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- Broman, K. K., et al.
(författare)
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Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy trial II (MSLT-2)
- 2021
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:13, s. 2251-2261
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Tidskriftsartikel (refereegranskat)abstract
- Background For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. Methods In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. Results Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. Conclusions Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. Lay Summary For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.
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| 6. |
- Broman, K. K., et al.
(författare)
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Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
- 2021
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Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515. ; 232:4, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In sentinel lymph node (SLN)-positive melanoma, two randomized trials demonstrated equivalent melanoma-specific survival with nodal surveillance vs completion lymph node dissection (CLND). Patients with microsatellites, extranodal extension (ENE) in the SLN, or >3 positive SLNs constitute a high-risk group largely excluded from the randomized trials, for whom appropriate management remains unknown. STUDY DESIGN: SLN-positive patients with any of the three high-risk features were identified from an international cohort. CLND patients were matched 1:1 with surveillance patients using propensity scores. Risk of any-site recurrence, SLN-basin-only recurrence, and melanoma specific mortality were compared. RESULTS: Among 1,154 SLN-positive patients, 166 had ENE, microsatellites, and/or >3 positive SLN. At 18.5 months median follow-up, 49% had recurrence (vs 26% in patients without high-risk features, p < 0.01). Among high-risk patients, 52 (31%) underwent CLND and 114 (69%) received surveillance. Fifty-one CLND patients were matched to 51 surveillance patients. The matched cohort was balanced on tumor, nodal, and adjuvant treatment factors. There were no significant differences in any-site recurrence (CLND 49%, surveillance 45%, p = 0.99), SLN-basin-only recurrence (CLND 6%, surveillance 14%, p = 0.20), or melanoma-specific mortality (CLND 14%, surveillance 12%, p = 0.86). CONCLUSIONS: SLN-positive patients with microsatellites, ENE, or >3 positive SLN constitute a high-risk group with a 2-fold greater recurrence risk. For those managed with nodal surveillance, SLN-basin recurrences were more frequent, but all-site recurrence and melanoma-specific mortality were comparable to patients treated with CLND. Most recurrences were outside the SLN-basin, supporting use of nodal surveillance for SLN-positive patients with microsatellites, ENE, and/or >3 positive SLN. Crown Copyright (C) 2020 Published by Elsevier Inc. on behalf of the American College of Surgeons. All rights reserved.
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- Abdalmoaty, Mohamed R. H., 1986-, et al.
(författare)
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Identification of Non-Linear Differential-Algebraic Equation Models with Process Disturbances
- 2021
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Ingår i: 2021 60th IEEE Conference on Decision and Control (CDC). - : IEEE. - 9781665436595 - 9781665436588 - 9781665436601 ; , s. 2300-2305
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Konferensbidrag (refereegranskat)abstract
- Differential-algebraic equations (DAEs) arise naturally as a result of equation-based object-oriented modeling. In many cases, these models contain unknown parameters that have to be estimated using experimental data. However, often the system is subject to unknown disturbances which, if not taken into account in the estimation, can severely affect the model's accuracy. For non-linear state-space models, particle filter methods have been developed to tackle this issue. Unfortunately, applying such methods to non-linear DAEs requires a transformation into a state-space form, which is particularly difficult to obtain for models with process disturbances. In this paper, we propose a simulation-based prediction error method that can be used for non-linear DAEs where disturbances are modeled as continuous-time stochastic processes. To the authors' best knowledge, there are no general methods successfully dealing with parameter estimation for this type of model. One of the challenges in particle filtering methods are random variations in the minimized cost function due to the nature of the algorithm. In our approach, a similar phenomenon occurs and we explicitly consider how to sample the underlying continuous process to mitigate this problem. The method is illustrated numerically on a pendulum example. The results suggest that the method is able to deliver consistent estimates.
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| 19. |
- Ahlberg, Daniel, 1982, et al.
