Complex Aortoiliac Pelvic And Visceral Revascularization.

Aortoiliac occlusive disease (AIOD) remains an area of debate concerning open and endovascular treatment options. A case of a 63-year old female is reported, with previous known vascular intermittent claudication, that presented in the emergency room with acute ischemia of the right lower limb with 24-hours of evolution. The computer tomographic angiography unveiled occlusion of the superior mesenteric artery, occlusion of left common iliac artery (CIA), subocclusive stenosis of right CIA, occlusion of distal runoffs vessels in the right lower limb and diffuse aorto-iliac disease. The first approach was to place the patient under catheter directed thrombolysis (48h) which led to right pedal pulse recovery but the occlusion of left CIA remained. The patient was then electively submitted to Covered Endovascular Repair of Aortic Bifurcation (CERAB) with chimney to inferior mesenteric artery and with an additional bailout left iliac sandwich due to dissection. Distal pulses are still present after 18 months of follow-up. Endovascular techniques provide a low morbimortality option with similar symptomatic improvement, challenging open surgery as the standard of care even in complex AIOD.

Overview of evidence on risk factors and early management of acute carotid stent thrombosis during the last two decades.

OBJECTIVE: Acute carotid stent thrombosis (ACST) occurring in the first hours after the procedure is an exceedingly rare complication of carotid artery stenting, but it is potentially devastating. This review aimed to evaluate current literature, identifying all reported cases during the last two decades, with the final purpose of reporting predictive factors and early management. METHODS: A systematic review and meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. RESULTS: A total of 464 potentially relevant articles were selected. After review of records at title and abstract level, 29 articles with 60 patients were included. Twelve studies reported on ACST incidence rate in their cohorts, ranging from 0.36% to as high as 33%. In considering etiology, antiplatelet noncompliance or resistance is the most frequently reported risk factor. Emergency procedures seemed to be associated with greater risk for ACST, reaching 5.6% to 33% incidence. Dual-layer stents were also associated with greater risk (45% vs 3.7%; P = .0001; odds ratio, 21.3). Use of an overlapping stent as a bailout procedure because of dissection, malposition, or long lesions was correlated with increased risk (7.3% vs 0.002%), as were long stenotic lesions (22.9 ± 6.83 mm vs 14.2 ± 6.42 mm; P = .0034) and stent length (3.8 ± 0.4 cm vs 2.8 ± 0.86 cm; P = .0055). ACST was associated with neurologic status deterioration in 56.7% of cases. Time to symptoms or ACST diagnosis had a median of 1.5 hours, with 30% occurring intraprocedurally. In asymptomatic ACST, conservative management was unanimous. Endovascular treatment was the most common approach to intraprocedural ACST. Surgical options included carotid endarterectomy with stent explantation (n = 9), which was also a bailout after failed endovascular treatment in two cases. CONCLUSIONS: ACST incidence is higher in emergent, neurologically unstable patients. Antiplatelet noncompliance, antiplatelet resistance, long stenotic lesions, use of more than one stent, and dual-layer stents are also associated with increased risk. The decision as to the best approach depends on whether ACST occurs intraprocedurally or afterward, the development of neurologic status deterioration, and the center's experience. However, additional studies must be undertaken to better define optimal management.

Impact of Post-EVAR Graft Limb Kinking in EVAR Limb Occlusion: Aetiology, Early Diagnosis, and Management.

OBJECTIVE/BACKGROUND: Endograft limb occlusion is a potential complication of endovascular aneurysm repair (EVAR), being one of the major causes of secondary interventions and rehospitalisation. The aim of this review is to report on the impact of endograft kinking in endograft limb occlusion, as well as on risk factors, prevention, early diagnosis, and management. METHODS: A systematic review and meta-analysis was conducted according to the recommendations of the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) statement. RESULTS: After a MEDLINE and Scopus search, 55 articles (27,509 patients) were included in the qualitative analysis and eight in the quantitative analysis. In this meta-analysis, 179 at risk limbs were treated by pre-emptive stenting, which significantly reduced the risk of limb occlusion: not pre-emptively stenting limbs at risk had a negative impact on graft limb patency (odds ratio 4.30, 95% confidence interval 1.45-12.78). Post-operatively, a kink was identified in 422 patients (1.5%), contributing to 42.8% of all limb occlusions. Relevant data support that completion angiography is an inadequate means of diagnosing high risk limbs, proposing cone beam computed tomography and intravascular ultrasound as adjuncts. The post-operative limb occlusion rate ranged from 0% to 10.6%, affecting 984 patients. Several risk factors for limb occlusion have been identified. Regarding treatment, most patients were submitted to femorofemoral bypass (52.3%) or to deployment of a bare metal stent, either alone or associated with catheter directed thrombolysis or mechanical thrombectomy (26.4%). Complications and outcome after re-intervention for limb occlusion are described infrequently in the literature, but single studies have reported on re-occlusion, major amputation, and limb occlusion related mortality rates. CONCLUSION: Pre-EVAR planning should focus on identification of risk factors for kinking. Adjunctive stenting is an effective prophylaxis for selected high risk limbs, yet intra-operative identification remains problematic. Also, it is noteworthy that most limb occlusions occur in the first year after EVAR, emphasising the importance of careful early follow up of high risk patients.

