Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing...
Purpose: Hospital-acquired (HA) sepsis is associated with increased resource utilization and mortality compared with community acquired (CA) sepsis. The purpose of this study was to identify independent predictors of in-hospital mortality from HA-sepsis. Materials and methods:Retrospective study of adult patients admitted with HA or CA-sepsis. Predictors were identified using logistic regression.Results: There were 3917 sepsis encounters, of which 3186 were CA and 731 were HA. History of stroke (83/731, 11%) and myocardial infarction (70/731, 10%) were higher in HA than CAsepsis (stroke: 258/3186, 8%, p = .005; myocardial infarction: 213/3186, 7%, p = .007). HA-sepsis patients required more mechanical ventilation (153/731, 21%) than CA-patients (218/3186, 7%, p < .001) and had a higher rate of vasopressor use (334/731, 46%) than CA patients (832/3186,26%, p < .001). The HA group had longer ICU lengths of stay (LOS) than CA patients did at 9 days and 2.8 days, respectively (p < .0001). Moderate to severe liver disease (OR = 27, 95%CI 1.4,513, p = . 031) and congestive heart failure (CHF, 5.81, 95% CI 1.3, 26, p = .025) were predictive of inhospital mortality from HA-sepsis.Conclusions: Liver disease and CHF were independent predictors of in-hospital mortality in HA-sepsis. HA-sepsis patients had increased prevalence of previous stroke, myocardial infarction, and liver disease.
Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy, which is characterized by areflexia and ascending paresthesia which can progress to a respiratory failure. Certain conditions, such as vasculitis and heavy metal and drug toxicity, may have misleadingly similar clinical presentation to GBS. We describe a case of a patient with cystic fibrosis and intravenous colistin-induced neurotoxicity mimicking GBS. The patient had used inhaled colistin on five occasions with no adverse effects, however, developed symptoms on the second day of intravenous treatment. Overlapping findings between immune-mediated polyneuropathy and drug-induced neurotoxicity include limb paresthesia and decreased reflexes. Perioral tingling, however, is a common presentation of colistin-induced neurotoxicity, and therefore, is an important differentiating factor. Early diagnosis prevents further neurologic decline, extensive unnecessary workup and potentially harmful incorrect management.
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