(författare)
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Noise sensitivity in continuum percolation
- 2014
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Ingår i: Israel Journal of Mathematics. - : Springer Science and Business Media LLC. - 0021-2172 .- 1565-8511. ; 201:2, s. 847-899
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Tidskriftsartikel (refereegranskat)abstract
- We prove that the Poisson Boolean model, also known as the Gilbert disc model, is noise sensitive at criticality. This is the first such result for a Continuum Percolation model, and the first which involves a percolation model with critical probability pc not equal 1/2. Our proof uses a version of the Benjamini-Kalai-Schramm Theorem for biased product measures. A quantitative version of this result was recently proved by Keller and Kindler. We give a simple deduction of the non-quantitative result from the unbiased version. We also develop a quite general method of approximating Continuum Percolation models by discrete models with pc bounded away from zero; this method is based on an extremal result on non-uniform hypergraphs.
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| 20. |
- Andren, M., et al.
(författare)
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Coupling between mineral reactions, chemical changes in groundwater, and earthquakes in Iceland
- 2016
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Ingår i: Journal of Geophysical Research-Solid Earth. - : American Geophysical Union (AGU). - 2169-9313. ; 121:4, s. 2315-2337
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Tidskriftsartikel (refereegranskat)abstract
- Chemical analysis of groundwater samples collected from a borehole at Hafralaekur, northern Iceland, from October 2008 to June 2015 revealed (1) a long-term decrease in concentration of Si and Na and (2) an abrupt increase in concentration of Na before each of two consecutive M 5 earthquakes which occurred in 2012 and 2013, both 76km from Hafralaekur. Based on a geochemical (major elements and stable isotopes), petrological, and mineralogical study of drill cuttings taken from an adjacent borehole, we are able to show that (1) the long-term decrease in concentration of Si and Na was caused by constant volume replacement of labradorite by analcime coupled with precipitation of zeolites in vesicles and along fractures and (2) the abrupt increase of Na concentration before the first earthquake records a switchover to nonstoichiometric dissolution of analcime with preferential release of Na into groundwater. We attribute decay of the Na peaks, which followed and coincided with each earthquake to uptake of Na along fractured or porous boundaries between labradorite and analcime crystals. Possible causes of these Na peaks are an increase of reactive surface area caused by fracturing or a shift from chemical equilibrium caused by mixing between groundwater components. Both could have been triggered by preseismic dilation, which was also inferred in a previous study by Skelton et al. (2014). The mechanism behind preseismic dilation so far from the focus of an earthquake remains unknown.
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- Belliato, M, et al.
(författare)
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Mechanical Power during Veno-Venous Extracorporeal Membrane Oxygenation Initiation: A Pilot-Study
- 2021
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Ingår i: Membranes. - : MDPI AG. - 2077-0375. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mechanical power (MP) represents a useful parameter to describe and quantify the forces applied to the lungs during mechanical ventilation (MV). In this multi-center, prospective, observational study, we analyzed MP variations following MV adjustments after veno-venous extra-corporeal membrane oxygenation (VV ECMO) initiation. We also investigated whether the MV parameters (including MP) in the early phases of VV ECMO run may be related to the intensive care unit (ICU) mortality. Thirty-five patients with severe acute respiratory distress syndrome were prospectively enrolled and analyzed. After VV ECMO initiation, we observed a significant decrease in median MP (32.4 vs. 8.2 J/min, p < 0.001), plateau pressure (27 vs. 21 cmH2O, p = 0.012), driving pressure (11 vs. 8 cmH2O, p = 0.014), respiratory rate (RR, 22 vs. 14 breaths/min, p < 0.001), and tidal volume adjusted to patient ideal body weight (VT/IBW, 5.5 vs. 4.0 mL/kg, p = 0.001) values. During the early phase of ECMO run, RR (17 vs. 13 breaths/min, p = 0.003) was significantly higher, while positive end-expiratory pressure (10 vs. 14 cmH2O, p = 0.048) and VT/IBW (3.0 vs. 4.0 mL/kg, p = 0.028) were lower in ICU non-survivors, when compared to the survivors. The observed decrease in MP after ECMO initiation did not influence ICU outcome. Waiting for large studies assessing the role of these parameters in VV ECMO patients, RR and MP monitoring should not be underrated during ECMO.