Assessing corneal biomechanics with Brillouin spectro-microscopy.

A new Brillouin spectro-microscope was designed and built to investigate the mechanical properties of bovine and human corneas. This instrument integrates a single-stage virtually imaged phased array spectrometer with a novel adaptive-optics interferometric filter to achieve unprecedented rejection of the elastic background signal. As a result, highly-resolved, reproducible data from both thin and thick collagen-based materials were obtained. In particular, this technique is capable of rigorously measuring the relative stiffness of different areas of human corneas, thus providing a true non-contact method to characterise the fundamental mechanical features of both live and fixed biological tissue samples.

Acute Mesenteric Ischemia: Epidemiology, Risk Ractors and Determinants of Mortality.

INTRODUCTION: Acute mesenteric ischemia (AMI) is a condition with a difficult diagnosis and a high mortality rate. Despite the fact that AMI is a rather common condition in the elderly, review of the literature evidences lack of data concerning perioperative assessment of risk of death. The purpose of this study was to evaluate clinical, laboratory and imagiologic findings at admission and identify variables associated with adverse outcome with the final purpose of supporting treatment decision. METHODS: The clinical data of all patients admitted to Centro Hospitalar de Vila Nova de Gaia e Espinho with the diagnosis of AMI from January 2010 to December 2014 were retrospectively reviewed. RESULTS: A total of 64 patients (40 females and 24 males) with a mean age of 78±9.7 years were included. The most common aetiology was arterial embolization (36% of cases) followed by arterial thrombosis (34%), non-occlusive mesenteric ischemia in 22% and venous thrombosis in 8%. Global mortality rate reached 62.3%, with higher rates amongst patients submitted to revascularization and bowel resection (80%). Several clinical and laboratory findings were evaluated. Univariate analysis showed that leucocytosis, lactate level >2 mmol/L, age >80 years and colon involvement were associated with higher mortality (p<0.05). CONCLUSION: Contemporary management of AMI requires a high index of suspicion and rapid surgical intervention, if the time frame for intervention has not already elapsed. A better definition of determinants of mortality seems vital for treatment decision. More studies are needed to support clinical decision making in AMI.

Introdução: A isquemia mesentérica aguda é uma entidade clínica com um diagnóstico complexo fruto do quadro clínico inespecífico e com uma elevada taxa de mortalidade associada. Apesar de se tratar de um diagnóstico relativamente comum em idosos, uma revisão da literatura revela dados escassos relativos à avaliação de risco peri-operatório. Neste estudo pretendeu-se a avaliação de achados clínicos, laboratoriais e imagiológicos à admissão e identificar variáveis associadas com mau prognóstico. Métodos: Selecionaram-se retrospetivamente de todos os pacientes admitidos no Centro Hospitalar de Vila Nova de Gaia e Espinho com o diagnóstico de IMA de janeiro de 2010 a dezembro de 2014. Resultados: Um total de 64 doentes (40 do sexo feminino e 24 do sexo masculino), com idade média de 78±9,7 anos foram identificados. A etiologia mais comum foi a embolização arterial (36% dos casos), seguido de trombose arterial (34%), isquemia mesentérica não oclusiva (22%) e por último trombose venosa (8%). A taxa de mortalidade global foi de 62,3%, com taxas mais elevadas em doentes submetidos a revascularização e ressecção intestinal (80%). Foram avaliados vários achados clínicos e laboratoriais. A análise univariada mostrou que leucocitose, níveis de lactatos superiores a 2 mmol/L, idade superior a 80 anos e envolvimento do cólon (imagiológico ou intra-operatório) foram associados a maior mortalidade (p <0,05). Conclusão: O tratamento de IMA requer um elevado índice de suspeição e intervenção cirúrgica emergente, assumindo que a viabilidade do intestino já não foi ultrapassada. Uma melhor definição dos determinantes da mortalidade parece vital para suportar a decisão terapêutica.

