| 1. |
- Bluth, Thomas, et al.
(författare)
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Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients : A Randomized Clinical Trial.
- 2019
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 321:23, s. 2292-2305
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Tidskriftsartikel (refereegranskat)abstract
- Importance: An intraoperative higher level of positive end-expiratory positive pressure (PEEP) with alveolar recruitment maneuvers improves respiratory function in obese patients undergoing surgery, but the effect on clinical outcomes is uncertain.Objective: To determine whether a higher level of PEEP with alveolar recruitment maneuvers decreases postoperative pulmonary complications in obese patients undergoing surgery compared with a lower level of PEEP.Design, Setting, and Participants: Randomized clinical trial of 2013 adults with body mass indices of 35 or greater and substantial risk for postoperative pulmonary complications who were undergoing noncardiac, nonneurological surgery under general anesthesia. The trial was conducted at 77 sites in 23 countries from July 2014-February 2018; final follow-up: May 2018.Interventions: Patients were randomized to the high level of PEEP group (n = 989), consisting of a PEEP level of 12 cm H2O with alveolar recruitment maneuvers (a stepwise increase of tidal volume and eventually PEEP) or to the low level of PEEP group (n = 987), consisting of a PEEP level of 4 cm H2O. All patients received volume-controlled ventilation with a tidal volume of 7 mL/kg of predicted body weight.Main Outcomes and Measures: The primary outcome was a composite of pulmonary complications within the first 5 postoperative days, including respiratory failure, acute respiratory distress syndrome, bronchospasm, new pulmonary infiltrates, pulmonary infection, aspiration pneumonitis, pleural effusion, atelectasis, cardiopulmonary edema, and pneumothorax. Among the 9 prespecified secondary outcomes, 3 were intraoperative complications, including hypoxemia (oxygen desaturation with Spo2 ≤92% for >1 minute).Results: Among 2013 adults who were randomized, 1976 (98.2%) completed the trial (mean age, 48.8 years; 1381 [69.9%] women; 1778 [90.1%] underwent abdominal operations). In the intention-to-treat analysis, the primary outcome occurred in 211 of 989 patients (21.3%) in the high level of PEEP group compared with 233 of 987 patients (23.6%) in the low level of PEEP group (difference, -2.3% [95% CI, -5.9% to 1.4%]; risk ratio, 0.93 [95% CI, 0.83 to 1.04]; P = .23). Among the 9 prespecified secondary outcomes, 6 were not significantly different between the high and low level of PEEP groups, and 3 were significantly different, including fewer patients with hypoxemia (5.0% in the high level of PEEP group vs 13.6% in the low level of PEEP group; difference, -8.6% [95% CI, -11.1% to 6.1%]; P < .001).Conclusions and Relevance: Among obese patients undergoing surgery under general anesthesia, an intraoperative mechanical ventilation strategy with a higher level of PEEP and alveolar recruitment maneuvers, compared with a strategy with a lower level of PEEP, did not reduce postoperative pulmonary complications.Trial Registration: ClinicalTrials.gov Identifier: NCT02148692.
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| 2. |
- Bluth, T., et al.
