship between a treatment and clinical outcome are challenging to extract. To address this fundamental challenge and accelerate the reliable use of EHRs for RWE, we introduce an integrated data curation and modeling pipeline consisting of 4 modules that leverage recent advances in natural language processing, computational phenotyping, and causal modeling techniques with noisy data. Module 1 consists of techniques for data harmonization. We use natural language processing to recognize clinical variables from RCT design documents and map the extracted variables to EHR features with description matching and knowledge networks. Module 2 then develops techniques for cohort construction using advanced phenotyping algorithms to both identify patients with diseases of interest and define the treatment arms. Module 3 introduces methods for variable curation, including a list of existing tools to extract baseline variables from different sources (eg, codified, free text, and medical imaging) and end points of various types (eg, death, binary, temporal, and numerical). Finally, module 4 presents validation and robust modeling methods, and we propose a strategy to create gold-standard labels for EHR variables of interest to validate data curation quality and perform subsequent causal modeling for RWE. In addition to the workflow proposed in our pipeline, we also develop a reporting guideline for RWE that covers the necessary information to facilitate transparent reporting and reproducibility of results. Moreover, our pipeline is highly data driven, enhancing study data with a rich variety of publicly available information and knowledge sources. We also showcase our pipeline and provide guidance on the deployment of relevant tools by revisiting the emulation of the Clinical Outcomes of Surgical Therapy Study Group Trial on laparoscopy-assisted colectomy versus open colectomy in patients with early-stage colon cancer. We also draw on existing literature on EHR emulation of RCTs together with our own studies with the Mass General Brigham EHR.

Glucose Increases STAT3 Activation, Promoting Sustained XRCC1 Expression and Increasing DNA Repair.

Dysregulation of DNA repair is a hallmark of cancer, though few cancer-specific mechanisms that drive the overexpression of DNA repair proteins are known. We previously identified STAT3 as a novel transcriptional regulator of X-ray cross-complementing group 1 (XRCC1), an essential scaffold protein in base excision repair in triple-negative breast cancers. We also identified an inducible response to IL-6 and epidermal growth factor stimulation in the non-tumorigenic embryonic kidney cell line HEK293T. As IL-6 and EGF signaling are growth and inflammatory-inducible responses, we examined if glucose challenge can increase STAT3 activation, promoting adaptive changes in XRCC1 expression in different cell types. Acute high glucose exposure promoted XRCC1 expression through STAT3 activation, increasing the repair of methyl methanesulfonate-induced DNA damage in HEK293T cells and the osteosarcoma cell line U2OS. Sustained exposure to high glucose promoted the overexpression of XRCC1, which can be reversed upon glucose restriction and down-regulation of STAT3 activation. Thus, we have identified a novel link between XRCC1 expression and STAT3 activation following exogenous exposures, which could play a critical role in dictating a cancer cell's response to DNA-damaging agents.

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors.

Although intracranial hemorrhage (ICH) is frequent in the setting of brain metastases, there are limited data on the influence of antiplatelet agents on the development of brain tumor-associated ICH. To evaluate whether the administration of antiplatelet agents increases the risk of ICH, we performed a matched cohort analysis of patients with metastatic brain tumors with blinded radiology review. The study population included 392 patients with metastatic brain tumors (134 received antiplatelet agents and 258 acted as controls). Non-small cell lung cancer was the most common malignancy in the cohort (74.0%), followed by small cell lung cancer (9.9%), melanoma (4.6%), and renal cell cancer (4.3%). Among those who received an antiplatelet agent, 86.6% received aspirin alone and 23.1% received therapeutic anticoagulation during the study period. The cumulative incidence of any ICH at 1 year was 19.3% (95% CI, 14.1-24.4) in patients not receiving antiplatelet agents compared with 22.5% (95% CI, 15.2-29.8; P = .22, Gray test) in those receiving antiplatelet agents. The cumulative incidence of major ICH was 5.4% (95% CI, 2.6-8.3) among controls compared with 5.5% (95% CI, 1.5-9.5; P = .80) in those exposed to antiplatelet agents. The combination of anticoagulation plus antiplatelet agents did not increase the risk of major ICH. The use of antiplatelet agents was not associated with an increase in the incidence, size, or severity of ICH in the setting of brain metastases.