Endoleak type II post-EVAR - predictive factors and therapeutic intervention - single centre experience in 100 EVAR procedures.

INTRODUCTION: Endovascular aortic repair (EVAR) has significantly altered the therapeutic strategy for abdominal aortic aneurysm (AAA), due to less invasiveness and lower perioperative morbi-mortality. However, specific complications such as persistent type 2 endoleak (pT2E, present > 6 months after EVAR) have been associated with adverse outcomes. However conflicting results from heterogeneous studies, failed to support an optimal threshold for intervention. The purpose of this study was to identify predictive factors associated with pT2E. METHODS: The clinical data of the last 100 patients admitted for EVAR in our hospital until April 2016 were retrospec- tively reviewed. Statistical analysis was performed using SPSS V.22. RESULTS: We analyzed 100 cases of EVAR, performed with a branched stentgraft for AAA or aorto-iliac aneurysms. Most cases (n=83) were performed electively but 17 were performed for ruptured AAA. No pre-operative inferior mesen- teric artery (IMA) coil embolization was performed. A pT2E was observed by Computed Tomography Angiography (CTA) in 21 cases (21%). Univariate analysis of risk factors for pT2E revealed that the number of patent lumbar arteries, patent IMA, platelet antiaggregants, absence of thoracic aortic aneurysm, and ruptured AAA were risk factors for pT2E (p<0.05). Binary logistic regression concluded platelet antiaggregants and increasing number of patent lumbars were independent risk factors for pT2E (p<0.05). DISCUSSION: Recently, pT2E that persists over a long period of time following EVAR has been reported to be involved in aneurysm sac growth, open conversion and rupture. Identification of pT2E predictive factors is crucial to prevent compli- cations and to consider measures such as pre-operative IMA coil embolization. We identified the number of patent lumbar arteries, the presence of patent IMA, platelet antiaggregants, absence of thoracic aortic aneurysm and ruptured AAA as sta- tistically significant risk factors for pT2E (p<0.05).

Introdução: A reparação endovascular de aneurisma da aorta abdominal (EVAR) alterou progressivamente a estratégia terapêutica devido à menor morbi-mortalidade peri-operatória associada. No entanto existem complicações específicas associa- das, como o endoleak tipo 2 persistente (pT2E, presente> 6 meses após EVAR). O principal objetivo deste estudo foi a identifi- cação de fatores preditivos associados a pT2E. Métodos: Os dados clínicos dos últimos 100 doentes admitidos para EVAR no nosso centro até abril de 2016 foram retrospetivamente analisados. O estudo estatístico foi realizado utilizando o SPSS V.22. Resultados: Foram analisados 100 casos de EVAR, realizados com endoprótese ramificada para aneurisma da aorta abdominal (AAA) ou aneurismas aorto-ilíacos. A maioria dos casos (n=83) foram realizados eletivamente, mas 17 foram reali- zados por rotura de AAA. Não houve nenhum caso de embolização pré-operatória da artéria mesentérica inferior (AMI). pT2E foi diagnosticado por Angio-Tomografia Computadorizada (AngioTC) em 21 casos (21%). A análise univariada dos fatores de risco para pT2E revelou que o número de artérias lombares (AL) permeáveis, permeabilidade da AMI, antiagregação plaquetária, ausência de aneurisma aórtico torácico e rotura de AAA são fatores de risco para pT2E (p<0,05). Uma regressão logística binária foi realizada e permitiu concluir que a antiagregação plaquetária e o número crescente de AL permeáveis são fatores de risco independentes para pT2E (p<0,05). Discussão: Atualmente, o pT2E tem sido cada vez mais associado a outcomes adversos como o crescimento do saco aneurismático, re-intervenção endovascular, conversão aberta e rotura. No entanto, a discrepância de dados na literatura condu- zem à ausência de um limiar consensual para tratamento. A identificação dos fatores preditivos de pT2E é crucial para prevenir complicações e considerar medidas como a embolização pré-operatória da AMI. Identificamos o número de AL permeáveis, AMI permeável, antiagregação plaquetária, ausência de aneurisma aórtico torácico e rotura de AAA como fatores de risco estatistica- mente significativos para pT2E (p<0,05).

