White Clot Research Articles

Abstract TP214: In-Silico versus In-Vitro Evaluation of a New Stent-Retriever Design: A Novel Approach to Pre-Clinical Device Development

Introduction: In-vitro evaluation (analysis in a bench top flow model) is the gold standard for pre-clinical investigation of devices being developed for endovascular thrombectomy (EVT). In-silico evaluation (computer simulated analysis in a virtual stroke model) has the potential to test and optimize large number of stent-retriever design variations in a relatively time and cost-effective manner. We aim to validate the utility of in-silico evaluation when compared with in-vitro evaluation for the SuperNova Stent-retriever. Methods: In-silico analysis was performed using a virtual thrombectomy model, built using data from a fine-grained finite-element model, to estimate the probability of successful recanalization. Neurovascular anatomy of the virtual model was built based on digital subtraction angiography of an in-vitro model (Sim Agility, Mentice, Inc). Gravity Medical Technology’s SuperNova Stent-retriever was the device under investigation. Multiple thrombectomy scenarios were defined and validation analysis was performed. Results: We defined multiple thrombectomy scenarios including 1 cm red blood clot in M1 artery, 2 cm bifurcation M1-M2 red blood clot (Y-shaped clot), 1 cm white blood clot in M1 artery, and 1 cm white blood clot in superior M2 artery. The figure below demonstrates a pictorial representation of the first scenario- 1 cm red blood clot in M1 artery followed by mechanical thrombectomy simulation using the SuperNova stent-retriever. Per our in-vitro analysis (10 thrombectomy experiments), the rate of first pass effect and the rate of complete recanalization after a maximum of 3 passes using SuperNova stent-retriever was 50% and 90%, respectively. Preliminary data suggests 97% concordance. Conclusion: In-silico analysis has the potential to improve and expedite pre-clinical thrombectomy device development. Further studies are required to better understand the scope and potential of this technology.

Abstract 249: In‐silico Versus In‐Vitro Evaluation of a New Stent‐Retriever Design: A Novel Approach to Pre‐clinical Development

Introduction In‐vitro evaluation (analysis in a bench top flow model) is the gold standard and a regulatory requirement for pre‐clinical investigation of devices being developed for endovascular thrombectomy (EVT). In‐silico evaluation (computer simulated analysis in a virtual stroke model) has the potential to test and optimize large number of stent‐retriever design variations in a relatively time and cost‐effective manner. Further, new design concepts can be tested across multiple anatomical scenarios. We aim to validate the utility of in‐silico evaluation when compared with in‐vitro evaluation for the SuperNova Stent‐retriever. Methods In‐silico analysis was performed using a virtual thrombectomy model, built using data from a fine‐grained finite‐element model, to estimate the probability of successful recanalization and emboli in new/distal territory. Neurovascular anatomy of the virtual model was built based on digital subtraction angiography of an in‐vitro model (Sim Agility, Mentice, Inc). Gravity Medical Technology’s SuperNova Stent‐retriever was the device under investigation‐ physical device for in‐vitro analysis and virtual replica for in‐silico analysis (built using finite element analysis incorporating various physical metrics of the stent‐retriever). Experiments performed for in‐vitro analysis were replicated for in‐silico analysis. Multiple thrombectomy scenarios were defined and validation analysis was performed. Data was analyzed using SPSS 23 (IBM, Armonk, NY) Results We defined multiple thrombectomy scenarios including 1 cm red blood clot in M1 artery, 2 cm bifurcation M1‐M2 red blood clot (Y‐shaped clot), 1 cm white blood clot in M1 artery, and 1 cm white blood clot in superior M2 artery. The figure below demonstrates a pictorial representation of the first scenario‐ 1 cm red blood clot in M1 artery followed by mechanical thrombectomy simulation using the SuperNova stent‐retriever. Per our in‐vitro analysis (10 thrombectomy experiments), the rate of first pass effect and the rate of complete recanalization after a maximum of 3 passes using SuperNova stent‐retriever was 50% and 90%, respectively. Complete data from in‐silico analysis is being generated and will be presented at the conference. Preliminary data suggests high degree of concordance. Conclusion In‐silico analysis has the potential to improve and expedite pre‐clinical thrombectomy device development. Further studies are required to better understand the scope and potential of this technology.

