Retrograde Flow Research Articles

Cdc42 activity in the trailing edge is required for persistent directional migration of keratinocytes.

Fibroblasts migrate discontinuously by generating transient leading-edge protrusions and irregular, abrupt retractions of a narrow trailing edge. In contrast, keratinocytes migrate persistently and directionally via a single, stable, broad protrusion paired with a stable trailing-edge. The Rho GTPases Rac1, Cdc42 and RhoA are key regulators of cell protrusions and retractions. However, how these molecules mediate cell-type specific migration modes is still poorly understood. In fibroblasts, all three Rho proteins are active at the leading edge, suggesting short-range coordination of protrusive Rac1 and Cdc42 signals with RhoA retraction signals. Here, we show that Cdc42 was surprisingly active in the trailing-edge of migrating keratinocytes. Elevated Cdc42 activity colocalized with the effectors MRCK and N-WASP suggesting that Cdc42 controls both myosin activation and actin polymerization in the back. Indeed, Cdc42 was required to maintain the highly dynamic contractile acto-myosin retrograde flow at the trailing edge of keratinocytes, and its depletion induced ectopic protrusions in the back, leading to decreased migration directionality. These findings suggest that Cdc42 is required to stabilize the dynamic cytoskeletal polarization in keratinocytes, to enable persistent, directional migration.

Abstract 114: “Failing” DAPT? Think Again

Introduction Bow Hunter’s Syndrome (BHS) is a rare etiology of vertebrobasilar insufficiency that usually occurs with head turn, which causes compression of the vertebral artery by an osteophyte. There is subsequent hypoperfusion of brain tissue, but thromboembolism and ischemic stroke is rare. Timely diagnosis is imperative, as decompressive surgery can be curative. This unique case highlights the diagnostic and therapeutic challenges of a patient with multiple vascular risk factors who suffered from strokes secondary to BHS. Methods A 79‐year‐old man with a past medical history of peripheral artery disease, abdominal aortic aneurysm, myocardial infarction with drug eluding stents (on dual antiplatelet therapy (DAPT)), complete heart block with pacemaker, heart failure with reduced ejection fraction, hypertension, hyperlipidemia, and diabetes mellitus presented to an outside hospital with recurrent episodes of right‐sided weakness every 1‐2 days over the previous 3 weeks. Episodes always occurred after activity and only upon sitting. He had previously undergone non‐contrasted head computed tomography (NCHCT) (magnetic resonance imaging (MRI) was unable to be performed secondary to pacemaker), which did not reveal strokes. His initial computed tomography angiogram (CTA) of the head and neck was unremarkable. However, CTA head and neck 4 days later demonstrated 90 percent stenosis of the mid left V2 at the C3‐4 level and a 75‐90 percent stenosis of the left mid V2 segment at the C5‐6 level (hard and soft plaque in these areas). He was switched from DAPT to aspirin and warfarin because he was considered a “DAPT failure.” He continued to have episodes, so he was transferred to our institution for a second opinion. Results On arrival, the exam was notable for right‐sided hemiparesis and dysmetria. Repeat CTA head and neck demonstrated multifocal intracranial atherosclerosis with marked stenosis of the left V4 segment. However, marked stenosis at V2 appeared to be owed to external compression from facet arthrosis rather than atherosclerosis. He also had moderate stenosis of the right V4 segment. Eventually, he underwent an MRI brain, which demonstrated acute to subacute infarcts in the left pons. He was taken for a cerebral angiogram on the same day, which demonstrated stenosis of the distal V2 segment of the left vertebral artery (at the level of C3‐C4) with interval development of marked stenosis following neck flexion and occlusion of the left vertebral artery following leftward head rotation. Findings were most consistent with rotational occlusion of the left vertebral artery, which is also known as BHS. The patient underwent surgery, but suffered from a gastrointestinal bleed and developed post‐operative atrial fibrillation; after a risks/benefits discussion, he was discharged on anticoagulation only. He had no further strokes. Conclusion This patient suffered from ischemic strokes, which occur in less than 10% of BHS cases. Contralateral vertebral artery stenosis, which is unable to supply retrograde flow during compression, is the likely etiology of this patient's strokes. Recurrent posterior circulation strokes in the setting of optimal medical management should clue clinicians to consider other etiologies of stroke. Dynamic angiography is the gold standard for BHS and decompressive surgery is often curative.

