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BACKGROUND: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis. METHODS: Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes. RESULTS: 47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 â%,p â= â0.001) and less likely to survive(16%vs56 â%,p â= â0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46]). CONCLUSIONS: TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.
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BACKGROUND: Direct peritoneal resuscitation (DPR) is associated with improved outcomes in trauma. Animal models suggest DPR has favorable effects on the liver. We sought to evaluate its safety and assess for improved outcomes in liver transplantation (LT). METHODS: LT patients with renal dysfunction and/or obesity were enrolled in a phase-I clinical trial. DPR lasted 8-24 âh depending on postoperative disposition. Primary outcome was percent of patients completing DPR. Secondary outcomes evaluated complications. Controls with either obesity (control-1) or both risk factors (obesity â+ ârenal dysfunction, control-2) were analyzed. RESULTS: Fifteen patients were enrolled (seven with both criteria and eight with obesity alone). DPR was completed in 87 â% of patients, with one meeting stopping criteria. Controls included 45 (control-1) and 24 (control-2) patients. Return to operating room, graft loss, and late infections were lower with DPR. CONCLUSION: DPR appears to be safe in closed abdomens following LT, warranting a follow-up phase-II trial to assess efficacy.
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Here, we present a series of illustrated capsules from the State of the Art (SOA) speakers at the 2024 International Society on Thrombosis and Haemostasis Congress in Bangkok, Thailand. This year's Congress marks the first time that the International Society on Thrombosis and Haemostasis has held its flagship scientific meeting in Southeast Asia and is the first to be organized by an international Planning Committee. The Bangkok program will feature innovative science and clinical updates from around the world, reflecting the diversity and multidisciplinary growth of our field. In these illustrated SOA capsules, you will find an exploration of novel models of thrombosis and bleeding and biomaterial discoveries that can trigger or block coagulation. Thromboinflammation is now understood to drive many disease states, and the SOA speakers cover cellular and coagulation responses to COVID-19 and other infections. The theme of crosstalk between coagulation and inflammation expands with capsules on protein S signaling, complement, and fibrinolytic inhibitors. Novel agents for hemophilia and thrombosis prevention are introduced. Challenging clinical conditions are also covered, such as inherited platelet disorders and antiphospholipid antibody syndrome. The scientific program in Bangkok will also showcase the work of clinicians and scientists from all parts of the world and chronicle real-world challenges. For example, 2 SOA capsules address the diagnosis and management of von Willebrand disease in low-income settings. Take some time to browse through these short illustrated reviews; we're sure that you'll be entertained, educated, and inspired to further explore the world of thrombosis and hemostasis.
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Integration of physiological sensing modalities within tissue and organ perfusion systems is becoming a steadily expanding field of research, aimed at achieving technological breakthrough innovations that will expand the sites and clinical settings at which such systems can be used. This is becoming possible in part due to the advancement of user-friendly optical sensors in recent years, which rely both on synthetic, luminescent sensor molecules and inexpensive, low-power electronic components for device engineering. In this article we report a novel approach towards enabling automated, continuous monitoring of oxygenation during ex vivo organ perfusion, by combining versatile flow cell components and low-power, programmable electronic readout devices. The sensing element comprises a 3D printed, miniature flow cell with tubing connectors and an affixed oxygen-sensing thin film material containing in-house developed, brightly-emitting metalloporphyrin phosphor molecules embedded within a polymer matrix. Proof-of-concept validation of this technology is demonstrated through integration within the tubing circuit of a transportable medical device for hypothermic oxygenated machine perfusion of extracted kidneys as a model for organs to be preserved as transplants.
