Orbit image analysis machine learning software can be used for the histological quantification of acute ischemic stroke blood clots

Our aim was to assess the utility of a novel machine learning software (Orbit Image Analysis) in the histological quantification of acute ischemic stroke (AIS) clots. We analyzed 50 AIS blood clots retrieved using mechanical thrombectomy procedures. Following HandE staining, quantification of clot components was performed by two different methods: a pathologist using a reference standard method (Adobe Photoshop CC) and an experienced researcher using Orbit Image Analysis. Following quantification, the clots were categorized into 3 types: RBC dominant (\u3e/=60% RBCs), Mixed and Fibrin dominant ( \u3e /=60% Fibrin). Correlations between clot composition and Hounsfield Units density on Computed Tomography (CT) were assessed. There was a significant correlation between the components of clots as quantified by the Orbit Image Analysis algorithm and the reference standard approach (rho = 0.944**, p \u3c 0.001, n = 150). A significant relationship was found between clot composition (RBC-Rich, Mixed, Fibrin-Rich) and the presence of a Hyperdense artery sign using the algorithmic method (X2(2) = 6.712, p = 0.035*) but not using the reference standard method (X2(2) = 3.924, p = 0.141). Orbit Image Analysis machine learning software can be used for the histological quantification of AIS clots, reproducibly generating composition analyses similar to current reference standard methods

A simplified mesoscale 3D model for characterizing fibrinolysis under flow conditions

One of the routine clinical treatments to eliminate ischemic stroke thrombi is injecting a biochemical product into the patient’s bloodstream, which breaks down the thrombi’s fibrin fibers: intravenous or intravascular thrombolysis. However, this procedure is not without risk for the patient; the worst circumstances can cause a brain hemorrhage or embolism that can be fatal. Improvement in patient management drastically reduced these risks, and patients who benefited from thrombolysis soon after the onset of the stroke have a significantly better 3-month prognosis, but treatment success is highly variable. The causes of this variability remain unclear, and it is likely that some fundamental aspects still require thorough investigations. For that reason, we conducted in vitro flow-driven fibrinolysis experiments to study pure fibrin thrombi breakdown in controlled conditions and observed that the lysis front evolved non-linearly in time. To understand these results, we developed an analytical 1D lysis model in which the thrombus is considered a porous medium. The lytic cascade is reduced to a second-order reaction involving fibrin and a surrogate pro-fibrinolytic agent. The model was able to reproduce the observed lysis evolution under the assumptions of constant fluid velocity and lysis occurring only at the front. For adding complexity, such as clot heterogeneity or complex flow conditions, we propose a 3-dimensional mesoscopic numerical model of blood flow and fibrinolysis, which validates the analytical model’s results. Such a numerical model could help us better understand the spatial evolution of the thrombi breakdown, extract the most relevant physiological parameters to lysis efficiency, and possibly explain the failure of the clinical treatment. These findings suggest that even though real-world fibrinolysis is a complex biological process, a simplified model can recover the main features of lysis evolution.</p

Treatment and Intervention for Opiate Dependence in the United Kingdom:Lessons from Triumph and Failure

The history of opiate treatment in the United Kingdom (UK) since the early 1980s is a rich source of learning about the benefits and pitfalls of drug treatment policy. We present five possible lessons to be learnt about how factors outside the clinic, including government, charities and researchers can influence treatment and outcomes. First, do not let a crisis go to waste. The philosophical shift from abstinence to harm reduction in the 1980s, in response to an HIV outbreak in injecting users, facilitated expansion in addiction services and made a harm reduction approach more acceptable. Second, studies of drug-related deaths can lead to advances in care. By elucidating the pattern of mortality, and designing interventions to address the causes, researchers have improved patient safety in certain contexts, though significant investment in Scotland has not arrested rising mortality. Third, collection of longitudinal data and its use to inform clinical guidelines, as pursued from the mid-1990s, can form an enduring evidence base and shape policy, sometimes in unintended ways. Fourth, beware of the presentation of harm reduction and recovery as in conflict. At the least, this reduces patient choice, and at worst, it has caused some services to be redesigned in a manner that jeopardises patient safety. Fifth, the relationship between the third and state sectors must be carefully nurtured. In the UK, early collaboration has been replaced by competition, driven by changes in funding, to the detriment of service provision

