| 1. |
- Grand, Johannes, et al.
(författare)
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Mean arterial pressure during targeted temperature management and renal function after out-of-hospital cardiac arrest
- 2019
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Ingår i: Journal of Critical Care. - : Elsevier BV. - 0883-9441. ; 50, s. 234-241
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigates the association between mean arterial pressure (MAP) and renal function after out-of-hospital cardiac arrest (OHCA). Materials and methods: Post-hoc analysis of 851 comatose OHCA-patients surviving >48 h included in the targeted temperature management (TTM)-trial. Results: Patients were stratified by mean MAP during TTM in the following groups; <70 mmHg (22%), 70–80 mmHg (43%), and > 80 mmHg (35%). Median (interquartile range) eGFR (ml/min/1.73 m2) 48 h after OHCA was inversely associated with MAP-group (70 (47–102), 84 (56–113), 94 (61–124), p <.001, for the <70-group, 70–80-group and > 80-group respectively). After adjusting for potential confounders, in a mixed model including eGFR after 1, 2 and 3 days this association remained significant (pgroup_adjusted = 0.0002). Higher mean MAP was independently associated with lower odds of renal replacement therapy (odds ratioadjusted = 0.77 [95% confidence interval, 0.65–0.91] per 5 mmHg increase; p =.002]). Conclusions: Low mean MAP during TTM was independently associated with decreased renal function and need of renal replacement therapy in a large cohort of comatose OHCA-patients. Increasing MAP above the recommended 65 mmHg could potentially be renal-protective. This hypothesis should be investigated in prospective trials.
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| 2. |
- Grand, Johannes, et al.
(författare)
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Prevalence and Prognostic Implications of Bundle Branch Block in Comatose Survivors of Out-of-Hospital Cardiac Arrest
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 118:8, s. 1194-1200
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Tidskriftsartikel (refereegranskat)abstract
- This study reports the prevalence and prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in the admission electrocardiogram (ECG) of comatose survivors of out-of-hospital cardiac arrest (OHCA). The present study is part of the predefined electrocardiographic substudy of the prospective randomized target temperature management trial, which found no benefit of targeting 33°C over 36°C in terms of outcome. Six-hundred eighty-two patients were included in the substudy. An admission ECG, which defined the present study population, was available in 602 patients (88%). These ECGs were stratified by the presence of LBBB, RBBB, or no-BBB (reference) on admission. End points were mortality and neurologic outcome 6 months after OHCA. RBBB was present in 79 patients (13%) and LBBB in 65 patients (11%), and the majority of BBBs (92%) had resolved 4 hours after admission. RBBB was associated with significantly higher 6 months mortality (RBBB: hazard ratio [HR]unadjusted 1.78, 95% confidence interval [CI] 1.30 to 2.43; LBBB: HRunadjusted 1.26, 95% CI 0.87 to 1.81), but this did not reach a level of significance in the adjusted model (HRadjusted 1.33, 95% CI 0.94 to 1.87). Similar findings were seen for neurologic outcome in the unadjusted and adjusted analyses. RBBB was further independently associated with higher odds of unfavorable neurologic outcome (RBBB: adjusted odds ratio 1.97, 95% CI 1.05 to 3.71). In conclusion, BBBs after OHCA were transient in most patients, and RBBB was directly associated with higher mortality and independently associated with higher odds of unfavorable neurologic outcome. RBBB is seemingly an early indicator of an unfavorable prognosis after OHCA.
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| 3. |
- Howells, Mark I., et al.
(författare)
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Integrated analysis of climate change, land-use, energy and water strategies
- 2013
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Ingår i: Nature Climate Change. - : Springer Nature. - 1758-678X .- 1758-6798. ; 3:7, s. 621-626
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Tidskriftsartikel (refereegranskat)abstract
- Land, energy and water are our most precious resources, but the manner and extent to which they are exploited contributes to climate change. Meanwhile, the systems that provide these resources are themselves highly vulnerable to changes in climate. Efficient resource management is therefore of great importance, both for mitigation and for adaptation purposes. We postulate that the lack of integration in resource assessments and policy-making leads to inconsistent strategies and inefficient use of resources. We present CLEWs (climate, land-use, energy and water strategies), a new paradigm for resource assessments that we believe can help to remedy some of these shortcomings.
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| 4. |
- Lauren, Ida, et al.