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| 26. |
- Bereza-Jarocinski, Robert, et al.
(författare)
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Stochastic Approximation for Identification of Non-Linear Differential-Algebraic Equations with Process Disturbances
- 2022
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Ingår i: 2022 IEEE 61ST CONFERENCE ON DECISION AND CONTROL (CDC). - : Institute of Electrical and Electronics Engineers (IEEE). - 9781665467612 - 9781665467605 - 9781665467629 ; , s. 6712-6717
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Konferensbidrag (refereegranskat)abstract
- Differential-algebraic equations, commonly used to model physical systems, are the basis for many equation-based object-oriented modeling languages. When systems described by such equations are influenced by unknown process disturbances, estimating unknown parameters from experimental data becomes difficult. This is because of problems with the existence of well-defined solutions and the computational tractability of estimators. In this paper, we propose a way to minimize a cost function-whose minimizer is a consistent estimator of the true parameters-using stochastic gradient descent. This approach scales significantly better with the number of unknown parameters than other currently available methods for the same type of problem. The performance of the method is demonstrated through a simulation study with three unknown parameters. The experiments show a significantly reduced variance of the estimator, compared to an output error method neglecting the influence of process disturbances, as well as an ability to reduce the estimation bias of parameters that the output error method particularly struggles with.
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| 27. |
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| 28. |
- Broman, Aimee Teo, et al.
(författare)
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Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data
- 2008
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Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:1, s. 66-76
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE. To estimate the rate of visual field progression in open-angle glaucoma (OAG) subjects, by using data from population-based cross-sectional studies. METHODS. Subjects with OAG were identified in nine surveys of randomly sampled populations using standard criteria for glaucomatous optic neuropathy. Subjects were of European, African, Chinese, and Hispanic ethnicity. The measure of OAG damage was the mean deviation (MD) of an automated visual field test (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA). The rate of progression was the mean of all subjects' damage in the worse eye divided by an average time since onset. Time since onset was estimated from age-specific prevalence rates. RESULTS. A total of 1066 subjects with OAG contributed visual field data. The mean worsening in decibels per year was: European-derived, -1.12; Hispanic, -1.26; African-derived, -1.33; and Chinese -1.56 (difference among ethnicities, P = 0.16). The mean duration of disease was lowest among Chinese persons at 10.5 years (95% CI: 8.8-12.6) and was highest in African-derived subjects at 15.4 years (95% CI: 14.6-15.9). The progression rate was not consistently related to age or gender. By combining disease duration and progression rate, the model predicted that 15% or fewer of the worse eyes would reach the end of the field damage scale in the patient's lifetime. CONCLUSIONS. The estimates of typical worsening per year in the worse eye among subjects with OAG suggested slightly more rapid progression than in some clinic-based studies. The rate did not differ significantly by ethnicity or gender, but was worse in those with known, treated OAG and in pseudophakic subjects.
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| 29. |
- Broman, Erik, 1977, et al.
(författare)
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Phase Transition and Uniqueness of Levelset Percolation
- 2017
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Ingår i: Journal of Statistical Physics. - : Springer Science and Business Media LLC. - 1572-9613 .- 0022-4715. ; 167:6, s. 1376-1400
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Tidskriftsartikel (refereegranskat)abstract
- The main purpose of this paper is to introduce and establish basic results of a natural extension of the classical Boolean percolation model (also known as the Gilbert disc model). We replace the balls of that model by a positive non-increasing attenuation function l: (0 , ?) ? [ 0 , ?) to create the random field ? (y) = ? x ? ?l(| x- y|) , where ? is a homogeneous Poisson process in Rd. The field ? is then a random potential field with infinite range dependencies whenever the support of the function l is unbounded. In particular, we study the level sets ? ? h(y) containing the points y? Rd such that ? (y) ? h. In the case where l has unbounded support, we give, for any d? 2 , a necessary and sufficient condition on l for ? ? h(y) to have a percolative phase transition as a function of h. We also prove that when l is continuous then so is ? almost surely. Moreover, in this case and for d= 2 , we prove uniqueness of the infinite component of ? ? h when such exists, and we also show that the so-called percolation function is continuous below the critical value hc.
