tbuckley/cabot-search huggingface dataset:
Activation of the orphan receptor COUP-TF1 by 1,1-bis(3’-indolyl)-1-(4-pyridyl)methane.
Authors: Kyungsil Yoon, Chien-Cheng Chen, Iman Al-Swaiti, Stephen Safe
Journal: Cancer Research (2006)

5348  Chicken ovalbumin upstream promoter-transcription factor (COUP-TF) is an orphan nuclear receptor that can bind DNA as a homodimer or a heterodimer with retinoid X receptor or thyroid hormone receptor. COUP-TF exhibits multiple tissue-specific functions and these include silencing of other nuclear receptors and transcription factors. Ligand-dependent activation of COUP-TF has hitherto not been reported. Studies in this laboratory have demonstrated that different structural classes of triaryl methanes containing two bis-indole substituents activate several orphan receptors and a subclass of 1,1-bis(3’-indolyl)-1-(heteroaromatic)methanes were identified as COUP-TF1 activators. In MCF-7 breast cancer cells transfected with chimeric Gal4-COUP-TF1-FL (full length) expression and a pGal4 construct containing 5 tandem Gal4 response elements linked to a luciferase receptor gene, 10-20uM 1,1-bis(3’-indolyl)-1-(4-pyridyl)methane (DIM-C-Pyr-4) induced transactivation. The effect of several other analogs containing heteroaromatic rings including the 3- and 2-pyridyl isomers were also investigated and exhibited minimal activation of Gal4-COUP-TF1. We also determined the effects of DIM-C-Pyr-4 on activation of chimeric COUP-TF1-ΔC (aa 1-211) and COUP-TF1-ΔN (aa 151-423) and in which regions of the ligand binding domain E and the A/B domain were deleted respectively. DIM-C-Pyr-4 induced transactivation > 15 fold in cells transfected with COUP-TF1-ΔC (aa 1-211) whereas decreased (>3 fold) but significant transactivation was observed in cells transfected with COUP-TF1-ΔN (aa 151-423). Cotreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor blocked the DIM-C-Pyr-4-induced transcriptional activation of COUP-TF1-ΔC (aa 1-211) by 70%. We also investigated ligand-dependent interaction of Gal4-coactivator (SRC-1, SRC-2, SRC-3, TRAP220, CARM1 and PGC-1) and VP16-COUP-TF1 (full-length) in a mammalian two-hybrid assay in LNCaP cells and SRC-1 and SRC-2 were the major COUP-TF1 interacting coactivators. This represents the first report of COUP-TF1 activation and current studies are investigating the mechanisms of this response and the effects on gene expression.
Money to transform NHS services is diverted to reducing deficits, watchdog finds
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Extra government money pledged by the government to help the NHS transform services has instead been diverted to reducing financial deficits, a report from the National Audit Office (NAO) has found.1

The NHS received an additional £1.8bn (€2bn; $2.5bn) sustainability and transformation fund in 2016-17. This was intended to mitigate the future impact of significantly less funding growth from 2017-18 onwards, and to provide the necessary stability to improve performance and transform services in parallel.

But while the NAO said that the fund had helped the NHS improve its financial position from a £1.8bn deficit in 2015-16 to a £111m surplus …
Abstract 20681: Drug Discovery for PH-HFpEF: High Throughput Screening in Identification of SIRT3 Activators
Authors: Andrea R Levine, Travis Lear, Bill B Chen, Yen-Chun Lai, Mark T Gladwin
Journal: Circulation (2017)

