Thrombotic Embolism Research Articles

Insights from preventability assessments across 42 state and city maternal mortality reviews in the United States

BackgroundThe rising trend in maternal mortality over the past three decades sets the United States (U.S.) apart from all other high-income countries. Multidisciplinary state and city Maternal Mortality Review Committees (MMRCs) conduct comprehensive reviews of maternal deaths, including assessments of preventability and contributing factors. Objective(s)Assess preventability of and contributing factors to maternal mortality in the U.S. Study DesignThis study is a secondary analysis of cross-sectional, population-based data from the most recent, publicly available MMRC data from 40 state and 2 cities in the U.S. Preventability was analyzed among all deaths during pregnancy or within one year postpartum from any cause (pregnancy-associated deaths, PAD) and deaths during pregnancy or within one year postpartum from causes related to pregnancy or its management, but not from accidental causes (pregnancy-related deaths, PRD). We also explored preventability by cause-of-death and contributing factors grouped as community, patient-family, provider, facility, and health system factors. ResultsOf deaths that occurred after 2010, between 53%-93.8% of PADs and 45%-100% of PRDs were deemed preventable across the 42 states and cities. Across the ten states reporting PRD preventability by cause-of-death, MMRCs deemed preventable >90% of deaths from preeclampsia-eclampsia and mental health conditions, >80% of deaths from hemorrhage and cardiovascular conditions, about 70% of deaths from infection and thrombotic embolism, and about 40% of deaths from amniotic fluid embolism and stroke. A total of 3,345 contributing factors were described in MMRC reports from 14 states in relation to 739 PRDs. While collectively patient-family and provider factors were most frequently noted as contributing to PRDs, the contribution of such factors varied between 6%-56% and 18%-42.3%, respectively, across the states. Based on data from 20 MMRCs with available information, racism or discrimination were noted in relation to 37.7% of PRDs. ConclusionsA large proportion of PADs and PRDs in the U.S. are preventable. However, likely due to differences in MMRC membership, available data, and judgement employed to determine preventability, wide variation exists in the proportion of deaths deemed preventable and factors identified as contributing to such deaths across states. There is need to reevaluate the definitions, structure, and outputs for maternal death preventability assessments currently employed by a majority MMRCs to adequately inform state and national programming and policies.

The Association between Sickle Cell Disease and Postpartum Severe Maternal Morbidity.

To compare the risk of severe maternal morbidity (SMM) from the delivery admission to 42 days' postdischarge among persons with sickle cell disease (SCD) to those without SCD. This retrospective cohort study included deliveries ≥20 weeks' gestation at an urban safety net hospital in Atlanta, GA from 2011 to 2019. The exposure was SCD diagnosis. The outcome was a composite of SMM from the delivery admission to 42 days' postdischarge. SMM indicators as defined by the Centers for Disease Control and Prevention were identified using the International Classification of Diseases, Ninth and Tenth Revisions (ICD-9/10) codes; transfusion of blood products and sickle cell crisis were excluded. Of N = 17,354 delivery admissions, n = 92 (0.53%) had SCD. Persons with SCD versus without SCD had an increased risk of composite SMM (15.22 vs. 2.29%, p < 0.001), acute renal failure (6.52 vs. 0.71%, p < 0.001), acute respiratory distress syndrome (4.35 vs. 0.17%, p < 0.001), puerperal cerebrovascular disorders (3.26 vs. 0.10%, p < 0.001), sepsis (4.35 vs. 0.42%, p < 0.01), air and thrombotic embolism (5.43 vs. 0.10%, p < 0.001), and ventilation (2.17 vs. 0.09%, p < 0.01). Ultimately, those with SCD had an approximately 6-fold higher incidence risk ratio of SMM, which remained after adjustment for confounders (adjusted incidence risk ratio [aIRR]: 5.96, 95% confidence interval [CI]: 3.4-9.19, p < 0.001). Persons with SCD in active vaso-occlusive crisis at the delivery admission had an approximately 9-fold higher risk of SMM up to 42 days' postdischarge compared with those with SCD not in crisis at the delivery admission (incidence: 25.71 vs. 8.77%, p < 0.05; aIRR: 8.92, 95% CI: 4.5-10.04, p < 0.05). Among those with SCD, SMM at the delivery admission was primarily related to renal and cerebrovascular events, whereas most postpartum SMM was related to respiratory events or sepsis. SCD is significantly associated with an increased risk of SMM during the delivery admission and through 42 days' postdischarge. Active crisis at delivery further increases the risk of SMM. · Sickle cell disease was associated with an approximately 6-fold increased risk of SMM.. · Active vaso-occlusive crisis at delivery was associated with an approximately 9-fold increased risk of SMM.. · 48% of SMM events in persons with SCD occurred postpartum and were respiratory- or sepsis-related..