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Coagulação Intravascular Disseminada , Fibrinólise , Hemostasia , Humanos , Fibrinólise/fisiologia , Fibrinólise/efeitos dos fármacos , Coagulação Intravascular Disseminada/sangue , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/fisiopatologia , Hemostasia/fisiologiaRESUMO
BACKGROUND: Complex pleural space infections often require treatment with multiple doses of intrapleural tissue plasminogen activator (tPA) and deoxyribonuclease, with treatment failure frequently necessitating surgery. Pleural infections are rich in neutrophils, and neutrophil elastase degrades plasminogen, the target substrate of tPA, that is required to generate fibrinolysis. We hypothesized that pleural fluid from patients with pleural space infection would show high elastase activity, evidence of inflammatory plasminogen degradation, and low fibrinolytic potential in response to tPA that could be rescued with plasminogen supplementation. RESEARCH QUESTION: Does neutrophil elastase degradation of plasminogen contribute to intrapleural fibrinolytic failure? STUDY DESIGN AND METHODS: We obtained infected pleural fluid and circulating plasma from hospitalized adults (n = 10) with institutional review board approval from a randomized trial evaluating intrapleural fibrinolytics vs surgery for initial management of pleural space infection. Samples were collected before the intervention and on days 1, 2, and 3 after the intervention. Activity assays, enzyme-linked immunosorbent assays, and Western blot analysis were performed, and turbidimetric measurements of fibrinolysis were obtained from pleural fluid with and without exogenous plasminogen supplementation. Results are reported as median (interquartile range) or number (percentage) as appropriate, with an α value of .05. RESULTS: Pleural fluid elastase activity was more than fourfold higher (P = .02) and plasminogen antigen levels were more than threefold lower (P = .04) than their corresponding plasma values. Pleural fluid Western blot analysis demonstrated abundant plasminogen degradation fragments consistent with elastase degradation patterns. We found that plasminogen activator inhibitor 1 (PAI-1), the native tPA inhibitor, showed high antigen levels before the intervention, but the overwhelming majority of this PAI-1 (82%) was not active (P = .003), and all PAI-1 activity was lost by day 2 after the intervention in patients receiving intrapleural tPA and deoxyribonuclease. Finally, using turbidity clot lysis assays, we found that the pleural fluid of 9 of 10 patients was unable to generate a significant fibrinolytic response when challenged with tPA and that plasminogen supplementation rescued fibrinolysis in all patients. INTERPRETATION: Our findings suggest that inflammatory plasminogen deficiency, not high PAI-1 activity, is a significant contributor to intrapleural fibrinolytic failure. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03583931; URL: www. CLINICALTRIALS: gov.
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Índice de Massa Corporal , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores Sexuais , Prognóstico , Fatores de Risco , Adulto , Resultado do Tratamento , Obesidade/complicações , Obesidade/cirurgia , Obesidade/diagnósticoRESUMO
BACKGROUND: Conventional rapid thrombelastography (rTEG) cannot differentiate fibrinolysis shutdown from hypofibrinolysis, as both of these patient populations have low fibrinolytic activity. Tissue plasminogen activator (tPA) TEG can identify depletion of fibrinolytic inhibitors, and its use in combination with rTEG has the potential to differentiate all 3 pathologic fibrinolytic phenotypes after trauma. We hypothesize tPA-TEG and rTEG in combination can further stratify fibrinolysis phenotypes postinjury to better stratify risk for mortality. STUDY DESIGN: Adult trauma patients (981) with both rTEG and tPA-TEG performed less than 2 hours postinjury were included. rTEG lysis at 30 minutes after maximum amplitude (LY30) was used to initially define fibrinolysis phenotypes (hyperfibrinolysis >3%, physiologic 0.9% to 3%, and shutdown <0.9%), with Youden Index then used to define pathologic extremes of tPA-TEG LY30 (tPA sensitive [depletion of fibrinolytic inhibitors] vs resistant) resulting in 9 groups that were assessed for risk of death. RESULTS: The median New Injury Severity Score was 22, 21% were female, 45% had penetrating injury, and overall mortality was 13%. The tPA-TEG LY30 inflection point for increased mortality was >35.5% (tPA sensitive, odds ratio mortality 9.2, p < 0.001) and <0.3% (tPA resistance, odds ratio mortality 6.3, p = 0.04). Of the 9 potential fibrinolytic phenotypes, 5 were associated with increased mortality. Overall, the 9 phenotypes provided a significantly better prediction of mortality than rTEG or tPA-TEG alone (areas under the operating characteristics curves = 0.80 vs 0.63 and 0.75, respectively, p < 0.0001). These could be condensed to 3 pathologic phenotypes (true hyperfibrinolysis, early fibrinolysis shutdown, and hypofibrinolysis). CONCLUSIONS: The combination of rTEG and tPA-TEG increases the ability to predict mortality and suggests patient-specific strategies for improved outcomes.
