| 1. |
- Abrahamsson, A., et al.
(författare)
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Perioperative COX-2 inhibitors may increase the risk of post-operative acute kidney injury
- 2017
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 61:7, s. 714-721
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundIn enhanced recovery protocols (ERP), a restrictive fluid regimen is proposed. Patients who undergo major surgery have an increased risk of post-operative acute kidney injury (AKI). This combination may pose difficulties when ERP is used for patients undergoing major surgery. The aim of this study was to evaluate whether patients undergoing pancreatic surgery and treated with a restrictive fluid regimen are at greater risk of post-operative AKI. Furthermore, if there was an increased risk of AKI, we aimed to identify its cause. MethodsWe reviewed the medical records of patients who underwent pancreatic surgery during 2014 (preERP, n = 58) and 2015 (ERP, n = 65). Fluid balance, the administration of cyclooxygenase-2 inhibitors, creatinine levels and mean arterial pressure were recorded. The Kidney Disease: Improving Global Outcomes criteria were used to define AKI. ResultsThe incidence of AKI was higher in the ERP group than in the PreERP group (12.5% vs. 1.8%, respectively, P = 0.035). The increased incidence of AKI could not be explained by differences in comorbidities, age, pre-operative creatinine or perioperative hypotension. Administration of coxibs was higher in the ERP group and was associated with increased incidence of post-operative AKI (P = 0.018). The combination of coxibs and restrictive fluid regimen seems particularly harmful. ConclusionPancreatic surgery with a restrictive fluid regimen carries an increased risk of post-operative AKI if patients are also treated with cyclooxygenase-2 inhibitors. It is therefore suggested that in protocols including a restrictive fluid regimen for open pancreatic surgery, the use of cyclooxygenase-2 inhibitors should be avoided.
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| 2. |
- Bjerkne Wenneberg, Sandra, et al.
(författare)
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Association between inflammatory response and outcome after subarachnoid haemorrhage.
- 2021
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 143:2, s. 195-205
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Tidskriftsartikel (refereegranskat)abstract
- Recent reports suggest an association between the inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) and patients' outcome. The primary aim of this study was to identify a potential association between the inflammatory response after aSAH and 1-year outcome. The secondary aim was to investigate whether the inflammatory response after aSAH could predict the development of delayed cerebral ischaemia (DCI).This prospective observational pilot study included patients with an aSAH admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, between May 2015 and October 2016. The patients were stratified according to the extended Glasgow Outcome Scale (GOSE) as having an unfavourable (score: 1-4) or favourable outcome (score: 5-8). Furthermore, patients were stratified depending on development of DCI or not. Patient data and blood samples were collected and analysed at admission and after 10days.Elevated serum concentrations of inflammatory markers such as tumour necrosis factor-α and interleukin (IL)-6, IL-1Ra, C-reactive protein and intercellular adhesion molecule-1 were detected in patients with unfavourable outcome. When adjustments for Glasgow coma scale were made, only IL-1Ra remained significantly associated with poor outcome (p=0.012). The inflammatory response after aSAH was not predictive of the development of DCI.Elevated serum concentrations of inflammatory markers were associated with poor neurological outcome 1-year after aSAH. However, inflammatory markers are affected by many clinical events, and when adjustments were made, only IL-1Ra remained significantly associated with poor outcome. The robustness of these results needs to be tested in a larger trial.
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| 3. |
- Bjerkne Wenneberg, Sandra, et al.
(författare)
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Heart rate variability monitoring for the detection of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
- 2020
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Ingår i: Acta anaesthesiologica Scandinavica. - : Wiley. - 1399-6576 .- 0001-5172. ; 64:7, s. 945-952
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Tidskriftsartikel (refereegranskat)abstract
- Delayed cerebral ischemia (DCI) is a major cause of impaired outcome after aneurysmal subarachnoidal hemorrhage (aSAH). In this observational cohort study we investigated whether changes in heart rate variability (HRV) that preced DCI could be detected.Sixty-four patients with aSAHwere included. HRV data were collected for up to 10 days and analyzed off-line.Correlationwith clinical status and/or radiologic findings was investigated. A linear mixed model was used for the evaluation of HRVparameters over time in patients with and without DCI. Extended Glascow outcome scale score was assessed after 1 year.In 55 patients HRV data could be analysed. Fifteen patients developed DCI. No changes in HRV parameters were observed 24 h before onset of DCI. Mean of the HRV parameters in the first 48 h did not correlate with the development of DCI. Low/high frequency (LF/HF) ratio increased more in patients developing DCI (β -0.07 (95% confidence interval,0.12-0.01);p=0.012). Lower STRDRR (standard deviation of RR intervals), RMSSD (root mean square of the successive differences between adjacent RR intervals),and total power(p=0.003, p=0.007 and p=0.004respectively) in the first 48 h was seen in patients who died within 1 year.Impaired HRV correlated with 1-year mortality and LF/HF ratio increased more in patients developing DCI. Even though DCI could not be detected by the intermittent analysis of HRV used in this study, continuous HRV monitoring may have potential in the detection of DCI after aSAH using different methods of analysis.
