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- Forsberg, A., et al.
(author)
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The Immune Response of the Human Brain to Abdominal Surgery
- 2017
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 81:4, s. 572-582
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Journal article (peer-reviewed)abstract
- Objective: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short-and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. Methods: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [C-11]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. Results: Patients showed a global downregulation of gray matter [C-11]PBR28 binding of 26 +/- 26% (mean +/- standard deviation) at 3 to 4 days postoperatively compared to baseline (p=0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-a in blood displayed a reduction (41 +/- 39%) on the 3rd to 4th postoperative day, corresponding to changes in [C-11]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [C-11]PBR28 binding (p=0.027). Interpretation: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function.
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- Danielson, Mattias, et al.
(author)
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Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study
- 2020
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In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 87:3, s. 370-382
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Journal article (peer-reviewed)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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- Hildenborg, M., et al.
(author)
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The Neuroimmune Response to Surgery - An Exploratory Study of Trauma-Induced Changes in Innate Immunity and Heart Rate Variability
- 2022
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In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Journal article (peer-reviewed)abstract
- Surgery triggers a systemic inflammatory response that ultimately impacts the brain and associates with long-term cognitive impairment. Adequate regulation of this immune surge is pivotal for a successful surgical recovery. We explored the temporal immune response in a surgical cohort and its associations with neuroimmune regulatory pathways and cognition, in keeping with the growing body of evidence pointing towards the brain as a regulator of peripheral inflammation. Brain-to-immune communication acts through cellular, humoral and neural pathways. In this context, the vagal nerve and the cholinergic anti-inflammatory pathway (CAP) have been shown to modify peripheral immune cell activity in both acute and chronic inflammatory conditions. However, the relevance of neuroimmune regulatory mechanisms following a surgical trauma is not yet elucidated. Twenty-five male patients undergoing elective laparoscopic abdominal surgery were included in this observational prospective study. Serial blood samples with extensive immune characterization, assessments of heart rate variability (HRV) and cognitive tests were performed before surgery and continuing up to 6 months post-surgery. Temporal immune responses revealed biphasic reaction patterns with most pronounced changes at 5 hours after skin incision and 14 days following surgery. Estimations of cardiac vagal nerve activity through HRV recordings revealed great individual variations depending on the pre-operative HRV baseline. A principal component analysis displayed distinct differences in systemic inflammatory biomarker trajectories primarily based on pre-operative HRV, with potiential consequences for long-term surgical outcomes. In conclusion, individual pre-operative HRV generates differential response patterns that associate with distinct inflammatory trajectories following surgery. Long-term surgical outcomes need to be examined further in larger studies with mixed gender cohorts.
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- Bjorkholm, B, et al.
(author)
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Booster effect of low doses of tetanus toxoid in elderly vaccinees
- 2000
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In: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. - : Springer Science and Business Media LLC. - 0934-9723. ; 19:3, s. 195-199
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Journal article (peer-reviewed)
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- Bullarbo, Maria, 1958, et al.
(author)
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Outpatient vaginal administration of the nitric oxide donor isosorbide mononitrate for cervical ripening and labor induction postterm: a randomized controlled study
- 2007
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In: Am J Obstet Gynecol. ; 196:1
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Our aim was to examine the efficacy, safety, and acceptability of isosorbide mononitrate for cervical ripening and labor induction in women in an outpatient setting. STUDY DESIGN: Two hundred pregnant women of at least 42 weeks' gestation with an unripe cervix were randomly selected to receive vaginally either 40 mg isosorbide mononitrate or placebo tablets. RESULTS: Twenty-two women treated with isosorbide mononitrate went into labor within 24 hours compared to 8 women in the placebo group (P < .05). In women who did not go into labor, cervical status was similar in the 2 groups the next day. Headache was a common side effect. No maternal or fetal side effects of clinical importance were registered. CONCLUSION: Outpatient cervical ripening and labor induction with isosorbide mononitrate seems to be an effective, safe, and well tolerated procedure. The definitive clinical efficacy and safety needs to be evaluated in larger series of patients.
