| 1. |
- Legouis, D., et al.
(författare)
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Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality
- 2020
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 2:8
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Tidskriftsartikel (refereegranskat)abstract
- Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options.
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| 2. |
- Blomberg, S, et al.
(författare)
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Thoracic epidural anaesthesia in patients with unstable angina pectoris
- 1989
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 10:5, s. 437-444
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Tidskriftsartikel (refereegranskat)abstract
- The effect of high thoracic epidural anaesthesia with intermittent epidural bolus injections of bupivacaine (2.5 or 5 mg ml-1) was studied in 28 patients with unstable angina pectoris. The majority of the patients had a history of previous acute myocardial infarction(s) and/or angina pectoris and severe coronary artery disease. All patients were treated wth nitroglycerin infusion for gt;24 h and were included in the study if they had chest pain, not caused by acute myocardial infarction, at bed rest or recurrent anginal pain at rest < 2 days after infarction. 4.4 ± 0.3 ml of bupivacaine induced a blockade of the upper seven sympathetic segments ( Th1-7) for 98 ± 9min. Heart rate decreased significantly from 70 ± 3 to 64 ± 3 beats min-1 while blood pressure was unaffected by thoracic epidural anaesthesia. In 27 patients (96%) the anaesthesia induced complete analgesia. Nitroglycerin infusion was discontinued definitely within 3 h in 26 patients (93%) and pain was thereafter controlled by means of thoracic epidural anaesthesia as the sole treatment in 23 patients (82%) and as the major treatment in 25 patients (89%). Twenty-one patients (75%) were fully mobilized and stabilized. Treatment with thoracic epidural anaesthesia lasted for 6.0 ± 1.1 days. The number of daily epidural injections decreased significantly with time from 2.7 ±0.3 the first day to 0.9 ± 0.3 the fourth day (P>0.01, n = 19). Two patients developed acute myocardial infarction during the anaesthesia treatment period, and one of these patients died. Exercise stress testing was performed on eight patients three to five days after the start of thoracic epidural anaesthesia. At a comparable workload, ST-segment depression was significantly (P>0.05) less pronounced during anaesthesia ( − 0.6 ± 0.1 mm) compared with control ( − 1.3 ± 0.2mm). The respective heart rate values were 95 ± 7 and 107 ± 7 beats min -1 (P > 0.05), while systolic or diastolic blood pressure did not differ between the two conditions. We conclude that blockade of cardiac sympathetic afferents and efferents by means of thoracic epidural anaesthesia can effectively treat pain and stabilize patients with unstable angina pectoris refractory to medical treatment. Furthermore, thoracic epidural anaesthesia attenuates stress-induced myocardial ischaemia; thus, it may be an efficient supplementary treatment for the control of pain and for stabilizing patients with unstable angina pectoris during diagnostic procedures and prior to coronary surgery or angioplasty.
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| 3. |
- Danielson, Mattias, et al.
(författare)
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Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study
- 2020
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Ingår i: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 370-382
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Tidskriftsartikel (refereegranskat)abstract
- Objective Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of >= 1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. Methods Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. Results Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). Interpretation Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort.
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| 4. |
- Verissimo, T., et al.
(författare)
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Decreased Renal Gluconeogenesis Is a Hallmark of Chronic Kidney Disease
- 2022
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Ingår i: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 33:4, s. 810-827
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Tidskriftsartikel (refereegranskat)abstract
- Introduction CKD is associated with alterations of tubular function. Renal gluconeogenesis is responsible for 40% of systemic gluconeogenesis during fasting, but how and why CKD affects this process and the repercussions of such regulation are unknown.Methods We used data on the renal gluconeogenic pathway from more than 200 renal biopsies performed on CKD patients and from 43 kidney allograft patients, and studied three mouse models, of proteinuric CKD (POD-ATTAC), of ischemic CKD, and of unilateral urinary tract obstruction. We analyzed a cohort of patients who benefitted from renal catheterization and a retrospective cohort of patients hospitalized in the intensive care unit.Results Renal biopsies of CKD and kidney allograft patients revealed a stage-dependent decrease in the renal gluconeogenic pathway. Two animal models of CKD and one model of kidney fibrosis confirm gluconeogenic downregulation in injured proximal tubule cells. This shift resulted in an alteration of renal glucose production and lactate clearance during an exogenous lactate load. The isolated perfused kidney technique in animal models and renal venous catheterization in CKD patients confirmed decreased renal glucose production and lactate clearance. In CKD patients hospitalized in the intensive care unit, systemic alterations of glucose and lactate levels were more prevalent and associated with increased mortality and a worse renal prognosis at follow-up. Decreased expression of the gluconeogenesis pathway and its regulators predicted faster histologic progression of kidney disease in kidney allograft biopsies.Conclusion Renal gluconeogenic function is impaired in CKD. Altered renal gluconeogenesis leads to systemic metabolic changes with a decrease in glucose and increase in lactate level, and is associated with a worse renal prognosis.