(författare)
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Protective intraoperative ventilation with higher versus lower levels of positive end-expiratory pressure in obese patients (PROBESE) : study protocol for a randomized controlled trial
- 2017
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pulmonary complications (PPCs) increase the morbidity and mortality of surgery in obese patients. High levels of positive end-expiratory pressure (PEEP) with lung recruitment maneuvers may improve intraoperative respiratory function, but they can also compromise hemodynamics, and the effects on PPCs are uncertain. We hypothesized that intraoperative mechanical ventilation using high PEEP with periodic recruitment maneuvers, as compared with low PEEP without recruitment maneuvers, prevents PPCs in obese patients.Methods/design: The PRotective Ventilation with Higher versus Lower PEEP during General Anesthesia for Surgery in OBESE Patients (PROBESE) study is a multicenter, two-arm, international randomized controlled trial. In total, 2013 obese patients with body mass index >= 35 kg/m(2) scheduled for at least 2 h of surgery under general anesthesia and at intermediate to high risk for PPCs will be included. Patients are ventilated intraoperatively with a low tidal volume of 7 ml/kg (predicted body weight) and randomly assigned to PEEP of 12 cmH(2)O with lung recruitment maneuvers (high PEEP) or PEEP of 4 cmH(2)O without recruitment maneuvers (low PEEP). The occurrence of PPCs will be recorded as collapsed composite of single adverse pulmonary events and represents the primary endpoint.Discussion: To our knowledge, the PROBESE trial is the first multicenter, international randomized controlled trial to compare the effects of two different levels of intraoperative PEEP during protective low tidal volume ventilation on PPCs in obese patients. The results of the PROBESE trial will support anesthesiologists in their decision to choose a certain PEEP level during general anesthesia for surgery in obese patients in an attempt to prevent PPCs.
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| 10. |
- Borges, Joao Batista, et al.
(författare)
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First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity
- 2015
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 115:2, s. 353-363
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Tidskriftsartikel (refereegranskat)abstract
- Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+G(z)), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +G(z) accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5G(z). They performed this sequence three times, breathing AIR, 44.5 % O-2 or 100 % O-2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5G(z), compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (V-T) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O-2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional V-T measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O-2, EELV and V-T decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.
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| 11. |
- Borges, Joao Batista, et al.
(författare)
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Lung Inflammation Persists After 27 Hours of Protective Acute Respiratory Distress Syndrome Network Strategy and Is Concentrated in the Nondependent Lung
- 2015
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Ingår i: Critical Care Medicine. - 0090-3493 .- 1530-0293. ; 43:5, s. E123-E132
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Tidskriftsartikel (refereegranskat)abstract
- Objective: PET with [F-18]fluoro-2-deoxy-D-glucose can be used to image cellular metabolism, which during lung inflammation mainly reflects neutrophil activity, allowing the study of regional lung inflammation in vivo. We aimed at studying the location and evolution of inflammation by PET imaging, relating it to morphology (CT), during the first 27 hours of application of protective-ventilation strategy as suggested by the Acute Respiratory Distress Syndrome Network, in a porcine experimental model of acute respiratory distress syndrome. Design: Prospective laboratory investigation. Setting: University animal research laboratory. Subjects: Ten piglets submitted to an experimental model of acute respiratory distress syndrome. Interventions: Lung injury was induced by lung lavages and 210 minutes of injurious mechanical ventilation using low positive end-expiratory pressure and high inspiratory pressures. During 27 hours of controlled mechanical ventilation according to Acute Respiratory Distress Syndrome Network strategy, the animals were studied with dynamic PET imaging of [F-18]fluoro-2-deoxy-D-glucose at two occasions with 24-hour interval between them. Measurements and Main Results: [F-18]fluoro-2-deoxy-D-glucose uptake rate was computed for the total lung, four horizontal regions from top to bottom (nondependent to dependent regions) and for voxels grouped by similar density using standard Hounsfield units classification. The global lung uptake was elevated at 3 and 27 hours, suggesting persisting inflammation. In both PET acquisitions, nondependent regions presented the highest uptake (p = 0.002 and p = 0.006). Furthermore, from 3 to 27 hours, there was a change in the distribution of regional uptake (p = 0.003), with more pronounced concentration of inflammation in nondependent regions. Additionally, the poorly aerated tissue presented the largest uptake concentration after 27 hours. Conclusions: Protective Acute Respiratory Distress Syndrome Network strategy did not attenuate global pulmonary inflammation during the first 27 hours after severe lung insult. The strategy led to a concentration of inflammatory activity in the upper lung regions and in the poorly aerated lung regions. The present findings suggest that the poorly aerated lung tissue is an important target of the perpetuation of the inflammatory process occurring during ventilation according to the Acute Respiratory Distress Syndrome Network strategy.