Direct Oral Anticoagulation in Lung Transplant Recipients.

Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients. We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants. Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies. Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.

Performance of ChatGPT as an AI-assisted decision support tool in medicine: a proof-of-concept study for interpreting symptoms and management of common cardiac conditions (AMSTELHEART-2)

Background It is thought that ChatGPT, an advanced language model developed by OpenAI, may in the future serve as an AI-assisted decision support tool in medicine. Objective To evaluate the accuracy of ChatGPT’s recommendations on medical questions related to common cardiac symptoms or conditions. Methods We tested ChatGPT’s ability to address medical questions in two ways. First, we assessed its accuracy in correctly answering cardiovascular trivia questions (n = 50), based on quizzes for medical professionals. Second, we entered 20 clinical case vignettes on the ChatGPT platform and evaluated its accuracy compared to expert opinion and clinical course. Lastly, we compared the latest research version (v3.5; 27 September 2023) with a prior version (v3.5; 30 January 2023) to evaluate improvement over time. Results We found that ChatGPT latest version correctly answered 92% of the trivia questions, with slight variation in accuracy in the domains coronary artery disease (100%), pulmonary and venous thrombotic embolism (100%), atrial fibrillation (90%), heart failure (90%) and cardiovascular risk management (80%). In the 20 case vignettes, ChatGPT’s response matched in 17 (85%) of the cases with the actual advice given. Straightforward patient-to-physician questions were all answered correctly (10/10). In more complex cases, where physicians (general practitioners) asked other physicians (cardiologists) for assistance or decision support, ChatGPT was correct in 70% of cases, and otherwise provided incomplete, inconclusive, or inappropriate recommendations when compared with expert consultation. ChatGPT showed significant improvement over time; as the January version correctly answered 74% (vs 92%) of trivia questions (p = 0.031), and correctly answered a mere 50% of complex cases. Conclusions Our study suggests that ChatGPT has potential as an AI-assisted decision support tool in medicine, particularly for straightforward, low-complex medical questions, but further research is needed to fully evaluate its potential.

Mechanics and microstructure of blood plasma clots in shear driven rupture.

Intravascular blood clots are subject to hydrodynamic shear and other forces that cause clot deformation and rupture (embolization). A portion of the ruptured clot can block blood flow in downstream vessels. The mechanical stability of blood clots is determined primarily by the 3D polymeric fibrin network that forms a gel. Previous studies have primarily focused on the rupture of blood plasma clots under tensile loading (Mode I), our current study investigates the rupture of fibrin induced by shear loading (Mode II), dominating under physiological conditions induced by blood flow. Using experimental and theoretical approaches, we show that fracture toughness, i.e. the critical energy release rate, is relatively independent of the type of loading and is therefore a fundamental property of the gel. Ultrastructural studies and finite element simulations demonstrate that cracks propagate perpendicular to the direction of maximum stretch at the crack tip. These observations indicate that locally, the mechanism of rupture is predominantly tensile. Knowledge gained from this study will aid in the development of methods for prediction/prevention of thrombotic embolization.

High prevalence of thrombophilic risk factors in patients with central retinal artery occlusion