Self-assembly of a dual functional bioactive peptide amphiphile incorporating both matrix metalloprotease substrate and cell adhesion motifs.

We describe a bioactive lipopeptide that combines the capacity to promote the adhesion and subsequent self-detachment of live cells, using template-cell-environment feedback interactions. This self-assembling peptide amphiphile comprises a diene-containing hexadecyl lipid chain (C16e) linked to a matrix metalloprotease-cleavable sequence, Thr-Pro-Gly-Pro-Gln-Gly-Ile-Ala-Gly-Gln, and contiguous with a cell-attachment and signalling motif, Arg-Gly-Asp-Ser. Biophysical characterisation revealed that the PA self-assembles into 3 nm diameter spherical micelles above a critical aggregation concentration (cac). In addition, when used in solution at 5-150 nM (well below the cac), the PA is capable of forming film coatings that provide a stable surface for human corneal fibroblasts to attach and grow. Furthermore, these coatings were demonstrated to be sensitive to metalloproteases expressed endogenously by the attached cells, and consequently to elicit the controlled detachment of cells without compromising their viability. As such, this material constitutes a novel class of multi-functional coating for both fundamental and clinical applications in tissue engineering.

Bio-fabrication and physiological self-release of tissue equivalents using smart peptide amphiphile templates.

In this study we applied a smart biomaterial formed from a self-assembling, multi-functional synthetic peptide amphiphile (PA) to coat substrates with various surface chemistries. The combination of PA coating and alignment-inducing functionalised substrates provided a template to instruct human corneal stromal fibroblasts to adhere, become aligned and then bio-fabricate a highly-ordered, multi-layered, three-dimensional tissue by depositing an aligned, native-like extracellular matrix. The newly-formed corneal tissue equivalent was subsequently able to eliminate the adhesive properties of the template and govern its own complete release via the action of endogenous proteases. Tissues recovered through this method were structurally stable, easily handled, and carrier-free. Furthermore, topographical and mechanical analysis by atomic force microscopy showed that tissue equivalents formed on the alignment-inducing PA template had highly-ordered, compact collagen deposition, with a two-fold higher elastic modulus compared to the less compact tissues produced on the non-alignment template, the PA-coated glass. We suggest that this technology represents a new paradigm in tissue engineering and regenerative medicine, whereby all processes for the bio-fabrication and subsequent self-release of natural, bio-prosthetic human tissues depend solely on simple template-tissue feedback interactions.

Differential nuclear expression of Yap in basal epithelial cells across the cornea and substrates of differing stiffness.

Corneal epithelium is maintained throughout life by well-orchestrated proliferation of limbal epithelial stem cells, followed by migration and maturation centripetally across the ocular surface. The present study sets out to explore the role tissue stiffness (compliance) may have in directing both differentiation and centripetal migration of limbal epithelial stem cells during homeostasis. For that, we analysed the localization of the Yes-associated protein (Yap), a transcriptional co-activator previously shown to mediate cellular response and mechanical stimuli. Using both models of ocular surface compliance and normal bovine corneas we evaluated the nuclear/cytoplasmic expression ratio of Yap. Expression levels within corneal epithelial cells were compared in situ between the limbus and central cornea, and in vitro between limbal epithelial stem cells expanded upon biomimetic collagen gels of increasing stiffness. Nuclear expression of Yap was shown to increase within the expanded cells upon substrates of increasing stiffness. Subsequently, Yap was used as a novel molecular probe to investigate the mechanical microenvironment within a normal ocular surface. The in situ localization of Yap was predominantly cytoplasmic within basal limbal epithelial cells and nuclear within basal central corneal epithelial cells. Furthermore, nuclear p63 expression was not co-localized with Yap in basal limbal epithelial cells. In conclusion, the current investigation provides new insights into the relationship between Yap and distinct cell populations across the ocular surface indicating that cells experience a different mechanical environment between the limbus and central cornea. A new hypothesis is put forward, in which centripetal differences in substrate stiffness drives the migration and differentiation of limbal epithelial stem cells, thus controlling corneal epithelium homeostasis.

Expression of glycogenes in differentiating human NT2N neurons. Downregulation of fucosyltransferase 9 leads to decreased Lewis(x) levels and impaired neurite outgrowth.