(författare)
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Long-term SARS-CoV-2-specific and cross-reactive cellular immune responses correlate with humoral responses, disease severity, and symptomatology
- 2022
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Ingår i: Immunity, Inflammation and Disease. - : John Wiley & Sons. - 2050-4527. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cellular immune memory responses post coronavirus disease 2019 (COVID-19) have been difficult to assess due to the risks of contaminating the immune response readout with memory responses stemming from previous exposure to endemic coronaviruses. The work herein presents a large-scale long-term follow-up study investigating the correlation between symptomology and cellular immune responses four to five months post seroconversion based on a unique severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific peptide pool that contains no overlapping peptides with endemic human coronaviruses. Methods: Peptide stimulated memory T cell responses were assessed with dual interferon-gamma (IFN gamma) and interleukin (IL)-2 Fluorospot. Serological analyses were performed using a multiplex antigen bead array. Results: Our work demonstrates that long-term SARS-CoV-2-specific memory T cell responses feature dual IFN gamma and IL-2 responses, whereas cross-reactive memory T cell responses primarily generate IFN gamma in response to SARS-CoV-2 peptide stimulation. T cell responses correlated to long-term humoral immune responses. Disease severity as well as specific COVID-19 symptoms correlated with the magnitude of the SARS-CoV-2-specific memory T cell response four to five months post seroconversion. Conclusion: Using a large cohort and a SARS-CoV-2-specific peptide pool we were able to substantiate that initial disease severity and symptoms correlate with the magnitude of the SARS-CoV-2-specific memory T cell responses.
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| 5. |
- Sterpu, Irene, et al.
(författare)
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No evidence for a placental microbiome in human pregnancies at term
- 2021
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 224:3, s. 296.e1-296.e23
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Tidskriftsartikel (refereegranskat)abstract
- Background: The placenta plays an important role in the modulation of pregnancy immunity; however, there is no consensus regarding the existence of a placental microbiome in healthy full-term pregnancies.Objective: This study aimed to investigate the existence and origin of a placental microbiome.Study Design: A cross-sectional study comparing samples (3 layers of placental tissue, amniotic fluid, vernix caseosa, and saliva, vaginal, and rectal samples) from 2 groups of full-term births: 50 women not in labor with elective cesarean deliveries and 26 with vaginal deliveries. The comparisons were performed using polymerase chain reaction amplification and DNA sequencing techniques and bacterial culture experiments.Result: There were no significant differences regarding background characteristics between women who delivered by elective cesarean and those who delivered vaginally. Quantitative measurements of bacterial content in all 3 placental layers (quantitative polymerase chain reaction of the 16S ribosomal RNA gene) did not show any significant difference among any of the sample types and the negative controls. Here, 16S ribosomal RNA gene sequencing of the maternal side of the placenta could not differentiate between bacteria in the placental tissue and contamination of the laboratory reagents with bacterial DNA. Probe-specific quantitative polymerase chain reaction for bacterial taxa suspected to be present in the placenta could not detect any statistically significant difference between the 2 groups. In bacterial cultures, substantially more bacteria were observed in the placenta layers from vaginal deliveries than those from cesarean deliveries. In addition, 16S ribosomal RNA gene sequencing of bacterial colonies revealed that most of the bacteria that grew on the plates were genera typically found in human skin; moreover, it revealed that placentas delivered vaginally contained a high prevalence of common vaginal bacteria. Bacterial growth inhibition experiments indicated that placental tissue may facilitate the inhibition of bacterial growth.Conclusion: We found no evidence to support the existence of a placental microbiome in our study of 76 term pregnancies, which used polymerase chain reaction amplification and sequencing techniques and bacterial culture experiments. Incidental findings of bacterial species could be due to contamination or to low-grade bacterial presence in some locations; such bacteria do not represent a placental microbiome per se.
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| 6. |
- Wiberg, Rebecca, 1988-, et al.
(författare)
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Outcome following soft tissue coverage with a medial gastrocnemius flap of an exposed or infected total knee arthroplasty
- 2023
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Ingår i: Scandinavian Journal of Surgery. - : Sage Publications. - 1457-4969 .- 1799-7267. ; 112:3, s. 173-179
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Soft tissue defects or periprosthetic infections after total knee arthroplasty (TKA) are severe complications that may lead to loss of the arthroplasty or the limb. Reconstructions with medial gastrocnemius flaps (MGF) are occasionally used to provide soft tissue coverage around the knee.AIMS: The study aimed to establish the rate of implant survivorship after MGF reconstruction for soft tissue coverage in the treatment of exposed or infected TKA and to establish functional outcome.METHODS: A retrospective analysis was performed on all patients who received soft tissue coverage with an MGF of an exposed or infected TKA between 2000 and 2017 at the Department of Hand and Plastic Surgery at Umeå University Hospital. The outcomes were implant survivorship and patient-reported outcome measures (PROMs) using the five-level EQ-5D version and The Knee Injury and Osteoarthritis Outcome Score.RESULTS: Forty-seven patients (mean age = 67 years, 30 women) were included. The mean time between flap coverage and follow-up was 6.7 (±3.4) years. Implant survivorship was observed in 28 of 47 (59.6%) patients at follow-up. Flap failure was rare, with only 3 of 47 (6.4%) cases. Of the 20 patients who answered the PROMs, 10 of 20 experienced moderate to severe pain or discomfort.CONCLUSIONS: Due to unfavorable underlying conditions, MGF reconstruction after TKA is often associated with a compromised functional outcome. Because donor site morbidity is limited and flap failure is unusual, the procedure can be considered prophylactically in a small subset of patients with risk factors to prevent soft tissue defects and periprosthetic joint infection.
