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Background: Cold renal perfusion (CRP) with 4[degrees]C crystalloid fluids has been described as a method to reduce renal injury during open surgical repair of complex aortic aneurysms (cAAs) (those requiring at least a suprarenal clamp site). We performed a meta-analysis to ascertain whether CRP improves kidney-related outcomes after open surgical cAA repair. Methods: Patients of any age or gender who had undergone open surgical repair of cAAs were included. Primary outcomes were the presence of postoperative kidney injury, the need for dialysis and mortality related to kidney injury. We compared patients who were treated with any intraoperative CRP strategy to a control population without CRP. We used a fixed-effects model to analyze derived odds ratios (ORs) and assess heterogeneity. We performed risk of bias analysis to identify potential confounding elements. Results: Among the 935 studies screened, 5 primary articles met the inclusion criteria. Cold renal perfusion significantly reduced postoperative acute kidney injury (OR 0.46 [95% confidence interval 0.32-0.68], Z = 3.98, p = 0.001). Only 1 study included data for the other primary outcomes. The data were considered homogeneous, with Cochrane Q = 0.23 and P of 0%. Conclusion: This meta-analysis showed reduced postoperative acute kidney injury with the use of CRP during open cAA repair. A prospective randomized controlled trial to perform further subgroup analysis and research the various types of CRP solutions may be warranted to identify further possible benefits. Contexte : La protection rénale hypothermique (PRH) au moyen de liquides cristal-loïdes à 4[degrees]C a été décrite en tant que méthode pour prévenir l'atteinte rénale lors des réparations d'anévrisme de l'aorte complexes (AAC) par chirurgie ouverte (qui nécessite au moins un clampage suprarénal). Nous avons procédé à une méta-analyse pour vérifier si la PRH améliore les paramètres rénaux après une réparation d'AAC par chirurgie ouverte. Méthodes : Nous avons inclus toutes les personnes (tous âges et sexes confondus) ayant subi une réparation d'AAC par chirurgie ouverte. Les paramètres principaux étaient atteinte rénale postopératoire, recours à la dialyse ou mortalité en lien avec l'insuffisance rénale. Nous avons comparé la population soumise à toute forme de PRH peropératoire à la population témoin non soumise à la PRH. Nous avons utilisé un modèle à effets fixes pour analyser les rapports des cotes (RC) dérivés et mesurer l'hétérogénéité. Nous avons effectué une analyse des risques de biais pour dégager de possibles variables de confusion. Résultats : Parmi les 935 études recensées, 5 articles principaux répondaient aux critères d'inclusion. La PRH a signifieativement contribué à réduire l'atteinte rénale postopératoire aiguë (RC 0,46 [intervalle de confiance de 95% 0,32-0,68], Z= 3,98, p = 0,001). Une seule étude incluait des données concernant les autres paramètres principaux. Les données ont été considérées homogènes, avec un test Q de Cochran = 0,23 et un coefficient P de 0%. Conclusion : Cette méta-analyse a montré une diminution de l'atteinte rénale postopératoire aiguë avec l'utilisation de la PRH en cours d'intervention pour réparation d'AAC ouverte. Il serait souhaitable de procéder à un essai randomisé et contrôlé prospectif pour approfondir l'analyse de sous-groupes et des divers types de solutions pour PRH, afin d'en connaître les autres avantage possibles., Patients undergoing major open surgical repair of complex aortic aneurysms (cAAs) are at heightened postoperative risk for acute kidney injury (AKI). (1-9) Renal insufficiency has been reported in up to [...]

Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV- PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy. Moreover, globally enhanced tumor vessel perfusion could be detected by Doppler ultrasonography before changes in tumor size, which predicted final therapeutic efficacy with more than 90% sensitivity and specificity. Mechanistically, [CD8.sup.+] T cell depletion, IFN-[gamma] neutralization, or implantation of tumors in IFN-[gamma] receptor knockout mice abrogated the vessel perfusion enhancement and antitumor effects of ICB. These results demonstrated that ICB increased vessel perfusion by promoting [CD8.sup.+] T cell accumulation and IFN-[gamma] production, indicating that increased vessel perfusion reflects the successful activation of antitumor T cell immunity by ICB. Our findings suggest that vessel perfusion can be used as a novel noninvasive indicator for predicting ICB responsiveness., Introduction Recent advances in cancer immunotherapy have revolutionized cancer treatment. Immune checkpoint blockade (ICB), designed to target immune suppressive signals such as cytotoxic T lymphocyte-associated protein 4 (CTLA4) or programmed [...]