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| 4. |
- Bjerkne Wenneberg, Sandra, et al.
(författare)
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Long-term outcomes after aneurysmal subarachnoid hemorrhage: A prospective observational cohort study
- 2022
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 146:5, s. 525-536
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The survival rates for patients affected by aneurysmal subarachnoid hemorrhage (aSAH) have increased in recent years; however, many patients continue to develop cognitive dysfunctions that affect their quality of life. The commonly used outcome measures often fail to identify these cognitive dysfunctions. This study aimed to evaluate the long-term outcomes at 1 and 3 years after aSAH to assess changes over time and relate outcomes to patient characteristics and events during the acute phase. Materials and Methods This prospective observational study included patients that experienced aSAH. Patients were assessed according to the extended Glasgow Outcome Scale, Life Satisfaction Questionnaire, Mayo-Portland Adaptability inventory-4, and Mental Fatigue scale. Results Patients were assessed after 1 year (n = 62) and 3 years (n = 54). At 3 years, the extended Glasgow Outcome Scale score improved in 15% and worsened in 12% of the patients. Mental fatigue was observed in 57% of the patients at 1 year. Patients <60 years of age at the time of aSAH had more self-assessed problems, including pain/headache (p < .01), than patients >60 years of age. Patients with delayed cerebral ischemia during the acute phase reported more dissatisfaction at 3 years, whereas no significant result was seen at 1 year. Conclusions Cognitive dysfunction, especially mental fatigue, is common in patients with aSAH, which affects quality of life and recovery. Patient outcome is a dynamic process developing throughout years after aSAH, involving both improvement and deterioration. This study indicates the importance of longer follow-up periods with broad outcome assessments.
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| 5. |
- Block, Linda, et al.
(författare)
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A new concept affecting restoration of inflammation-reactive astrocytes.
- 2013
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 250, s. 536-45
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Tidskriftsartikel (refereegranskat)abstract
- Long-lasting pain may partly be a consequence of ongoing neuroinflammation, in which astrocytes play a significant role. Following noxious stimuli, increased inflammatory receptor activity, influences in Na(+)/K(+)-ATPase activity and actin filament organization occur within the central nervous system. In astrocytes, the Ca(2+) signaling system, Na(+) transporters, cytoskeleton, and release of pro-inflammatory cytokines change during inflammation. The aim of this study was to restore these cell parameters in inflammation-reactive astrocytes. We found that the combination of (1) endomorphin-1, an opioid agonist that stimulates the Gi/o protein of the μ-opioid receptor; (2) naloxone, an opioid antagonist that inhibits the Gs protein of the μ-opioid receptor at ultralow concentrations; and (3) levetiracetam, an anti-epileptic agent that counteracts the release of IL-1β, managed to activate the Gi/o protein and Na(+)/K(+)-ATPase activity, inhibit the Gs protein, and decrease the release of IL-1β. The cell functions of astrocytes in an inflammatory state were virtually restored to their normal non-inflammatory state and it could be of clinical significance and may be useful for the treatment of long-term pain.
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| 6. |
- Block, Linda, et al.
(författare)
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Age, SAPS 3 and female sex are associated with decisions to withdraw or withhold intensive care
- 2019
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 63:9, s. 1210-1215
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Tidskriftsartikel (refereegranskat)abstract
- Background: Intensive care treat critically ill patients. When intensive care is not considered beneficial for the patient, decisions to withdraw or withhold treatments are made. We aimed to identify independent patient variables that increase the odds for receiving a decision to withdraw or withhold intensive care. Methods: Registry study using data from the Swedish Intensive Care Registry (SIR) 2014-2016. Age, condition at admission, including co-morbidities (Simplified Acute Physiology Score version 3, SAPS 3), diagnosis, sex, and decisions on treatment limitations were extracted. Patient data were divided into a full care (FC) group, and a withhold or withdraw (WW) treatment group. Results: Of all 97095 cases, 47.1% were 61-80 years old, 41.9% were women and 58.1% men. 14996 (15.4%) were allocated to the WW group and 82149 (84.6%) to the FC group. The WW group, compared with the FC group, was older (P < 0.001), had higher SAPS 3 (P < 0.001) and were predominantly female (P < 0.001). Compared to patients 16-20 years old, patients >81 years old had 11 times higher odds of being allocated to the WW group. Higher SAPS 3 (continuous) increased the odds of being allocated to the WW group by odds ratio [OR] 1.085, (CI 1.084-1.087). Female sex increased the odds of being allocated to the WW group by 18% (1.18; CI 1.13- 1.23). Conclusion: Older age, higher SAPS 3 at admission and female sex were found to be independent variables that increased the odds to receive a decision to withdraw or withhold intensive care. © 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd
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| 7. |
- Block, Linda, et al.
