Thrombopoietin as Biomarker and Mediator of Cardiovascular Damage in Critical Diseases

Thrombopoietin (TPO) is a humoral growth factor originally identified for its ability to stimulate the proliferation and differentiation of megakaryocytes. In addition to its actions on thrombopoiesis, TPO directly modulates the homeostatic potential of mature platelets by influencing their response to several stimuli. In particular, TPO does not induce platelet aggregation per se but is able to enhance platelet aggregation in response to different agonists (“priming effect”). Our research group was actively involved, in the last years, in characterizing the effects of TPO in several human critical diseases. In particular, we found that TPO enhances platelet activation and monocyte-platelet interaction in patients with unstable angina, chronic cigarette smokers, and patients with burn injury and burn injury complicated with sepsis. Moreover, we showed that TPO negatively modulates myocardial contractility by stimulating its receptor c-Mpl on cardiomyocytes and the subsequent production of NO, and it mediates the cardiodepressant activity exerted in vitro by serum of septic shock patients by cooperating with TNF-α and IL-1β. This paper will summarize the most recent results obtained by our research group on the pathogenic role of elevated TPO levels in these diseases and discuss them together with other recently published important studies on this topic

Platelets and multi-organ failure in sepsis

Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models

Psychiatric patients at the emergency department: factors associated with length of stay and likelihood of hospitalization

Emergency department (ED) care for psychiatric patients is currently understudied despite being highly utilized. Therefore, we aimed to analyze psychiatric patients' length of stay (LOS) and LOS-related factors at the ED and to investigate and quantify the likelihood of being hospitalized after an emergency psychiatric evaluation. Charts of 408 individuals who sought help at the ED were retrospectively assessed to identify patients' sociodemographic and clinical data upon ED admission and discharge. All interventions performed at the ED (e.g., medications, hospitalization, clinical advice at discharge) were collected as well. The LOS for psychiatric patients was relatively short (6.5 h), and substance/alcohol intoxication was the main factor impacting LOS. Upon ED arrival, hospitalized patients were mostly men, most often had a yellow/severe triage code, and most often had a positive history of psychiatric illness, psychotic symptoms, euphoric mood, or suicidal ideation. Manic symptoms and suicidal ideation were the conditions most frequently leading to hospitalization. Given the paucity of real-world data on psychiatric patients’ LOS and outcomes in the ED context, our findings show that psychiatric patients are evaluated in a reasonable amount of time. Their hospitalization is mostly influenced by clinical conditions rather than predisposing (e.g., age) or system-related factors (e.g., mode of arrival)

Pentosan polysulfate inhibits atherosclerosis in watanabe heritable hyperlipidemic rabbits; differential modulation of metalloproteinase-2 and -9

Pentosan polysulfate (PPS), a heparinoid compound essentially devoid of anticoagulant activity, modulates cell growth and decreases inflammation. We investigated the effect of PPS on the progression of established atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbits. After severe atherosclerosis developed on an atherogenic diet, WHHL rabbits were treated with oral PPS or tap water for 1 month. The aortic intima-to-media ratio and macrophage infiltration were reduced, plaque collagen content was increased, and plaque fibrous caps were preserved by PPS treatment. Plasma lipid levels and post-heparin hepatic lipase activity remained unchanged. However, net collagenolytic activity in aortic extracts was decreased, and the levels of matrix metalloproteinase (MMP)-2 and tissue inhibitor of metalloproteinase (TIMP) activity were increased by PPS. Moreover, PPS treatment decreased tumor necrosis factor α (TNFα)-stimulated proinflammatory responses, in particular activation of nuclear factor-κB and p38, and activation of MMPs in macrophages. In conclusion, oral PPS treatment prevents progression of established atherosclerosis in WHHL rabbits. This effect may be partially mediated by increased MMP-2 and TIMP activities in the aortic wall and reduced TNFα-stimulated inflammation and MMP activation in macrophages. Thus, PPS may be a useful agent in inhibiting the progression of atherosclerosis