MR microscopy to assess clot composition following mechanical thrombectomy predicts recanalization and clinical outcome

BackgroundMechanical thrombectomy (MT) is the standard of care for patients with a stroke and large vessel occlusion. Clot composition is not routinely assessed in clinical practice as no specific diagnostic...

Efficacy of a Homeopathic Complex (Masta-forte+Actino Cure) and Antibiotics in Treatment of Bovine Clinical Mastitis

The present study was aimed to treat bovine mastitis with homeopathic remedies Masta-forte+Actino Cure along with antibiotic therapy. A total 160 animals suffering from clinical bovine mastitis were used for study. All the animals were categories according to their physical condition of udder as redness, oedematous, fibrosis, bloody milk, white clot in milk, and watery milk. All the animals were group in to two groups A (n=80) and (n=80). All the animals were basically treated with higher antibiotics. In group A animal were treated with homeopathic medicine (2 ml. Masta-Forte+2 ml Actino Cure) orally with syringe bid for 20 days along with antibiotic therapy were as group B only treated with antibiotic therapy. Out of 160 animals 124 animals recovers with reduce normal milk. Among group A animals were recovery rate 90.00% (N=80) where as group B recovery rate 65.00% (n=80) animal. In group A animals having no fibrosis, where in group B animals having affected quarters were hard and fibrotic in nature. Homoeopathy drugs may be used as alternate therapy in organic farming system might be one of the preferred treatment methods.

Abstract 99: Clot Composition And Reperfusion Outcomes In 1430 Mechanical Thrombectomy Patients: Analysis Of The Stroke Thromboembolism Registry Of Imaging And Pathology

Background: Understanding clot composition may allow for better technical planning and improved outcomes in mechanical thrombectomy (MT). We sought to correlate clot composition with reperfusion outcomes in MT. Methods: Clinical, imaging, and clot data from patients enrolled in the STRIP Registry from September 2016 to September 2020 were analyzed. Samples were fixed in 10% phosphate-buffered formalin and stained with hematoxylin and eosin and Martius Scarlett Blue. Percent composition, richness, and gross appearance were evaluated. Outcome measures included the rate of First-Pass Effect (mTICI2c/3, FPE) and the number of device passes. Results: A total of 1430 patients (mean age, 68.4±13.5years; median [IQR] baseline NIHSS,17.2 [10.5-23]; IV-tPA use, 36%; Stent-Retrievers [SR], 27%; Contact Aspiration [CA], 27%; Combined SR + CA, 43%) were included. The median [IQR] number of passes was 1 [1-2]. FPE was achieved in 39.3% of the cases. There was no association between percent histological composition or clot richness and FPE in the overall population. However, the combined technique resulted in lower FPE rates for RBC-rich (P<0.0001), platelet-rich (P=0.003), and mixed (P<0.0001) clots. Fibrin-rich and platelet-rich clots required a higher number of passes compared to RBC-rich and mixed clots (median, 2 and 1.5 vs.1, respectively, P=0.02). CA displayed a trend towards a higher number of passes with fibrin-rich clots (2 vs.1, P=0.12). By gross appearance, mixed/heterogeneous clots had lower FPE rates than red and white clots. Conclusion: Despite the lack of correlation between clot histology and FPE in the overall population, our study adds to the growing body of evidence supporting the notion that clot composition influences reperfusion treatment strategy outcomes. Additional studies are needed.

Theme and Variation: Structuring Thrombus Formation from Jugular/Arterial Puncture Wounds to Occlusive Clots in a Mouse Model