Objective To investigate the short- and medium-term renal hemodynamic and functional responses to both short and sustained hypoperfusion. Subjects Eleven Merinos ewes. Setting Animal laboratory of the University Physiology Institute. Design Prospective observational study. Interventions Studies were performed in conscious sheep after unilateral nephrectomy with a vascular occluder and flow probe implanted on the remaining renal artery. In five sheep, renal blood flow (RBF) was reduced by 25, 50 and 75%, respectively, by acute vascular occlusion for 30 min at weekly intervals. In another six sheep, RBF was reduced by 80% for 2 h. Measurements and results After 25, 50 or 75% renal hypoperfusion for 30 min, there was no associated extended loss of renal function. During 2 h of 80% hypoperfusion, urine output decreased from 80 to 17 ml, and creatinine clearance from 32 to 3 ml/min, whereas plasma creatinine increased from 103 to 132 [mu]mol/l, and fractional excretion of sodium and urea increased. Release of occlusion induced brief hyperemia before all measured variables returned to normal within 8 h and remained normal for the following 72 h. At autopsy, the kidneys were histopathologically normal. Conclusions Various degrees of renal hypoperfusion for 30 min did not induce prolonged changes in renal function or blood flow. Even with sustained severe hypoperfusion, there was rapid recovery to baseline function and flow. Unlike total ischemia, severe hypoperfusion alone is insufficient to induce subsequent persistent AKI., Author(s): Takao Saotome [sup.1] , Ken Ishikawa [sup.1] , Clive N. May [sup.1] , Ian E. Birchall [sup.1] , Rinaldo Bellomo [sup.2] [sup.3] Author Affiliations: (1) grid.1008.9, 000000012179088X, Howard Florey [...]

Byline: Gregory M. T. Hare (1,2), Elaine Liu (1), Andrew J. Baker (1), C. David Mazer (1,2) Keywords: Hemoglobin based oxygen carrier; Hemodilution; Cerebral hypoxia; Lactate Abstract: Purpose To determine the oxygen affinity for optimal tissue oxygen delivery with a hemoglobin--hydroxyethyl starch conjugate (HRC 101). Methods Anesthetized rats were hemodiluted (180 ml kg.sup.-1) with low (P.sub.50 ~70 mmHg) or high affinity (P.sub.50 ~14 mmHg) HRC 101 at hemoglobin (Hb) concentrations near 100 or 70 g l.sup.-1 (n = 6--8). Hippocampal tissue oxygen tension ([P.sub.Br]O.sub.2), blood flow, arterial blood gases, Hb, hematocrit (Hct) and lactate were measured. Data (mean +- SD) were analyzed by two-way ANOVA. Results Hemodilution reduced the hematocrit to 1 +- 1% in all groups. [P.sub.Br]O.sub.2 was best maintained after hemodilution with low affinity HRC 101 at Hb 100 and 70 g l.sup.-1 (25.2 +- 7.6 and 16.6 +- 8.3 torr, respectively). [P.sub.Br]O.sub.2 decreased (9.5 +- 9.3 torr, P < 0.05) and serum lactate levels increased (5.0 +- 1.7 mmol l.sup.-1, P < 0.05) following hemodilution with the high affinity HRC 101 (Hb 100 g l.sup.-1). Conclusions HRC 101 with a lower oxygen affinity favored tissue perfusion and maintained [P.sub.Br]O.sub.2 after near complete blood volume exchange in rats. Author Affiliation: (1) Departments of Anesthesia and Critical Care, Cara Phelan Centre for Trauma Research, The Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada (2) Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada Article History: Registration Date: 28/05/2009 Received Date: 29/12/2008 Accepted Date: 16/05/2009 Online Date: 10/07/2009 Article note: Preliminary results were presented at the meeting of 10th International Society of Blood Substitutes, Providence, Rhode Island, 13 June 2005. Dr. Hare is a recipient of the Bristol-Myers Squibb-CAS Career Scientist Award. Electronic supplementary material The online version of this article (doi: 10.1007/s00134-009-1532-2) contains supplementary material, which is available to authorized users.