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| 13. |
- Dellaca, Raffaele L., et al.
(författare)
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Lung recruitment assessed by total respiratory system input reactance
- 2009
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 35:12, s. 2164-2172
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: ALI and ARDS are associated with lung volume derecruitment, usually counteracted by PEEP and recruitment maneuvers (RM), which should be accurately tailored to the patient's needs. The aim of this study was to investigate the possibility of monitoring the amount of derecruited lung by the forced oscillation technique (FOT). METHODS: We studied six piglets (26 +/- 2.5 kg) ventilated by a mechanical ventilator connected to a FOT device that produced sinusoidal pressure forcing at 5 Hz. The percentage of non-aerated lung tissue (V (tiss)NA%) was measured by whole-body CT scans at end-expiration with zero end-expiratory pressure. Respiratory system oscillatory input reactance (X (rs)) was measured simultaneously to CT and used to derive oscillatory compliance (C (X5)), which we used as an index of recruited lung. Measurements were performed at baseline and after several interventions in the following sequence: mono-lateral reabsorption atelectasis, RM, bi-lateral derecruitment induced by broncho-alveolar lavage and a second RM. RESULTS: By pooling data from all experimental conditions and all pigs, C (X5) was linearly correlated to V (tiss)NA% (r (2) = 0.89) regardless of the procedure used to de-recruit the lung (reabsorption atelectasis or pulmonary lavage). Separate correlation analysis on single pigs showed similar regression equations, with an even higher coefficient of determination (r (2) = 0.91 +/- 0.07). CONCLUSION: These results suggest that FOT and the measurement of C (X5) could be a useful tool for the non-invasive measurement of lung volume recruitment/derecruitment.
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| 14. |
- Dellaca, Raffaele L., et al.
(författare)
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Optimisation of positive end-expiratory pressure by forced oscillation technique in a lavage model of acute lung injury
- 2011
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 37:6, s. 1021-1030
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated whether oscillatory compliance (C-X5) measured by forced oscillation technique (FOT) at 5 Hz may be useful for positive end-expiratory pressure (PEEP) optimisation. We studied seven pigs in which lung injury was induced by broncho-alveolar lavage. The animals were ventilated in volume control mode with a tidal volume of 6 ml/kg. Forced oscillations were superimposed on the ventilation waveform for the assessment of respiratory mechanics. PEEP was increased from 0 to 24 cmH(2)O in steps of 4 cmH(2)O and subsequently decreased from 24 to 0 in steps of 2 cmH(2)O. At each 8-min step, a CT scan was acquired during an end-expiratory hold, and blood gas analysis was performed. C-X5 was monitored continuously, and data relative to the expiratory hold were selected and averaged for comparison with CT and oxygenation. Open lung PEEP (PEEPol) was defined as the level of PEEP corresponding to the maximum value of C-X5 on the decremental limb of the PEEP trial. PEEPol was on average 13.4 (+/- 1.0) cmH(2)O. For higher levels of PEEP, there were no significant changes in the amount of non-aerated tissue (V-tissNA%). In contrast, when PEEP was reduced below PEEPol, V-tissNA% dramatically increased. PEEPol was able to prevent a 5% drop in V-tissNA% with 100% sensitivity and 92% specificity. At PEEPol V-tissNA% was significantly lower than at the corresponding PEEP level on the incremental limb. The assessment of C-X5 allowed the definition of PEEPol to be in agreement with CT data. Thus, FOT measurements of C-X5 may provide a non-invasive bedside tool for PEEP titration.
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| 24. |
- Hedenstierna, M, et al.
(författare)
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Long-term follow-up of successful hepatitis C virus therapy : waning immune responses and disappearance of liver disease are consistent with cure.
- 2015
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Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley. - 0269-2813 .- 1365-2036. ; 41:6, s. 532-543
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR.METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.
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| 25. |
- Högman, Marieann, et al.