Sperm in the Mammalian Female Reproductive Tract: Surfing Through the Tract to Try to Beat the Odds.

Mammalian sperm are deposited in the vagina or the cervix/uterus at coitus or at artificial insemination, and the fertilizing sperm move through the female reproductive tract to the ampulla of the oviduct, the site of fertilization. But the destination of most sperm is not the oviduct. Most sperm are carried by retrograde fluid flow to the vagina, are phagocytosed, and/or do not pass barriers on the pathway to the oviduct. The sperm that reach the site of fertilization are the exceptions and winners of one of the most stringent selection processes in nature. This review discusses the challenges sperm encounter and how the few sperm that reach the site of fertilization overcome them. The sperm that reach the goal must navigate viscoelastic fluid, swim vigorously and cooperatively along the walls of the female tract, avoid the innate immune system, and respond to potential cues to direct their movement.

Downhill varices in the hypopharynx due to huge thyroid tumor: a case report.

Downhill varices are usually caused by superior vena cava (SVC) obstruction due to bronchogenic carcinoma or mediastinal tumors. These structures show retrograde blood flow and are located in the proximal esophagus. Varices in the hypopharynx resulting from mediastinal thyroid tumor are extremely rare. A 70-year-old man visited a local hospital with a 35-year history of enlarging thyroid tumor in the right neck. Fine needle aspiration cytology of the tumor revealed benign goiter. Contrast-enhanced computed tomography showed a huge tumor (13×10×5 cm) in the right to left lobe of the thyroid extending into the mediastinum. Further, a well-enhanced mass mimicking hypopharyngeal cancer was identified in the hypopharynx. Endoscopic examination demonstrated varices in the postcricoid region, so we avoided biopsy. The preoperative diagnosis was huge adenomatous goiter and hypopharyngeal varices caused by obstruction of the internal jugular and brachiocephalic vein by the goiter. Total thyroidectomy was performed and hypopharyngeal varices had disappeared by the next day. The histopathological diagnosis of the thyroid tumor was poorly differentiated carcinoma. Mediastinal thyroid tumor rarely causes downhill varices due to SVC obstruction. However, in this case, signs of SVC obstruction were absent and varices were found not in the upper esophagus, but in the hypopharynx. Obstructed venous flow from the thyroid plexus might circulate via superior laryngeal vein and cause varices in the postcricoid region. When a patient with large mediastinal tumor shows a tumor-like lesion in the hypopharynx, considering the possibility of downhill varices is important before conducting immediate biopsies.

Assessment of Rheological Models Applied to Blood Flow in Human Thoracic Aorta.

The purpose of this study is to assess the importance of non-Newtonian rheological models on blood flow in the human thoracic aorta. The pulsatile flow in the aorta is simulated using the models of Casson, Quemada and Walburn-Schneck in addition to a case of fixed (Newtonian) viscosity. The impact of the four rheological models (using constant hematocrit) was assessed with respect to (i) magnitude and deviation of the viscosity relative to a reference value (the Newtonian case); (ii) wall shear stress (WSS) and its time derivative; (iii) common WSS-related indicators, OSI, TAWSS and RRT; (iv) relative volume and surface-based retrograde flow; and (v) the impact of rheological models on the transport of small particles in the thoracic aorta. The time-dependent flow in the thoracic aorta implies relatively large variations in the instantaneous WSS, due to variations in the instantaneous viscosity by as much as an order of magnitude. The largest effect was observed for low shear rates (tens s-1). The different viscosity models had a small impact in terms of time- and spaced-averaged quantities. The significance of the rheological models was clearly demonstrated in the instantaneous WSS, for the space-averaged WSS (about 10%) and the corresponding temporal derivative of WSS (up to 20%). The longer-term accumulated effect of the rheological model was observed for the transport of spherical particles of 2 mm and 2 mm in diameter (density of 1200 kg/m3). Large particles' total residence time in the brachiocephalic artery was 60% longer compared to the smaller particles. For the left common carotid artery, the opposite was observed: the smaller particles resided considerably longer than their larger counterparts. The dependence on the non-Newtonian properties of blood is mostly important at low shear regions (near walls, stagnation regions). Time- and space-averaging parameters of interest reduce the impact of the rheological model and may thereby lead to under-estimation of viscous effects. The rheological model affects the local WSS and its temporal derivative. In addition, the transport of small particles includes the accumulated effect of the blood rheological model as the several forces (e.g., drag, added mass and lift) acting on the particles are viscosity dependent. Mass transport is an essential factor for the development of pathologies in the arterial wall, implying that rheological models are important for assessing such risks.