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| 7. |
- Wiberg, Sebastian, et al.
(författare)
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Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial.
- 2021
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Ingår i: Interactive cardiovascular and thoracic surgery. - : Oxford University Press (OUP). - 1569-9285. ; 32:2, s. 229-35
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac surgery is associated with risk of cerebral injury and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) is suggested to be associated with cerebral injury. The 'Perfusion Pressure Cerebral Infarcts' (PPCI) trial randomized patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement to a MAP of 40-50 or 70-80mmHg during CPB and found no difference in clinical or imaging outcomes between the groups. We here present PPCI trial predefined secondary end points, consisting of biomarkers of brain injury.Blood was collected from PPCI trial patients at baseline, 24 and 48h after induction of anaesthesia and at discharge from the surgical ward. Blood was analysed for neuron-specific enolase, tau, neurofilament light and the glial marker glial fibrillary acidic protein. Linear mixed models were used to analyse differences in biomarker value changes from baseline between the 2 MAP allocation groups.A total of 193 (98%) patients were included. We found no differences in biomarker levels over time from baseline to discharge between the 2 MAP allocation groups (PNSE = 0.14, PTau = 0.46, PNFL = 0.21, PGFAP = 0.13) and the result did not change after adjustment for age, sex and type of surgery.We found no significant differences in levels of biomarkers of neurological injury in patients undergoing elective or subacute CABG and/or aortic valve replacement randomized to either a target MAP of 40-50mmHg or a target MAP of 70-80mmHg during CBP.
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| 8. |
- Wiberg, Sebastian, et al.
(författare)
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Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery.
- 2022
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Ingår i: Journal of cardiothoracic and vascular anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 36:1, s. 125-132
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Tidskriftsartikel (refereegranskat)abstract
- To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery.Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial.Single-center study from a primary heart center in Denmark.Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement.Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD.A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p=0.02) and GFAP (p=0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability.Postoperative serum levels of tau and GFAP were elevated significantly in patients with POCD who underwent cardiac surgery at discharge; however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.
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| 9. |
- Wiberg, Sebastian, et al.
(författare)
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Single versus serial measurements of neuron-specific enolase and prediction of poor neurological outcome in persistently unconscious patients after out-of-hospital cardiac arrest - A TTM-trial substudy
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Prediction of neurological outcome is a crucial part of post cardiac arrest care and prediction in patients remaining unconscious and/or sedated after rewarming from targeted temperature management (TTM) remains difficult. Current guidelines suggest the use of serial measurements of the biomarker neuron-specific enolase (NSE) in combination with other predictors of outcome in patients admitted after out-of-hospital cardiac arrest (OHCA). This study sought to investigate the ability of NSE to predict poor outcome in patients remaining unconscious at day three after OHCA. In addition, this study sought to investigate if serial NSE measurements add incremental prognostic information compared to a single NSE measurement at 48 hours in this population. Methods: This study is a post-hoc sub-study of the TTM trial, randomizing OHCA patients to a course of TTM at either 33°C or 36°C. Patients were included from sites participating in the TTMPLOS trial biobank sub study. NSE was measured at 24, 48 and 72 hours after ROSC and followup was concluded after 180 days. The primary end point was poor neurological function or death defined by a cerebral performance category score (CPC-score) of 3 to 5. Results: A total of 685 (73%) patients participated in the study. At day three after OHCA 63 (9%) patients had died and 473 (69%) patients were not awake. In these patients, a single NSE measurement at 48 hours predicted poor outcome with an area under the receiver operating characteristics curve (AUC) of 0.83. A combination of all three NSE measurements yielded the highest discovered AUC (0.88, p = .0002). Easily applicable combinations of serial NSE measurements did not significantly improve prediction over a single measurement at 48 hours (AUC 0.58-0.84 versus 0.83). Conclusion: NSE is a strong predictor of poor outcome after OHCA in persistently unconscious patients undergoing TTM, and NSE is a promising surrogate marker of outcome in clinical trials. While combinations of serial NSE measurements may provide an increase in overall prognostic information, it is unclear whether actual clinical prognostication with low false-positive rates is improved by application of serial measurements in persistently unconscious patients. The findings of this study should be confirmed in another prospective cohort.
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