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| 30. |
- Broman, Erik, 1977, et al.
(författare)
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Stochastic domination and weak convergence of conditioned Bernoulli random vectors
- 2012
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Ingår i: Alea-Latin American Journal of Probability and Mathematical Statistics. - 1980-0436. ; 9:2, s. 403-434
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Tidskriftsartikel (refereegranskat)abstract
- For n >= 1 let X-n be a vector of n independent Bernoulli random variables. We assume that X-n consists of M "blocks" such that the Bernoulli random variables in block i have success probability p(i). Here M does not depend on n and the size of each block is essentially linear in n. Let (X) over tilde (n) be a random vector having the conditional distribution of X-n, conditioned on the total number of successes being at least k(n), where k(n) is also essentially linear in n. Define (Y) over tilde (n) similarly, but with success probabilities q(i) >= p(i). We prove that the law of (X) over tilde (n) converges weakly to a distribution that we can describe precisely. We then prove that sup P((X) over tilde <= (Y) over tilde (n)) converges to a constant, where the supremum is taken over all possible couplings of (X) over tilde and (Y) over tilde (n). This constant is expressed explicitly in terms of the parameters of the system.
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| 31. |
- Broman, J., et al.
(författare)
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Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study
- 2023
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Ingår i: European Journal of Neurology. - 1351-5101. ; 30:9, s. 2675-2683
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although the incidence of stroke in the young is rising, data on long-term outcomes in these patients are scarce. We thus aimed to investigate the long-term risk of recurrent vascular events and mortality in a multicenter study. Methods: We followed 396 consecutive patients aged 18-55 years with ischemic stroke (IS) or transient ischemic attack (TIA) enrolled in three European centers during the period 2007-2010. A detailed outpatient clinical follow-up assessment was performed between 2018 and 2020. When an in-person follow- -up visit was not possible, outcome events were assessed using electronic records and registry data. Results: During a median follow-up of 11.8 (IQR 10.4-12.7) years, 89 (22.5%) patients experienced any recurrent vascular event, 62 (15.7%) had any cerebrovascular event, 34 (8.6%) had other vascular events, and 27 (6.8%) patients died. Cumulative 10-year incidence rate per 1000 person-years was 21.6 (95% CI 17.1-26.9) for any recurrent vascular event and 14.9 (95% CI 11.3-19.3) for any cerebrovascular event. The prevalence of cardiovascular risk factors increased over time, and 22 (13.5%) patients lacked any secondary preventive medication at the in-person follow-up. After adjustment for demographics and comorbidities, atrial fibrillation at baseline was found to be significantly associated with recurrent vascular events. Conclusions: This multicenter study shows a considerable risk of recurrent vascular events in young IS and TIA patients. Further studies should investigate whether detailed individual risk assessment, modern secondary preventive strategies, and better patient adherence may reduce recurrence risk.
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| 33. |
- Broman, L. M., et al.