Impact of Variation in Commissural Angle between Fused Leaflets in the Functionally Bicuspid Aortic Valve on Hemodynamics and Tissue Biomechanics.

In subjects with functionally bicuspid aortic valves (BAVs) with fusion between the coronary leaflets, there is a natural variation of the commissural angle. What is not fully understood is how this variation influences the hemodynamics and tissue biomechanics. These variables may influence valvar durability and function, both in the native valve and following repair, and influence ongoing aortic dilation. A 3D aortic valvar model was reconstructed from a patient with a normal trileaflet aortic valve using cardiac magnetic resonance (CMR) imaging. Fluid-structure interaction (FSI) simulations were used to compare the effects of the varying commissural angles between the non-coronary with its adjacent coronary leaflet. The results showed that the BAV with very asymmetric commissures (120∘ degree commissural angle) reduces the aortic opening area during peak systole and with a jet that impacts on the right posterior wall proximally of the ascending aorta, giving rise to elevated wall shear stress. This manifests in a shear layer with a retrograde flow and strong swirling towards the fused leaflet side. In contrast, a more symmetrical commissural angle (180∘ degree commissural angle) reduces the jet impact on the posterior wall and leads to a linear decrease in stress and strain levels in the non-fused non-coronary leaflet. These findings highlight the importance of considering the commissural angle in the progression of aortic valvar stenosis, the regional distribution of stresses and strain levels experienced by the leaflets which may predispose to valvar deterioration, and progression in thoracic aortic dilation in patients with functionally bicuspid aortic valves. Understanding the hemodynamics and biomechanics of the functionally bicuspid aortic valve and its variation in structure may provide insight into predicting the risk of aortic valve dysfunction and thoracic aortic dilation, which could inform clinical decision making and potentially lead to improved aortic valvar surgical outcomes.

Echocardiography evaluation of neonatal vein of Galen aneurysmal malformation.

In neonatal vein of Galen aneurysmal malformation, vein of Galen aneurysmal malformation echocardiography remains the mainstay for early detection and explains various haemodynamic changes occurring due to a large systemic arterio-venous shunt. However, there is limited evidence of echocardiography in risk stratifying neonatal vein of Galen aneurysmal malformation vein of Galen aneurysmal malformation. The objective of this study was to identify echocardiographic parameters that could be associated with major outcomes and guide timing of neuro-intervention. In this retrospective chart review, infants < 28 days of age with the diagnosis of vein of Galen aneurysmal malformation vein of Galen aneurysmal malformation were included. Demographic, clinical, and echocardiographic parameters were compared in neonates who survived or died with neonatal presentation. A risk algorithm model based on key echocardiographic parameters was developed to determine those who are at risk of early death. Of the 19 neonates included, with median birth weight 3.1 kg (IQR 2.58-3.36), nine (47%) neonates died at median age of 5 days (IQR 4-17). All neonates showed retrograde diastolic flow at the level of descending aorta by colour Doppler on the first post-natal echocardiogram at median age of 2 days (IQR 1-5.5). An aortic antegrade-to-retrograde velocity time integral ratio of < 1.5 and supra-systemic pulmonary artery pressure had 100% positive predictive value of death (p = 0.029), whereas aortic antegrade-to-retrograde velocity time integral ratio of > 1.5 and sub-systemic pulmonary artery pressure had 100% positive predictive value of survival (p = 0.029). Combination of aorta antegrade-to-retrograde velocity time integral ratio and degree of pulmonary hypertension on the first post-natal echocardiogram may help stratify the severity of disease and guide optimal timing for neuro-intervention for neonatal vein of Galen aneurysmal malformation.

