Adoptive regulatory T-cell therapy protects against cerebral ischemia.

OBJECTIVE: Recent evidence suggests that functional deficiency in regulatory T cells (Tregs), an innate immunomodulator, exacerbates brain damage after cerebral ischemia. We therefore evaluated the effect of Treg transfer in rodent models of ischemic stroke and further investigated the mechanism underlying Treg-afforded neuroprotection. METHODS: We examined the therapeutic potential of Tregs and the mechanisms of neuroprotection in vivo in 2 rodent models of ischemic stroke and in vitro in Treg-neutrophil cocultures using a combined approach including cell-specific depletion, gene knockout mice, and bone marrow chimeras. RESULTS: Systemic administration of purified Tregs at 2, 6, or even 24 hours after middle cerebral artery occlusion resulted in a marked reduction of brain infarct and prolonged improvement of neurological functions lasting out to 4 weeks. Treg-afforded neuroprotection was accompanied by attenuated blood-brain barrier (BBB) disruption during early stages of ischemia, decreased cerebral inflammation, and reduced infiltration of peripheral inflammatory cells into the lesioned brain. Surprisingly, Tregs exerted early neuroprotection without penetrating into the brain parenchyma or inhibiting the activation of residential microglia. Rather, both in vivo and in vitro studies demonstrated that Tregs suppressed peripheral neutrophil-derived matrix metallopeptidase-9 production, thus preventing proteolytic damage of the BBB. In addition to its potent central neuroprotection, Treg treatment was shown to ameliorate poststroke lymphopenia, suggesting a beneficial effect on immune status. INTERPRETATION: Our study suggests that Treg adoptive therapy is a novel and potent cell-based therapy targeting poststroke inflammatory dysregulation and neurovascular disruption.

Intraoperative fluid management in open gastrointestinal surgery: goal-directed versus restrictive.

OBJECTIVE: The optimal strategy for fluid management during gastrointestinal surgery remains unclear. Minimizing the variation in arterial pulse pressure, which is induced by mechanical ventilation, is a potential strategy to improve postoperative outcomes. We tested this hypothesis in a prospective, randomized study with lactated Ringer's solution and 6% hydroxyethyl starch solution. METHOD: A total of 60 patients who were undergoing gastrointestinal surgery were randomized into a restrictive lactated Ringer's group (n = 20), a goal-directed lactated Ringer's group (n = 20) and a goal-directed hydroxyethyl starch group (n = 20). The goal-directed fluid treatment was guided by pulse pressure variation, which was recorded during surgery using a simple manual method with a Datex Ohmeda S/5 Monitor and minimized to 11% or less by volume loading with either lactated Ringer's solution or 6% hydroxyethyl starch solution (130/0.4). The postoperative flatus time, the length of hospital stay and the incidence of complications were recorded as endpoints. RESULTS: The goal-directed lactated Ringer's group received the greatest amount of total operative fluid compared with the two other groups. The flatus time and the length of hospital stay in the goal-directed hydroxyethyl starch group were shorter than those in the goal-directed lactated Ringer's group and the restrictive lactated Ringer's group. No significant differences were found in the postoperative complications among the three groups. CONCLUSION: Monitoring and minimizing pulse pressure variation by 6% hydroxyethyl starch solution (130/0.4) loading during gastrointestinal surgery improves postoperative outcomes and decreases the discharge time of patients who are graded American Society of Anesthesiologists physical status I/II.

Intraoperative fluid management in open gastrointestinal surgery: goal-directed versus restrictive

OBJECTIVE: The optimal strategy for fluid management during gastrointestinal surgery remains unclear. Minimizing the variation in arterial pulse pressure, which is induced by mechanical ventilation, is a potential strategy to improve postoperative outcomes. We tested this hypothesis in a prospective, randomized study with lactated Ringer's solution and 6% hydroxyethyl starch solution. METHOD: A total of 60 patients who were undergoing gastrointestinal surgery were randomized into a restrictive lactated Ringer's group (n = 20), a goal-directed lactated Ringer's group (n = 20) and a goal-directed hydroxyethyl starch group (n = 20). The goal-directed fluid treatment was guided by pulse pressure variation, which was recorded during surgery using a simple manual method with a Datex Ohmeda S/5 Monitor and minimized to 11% or less by volume loading with either lactated Ringer's solution or 6% hydroxyethyl starch solution (130/0.4). The postoperative flatus time, the length of hospital stay and the incidence of complications were recorded as endpoints. RESULTS: The goal-directed lactated Ringer's group received the greatest amount of total operative fluid compared with the two other groups. The flatus time and the length of hospital stay in the goal-directed hydroxyethyl starch group were shorter than those in the goal-directed lactated Ringer's group and the restrictive lactated Ringer's group. No significant differences were found in the postoperative complications among the three groups. CONCLUSION: Monitoring and minimizing pulse pressure variation by 6% hydroxyethyl starch solution (130/0.4) loading during gastrointestinal surgery improves postoperative outcomes and decreases the discharge time of patients who are graded American Society of Anesthesiologists physical status I/II.