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- Freedman, J, et al.
(author)
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Presence of bile in the oesophagus is associated with less effective oesophageal motility
- 2002
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In: Digestion. - : S. Karger AG. - 0012-2823 .- 1421-9867. ; 66:1, s. 42-48
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Journal article (peer-reviewed)abstract
- <i>Background/Aims:</i> Reflux of bile to the oesophagus has been shown to be of importance in the development of gastro-oesophageal reflux disease. This study aims to assess oesophageal motility patterns in relation to acid and bile reflux to the oesophagus. <i>Methods:</i> Forty-nine subjects with and without reflux disease underwent 24-hour ambulatory recordings of oesophageal pH, bile and 3-channel manometry. Gastroscopy was performed to assess severity of oesophagitis. The percentage of effective peristaltic contractions (oesophageal contractions with a peristaltic pattern and a pressure >30 mm Hg) were correlated to the degree of acid and bile reflux. Ten subjects were re-evaluated within 2 years post-fundoplication. <i>Results:</i> Acid and bile reflux were associated with fewer effective contractions (R<sup>2</sup> = 0.07, p = 0.06 and R<sup>2</sup> = 0.21, p = 0.008, respectively). However, in a multivariate model including acid, bile, age and gender dependency, only bile could show a systematic effect on the variation in percentage of effective peristaltic contractions (R<sup>2</sup> = 0.22, p = 0.001). One year after laparoscopic fundoplication, 24-hour oesophageal motility was unchanged. <i>Conclusion:</i> Reflux of duodenal juice to the oesophagus is associated with less effective oesophageal motility, which in turn can perpetuate the disease by less effective oesophageal clearance of bile and acid. The reduced oesophageal motility is not reversed by fundoplication.
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- Nelson, D. W., et al.
(author)
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The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors
- 2022
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In: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:6, s. 759-766
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Journal article (peer-reviewed)abstract
- Background: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health- systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. Methods: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. Results: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (similar to 4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. Conclusion: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.
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| 44. |
- Nilsson, L, et al.
(author)
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Pertussis IgE and atopic disease
- 1998
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In: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 53:12, s. 1195-1201
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Journal article (peer-reviewed)
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| 45. |
- Olsson, L I, et al.
(author)
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Socioeconomic Inequalities in Relative Survival of Rectal Cancer Most Obvious in Stage III
- 2014
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In: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 38:12, s. 3265-3275
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Journal article (peer-reviewed)abstract
- INTRODUCTION:The association between socioeconomic status (SES) and relative survival of rectal cancer is little investigated. We hypothesized that the impact on risk of death by SES would be much smaller when differences in background mortality (comorbidity, lifestyle factors) were taken into account, i.e. in modelling relative survival of rectal cancer.METHODS:Individual data on civil status, education, and income were linked to the Swedish Rectal Cancer Registry 1995-2005 (n = 16,713). Specific life tables by socioeconomic group were used to calculate relative survival, and modelling included age, sex, stage, time period, and SES. The same covariates were applied in a Cox regression based on absolute survival.RESULTS:Stage distribution was associated with civil status, education, and income (p < 0.001). In spite of modelling based on relative survival, an increased risk of death was found for all other patients compared with those who were married, as well as for all other patients compared with those with the highest income. The pattern was fundamentally the same as in a Cox regression model, only the point estimates were slightly reduced using the relative approach. In stage-specific modelling of relative survival, income was of particular importance in stage III; the hazard ratio (HR) for lowest versus the highest income was 1.37 [95 % confidence interval (CI) 1.15-1.64]. There were also significant differences by income among patients who had a major surgical resection (stage IV excluded).CONCLUSION:Large and clinically relevant socioeconomic inequalities remained in stage-adjusted analyses of relative survival, also in a setting of universal healthcare and no screening program operating.
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