The Impact of Left Ventricular Assist Device Outflow Graft Positioning on Aortic Hemodynamics: Improving Flow Dynamics to Mitigate Aortic Insufficiency.

Heart failure is a global health concern with significant implications for healthcare systems. Left ventricular assist devices (LVADs) provide mechanical support for patients with severe heart failure. However, the placement of the LVAD outflow graft within the aorta has substantial implications for hemodynamics and can lead to aortic insufficiency during long-term support. This study employs computational fluid dynamics (CFD) simulations to investigate the impact of different LVAD outflow graft locations on aortic hemodynamics. The introduction of valve morphology within the aorta geometry allows for a more detailed analysis of hemodynamics at the aortic root. The results demonstrate that the formation of vortex rings and subsequent vortices during the high-velocity jet flow from the graft interacted with the aortic wall. Time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) indicate that modification of the outflow graft location changes mechanical states within the aortic wall and aortic valve. Among the studied geometric factors, both the height and inclination angle of the LVAD outflow graft are important in controlling retrograde flow to the aortic root, while the azimuthal angle primarily determines the rotational direction of blood flow in the aortic arch. Thus, precise positioning of the LVAD outflow graft emerges as a critical factor in optimizing patient outcomes by improving the hemodynamic environment.

Distally Based Pedicled Fibula Flap for Reconstruction of Distal Tibia After Oncological Resection: A Case Series and Review of Literature.

Reconstruction of distal tibial defects pose a difficult challenge because the bone is subcutaneous and close to the tendons and neurovascular bundles. Distally based pedicled fibula with retrograde flow can be used for the reconstruction of distal tibial defects. This is based on the communicating branch of the peroneal artery to the posterior tibial artery. We present three cases of distal tibia primary tumours which were resected and reconstructed using recycled autograft plus distally based pedicled fibula and ankle arthrodesis. This pedicled retrograde fibula flap is a novel technique for the reconstruction of distal tibial defects after oncological resections. It provides a vascularized graft without the need for microvascular surgery and without violating the normal limb. Meticulous dissection of and preservation of the communicating branches between the peroneal artery and the posterior tibial artery with confirmation of retrograde flow before dividing the proximal peroneal pedicle is sine quo non for the success of this graft. This flap overcomes the drawback of the limited arc of rotation and limited reach of proximal pedicle-based flap for distal tibial reconstruction. Long-term functional outcomes, limb shortening associated with this flap, and its effect on functional outcomes remain to be ascertained.

Acute upper and lower limb hemodynamic responses during single sessions of low- versus high-intensity inspiratory muscle strength training.

Inspiratory muscle strength training (IMST) has shown potential to improve both respiratory and cardiovascular function in health and disease. Less is known about acute hemodynamic responses to a single IMST session, therefore we assessed upper and lower limb blood flow via Doppler ultrasound in the brachial and popliteal arteries, respectively. Mean, anterograde, and retrograde blood flow (BF) and shear rate (SR) were assessed relative to baseline during low-intensity (15% maximal inspiratory pressure - PImax) and high-intensity (75% PImax) IMST. During low-intensity IMST, popliteal BF and SR were reduced by ∼10%, and brachial BF and SR were reduced by ∼40%. During high-intensity IMST, popliteal BF and SR were reduced by ∼20%, and brachial BF and SR were reduced by ∼35%. BF and SR responses were not statistically different between low-intensity and high-intensity training for either blood vessel (P > 0.05). In addition, anterograde BF and SR were significantly decreased in the brachial artery for both low-intensity and high-intensity training (P < 0.05), but not the popliteal artery (P > 0.05). Finally, during IMST retrograde BF and SR were significantly increased in both the upper and lower limbs during low-intensity and high-intensity training (P < 0.05). These data provide novel insight into the acute BF and SR responses to a single bout of IMST and may enhance our understanding of the mechanism(s) by which IMST imparts its beneficial chronic effects on cardiovascular function.NEW & NOTEWORTHY Herein, we demonstrate for the first time that upper and lower limb blood flow and shear rate patterns are altered during a single bout of IMST, at low- and high-intensity training. Specifically, anterograde blood flow and shear rate are significantly reduced in the brachial artery, whereas retrograde blood flow is significantly elevated in both the brachial and popliteal arteries. These findings provide insight into the vascular impact of IMST, which may inform future mechanistic studies.