IntroductionCentral retinal artery occlusion (CRAO) is a common cause of blindness and visual morbidity. In the majority of cases, it is related to thrombotic embolism. Nevertheless, the role of inherited or acquired thrombophilic risk factors in CRAO pathogenesis has not been comprehensively studied.MethodsIn 126 CRAO patients (66 [52.4%] men, median age 55 [range: 18–80] years) and 107 matched controls (56 [52.3%] men, median age 53 [range: 34–78] years) we evaluated classical atherosclerotic risk factors, including serum lipid profile and glucose level, analyzed intima-media complex thickness (IMT) of external carotid arteries, and performed transthoracic echocardiography. Furthermore, we established the prevalence of inherited and acquired thrombophilic risk factors, such as factor V Leiden (FVL) and prothrombin 20210 G/A genetic variants, plasma activity of factor (F) VIII, protein C and antithrombin activity, and free protein S levels. We also assessed the presence of antiphospholipid antibodies (APLA) and evaluated blood homocysteine in all enrolled subjects. Additionally, we estimated the occurrence of Val34Leu polymorphism of the A subunit of coagulation factor XIII (FXIII-A) in both groups as a potential thrombosis-protecting factor.ResultsAmong traditional atherosclerotic risk components, obesity/overweight and hypercholesterolemia were the most common in the CRAO group and occurred in 103 (81.7%) and 85 (67.5%) patients, respectively. CRAO patients also had elevated IMT and altered echocardiographic parameters, indicating diastolic cardiac dysfunction. In thrombophilia investigations, at least one laboratory risk factor occurred in 72.2% (n = 91) of CRAO patients, with APLA as the most frequent, detected in 38.1% (n = 48) of them (almost seven times more frequent than in controls, p < 0.001). Deficiencies in protein C activity and free protein S levels were also common in the CRAO group, reported in 17.5% (n = 22) and 19.8% (n = 25) of patients, respectively. Interestingly, among two analyzed prothrombotic genetic variants, only the FVL was related to CRAO, with the allelic frequency 2.4 times more prevalent than in controls (p = 0.044). Finally, the CRAO group was characterized by hyperhomocysteinemia, almost twice as common as in controls (p = 0.026). Antithrombin deficiency, elevated FVIII, and FXIII-A Val34Leu polymorphism were not associated with CRAO.ConclusionsOur findings suggest that thrombophilia plays a vital role in the pathogenesis of CRAO. Thus, proper laboratory screening should be considered in the primary and secondary prevention of those episodes, with implementing appropriate therapy as needed.

Doula Support and Pregnancy-Related Complications and Death Among Childbearing Women in the United States: A Scoping Review.

The potential benefits of perinatal doula support are many; however, doulas are underutilized, which may heighten pregnancy-related complications. In this scoping review, we assess the influence of perinatal doula support on pregnancy-related complications and death in the United States. We searched PubMed, CINAHL, Scopus, and Alt HealthWatch for literature on doula support and its influence on pregnancy-related complications (maternal fever or infection, postpartum hemorrhage, amniotic fluid embolism, complications from anesthesia, preeclampsia, eclampsia, cardiomyopathy, pulmonary or thrombotic embolism, and cerebrovascular accident). Peer-reviewed articles written in English and conducted in the United States from 1969 to 2021 were included. Screening at all levels was blinded. We extracted data based on title, author, year, design, population, sample size, methods, limitations, recommendations, and definition of doula support. Following removal of duplicates, review of 3679 article titles and abstracts yielded 42 articles for full-text review; 3 articles met final inclusion criteria. One included study focused on intrapartum doula support and 2 on doula support that extended throughout the perinatal period. Within the included studies, doula support was associated with decreased rates of intrapartum maternal fever and gestational hypertension; however, it was not associated with decreased rates of gestational diabetes or depression. The literature has addressed the benefits of perinatal doula support, but studies with validated tools to examine associations between doula support and pregnancy-related complications and death are lacking. The studies that addressed intrapartum and continuous doula care included large generalizable samples, from which future research can draw to improve the practice of caring for patients during the perinatal period. Extensive research shows that unfavorable conditions can influence perinatal outcomes across generations. Implementing doula support may offer a potential approach to reduce and help alleviate resulting disparities in perinatal health.

Association of Sickle Cell Disease With Racial Disparities and Severe Maternal Morbidities in Black Individuals