Hemostasis in veins and arteries has been assumed to be different processes, e.g., white vs. red clots. We took the unbiased experimental approaches of 3D EM across full clot volumes and high-resolution heat mapping of platelet activation state to probe for commonalities and variations using controlled mouse models. Remarkably, the thrombi formed, 5 min post-puncture, in the jugular vein and femoral artery showed considerable consistency in organization. There were vaulted cavities within the puncture wound and apparent extravascular capping of the puncture hole to produce bleeding cessation. Notable differences in the venous thrombi were a greater activation of platelets lining the surfaces of the vaulted columns, an outcome that we attribute to lowr flow rates resulting in the longer retention of activating signals, and in the "hanging drop” nature of the arterial thrombi anchored to the extrema with an outward, extravascular bulge of the thrombus. We attribute these variations to arterial vessel wall properties and higher flow rates. At 20 min post-puncture, the intravascular crown of the venous wound thrombi was enriched in loosely adherent platelets in a low activation state. Similarly, the outer portion of the intravascular arterial thrombus was rich in low activation platelets including obviously discoid platelets. Strikingly, the arterial thrombus was subject to rebleeding and ate 20 min displayed fractured extravascular features indicative of an unstable clot. The puncture wound thrombi form in the relatively small volume of the immediate wound site. In contrast, occlusive clots fill the cylindrical volume of the vessel. To us, the overall structure of the wound thrombi suggested a predictive hypothesis for induced occlusive clotting. We propose that 1) the exposed intima lining the arterial vessel wall provides a cylindrical substratum for the generation of a tightly adherent platelet layer anchoring the forming clot and 2) the central volume of the clot resembles the intravascular crown of the puncture wound thrombus. Hence, the prediction of a central volume of the occlusive clot consisting of loosely adherent to discoid shaped platelets. That was result found for FeCl3 induced femoral clots by wide area-TEM (WA-TEM) i.e., a central volume rich in discoid shaped platelet and few red blood cells were trapped in the tightly adherent rim of the clot.. Using sequential block face SEM, we have begun to image and volume render carotid clots by sequential block face SEM. Analysis of 5,000 sequential images from the downstream half of the carotid clot, showed that the structure gradually tapered in a conical manner and contains few red blood cells. We propose that there are indeed organizational themes shared by the puncture wound thrombus in venous or arterial settings and the occlusive clot in which vascular damage is restricted to the endothelial cell layer. Work was supported by NIH grants (BS) R01 HL155519 and P20 HL146373 (Joel Bennett, principal investigator), R35 HL150118 (SWW) and by intramural NIBIB research program (RDL). An occlusive FeCl3 clot in the carotid artery of a C57BL/6 mouse imaged by sequential block face SEM over a length of 1.2 millimeters.A. cross section of the clot 200 microns in from the mid-occlusion starting point for sectioning. B. Zoom of A) to illustrate the low level of trapped red blood cells within the clot. C. cross section of the clot 900 microns in from the starting point showing how the clot has now tapered down and fills a minor portion of the artery. D. Rendering of 1.2 millimeters of the clot (blue), vessel wall (green) and in gray a single plane image. Flow was from left to right. Note that the clot progressively tapers to a point in the downstream direction.Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Towards rainbow portable Cytophone with laser diodes for global disease diagnostics

In vivo, Cytophone has demonstrated the capability for the early diagnosis of cancer, infection, and cardiovascular disorders through photoacoustic detection of circulating disease markers directly in the bloodstream with an unprecedented 1,000-fold improvement in sensitivity. Nevertheless, a Cytophone with higher specificity and portability is urgently needed. Here, we introduce a novel Cytophone platform that integrates a miniature multispectral laser diode array, time-color coding, and high-speed time-resolved signal processing. Using two-color (808 nm/915 nm) laser diodes, we demonstrated spectral identification of white and red clots, melanoma cells, and hemozoin in malaria-infected erythrocytes against a blood background and artifacts. Data from a Plasmodium yoelii murine model and cultured human P. falciparum were verified in vitro with confocal photothermal and fluorescent microscopy. With these techniques, we detected infected cells within 4 h after invasion, which makes hemozoin promising as a spectrally selective marker at the earliest stages of malaria progression. Along with the findings from our previous application of Cytophone with conventional lasers for the diagnosis of melanoma, bacteremia, sickle anemia, thrombosis, stroke, and abnormal hemoglobin forms, this current finding suggests the potential for the development of a portable rainbow Cytophone with multispectral laser diodes for the identification of these and other diseases.

MicroCT Can Characterize Clots Retrieved With Mechanical Thrombectomy From Acute Ischemic Stroke Patients-A Preliminary Report.