A case of stent-assisted balloon-induced intimal disruption and relamination of distal remaining aortic dissection after the ascending aorta and aortic arch replacement for acute aortic dissection

BackgroundThe early survival rate of patients with acute type A aortic dissection (TAAD) has improved remarkably over the past two decades. However, a false lumen may remain after proximal aortic repair and is a potential risk factor for aortic diameter enlargement, aortic rupture, and death in the chronic phase. In the stent-assisted balloon-induced intimal disruption and relamination of aortic dissection (STABILISE) technique, a stent graft is implanted at the proximal part of the aortic dissection, followed by bare-metal aortic stent placement over the distal aortic dissection. Next, an aortic balloon catheter is dilated inside the stent graft and the bare stent to disrupt the intima and collapse the false lumen, immediately restoring uniluminal thoracoabdominal aortic flow. This report describes our experience with the STABILISE technique for a residual aortic dissection after an ascending aorta, and partial aortic arch replacement for acute TAAD resulted in complications.Case presentationA 60-year-old man presented to our hospital with chest pain, paresthesia, and left lower-limb paralysis. He was diagnosed with acute type A aortic dissection (TAAD) and malperfusion of the left lower limb by computed tomography (CT), and an emergent ascending aorta and partial aortic arch replacement were performed. Immediately after surgery, the left femoral arterial pulse improved, and left lower limb revascularization was deferred. The postoperative course was good; however, back pain and intermittent claudication recurred on the 9th day after surgery. A CT examination revealed persistent antegrade false lumen flow in the descending thoracic aorta through the left subclavian artery dissection and retrograde false lumen flow from the thoracoabdominal segment, resulting in aortic diameter enlargement and narrowing of the true lumen. The symptoms did not improve, and the STABILISE technique was performed on the 12th day after the initial aortic surgery. The patient’s subsequent course was good; the back pain and intermittent claudication resolved. The patient was discharged on the 8th day after the STABILISE technique.ConclusionsThe STABILISE technique can obliterate the false lumen and resolve symptoms associated with a residual false lumen after proximal aortic repair for acute TAAD.

A perspective on the clinical relevance of weak or nonacid reflux.

Advances in ambulatory esophageal reflux monitoring that incorporated impedance electrodes to pH catheters have resulted in better characterization of retrograde bolus flow in the esophagus. With pH-impedance monitoring, in addition to acid reflux episodes identified by pH drops below 4.0, weakly acid reflux (WAR, pH 4-7) and nonacid reflux (NAR, pH >7.0) are also recognized, although both may be included under the umbrella term NAR. However, despite identification of ambulatory pH-impedance monitoring, data on clinical relevance and prognostic value of NAR are limited. The Lyon Consensus, an international expert review that defines conclusive metrics for gastroesophageal reflux disease (GERD), identifies NAR as "supportive" but not conclusive for GERD. This review provides perspectives on whether NAR fulfills three criteria for clinical relevance: whether NAR sufficiently explains pathogenesis of symptoms, whether it is associated with meaningful manifestations of GERD, and whether it can predict treatment efficacy.