Complications of an uncovered metallic tracheal stent managed by veno-venous extracorporeal membrane oxygenation: a case report.

Airway stents are primarily inserted for the management of airway obstruction associated with an inoperable malignancy and are rarely indicated in benign disease. We outline the complications associated with tracheal stents and describe the use of veno-venous extracorporeal membrane oxygenation (V-V ECMO) to facilitate open tracheal surgery in an apnoeic patient who had an uncovered metallic tracheal stent left in place for an inappropriately long period. Computerised tomography imaging of the neck and thorax provided information for operative planning and described of the stent in addition to the extensive granulation tissue at the distal end of the stent. Veno-venous extracorporeal membrane oxygenation was used to facilitate open tracheal surgery, removal of the tracheal stent and formation of a surgical tracheostomy. Prolonged use of an uncovered metallic airway stent in younger patients with benign disease may lead to the stent being difficult to remove. There may be an accumulation of granulation tissue with the risk of airway obstruction.

Postoperative Imaging Appearance of Iliac Crest Free Flaps Used for Palatomaxillary Reconstructions.

The osteomyocutaneous iliac crest free flap is a reconstructive option for segmental mandibular or complex palatomaxillary defects. Familiarity with the radiographic appearance of free flaps such as the iliac crest is necessary for the postoperative evaluation of patients after mandibular, maxillary, or palatal reconstructions because it allows radiologists to properly monitor and interpret the appearance of the flap over time. This study presents a retrospective review of 5 patients who underwent palatomaxillary reconstruction with an iliac crest free flap at our institution. The imaging appearances of the 5 patients were analyzed to determine the key radiographic characteristics of a healthy and successful iliac crest free flap. Radiographic fluency with the imaging appearance of the iliac crest free flap, as well as the new anatomy of the region in the postoperative period, will allow for better interpretation of the flap appearance on imaging and will prevent false identification of tumor recurrence.

Anticoagulation after intracranial hemorrhage in brain tumors: Risk of recurrent hemorrhage and venous thromboembolism.

BACKGROUND: Intracranial hemorrhage (ICH) is a common and often devastating outcome in patients with brain tumors. Despite this, there is little evidence to guide anticoagulation management following an initial ICH event. OBJECTIVES: To analyze the risk of recurrent hemorrhagic and thrombotic outcomes after an initial ICH event in patients with brain tumors and prior venous thromboembolism (VTE). PATIENTS AND METHODS: A retrospective cohort study was performed. Radiographic images obtained after initial ICH were reviewed for the primary outcomes of recurrent ICH and VTE. RESULTS AND CONCLUSIONS: A total of 79 patients with brain tumors who developed ICH on anticoagulation for VTE were analyzed. Fifty-four patients (68.4%) restarted anticoagulation following ICH. The cumulative incidence of recurrent ICH at 1 year was 6.1% (95% confidence interval [CI], 1.5-15.3) following reinitiation of anticoagulation. Following a major ICH (defined as an ICH >10 mL in size, causing symptoms, or requiring intervention), the rate of recurrent ICH upon reexposure to anticoagulation was 14.5% (95% CI, 2.1-38.35), whereas the rate of recurrent ICH following smaller ICH was 2.6% (95% CI, 0.2%-12.0%). Mortality following a recurrent ICH on anticoagulation was 67% at 30 days. The cumulative incidence of recurrent VTE was significantly lower in the restart cohort compared to patients who did not restart anticoagulation (8.1% vs 35.3%; P = .003). We conclude that resumption of anticoagulation is lowest among patients with metastatic brain tumors with small initial ICH. Following an initial major ICH, resumption of anticoagulation was associated with a high rate of recurrent ICH.