Introduction: SIRT3 is a NAD+ dependent protein deacetylase which, when under-expressed, has been linked to the metabolic syndrome and pulmonary arterial hypertension. Our laboratory has shown that...
Can Expiratory Electrical Diaphragmatic Activity Guide Setting Of Positive End-Expiratory Pressure During Spontaneous Breathing In Acute Respiratory Failure?
Authors: Mariangela Pellegrini, Agneta Roneus, T. Fiore, Göran Hedenstierna, A. Larsson, G. Perchiazzi
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Can Expiratory Electrical Diaphragmatic Activity Guide Setting Of Positive End-Expiratory Pressure During Spontaneous Breathing In Acute Respiratory Failure?
Preoperative staging with magnetic resonance imaging (MRI) and endorectal ultra-sonography (ERUS) for locally advanced rectal cancer (LARC) after chemoradiotherapy (CRT): Accuracy with histopathologic findings.
Authors: Marc Van Den Eynde, Nathalie Kouinche, Aline Van Maanen, Cristina Anca Dragean, Etienne Danse, Marie-Armelle Denis, Alex Kartheuser, Christophe Remue, Daniel Leonard, Pamela Baldin, Yves Humblet, Pierre Scalliet, Anne Jouret-Mourin
Journal: Journal of Clinical Oncology (2016)

3618 Background: Pre-operative CRT followed by total mesorectal excision (TME) is nowadays the standard for LARC (cT3-T4N0 or cTxN+). TME could be avoided for patients with pathologic complete response. Our aim was to determine whether preoperative staging (MRI/ERUS) after CRT could accurately predict a pathological response. Methods: Between 1998 and 2014, 331 patients with LARC who underwent TME after CRT were identified. Only patients with available and complete results for both preoperative MRI and ERUS (T and N staging) and pathological staging were analyzed. Relevant categories of tumor downstaging (yT0N0: complete; yT1-2N0: present; yT3-T4N0 or yTxN+: absence) were compared. Accuracy of MRI and EUS was assessed using the ROC method and agreement between them by the kappa test. Mc-Nemar’s test evaluated accuracy difference. Results: 154 patients (sex ratio M/F 1.96; mean age 62.0 years-old; upper (15.5%), mid (26.6%) and low rectum (57.7%)) were analyzed. T-stage was accurately estimated by MRI in 53.2% (overstating (O): 35.1%, understaging (U): 11.7%) and by ERUS in 55.8% (O: 33.8%, U: 10.4%); Kappa coefficient: 0.489 (moderate agreement). N-stage was accurately estimated by MRI in 64.3% (O: 23.4%, U: 12.3%) and by ERUS in 63.6% (O: 14.9%, U: 21.4%); Kappa coefficient: 0.326 (fair agreement). Accuracies in the prediction of absence of tumor downstaging were similar with MRI (66.9%) and ERUS (74.0%; p = 0.25) both with an ability to predict non-responders (sensitivity) of respectively 85.6% and 87.6% (specificity of 35.1% and 50.9% respectively). Accuracies in the prediction of complete tumor downstaging were similar for MRI (85.1%) and ERUS (84.4%; p = 0.491) with a low ability to predict complete responders (sensitivity MRI: 25.0%, ERUS: 30.0%; specificity: MRI: 94.0%, ERUS: 92.5%). Conclusions: After CRT, preoperative MRI and ERUS accurately predict an absence of tumor downstaging but seem unhelpful for adequately estimate a complete pathological response and a possible non operative patient management.
STUDIES IN OBSESSIVE RUMINATIVE TENSION STATES
Authors: Lawrence F. Woolley
Journal: American Journal of Psychiatry (1930)

Clinical observation of paraergastic components occurring in obsessive ruminative tension states have led us to a study of the fundamental gross relationships involved. Very little appears in the literature concerning this subject. A group of cases is presented which shows that a relationship does exist between these diagnostic groups on the basis of incidence according to sex, psychological type, clinical personality type, body type, complications with other functional mental conditions and rate of recovery. Two typical cases are presented and analyzed briefly with a view to determining the foundation of this relationship and a summary of 87 cases analyzed is given.
The association between air pollution and the incidence of idiopathic pulmonary fibrosis in Northern Italy
Authors: Sara Conti, Sergio Harari, Antonella Caminati, Antonella Zanobetti, Joel D. Schwartz, Pietro A. Bertazzi, Giancarlo Cesana, Fabiana Madotto
Journal: European Respiratory Journal (2018)