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| 5. |
- Barbu, Mikael, et al.
(författare)
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Hemostatic effects of a dextran-based priming solution for cardiopulmonary bypass: A secondary analysis of a randomized clinical trial
- 2023
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848. ; 223, s. 139-145
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solu-tions, one colloid-based (dextran 40) and one crystalloid-based.Materials and methods: Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelas-tometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion re-quirements were recorded.Results: Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot for-mation time (+41 +/- 21 % vs. +8 +/- 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (-37 +/- 12 % vs.-7 +/- 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (-14 +/- 29 % vs.-1 +/- 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed.Conclusions: Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on he-mostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.
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| 6. |
- Danielsson, Mattias, et al.
(författare)
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Association between cerebrospinal fluid biomarkers of neuronal injury or amyloidosis and cognitive decline after major surgery.
- 2021
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Ingår i: British journal of anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 126:2, s. 467-76
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative neurocognitive decline is a frequent complication in adult patients undergoing major surgery with increased risk for morbidity and mortality. The mechanisms behind cognitive decline after anaesthesia and surgery are not known. We studied the association between CSF and blood biomarkers of neuronal injury or brain amyloidosis and long-term changes in neurocognitive function.In patients undergoing major orthopaedic surgery (knee or hip replacement), blood and CSF samples were obtained before surgery and then at 4, 8, 24, 32, and 48 h after skin incision through an indwelling spinal catheter. CSF and blood concentrations of total tau (T-tau), neurofilament light, neurone-specific enolase and amyloid β (Aβ1-42) were measured. Neurocognitive function was assessed using the International Study of Postoperative Cognitive Dysfunction (ISPOCD) test battery 1-2 weeks before surgery, at discharge from the hospital (2-5 days after surgery), and at 3 months after surgery.CSF and blood concentrations of T-tau, neurone-specific enolase, and Aβ1-42 increased after surgery. A similar increase in serum neurofilament light was seen with no overall changes in CSF concentrations. There were no differences between patients having a poor or good late postoperative neurocognitive outcome with respect to these biomarkers of neuronal injury and Aβ1-42.The findings of the present explorative study showed that major orthopaedic surgery causes a release of CSF markers of neural injury and brain amyloidosis, suggesting neuronal damage or stress. We were unable to detect an association between the magnitude of biomarker changes and long-term postoperative neurocognitive dysfunction.
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| 7. |
- Farmakis, D., et al.
(författare)
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Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 222, s. 303-312
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Tidskriftsartikel (refereegranskat)abstract
- Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps. © 2016 The Authors
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| 8. |
- Keeble, T. R., et al.
(författare)
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Percutaneous haemodynamic and renal support in patients presenting with decompensated heart failure: A multi-centre efficacy study using the Reitan Catheter Pump (RCP)
- 2019
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 275, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worsening heart failure complicated by congestion, hypotension, and renal dysfunction is difficult to manage, increasingly common and predicts a poor outcome. Novel therapies are required to facilitate diuresis and implementation of disease-modifying interventions in preparation for hospital discharge. Accordingly, we investigated the haemodynamic and renal effects of the Reitan Catheter Pump (RCP) percutaneous support device in patients admitted with decompensated heart failure (DHF). Methods: This was a prospective observational study of 20 patients admitted with DHF, ejection fraction < 30%, and Cardiac index (CI) < 2.1 L/min/m(2) in need of inotropic/mechanical support. Results: Patients underwent RCP support for a mean of 18.3 (+/- 6.3) hours. The RCP increased CI from 1.84 L/min/m(2) (+/- 0.27), to 2.41 L/min/m(2) (+/- 0.45, p = 0.04), increased urine output (71 mL/h (+/- 65) to 227 ml/h (+/- 179) (p = 0.006) with a concomitant reduction in serum creatinine (188 mu mol/L (+/- 87) to 161 mu mol/L (+/- 78) (p = 0.0007). There were no clinically significant haemolysis, vascular injury, or thromboembolic complications. Conclusions: For patients admitted with DHF, the RCP improves cardiac index, diuresis and renal function without causing important complications. (c) 2018 Published by Elsevier B.V.
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