BACKGROUND: Several glycan structures are functionally relevant in biological events associated with differentiation and regeneration which occur in the central nervous system. Here we have analysed the glycogene expression and glycosylation patterns during human NT2N neuron differentiation. We have further studied the impact of downregulating fucosyltransferase 9 (FUT9) on neurite outgrowth. METHODS: The expression of glycogenes in human NT2N neurons differentiating from teratocarcinoma NTERA-2/cl.D1 cells has been analysed using the GlycoV4 GeneChip expression microarray. Changes in glycosylation have been monitored by immunoblot, immunofluorescence microscopy, HPLC and MALDI-TOF MS. Peptide mass fingerprinting and immunoprecipitation have been used for protein identification. FUT9 was downregulated using silencing RNA. RESULTS AND CONCLUSIONS: One hundred twelve mRNA transcripts showed statistically significant up-regulation, including the genes coding for proteins involved in the synthesis of the Lewis(x) motif (FUT9), polysialic acid (ST8SIA2 and ST8SIA4) and HNK-1 (B3GAT2). Accordingly, increased levels of the corresponding carbohydrate epitopes have been observed. The Lewis(x) structure was found in a carrier glycoprotein that was identified as the CRA-a isoform of human neural cell adhesion molecule 1. Downregulation of FUT9 caused significant decreases in the levels of Lewis(x), as well as GAP-43, a marker of neurite outgrowth. Concomitantly, a reduction in neurite formation and outgrowth has been observed that was reversed by FUT9 overexpression. GENERAL SIGNIFICANCE: These results provided information about the regulation of glycogenes during neuron differentiation and they showed that the Lewis(x) motif plays a functional role in neurite outgrowth from human neurons.

[Unruptured symptomatic abdominal aortic aneurysms]. / Aneurismas da aorta abdominal sintomáticos não rotos.

OBJECTIVES: The authors aim to present a case series of patients with unruptured symptomatic abdominal aortic aneurysms with atypical presentation or clinical manifestations. METHODS: A retrospective analysis from 2010 to 2013 of unruptured symptomatic abdominal aortic aneurysms was made in a Vascular Surgery department. RESULTS: 4 clinical cases were selected, all male, mean age of 72.2 years, with a history of smoking (75 %), hypertension (50 %), dyslipidemia (25 %) , DM (25 %) and CRI (25 %). Abdominal aortic aneurysms were diagnosed with unusual forms of presentation, from those associated to local events (venous or spinal compression), to infectious processes "in situ", complete thrombosis of the aneurysmal sac, to those with remotely manifestations (peripheral embolization). Medical and surgical treatments are described in this paper, taking into account the particularities of each patient. CONCLUSION: Rupture is the most common manifestation of abdominal aortic aneurysms. Although more rare, symptomatic unruptured AAA require a higher degree of suspicion, with some specific features to be considered, as we intend to demonstrate.

[Endovascular management of a thoracoabdominal aortic aneurysm in a chronic contained rupture using the "Sandwich technique"]. / Tratamento Endovascular de um Aneurisma da Aorta Toracoabdominal em Rotura Contida, Utilizando a Técnica de "Sandwich"

OBJECTIVE: The authors report the prompt diagnosis and endovascular treatment with the "Sandwich" technique of a chronic contained rupture of a thoracoabdominal aortic aneurysm in an unfit patient for open surgery. METHODS: A 57-year-old male patient with severe pulmonar and cardiac comorbilities presented at the emergency department with a contained rupture of a type V thoracoabdominal aneurysm, involving the celiac axis. A "Sandwich" technique was performed deploying a ViaBahn graft through a transbrachial access interlayed by two Gore TAG endoprothesis. RESULTS: At the term of the 1st month of follow-up, no endoleaks were observed. DISCUSSION: An impending ruptured thoracoabdominal aortic aneurysm was successfully excluded using the "Sandwich" technique, in a patient unfit for the conventional open correction.

[False aneurysm of the superficial temporal artery. Clinical report and literature review]. / Falso aneurisma da artéria temporal superficial: caso clínico e revisão da literatura.

Traumatic injuries of the external carotid artery and its branches are relatively rare in clinical practice and they may occur following head injuries. The superficial temporal artery is particularly susceptible to injury, given to its superficial course and the fact that it is overlying the temporal bone. The authors report the clinical case of a 88 years-old female treated of a false aneurysm of the superficial temporal artery and they proceed to a review of the literature.