Single-Dose Nirsevimab for Prevention of RSV in Preterm Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants, and a need exists for prevention of RSV in healthy infants. Nirsevimab is a monoclonal antibody with an extended half-life that is being developed to protect infants for an entire RSV season with a single intramuscular dose. METHODS: In this trial conducted in both northern and southern hemispheres, we evaluated nirsevimab for the prevention of RSV-associated lower respiratory tract infection in healthy infants who had been born preterm (29 weeks 0 days to 34 weeks 6 days of gestation). We randomly assigned the infants in a 2:1 ratio to receive nirsevimab, at a dose of 50 mg in a single intramuscular injection, or placebo at the start of an RSV season. The primary end point was medically attended RSV-associated lower respiratory tract infection through 150 days after administration of the dose. The secondary efficacy end point was hospitalization for RSV-associated lower respiratory tract infection through 150 days after administration of the dose. RESULTS: From November 2016 through November 2017, a total of 1453 infants were randomly assigned to receive nirsevimab (969 infants) or placebo (484 infants) at the start of the RSV season. The incidence of medically attended RSV-associated lower respiratory tract infection was 70.1% lower (95% confidence interval [CI], 52.3 to 81.2) with nirsevimab prophylaxis than with placebo (2.6% [25 infants] vs. 9.5% [46 infants]; P<0.001) and the incidence of hospitalization for RSV-associated lower respiratory tract infection was 78.4% lower (95% CI, 51.9 to 90.3) with nirsevimab than with placebo (0.8% [8 infants] vs. 4.1% [20 infants]; P<0.001). These differences were consistent throughout the 150-day period after the dose was administered and across geographic locations and RSV subtypes. Adverse events were similar in the two trial groups, with no notable hypersensitivity reactions. CONCLUSIONS: A single injection of nirsevimab resulted in fewer medically attended RSV-associated lower respiratory tract infections and hospitalizations than placebo throughout the RSV season in healthy preterm infants. (Funded by AstraZeneca and Sanofi Pasteur; ClinicalTrials.gov number, NCT02878330.).

Inhibition of Necroptosis to Prevent Long-term Cardiac Damage During Pneumococcal Pneumonia and Invasive Disease.

BACKGROUND: Streptococcus pneumoniae infection can result in bacteremia with devastating consequences including heart damage. Necroptosis is a proinflammatory form of cell death instigated by pore-forming toxins such as S. pneumoniae pneumolysin. Necroptosis-inhibiting drugs may lessen organ damage during invasive pneumococcal disease (IPD). METHODS: In vitro experiments were carried out with human and mouse cardiomyocytes. Long-term cardiac damage was assessed using high-resolution echocardiography in ampicillin-rescued mice 3 months after challenge with S. pneumoniae. Ponatinib, a necroptosis-inhibiting and Food and Drug Administration-approved drug for lymphocytic leukemia treatment, was administered intraperitoneally alongside ampicillin to test its therapeutic efficacy. Histology of heart sections included hematoxylin-eosin staining for overt damage, immunofluorescence for necroptosis, and Sirius red/fast green staining for collagen deposition. RESULTS: Cardiomyocyte death and heart damage was due to pneumolysin-mediated necroptosis. IPD leads to long-term cardiac damage, as evidenced by de novo collagen deposition in mouse hearts and a decrease in fractional shortening. Adjunct necroptosis inhibition reduced the number of S. pneumoniae foci observed in hearts of acutely infected mice and serum levels of troponin I. Ponatinib reduced collagen deposition and protected heart function in convalescence. CONCLUSIONS: Acute and long-term cardiac damage incurred during IPD is due in part to cardiomyocyte necroptosis. Necroptosis inhibitors may be a viable adjunct therapy.

Comparison of the compressive mechanical properties of auricular and costal cartilage from patients with microtia.