(författare)
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Pressure and flow properties of dual-lumen cannulae for extracorporeal membrane oxygenation
- 2020
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Ingår i: Perfusion. - : SAGE Publications Ltd. - 0267-6591 .- 1477-111X.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the last decade, dual-lumen cannulae have been increasingly applied in patients undergoing extracorporeal life support. Well-performing vascular access is crucial for efficient extracorporeal membrane oxygenation support; thus, guidance for proper cannulae size is required. Pressure–flow charts provided by manufacturers are often based on tests performed using water, rarely blood. However, blood is a shear-thinning and viscoelastic fluid characterized by different flow properties than water. Methods: We performed a study evaluating pressure–flow curves during standardized conditions using human whole blood in two commonly available dual-lumen cannulae used in neonates, pediatric, and adult patients. Results were merged and compared with the manufacturer’s corresponding curves obtained from the public domain. Results: The results showed that using blood as compared with water predominantly influenced drainage flow. A 10-80% higher pressure-drop was needed to obtain same drainage flow (hematocrit of 26%) compared with manufacturer’s water charts in 13-31 Fr bi-caval dual-lumen cannulae. The same net difference was found in cavo-atrial cannulae (16-32 Fr), where a lower drainage pressure was required (Hct of 26%) compared with the manufacturer’s test using blood with an Hct of 33%. Return pressure–flow data were similar, independent whether pumping blood or water, to the data reported by manufacturers. Conclusion: Non-standardized testing of pressure–flow properties of extracorporeal membrane oxygenation dual-lumen cannulae prevents an adequate prediction of pressure–flow results when these cannulae are used in patients. Properties of dual-lumen cannulae may vary between sizes within same cannula family, in particular concerning the drainage flow.
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| 34. |
- Broman, Marcus Ewert, et al.
(författare)
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Malignant hyperthermia, a Scandinavian update.
- 2015
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172. ; 59:8, s. 951-961
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Forskningsöversikt (refereegranskat)abstract
- Malignant Hyperthermia (MH) is a rare pharmacogenetic disorder, triggered by halogenated anesthetics and/or succinylcholine. In susceptible individuals, these drugs can activate an explosive life threatening clinical reaction. Leading symptoms are hypercarbia, muscle rigidity, and metabolic acidosis. MH is inherited in an autosomal-dominant manner and linked to mutations in the large ryanodine 1 gene (RYR1) gene in the majority of cases. Very few MH patients have been found to carry mutations in the CACNA1S gene.
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| 35. |
- Broman, M, et al.
(författare)
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Malignant hyperthermia and central core disease causative mutations in Swedish patients.
- 2007
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 51:Nov 1, s. 50-53
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Tidskriftsartikel (refereegranskat)abstract
- Background: Malignant hyperthermia (MH) susceptibility is a pharmacogenetic disorder of intracellular calcium homeostasis. In susceptible individuals, halogenated anaesthetics and/or suxamethonium may trigger an MH reaction. The diagnosis of MH susceptibility is made by an in vitro contracture test of biopsied muscle strips. Methods: In 27 MH susceptible (MHS) probands and four MH negative (MHN) probands, exons 17, 39, 40, 45 and 46 of the RYR1 gene were screened for MH causative mutations. In addition, in three patients with established central core disease (CCD), exons 17, 39, 40, 45 and 46 and exons 95, 100, 101 and 102 were screened for MH and CCD causative mutations. All screenings were performed by direct sequencing of the entire exons. Results: MH causative mutations were found in five of the 27 MHS probands (19%). CCD causative mutations were found in two of three CCD patients in the C-terminal exons. None of the CCD patients showed a mutation in N-terminal exon 17 or in the central exons. Conclusions: In a Swedish population, screening of N-terminal exon 17 and the central exons for MH causative mutations in the RYR1 gene covers 19% of families. Thus, other mutations must also be responsible for MH susceptibility in Sweden. Although the number of CCD patients in this study was small, screening of the C-terminal exons for CCD causative mutations seems to be a promising tool in the process of making a diagnosis.
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| 36. |
- Broman, M, et al.
(författare)
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Mutation screening of the RYR1-cDNA from peripheral B-lymphocytes in 15 Swedish malignant hyperthermia index cases.