Self-Induced Pneumoparotid as a Result of Covering Mouth While Coughing: A Case Report

Introduction Pneumoparotid is a rare condition characterized by the presence of air in the parotid gland, usually caused by the retrograde flow of air through the parotid duct. This report presents a rare occurrence of self-induced pneumoparotid. Case presentation A-41-year-old female presented with a recurrent painless right-sided parotid gland swelling for one month. She reported covering her mouth with her hands while coughing. Clinical examination revealed a right parotid swelling inferior to her right ear. The mass was non-tender and compressible. The neck and skull base computed tomography with contrast revealed a large thin wall cystic space with small air bubbles in the course of Stenson's duct. The patient underwent conservative management with good outcome. Conclusion Pneumoparotid is an extremely uncommon condition characterized by the presence of air in the parotid gland. Diagnostic imaging techniques such as ultrasound, sialography, or CT scans are valuable in confirming the diagnosis.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

An Experimental Model Exhibiting Anterograde and Retrograde Vascular Occlusion of Facial Fillers to Avoid Vision Loss.

Facial filler injection techniques that help decrease the risk of vascular occlusion are an important growing area of study. This study demonstrates a model of injecting fillers into a simulated bifurcated arterial system, using different sized needle gauges at a constant injection pressure. Three facial fillers were injected into a bifurcated intravenous tubing with continuous irrigation at a constant pressure to simulate a vascular system. Videography was used to observe for retrograde flow through the simulated supratrochlear artery to the bifurcation point, where the filler was redirected by anterograde flow into the branch representing the ophthalmic artery. Filler injection with retrograde flow to the bifurcation occurred with all the 27G needle trials. In comparison, the 30G needle trials were only able to reach the bifurcation point in three of the nine trials. The average time to the bifurcation point with subsequent ophthalmic artery anterograde flow with the 27G and 30G needles were 8.44 (95% confidence interval ±2.06) and 33.33 (95% confidence interval ±16.56) seconds, respectively. Larger 27G needles consistently reached retrograde flow and the bifurcation point faster than 30G needles. This study suggests thinner needles may be less likely to cause retrograde occlusion.

Ruptured vertebrobasilar junction aneurysm supplied by reversed flow from the anterior spinal artery: Illustrative case report.

In patients with vertebral artery (VA) occlusion, spontaneous flow reversal may occur in the anterior spinal artery (ASA) as a source of compensatory supply to the posterior circulation. Turbulent flow and increased flux through these small arteries may predispose to luminal damage and intracranial aneurysm formation. We report a novel case of a ruptured ASA-VA junction aneurysm in a patient with chronic bilateral VA occlusion, successfully treated with endovascular embolization. A 62-year-old female with uncontrolled hypertension presented with acute-onset headache, emesis, neck stiffness, and decreased level of consciousness. Head computed tomography demonstrated diffuse cisternal subarachnoid hemorrhage with intraventricular extension and ventriculomegaly. Computed tomography angiography showed left VA atresia and chronic right VA occlusion just distal to the posterior inferior cerebellar artery origin, as well as a complex, bilobed aneurysm at the ASA-VA junction. Angiography demonstrated flow reversal from the ASA into the distal stump of the occluded right VA, which in turn filled the aneurysm. Of note, the patient's posterior circulation was predominantly supplied by the dilated ASA, and associated collaterals from ASA and right VA stump. The aneurysm was accessed and embolized using superselective microcatheterization over a soft microguidewire through the right cervical VA perforators supplying retrograde flow into and through the ASA. ASA-VA aneurysms are exceedingly rare, and generally associated with atypical flow dynamics. Dynamic treatment strategies may be needed, especially in the setting of subarachnoid hemorrhage.

Femoral or Axillary Cannulation for Extracorporeal Circulation during Minimally Invasive Heart Valve Surgery (FAMI): Protocol for a Multi-Center Prospective Randomized Trial.

