The mottling score is reproducible and easy to evaluate at the bedside. The mottling score as well as its variation during resuscitation is a strong predictor of 14-day survival in patients with septic shock.

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Sepsis is one of the main reasons for intensive care unit admission and is responsible for high morbidity and mortality. The usual hemodynamic targets for resuscitation of patients with septic shock use macro-hemodynamic parameters (hearth rate, mean arterial pressure, central venous pressure). However, persistent alterations of microcirculatory blood flow despite restoration of macro-hemodynamic parameters can lead to organ failure. This dissociation between macro-and microcirculatory compartments brings a need to assess end organs tissue perfusion in patients with septic shock. Traditional markers of tissue perfusion may not be readily available (lactate) or may take time to assess (urine output). The skin, an easily accessible organ, allows clinicians to quickly evaluate the peripheral tissue perfusion with noninvasive bedside parameters such as the skin temperatures gradient, the capillary refill time, the extent of mottling and the peripheral perfusion index.

Objective-Abdominal aortic aneurysm is an inflammatory disease leading to destructive vascular remodeling and ultimately to lethal aortic rupture. Despite its frequent association with atherosclerosis, compelling studies have shown striking differences and potentially opposite roles of T-cell helper responses in aneurysm as compared with atherosclerosis, casting doubt on the relevance and suitability of T-cell-targeted therapies in this context. Approach and Results-Here, we show that selective depletion of T regulatory (Treg) cells using a CD25-specific monoclonal antibody significantly enhances the susceptibility of C57Bl/6 mice to angiotensin II-induced abdominal aortic aneurysm and promotes aortic rupture (n=25-44 mice/group). Similar results are observed in angiotensin II-treated Cd80or Cd28 −/− mice with impaired Treg cell homeostasis (n=18-23 mice/group). Treg cell depletion is associated with increased immune cell activation and a blunted interleukin (IL)-10 anti-inflammatory response, suggesting an immunoinflammatory imbalance. Interestingly, Il-10 −/− mice (n=20 mice/group) show increased susceptibility to angiotensin II-induced abdominal aortic aneurysm and aortic rupture and are insensitive to Treg cell depletion. Finally, reconstitution of Cd28Treg-deficient mice with Treg cells (n=22 mice/group) restores a balance in the immunoinflammatory response, rescues the animals from increased susceptibility to aneurysm, and prevents aortic dissection. Conclusions-These results identify a critical role for Materials and MethodsMaterials and Methods are available in the online-only supplement. Figure 1A) led to important T-cell activation ( Figure 1B), significantly increased the incidence and severity of aneurysm, and predisposed to fatal aortic rupture ( Figure 1C and 1D). Enhanced susceptibility to AAA in Treg-depleted mice was associated with increased vascular accumulation of T cells ( Figure 1E) and marked elastin degradation ( Figure 1F). −/− mice (n=18) already at day 7 after angiotensin II (AngII) infusion compared with controls (n=18). This is associated with a significant increase of T-cell infiltration within the aortic wall of CD28 −/− mice infused with AngII (B), mostly in the adventitia (n=8/group). C, A shift of the immune response toward reduced ratio of Having established that genetic or antibody-induced Treg deficiency promotes AAA formation and rupture, we wanted to address the underlying mechanisms. We found that Treg-deficient Cd28 −/− mice displayed increased AAA development already at day 7 after AngII infusion ( Figure 3A), indicating an early acceleration of the disease in the absence of Treg cells. Enhanced susceptibility to AAA in Cd28 −/− mice was associated with increased vascular accumulation of leukocytes ( Figure I in the onlineonly Data Supplement), particularly T cells ( Figure 3B), and an imbalance of the systemic (spleen, Figure 3C) and local (aortic, Figure 3D) immunoinflammatory response as reflected by low interleukin (IL)-10 but high expression of IL-12 and inter...

We identified TREM-1 as a major upstream proatherogenic receptor. We propose that TREM-1 activation orchestrates monocyte/macrophage proinflammatory responses and foam cell formation through coordinated and combined activation of CD36 and TLR4. Blockade of TREM-1 signaling may constitute an attractive novel and double-hit approach for the treatment of atherosclerosis.

Significance: Under homeostatic conditions, the endothelium dynamically regulates vascular barrier function, coagulation pathways, leukocyte adhesion, and vasomotor tone. During sepsis and acute inflammation, endothelial cells (ECs) undergo multiple phenotypic and functional modifications that are initially adaptive but eventually become harmful, leading to microvascular dysfunction and multiorgan failure. Critical Issues and Recent Advances: Sepsis unbalances the redox homeostasis toward a pro-oxidant state, characterized by an excess production of reactive oxygen species and reactive nitrogen species, mitochondrial dysfunction, and a breakdown of antioxidant systems. In return, oxidative stress (OS) alters multiple EC functions and promotes a proinflammatory, procoagulant, and proadhesive phenotype. The OS also induces glycocalyx deterioration, cell death, increased permeability, and impaired vasoreactivity. Thus, during sepsis, the ECs are both a significant source and one of the main targets of OS. Future Directions: This review aims at covering the current understanding of the role of OS in the endothelial adaptive or maladaptive multifaceted response to sepsis and to outline the therapeutic potential and issues of targeting OS and endothelial dysfunction during sepsis and septic shock. One of the many challenges in the management of sepsis is now based on the detection and correction of these anomalies of endothelial function. Antioxid. Redox Signal. 00, 000-000.

After initial septic shock resuscitation, StO(2) measured around the knee is a strong predictive factor of 14-day mortality.

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