BackgroundCharacterization of the clot occluding the arteries in acute ischemic stroke received ample attention, in terms of elucidating the relationship between the clot composition, its etiology and its amenability for pharmacological treatment and mechanical thrombectomy approaches. Traditional analytical techniques such as conventional 2D histopathology or electron microscopy sample only small parts of the clot. Visualization and analysis in 3D are necessary to depict and comprehend the overall organization of the clot. The aim of this study is to investigate the potential of microCT for characterizing the clot composition, structure, and organization.MethodsIn a pilot study, we analyzed with microCT clots retrieved from 14 patients with acute ischemic stroke. The following parameters were analyzed: overall clot density, clot segmentation with various density thresholds, clot volume.ResultsOur findings show that human clots are heterogeneous in terms of CT intra-clot density distribution. After fixation in formalin, the clots display a shift toward negative values. On average, we found the mean HU values of red clots retrieved from patients to be −153 HU, with SD = 23.8 HU, for the intermediate clots retrieved from patients −193 HU, SD = 23.7 HU, and for the white clots retrieved from patients −229 HU, SD = 64.8 HU.ConclusionOur study shows that volumetric and density analysis of the clot opens new perspectives for clot characterization and for a better understanding of thrombus structure and composition.

Abstract TP144: Extracellular Vesicles Derived From Stroke Patient Clots Impair Cerebral Endothelial Cell Function

Introduction: Most patients undergoing thrombectomy fail for full reperfusion. The present study tested whether small extracellular vesicles (sEVs) from stroke patient clots impair cerebral endothelial cell (CEC) function, which may contribute to dysfunction of downstream CECs, leading to reduction of cerebral tissue perfusion. Methods: Per IRB-approved protocol, clots were collected from 60 patients (30 males) with acute ischemic stroke subjected to thrombectomy. Red and white clots were determined by immunochemistry. Clot-sEVs were isolated and characterized using ultracentrifugation, size distribution, and Western blot. The effects of clot-sEVs on human CEC (hCEC) permeability and proteins were measured using trans-endothelial assay and trans-endothelial electrical resistance (TEER) and Western blot, respectively. Nystatin, an inhibitor of caveolin-dependent endocytosis, was employed to study hCEC uptake of clot-sEVs. Results: Clot-sEVs had a mean size of 73±2nm. Cellular source analysis of clot-sEVs revealed that 22%, 30%, and 44% of sEVs from red clots and 28%, 28%, and 52% of sEVs from white clots were from neutrophils, endothelial cells, and platelets, respectively. Compared to sEVs derived from donor plasma (plasma-sEVs), treatment of hCECs with clot-sEVs significantly increased cell permeability (227% vs 100% of plasma-sEVs) and reduced TEER (66.6ω.cm 2 vs 87.3ω.cm 2 ). Clot-sEVs significantly increased pro-inflammatory and pro-coagulation proteins in the hCECs including ICAM1, VCAM1, TNF-a, HMBG1, tissue factor, and significantly reduced tight junction proteins ZO-1 and Claudin-5. The effects of white clot-sEVs on hCEC dysfunction were greater than red clot-sEVs. Nystatin significantly reduced hCEC uptake of clot-sEV from 232% to 142% and the clot-sEV-increased permeability. Moreover, Pearson correlation showed that the severity of clot-sEV impaired hCEC function was significantly correlated with final TICI scores of the individual patients (permeability vs TICI, r=-0.3348, p=0.02; TEER vs TICI, r=0,3666, p=0.01). Conclusion: Clot-sEVs contribute to hCEC dysfunction by augmenting pro-inflammatory and pro-coagulation proteins. Blocking uptake of clot-sEVs by recipient cells may improve patient outcomes.

Direct aspiration through a balloon guide catheter can augment vessel wall injury

AbstractWe report a 75‐year‐old woman with extracranial internal carotid artery occlusion treated with neurointervention. The patient presented with tandem lesions for which mechanical thrombectomy was performed. Retrieval of massive white clots and endothelial tissue by forceful manual aspiration via a balloon guiding catheter after angioplasty can be indicative of augmentation of vessel wall injury.

Global Thrombosis Test: Occlusion by Coagulation or SIPA?

The global thrombosis test (GTT) is a point of care device that tests thrombotic and thrombolytic status. The device exposes whole blood flow to a combination of both high and low shear stress past and between ball bearings potentially causing thrombin and fibrin formation. The question arises as to whether thrombosis in the GTT is dominated by coagulation-triggered red clot or high shear-induced white clot. We investigated the nature of the thrombus formed in the GTT, the device efficacy, human factors use, and limitations. The GTT formed clots that were histologically fibrin-rich with trapped red blood cells. The occlusion time (OT) was more consistent with coagulation than high shear white clot and was strongly lengthened by heparin and citrate, two common anticoagulants. The clot was lysed by tissue plasminogen activator (tPA), also consistent with a fibrin-rich red clot. Changing the bead to a collagen-coated surface and eliminating the low shear zone between the beads induced a rapid OT consistent with a platelet-rich thrombus that was relatively resistant to heparin or tPA. The evidence points to the GTT as occluding primarily due to fibrin-rich red clot from coagulation rather than high shear platelet aggregation and occlusion associated with arterial thrombosis.

Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC).

The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N'-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.

Absence of susceptibility vessel sign is associated with aspiration-resistant fibrin/platelet-rich thrombi.

The composition of the thrombus influences its retrievability by mechanical thrombectomy. Our study aimed to report on thrombi resistant to aspiration, regarding susceptibility vessel sign and histologic composition. This observational study was based on a prospective database of acute anterior circulation ischemic strokes treated by mechanical thrombectomy. Endovascular first-line strategy was aspiration and in case of failure, combined therapy-rescue was performed. The positivity of susceptibility vessel sign (SVS+) or its negativity (SVS-) was assessed on T2* sequences. The thrombus composition was analyzed with hematoxylin eosin staining. Histological analysis was performed on 102 clots. Thrombi with SVS- were significantly richer in fibrin/platelets, p = 0.04. Out of 210 mechanical thrombectomy, aspiration first pass strategy was performed in 131/210 (62%) patients. Combined therapy-rescue was needed in 37% of aspiration first pass strategy cases (n = 131). Clots retrieved combined therapy-rescue were richer in fibrin/platelets 63.9% versus 50.8% for aspiration first pass strategy, p = 0.03. Logistic regression analysis showed that fibrin/platelet-poor clots (<60%) were significantly more likely to be recanalized by aspiration first pass strategy compared to fibrin/platelet-rich clots (>60%) that were more likely recanalized by combined therapy-rescue after aspiration first pass strategy failure (OR = 3.5; 95% CI = 1.2-10.8; p = 0.0054). Our results confirm that SVS- clots are rich in fibrin/platelets and suggest that these "white clots" are less likely to be retrieved by aspiration alone and more often require the use of combined therapy.

Choosing an Effective and Safe Direct Aspiration Setup for Tortuous Anatomy in Acute Ischemic Stroke: In vitro Study in a Physiological Flow Model.

A direct aspiration first pass technique (ADAPT) is an effective thrombectomy option in patients with acute ischemic stroke. Balloon guide catheters (BGC) seem to improve the efficacy of stent retrievers and ADAPT. The last generation 6F aspiration catheters require 9F BGCs, which are rigid devices that are challenging to position in a tortuous anatomy. In this experimental study the efficacy of 6F ADAPT alone and 5F ADAPT combined with 8F BGC was evaluated. Either a fibrin rich (white) clot or an RBC rich (red) clot was placed in the M1 segment of a transparent silicon phantom. Physiological hemodynamic conditions were maintained. The clots were retrieved by 6F aspiration catheter via 8F long sheath or 5F aspiration catheter via a flexible 8F BGC. Thrombectomy was performed under direct visual control. The primary endpoints were the number of passes and the number of distal emboli. Ten experiments were made with each clot model and thrombectomy technique (n = 40). Full recanalization could be achieved in every experiment. First pass mTICI 3 could be achieved by 6F ADAPT in 80 % of red clots and 90 % of white clots. Distal emboli were caused in 10 % and 20 %, respectively. When using 5F ADAPT combined with BGC, a first pass mTICI 3 rate of 90 % in red clots and 100 % in white clots could be achieved. A 10 % rate of distal emboli occurred in both groups. In almost all experiments (both techniques), the thrombi clogged the aspiration catheter. No statistically significant differences could be found between the techniques and clot models. 6F ADAPT without BGC was as effective as 5FADAPT combined with a flexible 8F BGC, with both techniques showing high first-pass recanalization rates and low distal emboli rates. Especially in the case of a tortuous anatomy, these setups should be considered as alternatives to a rigid 9F BGC. The thrombus compositions seemed to be irrelevant in this setting. · 6F ADAPT with no BGC and 5F ADAPT with BGC were very effective and performed equally.. · Both techniques should be considered in tortuous anatomy.. · In this setting the clot composition showed no effect on the recanalization rate.. · Madjidyar J, Nerkada L, Larsen N et al. Choosing an Effective and Safe Direct Aspiration Setup for Tortuous Anatomy in Acute Ischemic Stroke: In vitro Study in a Physiological Flow Model. Fortschr Röntgenstr 2021; 193: 544 - 550.