On the Free Energy That Drove Primordial Anabolism

A key problem in understanding the origin of life is to explain the mechanism(s) that led to the spontaneous assembly of molecular building blocks that ultimately resulted in the appearance of macromolecular structures as they are known in modern biochemistry today. An indispensable thermodynamic prerequisite for such a primordial anabolism is the mechanistic coupling to processes that supplied the free energy required. Here I review different sources of free energy and discuss the potential of each form having been involved in the very first anabolic reactions that were fundamental to increase molecular complexity and thus were essential for life

S100b in acute ischemic stroke clots is a biomarker for post-thrombectomy intracranial hemorrhages

Background and purposePost-thrombectomy intracranial hemorrhages (PTIH) are dangerous complications of acute ischemic stroke (AIS) following mechanical thrombectomy. We aimed to investigate if S100b levels in AIS clots removed by mechanical thrombectomy correlated to increased risk of PTIH.MethodsWe analyzed 122 thrombi from 80 AIS patients in the RESTORE Registry of AIS clots, selecting an equal number of patients having been pre-treated or not with rtPA (40 each group). Within each subgroup, 20 patients had developed PTIH and 20 patients showed no signs of hemorrhage. Gross photos of each clot were taken and extracted clot area (ECA) was measured using ImageJ. Immunohistochemistry for S100b was performed and Orbit Image Analysis was used for quantification. Immunofluorescence was performed to investigate co-localization between S100b and T-lymphocytes, neutrophils and macrophages. Chi-square or Kruskal-Wallis test were used for statistical analysis.ResultsPTIH was associated with higher S100b levels in clots (0.33 [0.08–0.85] vs. 0.07 [0.02–0.27] mm2, H1 = 6.021, P = 0.014*), but S100b levels were not significantly affected by acute thrombolytic treatment (P = 0.386). PTIH was also associated with patients having higher NIHSS at admission (20.0 [17.0–23.0] vs. 14.0 [10.5–19.0], H1 = 8.006, P = 0.005) and higher number of passes during thrombectomy (2 [1–4] vs. 1 [1–2.5], H1 = 5.995, P = 0.014*). S100b co-localized with neutrophils, macrophages and with T-lymphocytes in the clots.ConclusionsHigher S100b expression in AIS clots, higher NIHSS at admission and higher number of passes during thrombectomy are all associated with PTIH. Further investigation of S100b expression in AIS clots by neutrophils, macrophages and T-lymphocytes could provide insight into the role of S100b in thromboinflammation

Addressing the impact of non-dependent parental substance misuse upon children. A rapid review of the evidence of prevalence, impact and effective interventions.

This review examines the evidence of the impact of non-dependent parental substance misuse upon children and effective interventions for dependent and non-dependent substance misusing parents. It is intended that the evidence synthesised will be of benefit to practitioners and decision-makers within Local Authorities and their health and third sector partners in responding to the needs of substance misusing parents and their children, particularly those affected by high risky levels of misuse. The term parental substance misuse is used throughout to denote non-dependent levels of alcohol and/or drug misuse. When the source studies examine only alcohol or only drug misuse the terms parental alcohol or parental drug misuse will be used

Is pricing a way to affect share of fruits and vegetables in a diet?