(författare)
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A practical approach to the theoretical models to calculate NO parameters of the respiratory system
- 2014
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Ingår i: Journal of breath research. - : IOP Publishing. - 1752-7163 .- 1752-7155. ; 8:1, s. 016002-
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Tidskriftsartikel (refereegranskat)abstract
- Expired nitric oxide (NO) is used as a biomarker in different respiratory diseases. The recommended flow rate of 50 mL s⁻¹ (F(E)NO₀.₀₅) does not reveal from where in the lung NO production originated. Theoretical models of NO transfer from the respiratory system, linear or nonlinear approaches, have therefore been developed and applied. These models can estimate NO from distal lung (alveolar NO) and airways (bronchial flux). The aim of this study was to show the limitation in exhaled flow rate for the theoretical models of NO production in the respiratory system, linear and nonlinear models. Subjects (n = 32) exhaled at eight different flow rates between 10-350 mL s⁻¹ for the theoretical protocols. Additional subjects (n = 32) exhaled at tree flow rates (20, 100 and 350 mL s⁻¹) for the clinical protocol. When alveolar NO is calculated using high flow rates with the linear model, correction for axial back diffusion becomes negligible, -0.04 ppb and bronchial flux enhanced by 1.27. With Högman and Meriläinen algorithm (nonlinear model) the corrections factors can be understood to be embedded, and the flow rates to be used are ≤20, 100 and ≥350 mL s⁻¹. Applying these flow rates in a clinical setting any F(E)NO can be calculated necessitating fewer exhalations. Hence, measured F(E)NO₀.₀₅ 12.9 (7.2-18.7) ppb and calculated 12.9 (6.8-18.7) ppb. In conclusion, the only possibility to avoid inconsistencies between research groups is to use the measured NO values as such in modelling, and apply tight quality control to accuracies in both NO concentration and exhaled flow measurements.
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| 26. |
- Kostic, Peter, et al.
(författare)
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Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury : a controlled experimental study in pigs with saline lavage lung injury
- 2011
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 15:3, s. R126-
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Protocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach. Methods: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH(2)O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH(2)O in steps of 2 cmH(2)O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis. Results: The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO(2) and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group. Conclusions: In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.
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| 27. |
- Koulouras, Vasilios P., et al.
(författare)
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Effects of inhaled carbon monoxide and glucocorticoids in porcine endotoxin sepsis
- 2011
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Ingår i: International Journal of Clinical and Experimental Medicine. - 1940-5901. ; 4:1, s. 53-66
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Recent animal studies have demonstrated that pre-treatment with inhaled carbon monoxide (iCO) exert anti-inflammatory effects in various septic models. In all these models, there is no information whether iCO might act therapeutically after the onset of septic damage. The objective of this study was to investigate the potential anti-inflammatory effects of iCO to treat established injury in a model of porcine endotoxin sepsis.METHODS:Five groups of pigs (n=6 in each group), were studied under anesthesia and mechanical ventilation: healthy control group (HC); lipopolysaccharide (LPS) groups, animals received continuous IV infusion of LPS for 6 hours; 2.5 hours after of LPS infusion treated groups received either: 250 ppm of iCO for 3.5 h, (LPS+CO group); 3 mg/Kg hydrocorti-sone bolus [Steroid (ST)], (LPS+ST group); or both steroid and iCO, (LPS+CO+ST group). Measurements of haemodynamics, blood gases, respiratory mechanics and biochemistry of organ function, were made. At the end of the experiment lung tissue was taken for analysis of histology and inflammatory markers: tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), activator protein-1 (AP-1) and glucocorticoid receptor (GR).RESULTS:LPS administration induced a dramatic inflammatory injury in lungs, increased expression of TNF-α, NF-κB, AP-1, down regulation of GR, pulmonary hypertension and severe deterioration of respiratory mechanics, oxygenation and organ function. Treatment with steroids and to greater extent with iCO significantly improved the microscopic appearance of the lung but had no effect on inflammatory markers. iCO significantly decreased pulmonary hypertension induced by LPS, without an obvious protective effect on organ function.CONCLUSION:Using this porcine sepsis model we find that treatment with iCO after the septic damage decreases pulmonary hypertension and partially protects the lung tissue from the inflammatory destruction induced by LPS but has no beneficial effects on organ function.