Acute exacerbations and worsening of idiopathic pulmonary fibrosis (IPF) have been associated with exposure to ozone (O 3 ), nitrogen dioxide (NO 2 ) and particulate matter, but chronic exposure to air pollution might also affect the incidence of IPF. We investigated the association between chronic exposure to NO 2 , O 3 and particulate matter with an aerodynamic diameter &lt;10 μm (PM 10 ) and IPF incidence in Northern Italy between 2005 and 2010. Daily predictions of PM 10 concentrations were obtained from spatiotemporal models, and NO 2 and O 3 hourly concentrations from fixed monitoring stations. We identified areas with homogenous exposure to each pollutant. We built negative binomial models to assess the association between area-specific IPF incidence rate, estimated through administrative databases, and average overall and seasonal PM 10 , NO 2 , and 8-hour maximum O 3 concentrations. Using unadjusted models, an increment of 10 µg·m −3 in NO 2 concentration was associated with an increase between 7.93% (95% CI 0.36–16.08%) and 8.41% (95% CI −0.23–17.80%) in IPF incidence rate, depending on the season. After adjustment for potential confounders, estimated effects were similar in magnitude, but with larger confidence intervals. Although confirmatory studies are needed, our results trace a potential association between exposure to traffic pollution and the development of IPF.
Abstract 17885: Pulmonary Vascular Compliance Predicts Mortality in the Acute Respiratory Distress Syndrome
Authors: Thomas Metkus, Emmanouil Tampakakis, Christopher Mullin, Brian Houston, Todd Kolb, Stephen Mathai, Rachel Damico, Paul Hassoun, David Kass, Roy Brower, Ryan Tedford
Journal: Circulation (2015)

Introduction: Novel markers of prognosis in the acute respiratory distress syndrome (ARDS) are needed. Hypothesis: We hypothesized that pulmonary vascular compliance would predict outcome in ARDS, and that higher left heart filling pressure would be associated with increased pulsatile loading of the right ventricle manifested as reduced RC time. Methods: We performed a retrospective analysis of 392 subjects with a complete hemodynamic data set on trial day 0 in the ARDS Network Fluid and Catheter Treatment Trial of PA catheter use in ARDS. Pulmonary vascular compliance (Cpa) was calculated as stroke volume divided by PA pulse pressure. Pulmonary vascular resistance (PVR) was calculated as mean PA pressure minus pulmonary artery wedge pressure (PAWP) divided by cardiac output. The RC time was calculated as the product of PVR and Cpa. Cox proportional hazard modeling and Kaplan-Meier survival analysis were performed with primary outcome of death. Results: The mean age was 50 ± 16 years. Mean PA pressure and PAWP were both elevated (29 ± 8 mmHg and 15 ± 5 mmHg, respectively) as was cardiac output (7.7 ± 2.7 L/m). The mean PVR was 2.1 ± 1.2 Wood units and Cpa 4.6 ± 2.5 ml/mmHg. Mean RC time was 0.47 ± 0.24 seconds (s). With each 5 mmHg increase in PAWP, RC time decreased by 0.06 s (p&lt;0.0001 for slope). There was increased hazard of death per quartile decrease in Cp (HR 1.28, 95% CI 1.08-1.52; p = 0.004) and per quartile increase in PVR (HR 1.23, 95% CI 1.04-1.46; p = 0.02). Adjusted for APACHE III score, there remained a trend towards increased hazard of death per quartile increase in PVR (HR 1.2 95% CI 1.03-1.4, p = 0.02) and per quartile decrease in Cp (HR 1.18 95% CI 1.0-1.4, p = 0.055). Kaplan-Meier survival curves per quartile of Cp are shown in the Figure. Conclusion: Pulmonary vascular compliance predicts mortality in ARDS. Higher wedge pressure is associated with lower RC time in ARDS consistent with increased RV pulsatile loading.
Between a Rux and a Hard Place: Investigating Causes of Ruxolitinib Discontinuation, Salvage Treatment and Outcome in Myelofibrosis
Authors: Savan Shah, Chetasi Talati, Najla Al Ali, Eric Padron, David A Sallman, Kendra L. Sweet, Jeffrey E. Lancet, Alan F. List, Kenneth S. Zuckerman, Rami S. Komrokji, Andrew Kuykendall
Journal: Blood (2017)
The SMART-IgG Anti-hC5 Antibody (SKY59/RO7112689) Has Favorable PK, PD, Subcutaneous Bioavailability, and Safety Profile in Phase I HV Study
Authors: Alexander Roeth, Nagy Zsolt, Miklos Egyed, Erica Winter, Joy Hsu, Andreas Dieckmann, Judith Anzures-Cabrera, Marie Mannino, Elana Fernandez, Gregor Jordan, Barbara Klughammer, Kenji Shinomiya, Naoki Kotani, Ido Paz-Priel, Angelika Jahreis.
Journal: Blood (2017)
Quality of Life during the hay fever season after short-course subcutaneous immunotherapy with Lolium perenne peptides (LPP) in grass pollen related rhinoconjunctivitis: A RDBPCT
Authors: Ralph Mosges, Claus Bachert, Peter S. Creticos, Linda Cox, Stephen R. Durham, Sabine Pirotton, Marie-Alix Bonny, Thierry Legon, Ludo Haazen, Mohamed H. Shamji
Journal: Journal of Allergy and Clinical Immunology (2018)
A wormy surprise: ERCP for intrabiliary drainage of a hydatid cyst
Authors: Shawn Shah, Ming-ming Xu, Enad Dawod, Karim Halazun, Reem Sharaiha
Journal: Endoscopy (2018)