- 2009
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Ingår i: British Journal of Anaesthesia. - : Elsevier BV. - 1471-6771 .- 0007-0912. ; 102:5, s. 642-649
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant hyperthermia (MH), linked to the ryanodine receptor 1 gene (RYR1) on chromosome 19, is a potentially lethal pharmacogenetic disorder which may lead to a disturbance of intracellular calcium homeostasis when susceptible individuals are exposed to halogenated anaesthetics, suxamethonium, or both. Central core disease (CCD) is a rare dominantly inherited congenital myopathy allelic to MH-susceptibility. METHODS: In this study, 14 unrelated MH-susceptible probands and one CCD patient from Sweden were screened for mutations in the RYR1. Since the RYR1 is also expressed in B-lymphocytes, RYR1-cDNA was transcribed from total RNA extracted from white blood cells. RESULTS: We detected two known RYR1 mutations and two previously described unclassified sequence variants. In addition, six novel sequence variants were detected. All mutations or sequence variants were verified on genomic DNA. Seven of the probands did not show any candidate mutation, although the total coding region of RYR1 was sequenced. Segregation data in in vitro contracture tested family members of three probands support a causative role of three of the novel sequence variants. CONCLUSIONS: Our study contributes to the genetic aetiology of MH in Sweden, but also raises questions about the involvement of genes other than RYR1 since nearly half of the probands did not show any sequence variants in the total coding region of the RYR1.
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| 37. |
- Broman, Marcus, et al.
(författare)
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Next generation DNA sequencing of a Swedish Malignant Hyperthermia cohort.
- 2015
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Ingår i: Clinical Genetics. - : Wiley. - 0009-9163. ; 88:4, s. 381-385
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Tidskriftsartikel (refereegranskat)abstract
- Malignant Hyperthermia (MH) related mutations have been identified in the ryanodine receptor type 1 gene (RYR1) and in the dihydropyridine gene (CACNA1S), but about half of the patients do not have causative mutations in these genes. We wanted to study the contribution of other muscle genes to the RYR1 phenotypes.
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| 38. |
- Broman, T, et al.
(författare)
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Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters
- 2011
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Ingår i: International Journal of Microbiology. - : Hindawi Publishing Corporation. - 1687-918X .- 1687-9198. ; 2011, s. Article ID 851946-
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Tidskriftsartikel (refereegranskat)abstract
- Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.
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| 39. |
- Chi Fru, Ernest, et al.
(författare)
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Arsenic and high affinity phosphate uptake gene distribution in shallow submarine hydrothermal sediments
- 2018
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Ingår i: Biogeochemistry. - : Springer Science and Business Media LLC. - 0168-2563 .- 1573-515X. ; 141:1, s. 41-62
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Tidskriftsartikel (refereegranskat)abstract
- The toxicity of arsenic (As) towards life on Earth is apparent in the dense distribution of genes associated with As detoxification across the tree of life. The ability to defend against As is particularly vital for survival in As-rich shallow submarine hydrothermal ecosystems along the Hellenic Volcanic Arc (HVA), where life is exposed to hydrothermal fluids containing up to 3000 times more As than present in seawater. We propose that the removal of dissolved As and phosphorus (P) by sulfide and Fe(III)(oxyhydr)oxide minerals during sediment-seawater interaction, produces nutrient-deficient porewaters containing<2.0ppb P. The porewater arsenite-As(III) to arsenate-As(V) ratios, combined with sulfide concentration in the sediment and/or porewater, suggest a hydrothermally-induced seafloor redox gradient. This gradient overlaps with changing high affinity phosphate uptake gene abundance. High affinity phosphate uptake and As cycling genes are depleted in the sulfide-rich settings, relative to the more oxidizing habitats where mainly Fe(III)(oxyhydr)oxides are precipitated. In addition, a habitat-wide low As-respiring and As-oxidizing gene content relative to As resistance gene richness, suggests that As detoxification is prioritized over metabolic As cycling in the sediments. Collectively, the data point to redox control on Fe and S mineralization as a decisive factor in the regulation of high affinity phosphate uptake and As cycling gene content in shallow submarine hydrothermal ecosystems along the HVA.