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| 28. |
- Malbrain, M.L., et al.
(författare)
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Lymphatic drainage between thorax and abdomen : please take good care of this well-performing machinery
- 2007
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Ingår i: Acta Clinica Belgica. - 1784-3286 .- 2295-3337. ; 62:Supp/1, s. 152-161
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with sepsis often receive large amounts of fluids and the presence of capillary leak, trauma or bleeding results in ongoing fluid resuscitation. This increases interstitial and intestinal edema and finally leads to intra-abdominal hypertension (IAH), which in turn impedes lymphatic drainage. Patients with IAH often develop secondary respiratory failure needing mechanical ventilation with high intrathoracic pressure or PEEP that might further alter lymphatic drainage. This review will try to convince the reader of the importance of the lymphatics in septic patients with IAH. METHODS: A Medline and PubMed literature search was performed using the terms "abdominal pressure", "lymphatic drainage" and "ascites formation".The references from these studies were searched for relevant articles that may have been missed in the primary search. These articles served as the basis for the recommendations below. RESULTS: Induction of sepsis with lesion of the capillary alveolar barrier results in an increased water gradient between the capillaries and the interstitium in the lungs. The drainage flow to the thoracic duct is initially increased in order to protect the Lung and maintain the pulmonary interstitium as dry as possible, however this results in increased intrathoracic pressure. Sepsis also increases the permeability of the capillaries in the splanchnic beds. In analogy to the lungs the lymphatic flow in the splanchnic areas increases together with the pressure inside as a physiological response in order to limit the increase in IAP. At a critical IAP level (around 20 cmH2O) the lymph flow starts to decrease and the splanchnic water content progressively increases.The lymph flow from the abdomen to the thorax is progressively decreased resulting in increased splanchnic water content and ascites formation. The presence of mechanical ventilation with high PEEP reduces the lymph drainage further which together with the increase in IAP decreases the lymphatic pressure gradient in the splanchnic regions, with a further increase in water content and IAP triggering a vicious cycle. CONCLUSION: Although often overlooked the role of lymphatic flow is complex but very important to determine not only the fluid balance in the lung but also in the peripheral organs. Different pathologies and treatments can markedly influence the pathophysiology of the lymphatics with dramatic effects on endorgan function.
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| 29. |
- Margaryan, Ashot, et al.
(författare)
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Population genomics of the Viking world
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
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| 34. |
- Nowak, A, et al.
(författare)
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Efficacy of Routine Fecal Microbiota Transplantation for Treatment of Recurrent Clostridium difficile Infection: A Retrospective Cohort Study
- 2019
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Ingår i: International journal of microbiology. - : Hindawi Limited. - 1687-918X .- 1687-9198. ; 2019, s. 7395127-
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Tidskriftsartikel (refereegranskat)abstract
- Background. Patients with recurrent Clostridium difficile infections (CDIs) constitute an increasing treatment problem. Fecal microbiota transplantation (FMT) has shown promising results of treating recurrent CDI, where treatment with antibiotics fails repeatedly. Our study describes retrospective cohort treated with FMT at two major hospitals in Stockholm. Methods. Medical records of all patients with recurrent CDI treated with FMT during the period 2013–2017 were reviewed. We evaluated cure of CDI-related diarrhea without relapse 10 weeks after FMT. Results. 47 patients were included. One treatment cured 25 patients (53%), and more than one treatment cured 32 patients (68%). Treatment outcome did not vary significantly with treatment with fresh donor feces or frozen fecal culture, days of use of antibiotics or days of hospitalization prior to CDI, and renal function or time from the first CDI to therapy. Treatment failure was associated with a significantly lower Karnofsky performance status score (70 points vs 90, p=0.02). Conclusion. Fecal instillation, for the treatment of relapsing CDI, is a promising approach, with 68% success rate reported in this study. The success rate of FMT is high, regardless of multiple comorbidities, extended use of antibiotics, or long time hospitalization. Although generally FMT is performed with fresh donor feces, our data show that the usage of frozen fecal culture could be an effective treatment alternative in recurrent CDI.