Sahlgrenska Akademin vid Göteborgs universitet Avdelningen för invärtesmedicin och klinisk nutrition Sammanfattning Titel: Är priset ett sätt att påverka mängd frukt och grönsaker i kosten? Författare: Maria Popov Handledare: Heléne Bertéus Forslund Examinator: Ingrid Larsson Linje: Dietistprogrammet, 180/240 hp Typ av arbete: Examensarbete, 15 hp Datum: 2013-05-23 Bakgrund: Intag av frukt och grönsaker (FG) är viktigt för hälsan, bland annat för förekomst av fetma, diabetes och hjärt-kärlsjukdomar. I höginkomstländer är en ökning av FG-intaget önskvärd, då endast en liten del av befolkningen äter rekommenderade mängder, samtidigt som nämnda sjukdomar står för flest fall av ohälsa och död. Förutom generella informationskampanjer eller kostråd till individer finns ekonomiska metoder att påverka vad människor väljer att köpa. Syfte: Att undersöka om olika prissättning har samband till FG-intag eller -inköp. Sökväg: Sökningen gjordes i databaser PubMed, Scopus och Summon med sökord "vegetable consumption", "price/pricing policy" och "food choice" i olika kombinationer. Urvalskriterier: Studierna skulle vara gjorda under tiden efter 2000-talet på minst 18 år gamla personer i Nordamerika, Australien eller Europa, och undersöka prisändringar och FG-inköp. Vissa interventionsplatser och undersökta parametrar exkluderades. Datainsamling och analys: Elva artiklar valdes ut, varav fyra uppfyllde alla kriterier. De fyra granskades enligt SBU:s granskningsmallar och evidensstyrkan bedömdes enligt GU:s formulär. Resultat: En tvärsnittsstudie visade att högre FG-priser var associerade med lägre FG-intag, men förklarade inte ett möjligt orsakssamband. De tre resterande studierna var väldesignade RCT med verklighetstrogna köpsituationer och blandade grupper, men grupperna var små. Interventionen var olika stora rabatter på FG och resultaten i alla studier visade med signifikans att interventionsgrupperna köpte mer än kontroller. Underlaget bedömdes ha måttlig evidensstyrka. Slutsats: Resultaten är samstämmiga och signifikanta: prissänkning leder till större inköp av FG. Men det krävs fler studier på större grupper. Det finns dessutom andra faktorer som komplicerar bilden, till exempel köpt total kalorimängd och socioekonomisk tillhörighet.Sahlgrenska Academy at University of Gothenburg Department of Internal Medicine and Clinical Nutrition Abstract Title: Is pricing a way to affect share of fruits and vegetables in a diet? Author: Maria Popov Supervisor: Heléne Bertéus Forslund Examiner: Ingrid Larsson Programme: Dietician study programme, 180/240 ECTS Type of paper: Examination paper, 15 hp Date: May 23, 2013 Background: Fruits and vegetables (FV) are important for health, including occurrence of diabetes, obesity and cardiovascular diseases. Said diseases cause most cases of illness and death in high-income countries. Only a small part of the population achieves the FV-intake goal, so a higher FV-intake is desirable. Besides general information campaigns there is another method of influencing what people might buy. Objective: To examine whether different pricing is connected to FV-intake or –purchase. Search strategy: Databases PubMed, Scopus and Summon were searched with “vegetable consumption", "price/pricing policy" and "food choice” in different combinations. Selection criteria: Studies performed after year 2000 on at least 18 years old persons from North America, Europe or Australia, examining changes in FV-price and -purchase. Some additional parameters were excluded. Data collection and analysis: Eleven articles were selected, whereof four met all the criteria. They were reviewed and the evidence was compiled according to the certain templates. Main results: One cross-sectional study showed an association between higher FV-prices and lower FV-intake, but it didn’t explain any causation. Three RCTs with good design had small assorted groups who participated in realistic shopping situations. The intervention was different price discounts on FV. The studies showed consistent significant results of lower prices leading to higher FV-purchase. Evidence strength was deemed to be moderate. Conclusions: The lowering of prices on FV might increase FV-purchase. Yet the evidence is not strong enough and more research with a larger number of participants is needed. There are further additional factors which may complicate the picture, such as total amount of purchased calories or socioeconomic belonging

Systematic Review on Endovascular Access to Intracranial Arteries for Mechanical Thrombectomy in Acute Ischemic Stroke.

PURPOSE In acute ischemic stroke for large vessel occlusions, delayed or failed access to intracranial occlusions has a negative impact on procedural and clinical outcomes. The aim of this review is to identify and quantify access failures and challenges in mechanical thrombectomy. METHODS A systematic literature review of PubMed and Scopus databases from January 2014 to October 2020 was performed. Articles reporting consecutive patients were used to calculate a crude failure rate of femoral and alternative accesses. RESULTS A total of 50 articles met the inclusion criteria, totalling 12,838 interventions. Failure to access the occlusion through transfemoral access occurred in 4.4% of patients, most commonly due to challenging supra-aortic vessel anatomy, decreasing to 3.6% when all alternative access routes were attempted. Failed access from alternative routes (direct carotid, radial and brachial approaches) attempted first-line or after failed femoral attempt were reported in 7.3% of patients. The occurrence rate of potentially challenging features (anatomical, diseases or others) ranged from 4.7% to 47.4%, primarily impacting the access time, procedure time, recanalization and clinical outcomes. CONCLUSION Failure to access the occlusion is a significant contributor to failed recanalization, regardless of access routes. Challenging, but eventually successful access is also a relevant factor in procedural and clinical outcomes; however challenging access requires a universal definition to enable quantification, so that methods for procedural optimization can be critically assessed