Little is known about the association between sickle cell disease (SCD) and severe maternal morbidity (SMM). To examine the association of SCD with racial disparities in SMM and with SMM among Black individuals. This cohort study was a retrospective population-based investigation of individuals with and without SCD in 5 states (California [2008-2018], Michigan [2008-2020], Missouri [2008-2014], Pennsylvania [2008-2014], and South Carolina [2008-2020]) delivering a fetal death or live birth. Data were analyzed between July and December 2022. Sickle cell disease identified during the delivery admission by using International Classification of Diseases, Ninth Revision and Tenth Revision codes. The primary outcomes were SMM including and excluding blood transfusions during the delivery hospitalization. Modified Poisson regression was used to estimate risk ratios (RRs) adjusted for birth year, state, insurance type, education, maternal age, Adequacy of Prenatal Care Utilization Index, and obstetric comorbidity index. From a sample of 8 693 616 patients (mean [SD] age, 28.5 [6.1] years), 956 951 were Black individuals (11.0%), of whom 3586 (0.37%) had SCD. Black individuals with SCD vs Black individuals without SCD were more likely to have Medicaid insurance (70.2% vs 64.6%), to have a cesarean delivery (44.6% vs 34.0%), and to reside in South Carolina (25.2% vs 21.5%). Sickle cell disease accounted for 8.9% and for 14.3% of the Black-White disparity in SMM and nontransfusion SMM, respectively. Among Black individuals, SCD complicated 0.37% of the pregnancies but contributed to 4.3% of the SMM cases and to 6.9% of the nontransfusion SMM cases. Among Black individuals with SCD compared with those without, the crude RRs of SMM and nontransfusion SMM during the delivery hospitalization were 11.9 (95% CI, 11.3-12.5) and 19.8 (95% CI, 18.5-21.2), respectively, while the adjusted RRs were 3.8 (95% CI, 3.3-4.5) and 6.5 (95% CI, 5.3-8.0), respectively. The SMM indicators that incurred the highest adjusted RRs included air and thrombotic embolism (4.8; 95% CI, 2.9-7.8), puerperal cerebrovascular disorders (4.7; 95% CI, 3.0-7.4), and blood transfusion (3.7; 95% CI, 3.2-4.3). In this retrospective cohort study, SCD was found to be an important contributor to racial disparities in SMM and was associated with an elevated risk of SMM among Black individuals. Efforts from the research community, policy makers, and funding agencies are needed to advance care among individuals with SCD.

Fracture toughness of fibrin gels as a function of protein volume fraction: Mechanical origins.

The mechanical stability of blood clots necessary for their functions is provided by fibrin, a fibrous gel. Rupture of clots leads to life-threatening thrombotic embolization, which is little understood. Here, we combine experiments and simulations to determine the toughness of plasma clots as a function of fibrin content and correlate toughness with fibrin network structure characterized by confocal and scanning electron microscopy. We develop fibrin constitutive laws that scale with fibrin concentration and capture the force-stretch response of cracked clot specimens using only a few material parameters. Toughness is calculated from the path-independent J* integral that includes dissipative effects due to fluid flow and uses only the constitutive model and overall stretch at crack propagation as input. We show that internal fluid motion, which is not directly measurable, contributes significantly to clot toughness, with its effect increasing as fibrin content increases, because the reduced gel porosity at higher density results in greater expense of energy in fluid motion. Increasing fibrin content (1→10mg/mL) results in a significant increase in clot toughness (3→15N/m) in accordance with a power law relation reminiscent of cellular solids and elastomeric gels. These results provide a basis for understanding and predicting the tendency for thrombotic embolization. STATEMENT OF SIGNIFICANCE: Fibrin, a naturally occurring biomaterial, is the major determinant of the structural and mechanical integrity of blood clots. We determined that increasing the fibrin content in clots, as in some thrombi and fibrin-based anti-bleeding sealants, results in an increase in clot toughness. Toughness corresponds to the ability to resist rupturing in the presence of a defect. We couple bulk mechanical testing, microstructural measurements, and finite element modeling to capture the force-stretch response of fibrin clots and compute toughness. We show that increased fibrin content in clots reduces porosity and limits fluid motion and that fluid motion drastically alters the clot toughness. These results provide a fundamental understanding of blood clot rupture and could help in rational design of fibrin-containing biomaterials.

Pulse wave imaging of a stenotic artery model with plaque constituents of different stiffnesses: Experimental demonstration in phantoms and fluid-structure interaction simulation

Vulnerable plaques associated with softer components may rupture, releasing thrombotic emboli to smaller vessels in the brain, thus causing an ischemic stroke. Pulse Wave Imaging (PWI) is an ultrasound-based method that allows for pulse wave visualization while the regional pulse wave velocity (PWV) is mapped along the arterial wall to infer the underlying wall compliance. One potential application of PWI is the non-invasive estimation of plaque’s mechanical properties for investigating its vulnerability. In this study, the accuracy of PWV estimation in stenotic vessels was investigated by computational simulation and PWI in validation phantoms to evaluate this modality for assessing future stroke risk. Polyvinyl alcohol (PVA) phantoms with plaque constituents of different stiffnesses were designed and constructed to emulate stenotic arteries in the experiment, and the novel fabrication process was described. Finite-element fluid–structure interaction simulations were performed in a stenotic phantom model that matched the geometry and parameters of the experiment in phantoms. The peak distension acceleration of the phantom wall was tracked to estimate PWV. PWVs of 2.57 ms−1, 3.41 ms−1, and 4.48 ms−1 were respectively obtained in the soft, intermediate, and stiff plaque material in phantoms during the experiment using PWI. PWVs of 2.10 ms−1, 3.33 ms−1, and 4.02 ms−1 were respectively found in the soft, intermediate, and stiff plaque material in the computational simulation. These results demonstrate that PWI can effectively distinguish the mechanical properties of plaque in phantoms as compared to computational simulation.