A 41-year-old man with a known hepatic hydatid cyst presented with several months of abdominal pain and more recent onset of jaundice. Despite repeated courses of albendazole, he reported no clinical improvement. Upon presentation, he underwent magnetic resonance cholangiopancreatography (MRCP), which revealed a multiloculated cystic structure within hepatic segments 5 and 6, measuring approximately 7 × 4.5 × 6.5 cm with mildly enhancing septations, and diffuse intrahepatic biliary ductal dilatation ([Fig. 1]).
Advancing Clinical Improvements for Patients Using the Theory-Driven and Data-Driven Branches of Computational Psychiatry
Authors: Quentin J. M. Huys
Journal: JAMA Psychiatry (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Psychiatry journal
Abstract 19531: Low Polyunsaturated Fatty Acids Levels Predict Long-Term Mortality in Patients With Acute Decompensated Heart Failure Independent of the Geriatric Nutritional Risk Index
Authors: shohei ouchi, Tetsuro Miyazaki, Kazunori Shimada, Yurina Sugita, Megumi Shimizu, Takao Kato, Tatsuro Aikawa, Shoko Suda, Masaru Hiki, Shuhei Takahashi, Hiroshi Iwata, Takatoshi Kasai, Katsumi Miyauchi, Hiroyuki Daida
Journal: Circulation (2017)