Minimally invasive heart valve surgery via anterolateral mini-thoracotomy with full endoscopic 3D visualization (MIS) has become the standard treatment of patients with valvular heart disease and low operative risk over the past two decades. It requires extracorporeal circulation and cardioplegic arrest. The most established form of arterial cannulation for MIS is through the femoral artery and is used by most surgeons, but it is suspected to increase the risk of stroke through retrograde blood flow. An alternative route of cannulation is the axillary artery, producing antegrade blood flow during extracorporeal circulation. Femoral or axillary cannulation for extracorporeal circulation during minimally invasive heart valve surgery (FAMI) is a multicenter randomized controlled trial designed to determine whether axillary cannulation is superior to femoral cannulation for the outcome of a manifest stroke within 7 days postoperatively. The target sample size was 848 participants. Patients ≥ 18 years of age, with valvular regurgitation or stenosis scheduled for minimally invasive surgery via anterolateral mini-thoracotomy, were randomized to axillary cannulation (treatment group) or to femoral cannulation (standard care). Patients were followed up for seven days postoperatively. A CT scan was performed pre-operatively to screen patients for vascular calcifications and to assess the safety of femoral cannulation. The standard of care is femoral artery cannulation, but is performed only in patients without significant vascular calcifications or severe kinking of the iliac arteries and in patients with sufficient vessel diameter. The cannulation is performed via Seldinger's technique, and the vessel closed percutaneously using a plug-based vascular closure device. Only patients without significant vascular calcifications are considered for femoral cannulation, as an increased risk of stroke is assumed. In patients with vascular calcifications, axillary cannulation is the standard of care to avoid these risks. Retrospective studies have hinted that, even in patients without vascular calcifications, there may be a lower stroke risk with axillary cannulation compared to femoral cannulation. We present a protocol for a multi-center randomized trial to investigate this hypothesis. To date, evidence on the best access for peripheral artery cannulation during minimally invasive heart valve surgery has been scarce. Patients may benefit from axillary cannulation for extracorporeal circulation in terms of stroke risk and other neurological and vascular complications, though femoral cannulation is the gold standard. The aim of this study is to determine the risks of peri-operative stroke in a prospective randomized comparison of femoral vs. axillary cannulation.

Open and endovascular reinterventions after Candy Plug false lumen embolization of type B aortic dissection

ObjectiveIn the majority of patients with chronic type B aortic dissection, there is persistent retrograde flow in the false lumen (FL) through distal re-entry tears. Among several endovascular techniques proposed for FL management, the “Candy Plug” (CP) technique has gained acceptance with good early results. The aim of this study is to report the types and outcomes of open and endovascular reinterventions and identify mechanisms of procedure failure as well as other causes for reinterventions. MethodsAll patients with type B aortic dissection submitted to thoracic endovascular aneurysm repair and CP implantation for FL embolization from January 2016 to December 2022 at our institution were included in this study. The preoperative, intraoperative, and postoperative data of the primary intervention and secondary reinterventions, when performed, were prospectively collected and retrospectively analyzed. Preoperative and postoperative computed tomography angiography were also analyzed. ResultsDuring the study period, 33 patients were submitted to thoracic endovascular aneurysm repair and CP implantation. Twenty-three patients (69.7%) showed thoracic FL complete thrombosis with aortic stability or positive remodeling at a mean follow-up of 45 ± 23.1 months. Ten patients (30.3%) underwent aortic reinterventions (male, n = 9; mean age, 60.5 ± 7.6 years). Of these 10 patients, in four patients, complete thrombosis of the FL was never achieved, leading to ongoing perfusion of the FL, defined as “primary failure.” The other six patients underwent reinterventions for different causes: two patients, after initial sealing, showed a progressive enlargement of the abdominal FL leading to distal degeneration. One patient showed proximal degeneration, two patients showed a type II thoracoabdominal aortic aneurysm and CP implantation was used as a planned procedure to reduce the extent of the surgical procedure, and one patient had recurrent, intractable back pain despite complete thrombosis of the FL. Reinterventions were open in five cases and endovascular in five. One in-hospital death (postoperative day 27) after a type II thoracoabdominal aortic aneurysm open repair was recorded. In addition, two cases of delayed spinal cord ischemia after open reintervention were recorded: one resulting in permanent paraplegia and one transitory with complete recovery. ConclusionsThe CP technique was safe and effective; however, a significant rate of aortic-related reintervention was observed. Several mechanisms led to reinterventions either in terms of “primary failure” of the CP or subsequent aneurysmal degeneration. Complex reinterventions were often necessary, with a high rate of major complications in case of open repair. Life-long and closer surveillance might be required in these patients.