Children born with a small or absent ears undergo surgical reconstruction to restore their auricle. Currently, rib (costal) cartilage is used to carve the auricle. However as alternative, tissue engineered and synthetic materials are being developed to restore the auricle shape to overcome donor site morbidity and limited availability of rib cartilage. However, to date there is limited knowledge regarding the mechanical properties of the auricular and costal cartilage to optimise the required compressive properties of the graft. The remnant auricular and costal cartilage from 20 patients undergoing stage-1 microtia surgery was harvested. On the day of surgery, the cartilage was evaluated in compression, with each sample loaded to 300 g at 1 mm/s. RESULTS: The costal cartilage was observed to have a significantly higher Young's Elastic Modulus than auricular cartilage (average costal cartilage 11.43 MPa vs average auricular cartilage 2 MPa, p < 0.0001). The auricular cartilage showed a significantly higher relaxation rate than costal cartilage (average costal cartilage 0.72 MPa10-4 vs average auricular cartilage 1.93 MPa10-4, p < 0.05). The final absolute relaxation was significantly lower for elastic cartilage than costal cartilage (average costal cartilage 3.35 MPa vs average auricular cartilage 0.2 MPa, p < 0.0001). Alloplastic cartilage replacements used as alternatives for reconstruction were also evaluated. Silicone, Gore-Tex and Medpor were observed to have significantly higher Young's Elastic Modulus than costal and auricular cartilage. Costal cartilage has a higher Young's Elastic Modulus in compression compared to auricular cartilage. Current synthetic materials used to replace synthetic cartilage do not mimic costal cartilage, which should be addressed in the future.

Breast Reconstruction with a Tissue Engineering and Regenerative Medicine Approach (Systematic Review).

Current techniques for breast reconstruction include an autologous-tissue flap or an implant-based procedure, although both can impose further morbidity. This systematic review aims to explore the existing literature on breast reconstruction using a tissue engineering approach; conducted with the databases Medline and Embase. A total of 28 articles were included, mainly comprising of level-5 evidence with in vitro and animal studies focusing on utilizing scaffolds to support the migration and growth of new tissue; scaffolds can be either biological or synthetic. Biological scaffolds were composed of collagen or a decellularized tissue matrix scaffold. Synthetic scaffolds were primarily composed of polymers with customisable designs, adjusting the internal morphology and pore size. Implanting cells, including adipose-derived stem cells, with combined use of basic fibroblast growth factor has been studied in an attempt to enhance tissue regeneration. Lately, a level-4 evidence human case series was reported; successfully regenerating 210 mL of tissue using an arterio-venous pedicled fat flap within a tissue engineering chamber implanted on the chest wall. Further research is required to evaluate whether the use of cells and other growth factors could adjust the composition of regenerated tissue and improve vascularity; the latter a major limiting factor for creating larger volumes of tissue.

Argon plasma surface modification promotes the therapeutic angiogenesis and tissue formation of tissue-engineered scaffolds in vivo by adipose-derived stem cells.

BACKGROUND: Synthetic implants are being used to restore injured or damaged tissues following cancer resection and congenital diseases. However, the survival of large tissue implant replacements depends on their ability to support angiogenesis that if limited, causes extrusion and infection of the implant. This study assessed the beneficial effect of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) on synthetic biomaterials in combination with argon plasma surface modification to enhance vascularisation of tissue-engineered constructs. METHODS: Non-biodegradable polyurethane scaffolds were manufactured and modified with plasma surface modification using argon gas (PM). Donor rats were then used to extract ADSCs and PRP to modify the scaffolds further. Scaffolds with and without PM were modified with and without ADSCs and PRP and subcutaneously implanted in the dorsum of rats for 3 months. After 12 weeks, the scaffolds were excised and the degree of tissue integration using H&E staining and Masson's trichrome staining, angiogenesis by CD31 and immune response by CD45 and CD68 immunohistochemistry staining was examined. RESULTS: H&E and Masson's trichrome staining showed PM+PRP+ADSC and PM+ADSC scaffolds had the greatest tissue integration, but there was no significant difference between the two scaffolds (p < 0.05). The greatest vessel formation after 3 months was shown with PM+PRP+ADSC and PM+ADSC scaffolds using CD31 staining compared to all other scaffolds (p < 0.05). The CD45 and CD68 staining was similar between all scaffolds after 3 months showing the ADSCs or PRP had no effect on the immune response of the scaffolds. CONCLUSIONS: Argon plasma surface modification enhanced the effect of adipose-derived stem cells effect on angiogenesis and tissue integration of polyurethane scaffolds. The combination of ADSCs and argon plasma modification may improve the survival of large tissue implants for regenerative applications.