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| 36. |
- Reinius, Henrik, et al.
(författare)
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Real-time ventilation and perfusion distributions by electrical impedance tomography during one-lung ventilation with capnothorax
- 2015
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 59:3, s. 354-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Carbon dioxide insufflation into the pleural cavity, capnothorax, with one-lung ventilation (OLV) may entail respiratory and hemodynamic impairments. We investigated the online physiological effects of OLV/capnothorax by electrical impedance tomography (EIT) in a porcine model mimicking the clinical setting.Methods: Five anesthetized, muscle-relaxed piglets were subjected to first right and then left capnothorax with an intra-pleural pressure of 19cm H2O. The contra-lateral lung was mechanically ventilated with a double-lumen tube at positive end-expiratory pressure 5 and subsequently 10cm H2O. Regional lung perfusion and ventilation were assessed by EIT. Hemodynamics, cerebral tissue oxygenation and lung gas exchange were also measured.Results: During right-sided capnothorax, mixed venous oxygen saturation (P=0.018), as well as a tissue oxygenation index (P=0.038) decreased. There was also an increase in central venous pressure (P=0.006), and a decrease in mean arterial pressure (P=0.045) and cardiac output (P=0.017). During the left-sided capnothorax, the hemodynamic impairment was less than during the right side. EIT revealed that during the first period of OLV/capnothorax, no or very minor ventilation on the right side could be seen (33% vs. 97 +/- 3%, right vs. left, P=0.007), perfusion decreased in the non-ventilated and increased in the ventilated lung (18 +/- 2% vs. 82 +/- 2%, right vs. left, P=0.03). During the second OLV/capnothorax period, a similar distribution of perfusion was seen in the animals with successful separation (84 +/- 4% vs. 16 +/- 4%, right vs. left).Conclusion: EIT detected in real-time dynamic changes in pulmonary ventilation and perfusion distributions. OLV to the left lung with right-sided capnothorax caused a decrease in cardiac output, arterial oxygenation and mixed venous saturation.
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| 37. |
- Rodríguez-Varela, Ricardo, et al.
(författare)
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The genetic history of Scandinavia from the Roman Iron Age to the present
- 2023
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Ingår i: Cell. - : Elsevier. - 0092-8674 .- 1097-4172. ; 186:1, s. 32-46
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Tidskriftsartikel (refereegranskat)abstract
- We investigate a 2,000-year genetic transect through Scandinavia spanning the Iron Age to the present, based on 48 new and 249 published ancient genomes and genotypes from 16,638 modern individuals. We find regional variation in the timing and magnitude of gene flow from three sources: the eastern Baltic, the British-Irish Isles, and southern Europe. British-Irish ancestry was widespread in Scandinavia from the Viking period, whereas eastern Baltic ancestry is more localized to Gotland and central Sweden. In some regions, a drop in current levels of external ancestry suggests that ancient immigrants contributed proportionately less to the modern Scandinavian gene pool than indicated by the ancestry of genomes from the Viking and Medieval periods. Finally, we show that a north-south genetic cline that characterizes modern Scandinavians is mainly due to the differential levels of Uralic ancestry and that this cline existed in the Viking Age and possibly earlier.
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| 38. |
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- Zannin, Emanuela, et al.
(författare)
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Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension : an experimental study in a lavage model of lung injury
- 2012
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 16:6, s. R217-
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION:It is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury.METHODS:We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration.RESULTS:During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse.CONCLUSIONS:Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.
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