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| 40. |
- Cvetkovic, M, et al.
(författare)
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International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe
- 2023
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Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 38:2, s. 245-260
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Tidskriftsartikel (refereegranskat)abstract
- Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. Objective: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. Methods: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. Results: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS ( n = 88, 66.2%), electroencephalography ( n = 52, 39.1%), transcranial Doppler ( n = 38, 28.5%) and brain injury biomarkers ( n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority ( n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. Conclusions: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.
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| 41. |
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| 42. |
- Di Nardo, M, et al.
(författare)
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A narrative review of the technical standards for extracorporeal life support devices (pumps and oxygenators) in Europe
- 2018
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Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 33:7, s. 553-561
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the European rules to control the market when introducing new products. In particular, it shows all the steps to achieve the European Conformity (CE Mark), a certification that all new medical products must achieve before being used in Europe. Extracorporeal membrane oxygenation (ECMO) devices are exposed to the same procedures. Hereby, we present some regulatory issues regarding pumps and oxygenators, providing technical details as released by the manufacturers on their websites and information charts.
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| 43. |
- Di Nardo, M, et al.
(författare)
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Evaluation of a New Extracorporeal CO2 Removal Device in an Experimental Setting
- 2021
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Ingår i: Membranes. - : MDPI AG. - 2077-0375. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ultra-protective lung ventilation in acute respiratory distress syndrome or early weaning and/or avoidance of mechanical ventilation in decompensated chronic obstructive pulmonary disease may be facilitated by the use of extracorporeal CO2 removal (ECCO2R). We tested the CO2 removal performance of a new ECCO2R (CO2RESET) device in an experimental animal model. Methods: Three healthy pigs were mechanically ventilated and connected to the CO2RESET device (surface area = 1.8 m2, EUROSETS S.r.l., Medolla, Italy). Respiratory settings were adjusted to induce respiratory acidosis with the adjunct of an external source of pure CO2 (target pre membrane lung venous PCO2 (PpreCO2): 80–120 mmHg). The amount of CO2 removed (VCO2, mL/min) by the membrane lung was assessed directly by the ECCO2R device. Results: Before the initiation of ECCO2R, the median PpreCO2 was 102.50 (95.30–118.20) mmHg. Using fixed incremental steps of the sweep gas flow and maintaining a fixed blood flow of 600 mL/min, VCO2 progressively increased from 0 mL/min (gas flow of 0 mL/min) to 170.00 (160.00–200.00) mL/min at a gas flow of 10 L/min. In particular, a high increase of VCO2 was observed increasing the gas flow from 0 to 2 L/min, then, VCO2 tended to progressively achieve a steady-state for higher gas flows. No animal or pump complications were observed. Conclusions: Medium-flow ECCO2R devices with a blood flow of 600 mL/min and a high surface membrane lung (1.8 m2) provided a high VCO2 using moderate sweep gas flows (i.e., >2 L/min) in an experimental swine models with healthy lungs.
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| 44. |
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| 45. |
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| 46. |
- Eroglu, Z., et al.