Association of Sickle Cell Disease With Severe Maternal Morbidity.

To evaluate the association between sickle cell disease (SCD) and severe maternal morbidity (SMM) in a contemporary cohort of deliveries by non-Hispanic Black people. We retrospectively examined SMM by using electronic health record data on deliveries by non-Hispanic Black patients between 2011 and 2020 at a single tertiary, public institution. Sickle cell disease was identified during the delivery admission by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes. The primary outcome, SMM at delivery hospitalization, was ascertained using ICD-9-CM and ICD-10-CM codes and excluded sickle cell crisis as an indicator of SMM. We also constructed a secondary measure of SMM that excluded deliveries in which blood transfusion was the only indication of SMM. Poisson regression models were used to estimate risk ratios (RRs) and 95% CIs for the associations between SCD and SMM (overall and for individual indicators). Multivariable models adjusted for age, parity, insurance type, chronic conditions (chronic hypertension, diabetes mellitus, obesity), and multiple gestation. Among 17,493 deliveries by non-Hispanic Black patients during the study period, 132 (0.8%) had a diagnosis of SCD. Of those patients, 87 (65.9%, 95% CI 57.2-73.9) with SCD and 2,035 (11.7%), 95% CI 11.2-12.2) without SCD had SMM. Sickle cell disease was associated with increased risk of SMM (87 vs 2,035, adjusted risk ratio [aRR] 5.4, 95% CI 4.6-6.3) and nontransfusion SMM (51 vs 1,057, aRR 6.0, 95% CI 4.6-8.0). Effect estimates were highest for cardiac arrest (3 vs 14, RR 28.2, 95% CI 3.8-209.3), air and thrombotic embolism (14 vs 72, RR 25.6, 95% CI 12.0-54.6), and puerperal cerebrovascular disorders (10 vs 53, RR 24.8, 95% CI 10.2-60.5). Sickle cell disease was associated with a more than fivefold increased risk of SMM during the delivery hospitalization. Our data suggest cardiovascular morbidity as the driving major risk. The identification and monitoring of cardiovascular pathology in patients with SCD before and during pregnancy may reduce SMM.

This Month in Adult Urology

This Month in Adult Urology

Strength, deformability and toughness of uncrosslinked fibrin fibers from theoretical reconstruction of stress-strain curves

Structural mechanisms underlying the mechanical properties of fibrin fibers are elusive. We combined tensile testing of uncrosslinked fibrin polymers in vitro and in silico to explore their material properties. The experimental stress (σ) – strain (ε) curves for fibrin fibers are characterized by elastic deformations with a weaker elastic response for ε<160% due to unraveling of αC tethers and straightening of fibrin protofibrils, and a stronger response for ε>160% owing to unfolding of the coiled coils and γ nodules in fibrin monomers. Fiber rupture for strains ε>212% is due to dissociation of the knob-hole bonds and rupture of D:D interfaces. We developed the Fluctuating Bilinear Spring model to interpret the σ−ε profiles in terms of the free energy for protofibril alignment ΔG0 = 10.1–11.5 kBT, Young's moduli for protofibril alignment Yu = 1.9-3.2 MPa and stretching Ya = 5.7–9.7 MPa, strain scale ε˜≈ 12–40% for fiber rupture, and protofibril cooperativity m= 3.6–8. We applied the model to characterize the fiber strength σcr≈ 12-13 MPa, deformability εcr≈ 222%, and rupture toughness U≈ 9 MJ/m3, and to resolve thermodynamic state functions, 96.9 GJ/mol entropy change for protofibril alignment (at room temperature) and 113.6 GJ/mol enthalpy change for protofibril stretching, which add up to 210.5 GJ/mol free-energy change. Fiber elongation is associated with protofibril dehydration and sliding mechanism to create an ordered protofibril array. Fibrin fibers behave like a hydrogel; protofibril dehydration and water expulsion account for ∼94-98% of the total free-energy changes for fiber elongation and rupture. Statement of significanceStructural mechanisms underlying the mechanical properties of fibrin fibers, major components of blood clots and obstructive thrombi, are elusive. We performed tensile testing of uncrosslinked fibrin polymers in vitro and in silico to explore their material properties. Fluctuating Bilinear Spring theory was developed to interpret the stress-strain profiles in terms of the energy for protofibril alignment, elastic moduli for protofibril alignment and stretching, and strain scale for fiber rupture, and to probe the limits of fiber strength, extensibility and toughness. Fibrin fibers behave like a hydrogel. Fiber elongation is defined by the protofibril dehydration and sliding. Structural rearrangements in water matrix control fiber elasticity. These results contribute to fundamental understanding of blood clot breakage that underlies thrombotic embolization.