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Fibrinólise , Tromboelastografia , Ativador de Plasminogênio Tecidual , Ferimentos e Lesões , Humanos , Tromboelastografia/métodos , Feminino , Fibrinólise/fisiologia , Masculino , Adulto , Pessoa de Meia-Idade , Ferimentos e Lesões/sangue , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/mortalidade , Escala de Gravidade do Ferimento , Estudos Retrospectivos , Fenótipo , IdosoRESUMO
[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].
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Background: Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients and Methods: Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Results: Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Conclusions: Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.
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Choque Hemorrágico , Tromboembolia Venosa , Ferimentos e Lesões , Humanos , Fibrinólise , Ativador de Plasminogênio Tecidual , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Fatores de Risco , HospitaisRESUMO
Viscoelastic testing is a clinically available method to assess hypercoagulability. This systematic review aims to provide a comprehensive overview of the existing literature and the potential use of such testing in patients with breast cancer. A systematic literature search for studies investigating the application of viscoelastic testing for patients with breast cancer was conducted. Studies were included as long as they were original, peer-reviewed, and in the English language. Studies were excluded if they were review articles, did not include breast cancer patients, or if the full text was unavailable. This review identified 10 articles that met the inclusion criteria. Two of the studies utilized rotational thromboelastometry, and an additional four studies used thromboelastography, to assess hypercoagulability in patients with breast cancer. Three of the identified articles discussed the use of thromboelastometry in free flap breast reconstruction for patients with breast cancer. One study was a retrospective chart review looking at thromboelastography and microsurgical breast reconstruction. Current literature regarding the application of viscoelastic testing in breast cancer and free flap breast reconstruction is limited, with no randomized trials thus far. However, some studies suggest that there may be potential utility in viscoelastic testing to assess risk for thromboembolism in breast cancer patients, and future research in this area is warranted.
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Neoplasias da Mama , Retalhos de Tecido Biológico , Trombofilia , Trombose , Humanos , Feminino , Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Estudos Retrospectivos , Trombofilia/diagnóstico , Trombofilia/etiologiaRESUMO
Traumatic brain injury (TBI) is the leading cause of death and disability due to injury worldwide. Extracellular matrix (ECM) remodeling is known to significantly contribute to TBI pathophysiology. Glycosaminoglycans, which are long-chain, variably sulfated polysaccharides abundant within the ECM, have previously been shown to be substantially altered after TBI. In this study, we sought to delineate the dynamics of glycosaminoglycan alterations after TBI and discover the precise biologic processes responsible for observed glycosaminoglycan changes after injury. We performed state-of-the art mass spectrometry on brain tissues isolated from mice after TBI or craniotomy-alone. We observed dynamic changes in glycosaminoglycans at Day 1 and 7 post-TBI, with heparan sulfate, chondroitin sulfate, and hyaluronan remaining significantly increased after a week vis-à-vis craniotomy-alone tissues. We did not observe appreciable changes in circulating glycosaminoglycans in mice after experimental TBI compared to craniotomy-alone nor in patients with TBI and severe polytrauma compared to control patients with mild injuries, suggesting increases in injury site glycosaminoglycans are driven by local synthesis. We subsequently performed an unbiased whole genome transcriptomics analysis on mouse brain tissues 7 days post-TBI and discovered a significant induction of hyaluronan synthase 2, glypican-3, and decorin. The functional role of decorin after injury was further examined through multimodal behavioral testing comparing wild-type and Dcn-/- mice. We discovered that genetic ablation of Dcn led to an overall negative effect of TBI on function, exacerbating motor impairments after TBI. Collectively, our results provide a spatiotemporal characterization of post-TBI glycosaminoglycan alterations in the brain ECM and support an important adaptive role for decorin upregulation after TBI.