SYST-10 ENHANCING THE EFFICACY OF RADIATION THERAPY BY SURGICALLY TARGETED RADIATION-SENSITIZER LOADED FIBRIN GLUE

Abstract Radiation therapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic, relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiation sensitizers (RS) can potentially increase efficacy on tumor cells while maintaining normal tissue toxicity. Clinical trials, employing radiation sensitizers have been done, but so far, the results have been disappointing. An important factor that could account for the low efficacy of RS in clinical trials is the blood–brain barrier (BBB). The basis for this work was the development of a RS direct delivery system (DDS), that bypasses the BBB. This is implemented by the local implantation, into the tumor resection cavity, of RS loaded slow-release fibrin glue. Localized delivery significantly increases the concentration of RS reaching the remaining infiltrative tumor cells in the brain parenchyma, while avoiding systemic side effects. Additionally, the BBB would prevent retrograde flow of the RS into the circulatory system. and the RS is protected from degradation and clearance until locally released. FG has several characteristics that make it well suited for this form of agent delivery. It has been used clinically in surgery for decades, is FDA approved, its lack of toxicity has been clearly proven, it gels rapidly and spontaneously and is easily applied. Radiation protocols utilizing two sensitizers, 5FU and Motexafin-GD, have been optimized in vitro using 3D glioma spheroid models. The results obtained in vitro have been extended to an appropriate in vivo rat brain tumor model. The goal of this project is to improve the therapeutic index of radiation therapy and is therefore clearly aimed at eventually translating to new clinical treatment protocols.

Effect of arteriosclerotic intracranial arterial vessel wall enhancement on downstream collateral flow.

The effect of arteriosclerotic intracranial arterial vessel wall enhancement (IAVWE) on downstream collateral flow found in vessel wall imaging (VWI) is not clear. Regardless of the mechanism underlying IAVWE on VWI, damage to the patient's nervous system caused by IAVWE is likely achieved by affecting downstream cerebral blood flow. The present study aimed to investigate the effect of arteriosclerotic IAVWE on downstream collateral flow. The present study recruited 63 consecutive patients at the Second Hospital of Hebei Medical University from January 2021 to November 2021 with underlying atherosclerotic diseases and unilateral middle cerebral artery (MCA) M1-segment stenosis who underwent an magnetic resonance scan within 3 days of symptom onset. The patients were divided into 4 groups according to IAVWE and the stenosis ratio (Group 1, n = 17; Group 2, n = 19; Group 3, n = 13; Group 4, n = 14), and downstream collateral flow was analyzed using three-dimensional pseudocontinuous arterial spin labeling (3D-pCASL) and RAPID software. The National Institutes of Health Stroke Scale (NIHSS) scores of the patients were also recorded. Two-factor multivariate analysis of variance using Pillai's trace was used as the main statistical method. No statistically significant difference was found in baseline demographic characteristics among the groups. IAVWE, but not the stenosis ratio, had a statistically significant significance on the late-arriving retrograde flow proportion (LARFP), hypoperfusion intensity ratio (HIR), and NIHSS scores ( F = 20.941, P <0.001, Pillai's trace statistic = 0.567). The between-subject effects test showed that IAVWE had a significant effect on the three dependent variables: LARFP ( R2 = 0.088, F = 10.899, P = 0.002), HIR ( R2 = 0.234, F = 29.354, P <0.001), and NIHSS ( R2 = 114.339, F = 33.338, P <0.001). Arteriosclerotic IAVWE significantly reduced downstream collateral flow and affected relevant neurological deficits. It was an independent factor affecting downstream collateral flow and NIHSS scores, which should be a focus of future studies. ChiCTR.org.cn, ChiCTR2100053661.