Development and reliability of the histological THROMBEX-classification rule for thrombotic emboli of\xa0acute ischemic stroke patients

BackgroundThrombus histology has become a potential diagnostic tool for the etiology assessment of patients with ischemic stroke caused by embolic proximal vessel occlusion. We validated a classification rule that differentiates between cardiac and arteriosclerotic emboli in individual stroke patients. We aim to describe in detail the development of this classification rule and disclose its reliability.MethodsThe classification rule is based on the hypothesis that cardiac emboli arise out of separation thrombi and arteriosclerotic emboli result from agglutinative thrombi. 125 emboli recovered by thrombectomy from stroke patients and 11 thrombi serving as references for cardiac (n = 5) and arteriosclerotic emboli (n = 6) were Hematoxylin and eosin, Elastica-van Gieson and CD61 stained and rated independently by two histopathologists blinded to the presumed etiology by several pre-defined criteria. Intra- and interobserver reliabilities of all criteria were determined. Out of the different criteria, three criteria with the most satisfactory reliability values were selected to compose the classification rule that was finally adjusted to the reference thrombi. Reliabilities of the classification rule were calculated by using the emboli of stroke patients.ResultsThe classification rule reached intraobserver reliabilities for the two raters of 92.9% and 68.2%, respectively. Interobserver reliability was 69.9%.ConclusionsA new classification rule for emboli obtained from thrombectomy was established. Within the limitations of histological investigations, it is reliable and able to distinguish between cardioembolic and arteriosclerotic emboli.

Association of alcohol and other substance-related diagnoses with severe maternal morbidity.

Pregnant women with a substance-related diagnosis, such as an alcohol use disorder, are a vulnerable population that may experience higher rates of severe maternal morbidity, such as hemorrhage and eclampsia, than pregnant women with no substance-related diagnosis. This retrospective cross-sectional study reviewed electronic health record data on women (aged 18-44years) who delivered a single live birth or stillbirth at ≥ 20weeks of gestation from March 1, 2016, to August 30, 2019. Women with and without a substance-related diagnosis were matched on key demographic characteristics, such as age, at a 1:1 ratio. Adjusting for these covariates, odds ratios and 95% confidence intervals were calculated. A total of 10,125 deliveries met the eligibility criteria for this study. In the matched cohort of 1,346 deliveries, 673 (50.0%) had a substance-related diagnosis, and 94 (7.0%) had severe maternal morbidity. The most common indicators in women with a substance-related diagnosis included hysterectomy (17.7%), eclampsia (15.8%), air and thrombotic embolism (11.1%), and conversion of cardiac rhythm (11.1%). Having a substance-related diagnosis was associated with severe maternal morbidity (adjusted odds ratio=1.81 [95% CI, 1.14-2.88], p-value=0.0126). In the independent matched cohorts by substance type, an alcohol-related diagnosis was significantly associated with severe maternal morbidity (adjusted odds ratio=3.07 [95% CI, 1.58-5.95], p-value=0.0009), while the patterns for stimulant- and nicotine-related diagnoses were not as well resolved with severe maternal morbidity and opioid- and cannabis-related diagnoses were not associated with severe maternal morbidity. We found that an alcohol-related diagnosis, although lowest in prevalence of the substance-related diagnoses, had the highest odds of severe maternal morbidity of any substance-related diagnosis assessed in this study. These findings reinforce the need to identify alcohol-related diagnoses in pregnant women early to minimize potential harm through intervention and treatment.