Mechanical behavior of in vitro blood clots and the implications for acute ischemic stroke treatment

BACKGROUND: Clot mechanical properties are influenced by composition and the arrangement of components within the clot. This work investigates the effects of platelet-driven contraction on blood clot microstructure and mechanical behavior, and provides insight into some implications for mechanical thrombectomy. METHODS: Platelet-contracted clot analogues (PCCs) and non-contracted clot analogues (NCCs) were prepared from blood mixtures of various hematocrits (%H), that is, the volume percentage of red blood cells (RBCs) in the mixture. Mechanical testing was performed to compare the behavior of the analogues with previously tested human thromboemboli. Scanning electron microscopy and histology investigated the clot microstructure and composition. The association between clot properties and their behavior during mechanical behavior was also investigated. RESULTS: Overall, PCCs were found to be stiffer than NCCs, across all hematocrits. PCCs with a low %H resisted complete ingestion via contact aspiration alone or complete retrieval with stent-retrievers. PCCs with a higher %H and all NCCs were fully retrievable, although the likelihood of fragmentation was increased in clots with a greater %H. Histologically, there was little difference in the RBC and fibrin content between PCCs and NCCs with the same %H. However, the microstructure of the two groups differed significantly. CONCLUSION: A selection of repeatable clot analogues with a range of mechanical properties have been developed for in vitro modeling of acute ischemic stroke. Platelet contraction significantly affects clot volume and microstructure, and in turn clot stiffness. The significant difference in mechanical properties and microstructure, but without an appreciable difference in histology, implies that histological studies of explanted human clots alone may not prove to be predictive of the mechanical behavior of the clots in thrombectomy

Characterization of strut indentation during mechanical thrombectomy in acute ischemic stroke clot analogs.

BACKGROUND Although it is common practice to wait for an 'embedding time' during mechanical thrombectomy (MT) to allow strut integration of a stentriever device into an occluding thromboembolic clot, there is a scarcity of evidence demonstrating the value or optimal timing for the wide range of thrombus compositions. This work characterizes the behavior of clot analogs of varying fibrin and cellular compositions subject to indentation forces and embedding times representative of those imparted by a stentriever during MT. The purpose of this study is to quantify the effect of thrombus composition on device strut embedding, and to examine the precise nature of clot integration into a stentriever device at a microstructural level. METHOD Clot analogs with 0% (varying densities), 5%, 40%, and 80% red blood cell (RBC) content were created using ovine blood. Clot indentation behavior during an initial load application (loading phase) followed by a 5-min embedding time (creep phase) was analyzed using a mechanical tester under physiologically relevant conditions. The mechanism of strut integration was examined using micro-computed tomography (µCT) with an EmboTrap MT device (Cerenovus, Galway, Ireland) deployed in each clot type. Microstructural clot characteristics were identified using scanning electron microscopy (SEM). RESULTS Compressive clot stiffness measured during the initial loading phase was shown to be lowest in RBC-rich clots, with a corresponding greatest maximum indentation depth. Meanwhile, additional depth achieved during the simulated embedding time was most pronounced in fibrin-rich clots. SEM imaging identified variations in microstructural mechanisms (fibrin stretching vs rupturing) which was dependent on fibrin:cellular content, while µCT analysis demonstrated the mechanism of strut integration was predominantly the formation of surface undulations rather than clot penetration. CONCLUSIONS Disparities in indentation behavior between clot analogs were attributed to varying microstructural features induced by the cellular:fibrin content. Greater indentation was identified in clots with higher RBC content, but with an increased level of fibrin rupture, suggesting an increased propensity for fragmentation. Additional embedding time improves strut integration, especially in fibrin-rich clots, through the mechanism of fibrin stretching with the majority of additional integration occurring after 3 mins. The level of thrombus incorporation into the EmboTrap MT device (Cerenovus, Galway, Ireland) was primarily influenced by the stentriever design, with increased integration in regions of open architecture