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Lesões Encefálicas Traumáticas , Glicosaminoglicanos , Animais , Humanos , Camundongos , Lesões Encefálicas Traumáticas/genética , Sulfatos de Condroitina , Decorina/genética , Proteínas da Matriz Extracelular , Glicosaminoglicanos/químicaRESUMO
INTRODUCTION: Venous thromboembolism (VTE) remains a significant source of postinjury morbidity and mortality. Beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (rosuvastatin) significantly reduced pathologic clotting events in healthy populations in a prior trial. Furthermore, acetylsalicylic acid (ASA) has been shown to be noninferior to prophylactic heparinoids for VTE prevention following orthopedic surgery. We hypothesized that a combination of rosuvastatin/ASA, in addition to standard VTE chemoprophylaxis, would reduce VTE in critically ill trauma patients. METHODS: This was a double-blind, placebo-controlled, randomized trial, evaluating VTE rates in two groups: ASA + statin (Experimental) and identical placebos (Control). Injured adults, 18-65âyears old, admitted to the surgical intensive care unit without contraindications for VTE prophylaxis were eligible. Upon initiation of routine VTE chemoprophylaxis (i.e. heparin/heparin-derivatives), they were randomized to the Experimental or Control group. VTE was the primary outcome. RESULTS: Of 112 potentially eligible patients, 33% (nâ=â37, median new injury severity scaleâ=â27) were successfully randomized, of whom 11% had VTEs. The Experimental group had no VTEs, while the Control group had 6 VTEs (4 PEs and 2 DVTs) in 4 (22%) patients (Pâ=â0.046). The Experimental treatment was not associated with any serious adverse events. Due to the COVID-19 pandemic, the study was interrupted at the second interim analysis at <10% of the planned enrollment, with significance declared at Pâ<â0.012 at that stage. DISCUSSION: The combination of ASA and rosuvastatin with standard VTE prophylaxis showed a favorable trend toward reducing VTEs with no serious adverse events. An appropriately powered phase III multicenter trial is needed to further investigate this therapeutic approach. LEVEL OF EVIDENCE: Level II, Therapeutic.
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Tromboembolia Venosa , Adolescente , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Anticoagulantes/uso terapêutico , Aspirina , Heparina/uso terapêutico , Pandemias , Rosuvastatina Cálcica/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.
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Embolia Aérea , Trombose , Humanos , Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Embolia Aérea/terapia , Tromboinflamação , Inflamação/terapia , Inflamação/complicações , Trombose/complicações , Doença IatrogênicaRESUMO
Oxygenation is a crucial indicator of tissue viability and function. Oxygen tension ([Formula: see text]), i.e. the amount of molecular oxygen present in the tissue is a direct result of supply (perfusion) and consumption. Thus, measurement of [Formula: see text] is an effective method to monitor tissue viability. However, tissue oximetry sensors commonly used in clinical practice instead rely on measuring oxygen saturation ([Formula: see text]), largely due to the lack of reliable, affordable [Formula: see text] sensing solutions. To address this issue we present a proof-of-concept design and validation of a low-cost, lifetime-based oxygen sensing fiber. The sensor consists of readily-available off-the shelf components such as a microcontroller, a light-emitting diode (LED), an avalanche photodiode (APD), a temperature sensor, as well as a bright in-house developed porphyrin molecule. The device was calibrated using a benchtop setup and evaluated in three in vivo animal models. Our findings show that the new device design in combination with the bright porphyrin has the potential to be a useful and accurate tool for measuring [Formula: see text] in tissue, while also highlighting some of the limitations and challenges of oxygen measurements in this context.