New Interventional Therapies beyond Stenting to Treat ST-Segment Elevation Acute Myocardial Infarction.

Myocardial infarction remains the principal cause of death in Europe. In patients with ST-segment-elevation myocardial infarction (STEMI), a promptly revascularization with primary percutaneous intervention (PCI) has transformed prognosis in the last decades. However, despite increasing successful PCI procedures, mortality has remained unchanged in recent years. Also, due to an unsatisfactory reperfusion, some patients have significant myocardial damage and suffer left ventricular adverse remodeling with reduced function—all that resulting in the onset of heart failure with all its inherent clinical and socioeconomic burden. As a consequence of longer ischemic times, distal thrombotic embolization, ischemia-reperfusion injury and microvascular dysfunction, the resultant myocardial infarct size is the major prognostic determinant in STEMI patients. The improved understanding of all the pathophysiology underlying these events has derived to the development of several novel therapies aiming to reduce infarct size and to improve clinical outcomes in these patients. In this article, based on the mechanisms involved in myocardial infarction prognosis, we review the new interventional strategies beyond stenting that may solve the suboptimal results that STEMI patients still experience.

Acute myocardial infarction and arterial embolism in a patient with newly diagnosed renal mass: management dilemmas! A case report

BackgroundCancer is often associated with a hypercoagulable state and new thrombosis is often the first clinical manifestation of cancer. Surgical treatment of the primary tumor is crucial since it provides the only curative approach in most cases, but management of patients is highly complex, especially in the presence of new antiplatelet drugs and/or anticoagulants. Paraneoplastic syndromes (PNS) represent a frequent complication of renal cell carcinomas (RCC) and include different hematological symptoms in patients, whilst occlusion of arterial blood vessels displays a rare form of PNS accompanying renal tumors.Case presentationWe report the case of a 62-year old man who was initially hospitalized due to acute coronary syndrome. He subsequently underwent coronary angioplasty treatment including multiple stenting and treatment with ticagrelor and aspirin. Post-interventional, acute arterial thrombotic emboli of several limb arteries required thrombectomy. By computer tomography we identified a renal lesion suspicious for an RCC and suspected a PNS as underlying cause of the thrombotic complications. Triple anticoagulant therapy was maintained with therapeutic dose low molecular weight heparin (LMWH), aspirin, and clopidogrel, by which we replaced ticagrelor. Surgery was postponed for 4 weeks. We paused LMWH, aspirin and clopidogrel only at the day of surgery and perioperatively restored hemostasis by transfusion of two platelet concentrates. Laparoscopic nephrectomy was uneventful. Pathology confirmed a clear cell RCC. The patient fully recovered whilst slowly reducing anticoagulation dose.ConclusionsA multidisciplinary team approach of experts in urology, cardiology and hemostasis was key in managing this patient since a personalized thrombosis consult was needed to minimize the risk of reinfarction due to in-stent thrombosis. We report a therapeutic protocol that may be helpful for the management of similar cases. Furthermore, the finding of thrombotic arterial occlusions in larger blood vessels represents a novel complication of PNS in RCC and adds to the varied possible manifestations of this clinical chameleon.

Strength and deformability of fibrin clots: Biomechanics, thermodynamics, and mechanisms of rupture

Fibrin is the major determinant of the mechanical stability and integrity of blood clots and thrombi. To explore the rupture of blood clots, emulating thrombus breakage, we stretched fibrin gels with single-edge cracks of varying size. Ultrastructural alterations of the fibrin network correlated with three regimes of stress vs. strain profiles: the weakly non-linear regime due to alignment of fibrin fibers; linear regime owing to further alignment and stretching of fibers; and the rupture regime for large deformations reaching the critical strain and stress, at which irreversible breakage of fibers ahead of the crack tip occurs. To interpret the stress-strain curves, we developed a new Fluctuating Spring model, which maps the fibrin alignment at the characteristic strain, network stretching with the Young modulus, and simultaneous cooperative rupture of coupled fibrin fibers into a theoretical framework to obtain the closed-form expressions for the strain-dependent stress profiles. Cracks render network rupture stochastic, and the free energy change for fiber deformation and rupture decreases with the crack length, making network rupture more spontaneous. By contrast, mechanical cooperativity due to the presence of inter-fiber contacts strengthens fibrin networks. The results obtained provide a fundamental understanding of blood clot breakage that underlies thrombotic embolization. Statement of significanceFibrin, a naturally occurring biomaterial, is the major determinant of mechanical stability and integrity of blood clots and obstructive thrombi. We tested mechanically fibrin gels with single-edge cracks and followed ultrastructural alterations of the fibrin network. Rupture of fibrin gel involves initial alignment and elastic stretching of fibers followed by their eventual rupture for deformations reaching the critical level. To interpret the stress-strain curves, we developed Fluctuating Spring model, which showed that cracks render rupture of fibrin networks more spontaneous; yet, coupled fibrin fibers reinforce cracked fibrin networks. The results obtained provide fundamental understanding of blood clot breakage that underlies thrombotic embolization. Fluctuating Spring model can be applied to other protein networks with cracks and to interpret the stress-strain profiles.