High-speed visualization of ingested, ejected, adherent, and disintegrated thrombus in contemporary ventricular assist devices.

Biocompatibility of ventricular assist devices (VADs) has been steadily improving, yet the rate of neurological events remains unacceptably high. Recent speculation for elevated stroke rates centers on ingestion of thrombi originating upstream of the pump, such as in the ventricle or left atrial appendage. These thrombi may be ejected by the VAD or become deposited within the blood flow pathway, presenting serious complications to the patient. This study was performed to visualize and quantify the degree of disruption, adherence, and disintegration of thrombi that are ingested by the three most implanted VADs: the HeartMate II, HeartMate 3, and HVAD. Clot analogs of varying microstructure compositions (red, white) and sizes (0.5, 1, 2cm3 ) were synthesized in vitro based on clinical explant data. These were introduced individually into an in vitro flow loop with a transparent replica of the HMII, HM3, and HVAD operated at nominal steady flow (2.3-4.0L/min). High-speed videography (up to 10000fps) revealed the ingestion, disruption, ejection, and adherence of thrombus fragments. Thromboemboli of varying compositions and sizes were observed mechanically attaching to components in all 3 VAD models. In some instances, ingested thrombi physically obstructed portions of the blood flow path; 18% (3 of 17 total) of red thrombi adhered to the inflow straightener of the transparent HMII. In the HVAD model, fewer than 4% of clots were adherent or trapped within the pump, irrespective of microstructure or initial volume. In comparison, 100% (4 of 4 total) of 1-cm3 white (fibrin) clots became lodged within the transparent HM3 while, in contrast, less than 5% of macerated red clots (3 of 63 total) of the same volume were adherent inside the pump. A significant proportion of ingested thrombi were macerated into infinitesimal fragments; 84% and 74% of 2-cm3 red thrombi in the HVAD and HM3 models, respectively, were found to have disintegrated upon ingestion. However, large emboli were also discharged from both centrifugal VADs; these fragments, ranging from 0.01 to 0.29 cm3 regardless of microstructure and original volume, may be capable of occluding an intracranial vessel. Therefore, ingested thrombus may explain, in part, elevated stroke rates in contemporary blood pumps in the absence of adherent pump thrombosis.

Sa1264 USUAL VS MODIFIED EBL TECHNIQUE IN ACUTE VARICEAL BLEEDING

Endoscopic band ligation (EBL) is used for variceal bleeding control, despite improvements in therapy, the mortality related to variceal hemorrhage remains high. Other authors recommend initiate banding in the most distal portion of the esophagus near the GE junction (usual technique). However, some experts suggest targeting bleeding stigmata (white clot) first (modified technique). To our knowledge, there are no comparative studies between EBL approaches. This study was aimed to compare the bleeding events during the endoscopy between two EBL techniques procedures in patients with bleeding stigmata. Objectives: Compare bleeding rates, band dislodgments, and endotracheal tube placements (ETP) during endoscopic procedures with two different approaches. This was an observational ambispective, single-center study. We enrolled consecutive patients (>18 y) managed from December 2016 to September 2019, with bleeding stigmata or active bleeding assessed with upper endoscopy in our institution. We defined bleeding events during the endoscopy if they occurred after the passage of the scope by the stigma or the esophagus, this was unequivocally seen on video. A total of 98 patients were included, 57 (58.2%) patients were treated with the usual technique and 41 (41.8%) with the modified approach, 26 women, and 72 men were included, with an average of 52.3 years. The most frequent etiology was alcohol (58.2%) and 25.5% of the procedures were performed under ET. The usual technique was used in 58.2% of the patients and the modified one in 41.8%. Regarding the primary objective, a difference of 14.3% and 2.0% was found (p = 0.012). Only one band dislodgment was recorded. We observed 7 ETP with the usual and only 1 with the modified technique. Less bleeding and orotracheal intubations were found during endoscopic procedures with the modified technique. This study suggests that initiation of banding of the culprit lesion is safe and improves visualization in terms of less bleeding events during endoscopy.