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Tecnologia de Fibra Óptica , Porfirinas , Animais , Gasometria , Oximetria , OxigênioRESUMO
INTRODUCTION: Creatinine, bilirubin, and fibrinolysis resistance are associated with multi-organ dysfunction and likely risk factors for prolonged intensive care unit (pICU) stay following liver transplantation (LT). We hypothesize postoperative day-1 (POD-1) labs will predict pICU. METHODS: LT recipients had clinical laboratories and viscoelastic testing with tissue plasminogen activator thrombelastography (tPA TEG) to quantify fibrinolysis resistance (LY30) on POD-1. pICU was defined as one week or longer in the ICU. Logistic regression was used to identify the relationship between POD-1 labs and pICU. RESULTS: Of 304 patients, 50% went to the ICU, with 15% experiencing pICU. Elevated creatinine (OR 6.6, P â< â0.001) and low tPA TEG LY30 (OR 3.7, P â= â0.004) were independent predictors of pICU after controlling for other risk factors. A 9-fold increase in the rate of 90-day graft loss (19% vs 2% p â< â0.001) was observed patients who had these risk factors for pICU. CONCLUSION: Elevated creatine and fibrinolysis resistance are associated with pICU and poor outcomes following LT.
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Transplante de Fígado , Ativador de Plasminogênio Tecidual , Humanos , Creatinina , Fibrinólise , Cuidados CríticosRESUMO
BACKGROUND: End stage renal disease (ESRD) is associated with platelet dysfunction but also thromboembolic complications. The specific role of increased blood urea nitrogen (BUN) on coagulation is unclear. We aimed to characterize thromboelastography (TEG) parameters from males and females with ESRD and normal kidney function and evaluate if exogenous urea in vitro reproduced those TEG differences. METHODS: We collected blood samples from 20 living kidney donors and 20 kidney recipients. TEG was performed without and with two increasing urea concentrations in vitro. TEG parameters were compared between recipients and donors. RESULTS: Blood from kidney recipients showed baseline increased maximum amplitude (MA) and shortened time to maximum amplitude (TMA) compared to donors. These differences were not confirmed in females. In all patients, BUN was inversely correlated with TMA (r = -0.342; p = 0.031). In males, BUN and creatinine concentrations showed a direct correlation with MA (0.583; p = 0.007) and an inverse correlation with TMA (r = -0.520; p = 0.019). Urea in vitro decreased R-time (p = 0.005) and increased LY30 (p = 0.009) in donors but not recipients. CONCLUSIONS: ESRD is associated with increased MA and decreased TMA on TEG. No change in MA was observed with increasing urea concentrations in vitro. Gender-specific variability in TEG parameters were observed.
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Falência Renal Crônica , Tromboelastografia , Masculino , Feminino , Humanos , Coagulação Sanguínea , Diálise Renal , PacientesRESUMO
BACKGROUND: Tissue plasminogen activator (tPA) added to thrombelastography (TEG) detects hyperfibrinolysis by measuring clot lysis at 30 min (tPA-challenge-TEG). We hypothesize that tPA-challenge-TEG is a better predictor of massive transfusion (MT) than existing strategies in trauma patients with hypotension. METHODS: Trauma activation patients (TAP, 2014-2020) with 1) systolic blood pressure <90 mmHg (early) or 2) those who arrived normotensive but developed hypotension within 1H postinjury (delayed) were analyzed. MT was defined as >10 RBC U/6H postinjury or death within 6H after ≥1 RBC unit. Area under the receiver operating characteristics curves were used to compare predictive performance. Youden index determined optimal cutoffs. RESULTS: tPA-challenge-TEG was the best predictor of MT in the early hypotension subgroup (N = 212) with positive (PPV) and negative predictive values (NPV) of 75.0%, and 77.6%, respectively. tPA-challenge-TEG was a better predictor of MT than all but TASH (PPV = 65.0%, NPV = 93.3%) in the delayed hypotension group (N = 125). CONCLUSIONS: The tPA-challenge-TEG is the most accurate predictor of MT in trauma patients arriving hypotensive and offers early recognition of MT in patients with delayed hypotension.