Byline: Jorn Adolphs (1), Diego K. Schmidt (1), Ines Korsukewitz (1), Britta Kamin (1), Helmut Habazettl (2,3), Michael Schafer (1), Martin Welte (4) Keywords: Animal model; Sympathetic blockade; Sepsis; Intravital microscopy; Blood flow; Mucosa Abstract: Objective To investigate whether sympathetic blockade by means of thoracic epidural anaesthesia (TEA) increases intestinal perfusion during normotensive endotoxaemia. Design A prospective, randomised and controlled animal study. Setting Animal laboratory in a university hospital. Subjects Sprague-Dawley male rats. Interventions The rats were anaesthetised with urethane and ketamine, mechanically ventilated and haemodynamically monitored. Lidocaine or saline were infused continuously via thoracic epidural catheters followed by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (1.5 mg/kg per h). Densities of perfused and non-perfused capillaries (i.e., with and without erythrocyte perfusion, respectively) as well as erythrocyte velocity in both the mucosa and the muscularis of the terminal ileum were determined using intravital microscopy. Measurements and results Measurements were performed at baseline, after 30 min of epidural infusion as well as after 60 and 120 min of lipopolysaccharide infusion. In animals receiving TEA, mean arterial pressure and heart rate were significantly reduced throughout the experiment. In the muscularis the endotoxaemia-induced increase in non-perfused capillaries was absent with epidural lidocaine (0 [0/0] versus 39 [36/137] cm.sup.-1, median [25.sup.th/75.sup.th percentile]), whereas in the mucosa perfused capillary density declined to a greater extent than in controls (-47 [-53/-23]%) versus -19 [-34/+10]%, p Conclusions Microvascular perfusion data during endotoxaemia show a redistribution of blood flow towards the mucosa. TEA seems to impede this redistribution resulting in improved muscularis and worsened mucosal microvascular perfusion. Author Affiliation: (1) Department of Anaesthesiology and Critical Care Medicine, Campus Benjamin Franklin, Charite--Universitatsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany (2) Department of Physiology, Campus Benjamin Franklin, Charite--Universitatsmedizin Berlin, Arnimallee 22, 14095, Berlin, Germany (3) Department of Anaesthesiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353, Berlin, Germany (4) Department of Anaesthesiology and Intensive Care Medicine, Klinikum Darmstadt, Grafenstrasse 9, 64283, Darmstadt, Germany Article History: Registration Date: 05/08/2004 Received Date: 04/03/2004 Accepted Date: 30/07/2004 Online Date: 26/08/2004

Byline: T. Koivisto (1), M. Vapalahti (1), I. Parviainen (2), J. Takala (2) Keywords: Intensive care Endovascular therapy Splanchnic circulation Subarachnoid hemorrhage Surgery Tonometry Abstract: Objective: To evaluate splanchnic tissue perfusion, assessed by gastric tonometry, in patients with subarachnoid hemorrhage (SAH) and to study the effect of treatment, either surgical or endovascular, and the severity of initial SAH on splanchnic tissue perfusion. Design: Prospective observational substudy, part of a randomised controlled trial of early treatment of ruptured intracranial aneurysms. Setting: Intensive care unit (ICU) of a university hospital. Patients: A consecutive sample of 26 patients [13 surgical (7/6 Hunt & Hess Grade I--II/H & H Gr IV--V) and 13 endovascular (3/10 H & H Gr I--II/H & H Gr IV--V)] out of 56 SAH patients randomly assigned to either endovascular or surgical treatment during the substudy period between 1 May 1995 and 31 August 1996. All patients were treated within 72 h after SAH. Measurements and results: After treatment of a ruptured aneurysm, hemodynamics and gastric intramucosal pCO.sub.2 were measured during the first 4 h and between 6 h and 12 h after aneurysm treatment. In the whole sample, neither the gastric intramucosal-arterial pCO.sub.2 difference (pCO.sub.2 gap) (1.5+-1.9 kPa and 1.7+-1.2 kPa, NS) nor gastric intramucosal pH (7.28+-0.12 and 7.29+-0.08, NS) changed during the study. There were no differences in pCO.sub.2 gap or gastric intramucosal pH between treatment groups or Hunt & Hess grade groups during the study period. Conclusions: Splanchnic tissue perfusion may be insufficient even though there is no systemic hemodynamic disturbance in patients after SAH. Neither the therapeutic treatment nor pre-treatment Hunt & Hess grade is associated with a specific pattern of pCO.sub.2 gap. Author Affiliation: (1) Department of Neurosurgery, Kuopio University Hospital, Puijonlaaksontie 2, SF-70211 Kuopio, Finland (2) Department of Anesthesiology and Intensive Care, Kuopio University Hospital, Puijonlaaksontie, Kuopio, Finland Article History: Received Date: 03/11/2000 Accepted Date: 11/07/2001 Article note: Final revision received: 11 July 2001 Electronic Publication