Milliscale Substrate Curvature Promotes Myoblast Self-Organization and Differentiation.

Biological tissues comprise complex structural environments known to influence cell behavior via multiple interdependent sensing and transduction mechanisms. Yet, and despite the predominantly nonplanar geometry of these environments, the impact of tissue-size (milliscale) curvature on cell behavior is largely overlooked or underestimated. This study explores how concave, hemicylinder-shaped surfaces 3-50 mm in diameter affect the migration, proliferation, orientation, and differentiation of C2C12 myoblasts. Notably, these milliscale cues significantly affect cell responses compared with planar substrates, with myoblasts grown on surfaces 7.5-15 mm in diameter showing prevalent migration and alignment parallel to the curvature axis. Moreover, surfaces within this curvature range promote myoblast differentiation and the formation of denser, more compact tissues comprising highly oriented multinucleated myotubes. Based on the similarity of effects, it is further proposed that myoblast susceptibility to substrate curvature depends on mechanotransduction signaling. This model thus supports the notion that cellular responses to substrate curvature and compliance share the same molecular pathways and that control of cell behavior can be achieved via modulation of either individual parameter or in combination. This correlation is relevant for elucidating how muscle tissue forms and heals, as well as for designing better biomaterials and more appropriate cell-surface interfaces.

Covered Endovascular Repair of Innominate Artery Bifurcation After Thoracic Blunt Trauma.

Innominate artery (IA) injury is a rare entity with most patients dying before reaching the hospital. While open surgery remains the standard treatment, the endovascular approach is attractive as it may reduce perioperative morbidity and mortality. We report a case of IA blunt injury extending to the subclavian artery with pseudoaneurysm formation successfully treated with covered stenting of IA and its bifurcation. A 49-year-old male was admitted after suffering multiple trauma due to a high energy impact motorcycle crash. In the emergency room, the patient was hypotensive with a Glasgow coma score of 15. On physical examination, he had right peri-orbital ecchymosis, left otorrhagia and an open patella fracture. The computed tomographic angiography (CTA) revealed enlargement of the mediastinum and a 29 mm pseudoaneurysm involving the right brachiocephalic trunk and its bifurcation. Under general anesthesia, a covered balloon-expandable stent (CBES) was then placed in the IA followed by kissing stent of its bifurcation with an additional 2 covered balloon-expandable stents. Final subtraction angiography demonstrated complete pseudoaneurysm exclusion and stent patency without additional complications. No neurologic deficits or other intervention-related complications were found in the postoperative period. At 10 months follow-up, the patient remained asymptomatic and with palpable distal pulses. Endovascular management of IA injury may provide a good alternative to open surgery with low perioperative morbidity and mortality.

Biomechanical Modulation Therapy-A Stem Cell Therapy Without Stem Cells for the Treatment of Severe Ocular Burns.

Ocular injuries caused by chemical and thermal burns are often unmanageable and frequently result in disfigurement, corneal haze/opacification, and vision loss. Currently, a considerable number of surgical and pharmacological approaches are available to treat such injuries at either an acute or a chronic stage. However, these existing interventions are mainly directed at (and limited to) suppressing corneal inflammation and neovascularization while promoting re-epithelialization. Reconstruction of the ocular surface represents a suitable but last-option recourse in cases where epithelial healing is severely impaired, such as due to limbal stem cell deficiency. In this concise review, we discuss how biomechanical modulation therapy (BMT) may represent a more effective approach to promoting the regeneration of ocular tissues affected by burn injuries via restoration of the limbal stem cell niche. Specifically, the scientific basis supporting this new therapeutic modality is described, along with our growing understanding of the role that tissue biomechanics plays in stem cell fate and function. The potential impact of BMT as a future treatment option for the management of injuries affecting tissue compliance is also further discussed.

Autogenous Biofabrication of Nativelike, Scaffold-Free Human Skin Equivalents Using a Smart, Enzyme-Degradable Tissue Templating Coating.