(författare)
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Cerebral ischemia detection using artificial intelligence (CIDAI)-A study protocol
- 2020
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 64:9, s. 1335-1342
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Tidskriftsartikel (refereegranskat)abstract
- Background The onset of cerebral ischemia is difficult to predict in patients with altered consciousness using the methods available. We hypothesize that changes in Heart Rate Variability (HRV), Near-Infrared Spectroscopy (NIRS), and Electroencephalography (EEG) correlated with clinical data and processed by artificial intelligence (AI) can indicate the development of imminent cerebral ischemia and reperfusion, respectively. This study aimed to develop a method that enables detection of imminent cerebral ischemia in unconscious patients, noninvasively and with the support of AI. Methods This prospective observational study will include patients undergoing elective surgery for carotid endarterectomy and patients undergoing acute endovascular embolectomy for cerebral arterial embolism. HRV, NIRS, and EEG measurements and clinical information on patient status will be collected and processed using machine learning. The study will take place at Sahlgrenska University Hospital, Gothenburg, Sweden. Inclusion will start in September 2020, and patients will be included until a robust model can be constructed. By analyzing changes in HRV, EEG, and NIRS measurements in conjunction with cerebral ischemia or cerebral reperfusion, it should be possible to train artificial neural networks to detect patterns of impending cerebral ischemia. The analysis will be performed using machine learning with long short-term memory artificial neural networks combined with convolutional layers to identify patterns consistent with cerebral ischemia and reperfusion. Discussion Early signs of cerebral ischemia could be detected more rapidly by identifying patterns in integrated, continuously collected physiological data processed by AI. Clinicians could then be alerted, and appropriate actions could be taken to improve patient outcomes.
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| 8. |
- Block, Linda
(författare)
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Glial dysfunction and persistent neuropathic postsurgical pain
- 2016
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Ingår i: Scandinavian Journal of Pain. - : Walter de Gruyter GmbH. - 1877-8860 .- 1877-8879. ; 10, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute pain in response to injury is an important mechanism that serves to protect living beings from harm. However, persistent pain remaining long after the injury has healed serves no useful purpose and is a disabling condition. Persistent postsurgical pain, which is pain that lasts more than 3 months after surgery, affects 10-50% of patients undergoing elective surgery. Many of these patients are affected by neuropathic pain which is characterised as a pain caused by lesion or disease in the somatosensory nervous system. When established, this type of pain is difficult to treat and new approaches for prevention and treatment are needed. A possible contributing mechanism for the transition from acute physiological pain to persistent pain involves low-grade inflammation in the central nervous system (CNS), glial dysfunction and subsequently an imbalance in the neuron-glial interaction that causes enhanced and prolonged pain transmission. Aim: This topical review aims to highlight the contribution that inflammatory activated glial cell dysfunction may have for the development of persistent pain. Results: Immediately after an injury to a nerve ending in the periphery such as in surgery, the inflammatory cascade is activated and immunocompetent cells migrate to the site of injury. Macrophages infiltrate the injured nerve and cause an inflammatory reaction in the nerve cell. This reaction leads to microglia activation in the central nervous system and the release of pro-inflammatory cytokines that activate and alter astrocyte function. Once the astrocytes and microglia have become activated, they participate in the development, spread, and potentiation of low-grade neuroinflammation. The inflammatory activated glial cells exhibit cellular changes, and their communication to each other and to neurons is altered. This renders neurons more excitable and pain transmission is enhanced and prolonged. Astrocyte dysfunction can be experimentally restored using the combined actions of a mu-opioid receptor agonist, a mu-opioid receptor antagonist, and an anti-epileptic agent. To find these agents we searched the literature for substances with possible anti-inflammatory properties that are usually used for other purposes in medicine. Inflammatory induced glial cell dysfunction is restorable in vitro by a combination of endomorphine-1, ultralow doses of naloxone and levetiracetam. Restoring inflammatory-activated glial cells, thereby restoring astrocyte-neuron interaction has the potential to affect pain transmission in neurons. Conclusion: Surgery causes inflammation at the site of injury. Peripheral nerve injury can cause low-grade inflammation in the CNS known as neuroinflammation. Low-grade neuroinflammation can cause an imbalance in the glial-neuron interaction and communication. This renders neurons more excitable and pain transmission is enhanced and prolonged. Astrocytic dysfunction can be restored in vitro by a combination of endomorphin-1, ultralow doses of naloxone and levetiracetam. This restoration is essential for the interaction between astrocytes and neurons and hence also for modulation of synaptic pain transmission. Implications: Larger studies in clinical settings are needed before these findings can be applied in a clinical context. Potentially, by targeting inflammatory activated glial cells and not only neurons, a new arena for development of pharmacological agents for persistent pain is opened.