Introduction:  Geriatric nutritional risk index (GNRI) is one of the established parameters for the evaluation of nutritional status of patients. Low GNRI is related with mortality in patients with heart failure. Although polyunsaturated fatty acids (PUFAs), particularly omega-6 PUFAs (including dihomo-gamma-linolenic acid [DGLA] and arachidonic acid [AA]), are associated with long-term mortality in patients with acute decompensated heart failure (ADHF), the clinical significance of PUFAs in various nutrition statuses remains unclear. We investigated whether low PUFA levels predict poor prognosis of patients with ADHF, regardless of the GNRI.   Methods:  We enrolled 267 consecutive patients with ADHF admitted to the cardiac intensive care unit in our hospital from April 2012 to March 2014. Patients with malignant diseases, end-stage renal diseases, and patients who had received eicosapentaenoic acid (EPA) therapy were excluded. GNRI and fasting PUFA (DGLA, AA, EPA, and docosahexaenoic acid [DHA]) levels were measured within 24 hours after admission.   Results:  During the 22.6-month mean follow-up period, 62 patients died. The GNRI and individual PUFA levels were significantly lower in the non-survivor group compared with the survivor group (all  p   p   p  = 0.04, Figure). Multivariable cox regression analysis showed that low DGLA, AA, and DHA levels were predictors for all-cause mortality independent of the GNRI (all  p     Conclusion:  Decreased levels of PUFAs, especially DGLA, in patients with ADHF were significantly associated with long-term mortality, independent of the GNRI.
Long Term Outcome of Lenalidomide-Dexamethasone (Rd) Vs Melphalan-Lenalidomide-Prednisone (MPR) Vs Cyclophosphamide-Prednisone-Lenalidomide (CPR) As Induction Followed By Lenalidomide-Prednisone (RP) Vs Lenalidomide (R) As Maintenance in a Community-Based Newly Diagnosed Myeloma Population: Updated Analysis of EMN01 Phase III Study
Authors: Sara Bringhen, Massimo Offidani, Pellegrino Musto, Anna Marina Liberati, Giulia Benevolo, Nicola Cascavilla, Mariella Genuardi, Gianluca Gaidano, Donatella Zamagni, Paola Ferrando, Giovanni Pizzolo, Daniele Derudas, Manuela Gambella, Alida Dominietto, Ombretta Annibali, Giovanni Maria De Sabbata, Attilio Gabbas, Caterina Musolino, Chiara Pautasso, Renato Zambello, Giorgio La Nasa, Laura Maracci, Antonio Palumbo, Roman Hájek, Mario Boccadoro
Journal: Blood (2017)
Health care utilization and costs in women with metastatic breast cancer (mBC) receiving HER2-targeted agents (H2Ts).
Authors: Xue Song, Yanni Hao, Nicole Meyer, William M. Johnson, Nianwen Shi, Jaqueline Willemann Rogerio, Denise A. Yardley
Journal: Journal of Clinical Oncology (2014)

e11573 Background: Treatment (tx) costs of HER2+ mBC are substantial. Study objectives were to evaluate tx costs and utilization in mBC patients (pts) treated with H2Ts, by ER+ status, de novo vs recurrent, and age. Methods: Women ≥ 18 years, diagnosed with mBC (index) during 2008-2012 and treated with H2Ts were selected from a large claims database and followed until end of enrollment or death. Pts were stratified by ER+ status, de novo (≤90 days between initial BC dx and index) vs recurrent (>90 days between initial BC dx and index), and ages 18-44, 45-64, or 65+. Per patient per month utilization and costs were determined for all-cause and BC-related services. Multivariate analyses were used to derive total costs. Results: Of 2,629 eligible pts, 52% were ER+, 37% de novo, 15% 18-44, 69% 45-64 and 16% 65+. ER+ pts had lower utilization vs ER- for all services except all-cause RX fills and BC-related office administered and outpatient antineoplastics. Total costs were lower for ER+ vs ER- (mean (SE): all-cause $10,359 ($260) vs. $12,924 (336); BC-related $6,869 (195) vs. $7,757 (225)). De novo had lower all-cause inpatient admissions/days and emergency room visits, higher office visits, diagnostic radiology, lab and other outpatient, and higher BC-related utilization except emergency room and outpatient antineoplastics vs recurrent. Total costs were higher for de novo (all-cause $12,139 (357) vs. $11,184 ($253); BC-related $8,200 (269) vs $6,791 (174)). All-cause emergency room, other outpatient and RX fills increased with age. Total costs were highest for ages 18-44, declining with age (all-cause: $13,650 (500) 18-44 vs $13,101 (228) 45-64 vs $8,570 (334); BC-related: $9,075 (373) 18-44 vs $8,193 (161) vs $5,198 (231)). Conclusions: ER+ pts had lower total costs vs ER-, and lower utilization other than all-cause pharmacy and BC-related antineoplastics. Total costs were higher and utilization was higher in de novo vs recurrent except for all-cause inpatient, emergency room and RX fills, and BC-related emergency room and outpatient antineoplastics. Pts age 18-44 had the highest total costs and the highest utilization for all-cause labs and BC-related office visits, diagnostic radiology, labs and outpatient antineoplastics.
Effect of GemRIS (gemcitabine-releasing intravesical system, TAR-200) on antitumor activity in muscle-invasive bladder cancer (MIBC).
Authors: Siamak Daneshmand, Kamal S. Pohar, Gary D. Steinberg, Manju Aron, Christopher Cutie
Journal: Journal of Clinical Oncology (2017)