(författare)
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Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection
- 2022
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Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Until recently, most patients with sentinel lymph node-positive (SLN+) melanoma underwent a completion lymph node dissection (CLND), as mandated in published trials of adjuvant systemic therapies. Following multicenter selective lymphadenectomy trial-II, most patients with SLN+ melanoma no longer undergo a CLND prior to adjuvant systemic therapy. A retrospective analysis of clinical outcomes in SLN+ melanoma patients treated with adjuvant systemic therapy after July 2017 was performed in 21 international cancer centers. Of 462 patients who received systemic adjuvant therapy, 326 patients received adjuvant anti-PD-1 without prior immediate (IM) CLND, while 60 underwent IM CLND. With median follow-up of 21 months, 24-month relapse-free survival (RFS) was 67% (95% CI 62% to 73%) in the 326 patients. When the patient subgroups who would have been eligible for the two adjuvant anti-PD-1 clinical trials mandating IM CLND were analyzed separately, 24-month RFS rates were 64%, very similar to the RFS rates from those studies. Of these no-CLND patients, those with SLN tumor deposit >1 mm, stage IIIC/D and ulcerated primary had worse RFS. Of the patients who relapsed on adjuvant anti-PD-1, those without IM CLND had a higher rate of relapse in the regional nodal basin than those with IM CLND (46% vs 11%). Therefore, 55% of patients who relapsed without prior CLND underwent surgery including therapeutic lymph node dissection (TLND), with 30% relapsing a second time; there was no difference in subsequent relapse between patients who received observation vs secondary adjuvant therapy. Despite the increased frequency of nodal relapses, adjuvant anti-PD-1 therapy may be as effective in SLN+ pts who forego IM CLND and salvage surgery with TLND at relapse may be a viable option for these patients.
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| 47. |
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| 48. |
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| 49. |
- Iacobelli, R, et al.
(författare)
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Predictors of brain infarction in adult patients on extracorporeal membrane oxygenation: an observational cohort study
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 3809-
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Tidskriftsartikel (refereegranskat)abstract
- Non-hemorrhagic brain infarction (BI) is a recognized complication in adults treated with extracorporeal membrane oxygenation (ECMO) and associated with increased mortality. However, predictors of BI in these patients are poorly understood. The aim of this study was to identify predictors of BI in ECMO-treated adult patients. We conducted an observational cohort study of all adult patients treated with venovenous or venoarterial (VA) ECMO at our center between 2010 and 2018. The primary endpoint was a computed tomography (CT) verified BI. Logistic regression models were employed to identify BI predictors. In total, 275 patients were included, of whom 41 (15%) developed a BI. Pre-ECMO Simplified Acute Physiology Score III, pre-ECMO cardiac arrest, VA ECMO and conversion between ECMO modes were identified as predictors of BI. In the multivariable analysis, VA ECMO demonstrated independent risk association. VA ECMO also remained the independent BI predictor in a sub-group analysis excluding patients who did not undergo a head CT scan during ECMO treatment. The incidence of BI in adult ECMO patients may be higher than previously believed and is independently associated with VA ECMO mode. Larger prospective trials are warranted to validate these findings and ascertain their clinical significance.
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| 50. |
- Ishaq, R., et al.
(författare)
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PCNs, PCDD/Fs, and Non-orthoPCBs, in Water and Bottom Sediments from the Industrialized Norwegian Grenlandsfjords
- 2009
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Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 43:10, s. 3442-3447
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Tidskriftsartikel (refereegranskat)abstract
- Chlorinated toxic planar aromatic compounds were analyzed in the heavily industrialized Grenlandsfjords, which is a system of silled fjords in southern Norway. Surface water samples contained 7.4-160 ng/m(3) polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs), 14-410 ng/m(3) polychlorinated naphthalenes (PCNs), and 0.31-2.4 ng/m(3) non-orthochlorinated biphenyls (non-orthoPCBs). The concentrations of PCDD/Fs were about 300 times higher than in the Baltic Sea. Highest level of the compounds was found near a magnesium production plant. Hepta-CDFs and penta-CNs dominated in the inner-fiord waters, and tetra-CB77 was the major non-orthoPCB congener. Sediment samples had PCDD/F concentration of 25-730 ng/g dw. Highest concentration was detected close to the magnesium plant. Octa-CDF dominated in the fjord sediments, especially near the magnesium plant, indicating a discharge-specific contamination with this congener. The isomer composition of PCDD/Fs and of PCNs, was unchanged when comparing samples from different layers of a sediment core from the deep anoxic water. This concludes that essentially zero degradation had occurred during similar to 50 years in this environment
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