In this study, we used tissue templating technology to direct human dermal fibroblasts to biofabricate large-area tissues that closely emulate the natural dermis. This technology also allowed the new tissues to promote their own release from the template surface, thus facilitating their recovery as self-sustained, scaffold-free dermal equivalents solely comprising human cells and their own extracellular matrix. The structure and composition of these dermal self-lifting autogenous tissue equivalents (SLATEs) were evaluated in detail and were shown to closely correlate to normal tissue function. Specifically, dermal SLATEs were shown to be composed of a dense collagen-based matrix interwoven with dermal-characteristic elastic fibers. In addition, the mechanical properties of these tissues (i.e., robustness, elastic modulus, and resistance to contraction and enzymatic degradation) were comparable to those of the natural human dermis. Furthermore, dermal SLATEs were capable of constituting tissues with a higher-order complexity by serving as a substrate to support the growth of keratinocytes into stratified epithelia with distinct layers of differentiation. This work thus illustrates the great potential of tissue templating technologies and how these can pave the way for the biofabrication of easily retrievable, scaffold-free human skin tissues with a structure, composition, and function suitable for both clinical and nonclinical applications.

YAP, ΔNp63, and ß-Catenin Signaling Pathways Are Involved in the Modulation of Corneal Epithelial Stem Cell Phenotype Induced by Substrate Stiffness.

Recent studies have established that the phenotype of epithelial stem cells residing in the corneal periphery (the limbus) depends on this niche's distinct biomechanical properties. However, the signaling pathways underlying this dependency are still poorly understood. To address this issue, we investigated the effect of substrate stiffness on the migration, proliferation, and molecular phenotype of human limbal epithelial stem cells (LESCs). Specifically, we demonstrated that cells grown on collagen-based substrates with limbus-like compliance showed higher proliferation and stratification and lower migration capabilities, as well as higher levels of pro-proliferative markers Ki67 and ß-Catenin, and LESC markers ΔNp63, ABCG2, and CK15. In contrast, cells on stiffer substrates lost these stem/progenitor cell markers, but instead expressed the key mechanotransduction factor YAP, as well as elevated levels of BMP4, a promotor of cell differentiation known to be negatively regulated by Wnt/ß-Catenin signaling. This data allowed us to propose a new model that integrates the various molecular pathways involved in LESC response to substrate stiffness. This model will potentially be a useful guide to future research on the mechanisms underlying LESC loss following fibrosis-causing injuries.

Overview of evidence on emergency carotid stenting in patients with acute ischemic stroke due to tandem occlusions: a systematic review and meta-analysis.

INTRODUCTION: Endovascular intracranial thrombectomy (IT) has established itself as the standard of care in treating large-vessel anterior circulation acute ischemic stroke (AIS). However, internal carotid artery (ICA) stenosis/occlusion hampers distal access and controversy about simultaneous emergency ICA stenting ensues. The purpose of this review was to evaluate the safety of emergency ICA stenting in combination with IT for AIS with tandem occlusions. To our knowledge this is the first meta-analysis to evaluate emergency ICA stenting in tandem occlusions, combining results from studies with a control group. EVIDENCE ACQUISITION: A meta-analysis was conducted according to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. EVIDENCE SYNTHESIS: A total of 649 potentially relevant articles were initially selected. After reviewing at title or abstract level, 87 articles were read in full and 23 were included. These studies recruited 1000 patients, 220 submitted to IT with no emergency ICA stenting and 780 to IT and emergency ICA stenting. Successful revascularization (Thrombolysis in cerebral infarction scale [TICI] ≥2b) was achieved in 48.6-100%. Good outcome (modified Rankin scale [mRS] ≤2) ranged from 18.2-100%. Symptomatic intracranial hemorrhage (sICH) ranged from 0-45.7% (overall N.=168; 17.2%). Mortality at 90 days ranged from 0-45.4% (overall N.=114; 11.7%). Time to recanalization was significantly longer in the stenting group with an overall mean difference of 1.76 (95% CI: 1.59-1.93). CONCLUSIONS: In this meta-analysis time to recanalization was significantly longer in the emergency ICA stenting group. There was no benefit from emergency stenting in parameters such as successful revascularization (TICI≥2b), clinical outcome (mRS≤2) or 90-day mortality. Data on sICH were scarce. Emergency ICA stenting appears to increase time to revascularization and increase the risk of complications with no demonstrated clinical benefit. Furthermore, no prospective, randomized controlled trials demonstrating relative efficacy and safety of concomitant ICA stenting have been published to date. Additional studies must be undertaken to define the role of angioplasty and stenting of the extracranial carotid arteries in the early management of acute stroke in tandem occlusions. Until then, we recommend that ICA stenting concomitant to thrombectomy in acute stroke patients should be avoided.