Physicochemical and techno‐functional properties of acid‐aided pH‐shifted protein isolate from over‐salted duck egg (Anas platyrhucus) albumen

SummaryHere, potential physicochemical and techno‐functional properties of the albumen protein recovered from over‐salted albumen by an effective acid‐aided pH‐shift process (POA) were tested in comparison with the fresh albumen (FA) and albumen protein recovered from fresh albumen by acid‐aided pH‐shift process (PFA). POA contained 66.73% protein and 11.30% sodium (dry basis). Surface hydrophobicities of PFA and POA were higher than FA (P &lt; 0.05), whereas the reactive sulfhydryl content of FA was higher than PFA and POA (P &lt; 0.05). PFA had the highest whiteness followed by POA and FA, respectively. Single endothermic peak in DSC thermogram was found at 86.86, 89.67 and 98.96 °C for FA, PFA and POA, respectively. Long‐term salting impaired the solubility, viscosity, emulsifying activity and gelation but not for foaming of albumen protein isolate. FA can be softly gelled with continuously packed structure, whereas PFA and POA underwent agglutination to form white clot suspension with spongy network.

Association between acute ischemic stroke etiology and macroscopic aspect of retrieved clots: is a clot’s color a warning light for underlying pathologies?

BackgroundFew case reports have considered the chromatic aspect of retrieved clots and the possible association with their underlying etiology.ObjectiveThe aim of our study was to analyze the frequency of the...

Noninvasive label-free detection of circulating white and red blood clots in deep vessels with a focused photoacoustic probe.

Blood clotting is a serious clinical complication of many medical procedures and disorders including surgery, catheterization, transplantation, extracorporeal circuits, infections, and cancer. This complication leads to high patient morbidity and mortality due to clot-induced pulmonary embolism, stroke, and in some cases heart attack. Despite the clear medical significance, little progress has been made in developing the methods for detection of circulating blood clots (CBCs), also called emboli. We recently demonstrated the application of in vivo photoacoustic (PA) flow cytometry (PAFC) with unfocused ultrasound transducers for detection of CBCs in small vessels in a mouse model. In the current study, we extend applicability of PAFC for detection of CBCs in relatively large (1.5-2 mm) and deep (up to 5-6 mm) blood vessels in rat and rabbit models using a high pulse rate 1064 nm laser and focused ultrasound transducer with a central hole for an optic fiber. Employing phantoms and chemical activation of clotting, we demonstrated PA identification of white, red, and mixed CBCs producing negative, positive, and mixed PA contrast in blood background, respectively. We confirmed that PAFC can detect both red and white CBCs induced by microsurgical procedures, such as a needle or catheter insertion, as well as stroke modeled by injection of artificial clots. Our results show great potential for a PAFC diagnostic platform with a wearable PA fiber probe for diagnosis of thrombosis and embolism in vivo that is impossible with existing techniques.

Dynamic blood flow phantom with negative and positive photoacoustic contrasts.

In vivo photoacoustic (PA) flow cytometry (PAFC) has great clinical potential for early, noninvasive diagnosis of cancer, infections (e.g., malaria and bacteremia), sickle anemia, and cardiovascular disorders, including stroke prevention through detection of circulating white clots with negative PA contrast. For clinical applications, this diagnostic platform still requires optimization and calibration. We have already demonstrated that this need can be partially addressed by in vivo examination of large mouse blood vessels, which are similar to human vessels used. Here, we present an alternative method for PAFC optimization that utilizes novel, clinically relevant phantoms resembling pigmented skin, tissue, vessels, and flowing blood. This phantom consists of a scattering-absorbing medium with a melanin layer and plastic tube with flowing beads to model light-absorbing red blood cells (RBCs) and circulating tumor cells (CTCs), as well as transparent beads to model white blood cells and clots. Using a laser diode, we demonstrated the extraordinary ability of PAFC to dynamically detect fast-moving mimic CTCs with positive PA contrast and white clots with negative PA contrast in an RBC background. Time-resolved detection of the delayed PA signals from blood vessels demonstrated complete suppression of the PA background from the modeled pigmented skin. This novel, medically relevant, dynamic blood flow phantom can be used to calibrate and maintain PAFC parameters for routine clinical applications.