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| 9. |
- Block, Linda, et al.
(författare)
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Naloxone in ultralow concentration restores endomorphin-1-evoked Ca(2+) signaling in lipopolysaccharide pretreated astrocytes.
- 2012
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Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 205, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Long-term pain is a disabling condition that affects thousands of people. Pain may be sustained for a long time even after the physiological trigger has resolved. Possible mechanisms for this phenomenon include low-grade inflammation in the CNS. Astrocytes respond to inflammatory stimuli and may play an important role as modulators of the inflammatory response in the nervous system. This study aimed first to assess how astrocytes in a primary culture behave when exposed to the endogenous μ-opioid receptor agonist endomorphin-1 (EM-1), in a concentration-dependent manner, concerning intracellular Ca(2+) responses. EM-1 stimulated the μ-opioid receptor from 10(-15) M up to 10(-4) M with increasing intensity, usually reflected as one peak at low concentrations and two peaks at higher concentrations. Naloxone, pertussis toxin (PTX), or the μ-opioid receptor antagonists CTOP did not totally block the EM-1-evoked Ca(2+) responses. However, a combination of ultralow concentration naloxone (10(-12) M) and PTX (100 ng/ml) totally blocked the EM-1-evoked Ca(2+) responses. This suggests that ultralow (picomolar) concentrations of naloxone should block the μ-opioid receptor coupled G(s) protein, and that PTX should block the μ-opioid receptor coupled G(i/o) protein. The second aim was to investigate exposure of astrocytes with the inflammatory agent lipopolysaccharide (LPS). After 4 h of LPS incubation, the EM-1-evoked Ca(2+) transients were attenuated, and after 24 h of LPS incubation, the EM-1-evoked Ca(2+) transients were oscillated. To restore the EM-1-evoked Ca(2+) transients, naloxone was assessed as a proposed anti-inflammatory substance. In ultralow picomolar concentration, naloxone demonstrated the ability to restore the Ca(2+) transients.
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| 10. |
- Block, Linda
(författare)
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Neuroinflammation and pain
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACT Background: Persistent pain that remains long after the physiological trigger has been resolved is a disabling condition. A possible mechanism for the transition from acute physiological pain to persistent pain involves low-grade inflammation in the central nervous system, in which inflammatory-activated astrocytes play a significant role. Aims: The aims of this thesis were to explore novel means for the restoration of inflammatory-activated astrocytes and to investigate whether such experimentally obtained findings, when translated into a clinical setting, are associated with improved pain relief in patients with persistent pain. Methods: For the experimental studies in cell cultures, Ca2+ imaging, Western blot analysis, immunocytochemistry, and enzyme-linked immunosorbent assay (ELISA) were performed. In the clinical study, patients were treated with continuous intrathecal infusions of morphine in combination with naloxone or a placebo. Results: Inflammatory-activated astrocytes were restored to their normal state and function using a combination of the μ-opioid agonist endomorphin-1, ultralow doses of naloxone, and the antiepileptic drug levetiracetam. For patients with persistent pain who were treated with an ongoing intrathecal morphine infusion, the addition of an ultralow dose of naloxone significantly improved their perceived quality of sleep. Conclusion: We demonstrated that astrocyte dysfunction, which occurs as a component of low-grade neuroinflammation during prolonged pain states, is experimentally restorable by the combined actions of morphine, naloxone, and levetiracetam. To achieve this response, the choice of an ultralow dose of naloxone seems to be particularly crucial. Additionally, our findings in patients with difficult-to-treat pain show that intrathecal administration of an ultralow dose of naloxone in combination with morphine significantly improves perceived quality of sleep, although concurrent alterations in pain relief were not statistically significant. The concept of targeting inflammatory-activated astrocytes to reduce the development of persistent pain is a promising path that merits further evaluation in clinical settings. Keywords: Persistent pain, neuroinflammation, astrocytes, morphine, naloxone
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