e16000 Background: Efficacy of current intravesical cytotoxic therapy for bladder cancer is limited by suboptimal dwell times and dose, and may result in local toxicities. GemRIS™ is a novel drug-device combination product that continuously delivers gemcitabine into the bladder over 7 days. Preclinical models demonstrated that GemRIS was well tolerated and resulted in no appreciable systemic exposure. Methods: This Phase 1b study evaluating the safety and tolerability of 2 GemRIS system deployments of 7 days each, separated by a 14-day rest period, in patients with confirmed MIBC scheduled for radical cystectomy (RC). A secondary endpoint included pathologic tumor response. Patients were required to have grossly visible tumor measuring &gt; / = 3 cm in size at study entry. Pharmacokinetic (PK) analyses were conducted in blood and urine. Response to GemRIS was assessed grossly and by histopathologic analysis. Results: 10 subjects were dosed with GemRIS and underwent RC. There were no treatment-related SAEs or discontinuations; no subject requested GemRIS removal. There was no evidence of treatment-related cytopenias and no events that resulted in a delay in RC. PK analyses have demonstrated measurable levels of gemcitabine in the urine with no detectable levels in plasma. Eighty percent (8/10) of patients experienced a reduction in exophytic tumor volume; 40% exhibited complete ablation of muscle invasive disease within this short 4-week course of therapy. Conclusions: GemRIS has demonstrated encouraging preliminary efficacy and safety. Further evaluation of GemRIS in MIBC is warranted. Clinical trial information: NCT02722538. [Table: see text]
Abstract 16647: Implantation of the Watchman Left Atrial Appendage Closure Device: A Comparison of TEE-Guidance vs ICE-Guidance
Authors: Jin Iwasawa, Yoshinari Enomoto, Dinesh Sharma, Chandrasekar Palaniswamy, Sujata Baluad, Subbarao Choudry, Noelle Langan, Marc A Miller, Jacob S Koruth, Srinivas R Dukkipati, Vivek Y Reddy
Journal: Circulation (2016)

Background: High-risk patients with atrial fibrillation that are poor candidates for long-term oral anticoagulation are candidates for LAA occlusion with the Watchman device. Transesophageal echoca...
Tie2 protects the vasculature against thrombus formation in systemic inflammation
Authors: Sarah J. Higgins, Karen De Ceunynck, John A. Kellum, Xiuying Chen, Xuesong Gu, Sharjeel A. Chaudhry, Sol Schulman, Towia A. Libermann, Shulin Lu, Nathan I. Shapiro, David C. Christiani, Robert Flaumenhaft, Samir M. Parikh
Journal: Journal of Clinical Investigation (2018)

Disordered coagulation contributes to death in sepsis and lacks effective treatments. Existing markers of disseminated intravascular coagulation (DIC) reflect its sequelae rather than its causes, delaying diagnosis and treatment. Here we show that disruption of the endothelial Tie2 axis is a sentinel event in septic DIC. Proteomics in septic DIC patients revealed a network involving inflammation and coagulation with the Tie2 antagonist, angiopoietin-2 (Angpt-2), occupying a central node. Angpt-2 was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality in 2 large independent cohorts (combined N = 1,077). In endotoxemic mice, reduced Tie2 signaling preceded signs of overt DIC. During this early phase, intravital imaging of microvascular injury revealed excessive fibrin accumulation, a pattern remarkably mimicked by Tie2 deficiency even without inflammation. Conversely, Tie2 activation normalized prothrombotic responses by inhibiting endothelial tissue factor and phosphatidylserine exposure. Critically, Tie2 activation had no adverse effects on bleeding. These results mechanistically implicate Tie2 signaling as a central regulator of microvascular thrombus formation in septic DIC and indicate that circulating markers of the Tie2 axis could facilitate earlier diagnosis. Finally, interventions targeting Tie2 may normalize coagulation in inflammatory states while averting the bleeding risks of current DIC therapies.