Byline: Christoph Terborg (1), Wolfram Schummer (2), Melanie Albrecht (1), Konrad Reinhart (2), Cornelius Weiller (3), Joachim Rother (3) Keywords: Sepsis Spectroscopy, near-infrared Ultrasonography, Doppler, transcranial Vasomotor reactivity Abstract: Objective: Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock, leading to organ dysfunction. We investigated whether carbon dioxide (CO.sub.2)-induced vasomotor reactivity (VMR) is impaired in septic patients, compared with values obtained outside sepsis. Design: Prospective, clinical study. Setting: Six-bed neurologic critical care unit of a university hospital. Patients and participants: Eight consecutive patients with severe sepsis and septic shock. Measurements and results: CO.sub.2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy (NIRS). VMR was calculated as the percentage change of cerebral blood flow velocity (normalized CO.sub.2-reactivity, NCR) and absolute changes in concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO.sub.2, Hb, HbT) and Hbdiff (difference between HbO.sub.2 and Hb) in Aumol/l per 1% increase in end-tidal CO.sub.2 (CR-HbO.sub.2, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p Author Affiliation: (1) Department of Neurology, Friedrich-Schiller University of Jena, Philosophenweg 3, 07740 Jena, Germany (2) Department of Anesthesiology and Intensive Care Medicine, Friedrich-Schiller University of Jena, Bachstrasse 18, 07740 Jena, Germany (3) Department of Neurology, Universitatskrankenhaus Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany Article History: Received Date: 27/02/2001 Accepted Date: 08/05/2001 Article note: Final revision received: 4 May 2001 Electronic Publication

Byline: L. Mascia (1), P. J.D. Andrews (2), E. G. McKeating (2), M. J. Souter (2), M. V. Merrick (3), I. R. Piper (4) Keywords: Key words Cerebral blood flow; CPP management; Intracranial pressure; Pressure autoregulation Abstract: Objective: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI).APDesign: Prospective, interventional study.APSetting: Intensive care unit in a university hospital.APPatients: Twelve severely HI patients median Glasgow Coma Scale was 6 (range 3--8).APInterventions: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if %CPP/%CVR a$? 2.APResults: Cerebral blood flow (CBF: Xe.sup.133 inhalation technique), jugular bulb oxygen saturation (SjO.sub.2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % ( +- 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 +- 3 to 28 +- 3 ml/100 g/min in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO.sub.2 did not change significantly from baseline. TCD remained within the normal range.APConclusions: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI. Author Affiliation: (1) Istituto di Anestesiologia e Rianimazione, Ospedale Policlinico, Universita di Bari, Piazza G Cesare 11, 70 122 Bari, Italy e-mail: lmascia@teseo.it Tel.: + 39-0 80-5 47 87 94 Fax: 39-0 80-5 47 87 94), IT (2) Department of Anaesthetics, Western General Hospital, University of Edinburgh, UK, GB (3) Department of Nuclear Medicine, Western General Hospital, University of Edinburgh, UK, GB (4) Department of Clinical Physics, Institute of Neurological Sciences, Glasgow, UK, GB Article note: Received: 28 May 1999 Final revision received: 20 September 1999 Accepted: 5 November 1999