Severe maternal morbidity and mortality during delivery hospitalization of class I, II, III, and super obese women

Previous studies show that obesity predisposes patients to higher risks of adverse pregnancy outcomes. Data on the relationship between increasing degrees of obesity and risks of severe maternal morbidity, including mortality, are limited. We examined the association of increasing classes of obesity, especially super obesity, with the risk of severe maternal morbidity and mortality at the time of delivery hospitalization. Using New York City linked birth certificates and hospital discharge data, we conducted a retrospective cohort study. This study identified delivery hospitalizations for singleton, live births in 2008-2012. Women were classified as having obesity (class I, II, III, or super obesity), as opposed to normal weight or overweight, based on prepregnancy body mass index. Cases of severe maternal morbidity were identified based on International Classification of Diseases, Ninth Revision diagnosis and procedure codes according to Centers for Disease Control and Prevention criteria. Multivariable logistic regression was used to evaluate the association between obesity classes and severe maternal morbidity, adjusting for maternal sociodemographic characteristics. During 2008-2012, there were 570,997 live singleton births with available information on prepregnancy body mass index that met all inclusion criteria. After adjusting for maternal characteristics, women with class II (adjusted odds ratio, 1.14; 95% confidence interval, 1.05-1.23), class III (adjusted odds ratio, 1.34; 95% confidence interval, 1.21-1.49), and super obesity (adjusted odds ratio, 1.99; 95% confidence interval, 1.57-2.54) were all significantly more likely to have severe maternal morbidity than normal and overweight women. Super obesity was associated with specific severe maternal morbidity indicators, including renal failure, air and thrombotic embolism, blood transfusion, heart failure, and the need for mechanical ventilation. There is a significant dose-response relationship between increasing obesity class and the risk of severe maternal morbidity at delivery hospitalization. The risks of severe maternal morbidity are highest for women with super obesity. Given that this is a modifiable risk factor, women with prepregnancy obesity should be counseled on the specific risks associated with pregnancy before conception to optimize their pregnancy outcomes.

Porphyromonas gingivalis and left atrial appendage spontaneous echo contrast in atrial fibrillation ablation candidates.

Atrial fibrillation (AF) is associated with a fivefold risk of stroke and thrombotic embolism, which are usually derived from the left atrial appendage (LAA). Spontaneous echo contrast (SEC) is known as a risk factor for thrombosis. Porphyromonas gingivalis (P. gingivalis) has some prothrombotic effects and plays a key role in periodontitis and oral-systemic disease connection. We aimed to clarify the relationship between P. gingivalis and LAA SEC among AF patients. A total of 569 AF ablation candidates were enrolled in the present study. LAA SEC was categorized into nondense SEC and dense SEC based on transesophageal echocardiography. Serum immunoglobulin G antibody titers of P. gingivalis fimA subtypes (types I-IV) were measured with an enzyme-linked immunosorbent assay. The levels of antibody titers were categorized into high (> mean + 3 standard deviation) and low values. A total of 513 (90%) patients were included in the nondense SEC group, and 56 (10%) were included in the dense SEC group. Multivariate regression analysis revealed that the high-value serum antibody titers of P. gingivalis types II and IV were independently associated with dense SEC [type II: adjusted odds ratio (OR) 2.220; 95% confidence interval (CI) 1.062-4.643; P = 0.02; and type IV: adjusted OR 3.169; 95% CI 1.058-6.657; P = 0.002]. The results revealed that P. gingivalis types II and IV are related to LAA SEC severity among AF patients who receive appropriate anticoagulation therapy.