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  • Broman, K. K., et al. (författare)
  • 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
  • Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 127:13, s. 2251-2261
  • 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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  • Broman, K. K., et al. (författare)
  • Surveillance of Sentinel Node-Positive Melanoma Patients with Reasons for Exclusion from MSLT-II: Multi-Institutional Propensity Score Matched Analysis
  • 2021
  • Ingår i: Journal of the American College of Surgeons. - : Ovid Technologies (Wolters Kluwer Health). - 1072-7515. ; 232:4, s. 424-431
  • 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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  • Cvetkovic, M, et al. (författare)
  • International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe
  • 2023
  • Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 38:2, s. 245-260
  • 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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  • Eroglu, Z., et al. (författare)
  • Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection
  • 2022
  • Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 10:8
  • 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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  • Thelaus, J., et al. (författare)
  • Francisella tularensis Subspecies holarctica Occurs in Swedish Mosquitoes, Persists Through the Developmental Stages of Laboratory-Infected Mosquitoes and Is Transmissible During Blood Feeding
  • 2014
  • Ingår i: Microbial Ecology. - : Springer Science and Business Media LLC. - 0095-3628 .- 1432-184X. ; 67:1, s. 96-107
  • Tidskriftsartikel (refereegranskat)abstract
    • In Sweden, mosquitoes are considered the major vectors of the bacterium Francisella tularensis subsp. holarctica, which causes tularaemia. The aim of this study was to investigate whether mosquitoes acquire the bacterium as aquatic larvae and transmit the disease as adults. Mosquitoes sampled in a Swedish area where tularaemia is endemic (A-rebro) were positive for the presence of F. tularensis deoxyribonucleic acid throughout the summer. Presence of the clinically relevant F. tularensis subsp. holarctica was confirmed in 11 out of the 14 mosquito species sampled. Experiments performed using laboratory-reared Aedes aegypti confirmed that F. tularensis subsp. holarctica was transstadially maintained from orally infected larvae to adult mosquitoes and that 25 % of the adults exposed as larvae were positive for the presence of F. tularensis-specific sequences for at least 2 weeks. In addition, we found that F. tularensis subsp. holarctica was transmitted to 58 % of the adult mosquitoes feeding on diseased mice. In a small-scale in vivo transmission experiment with F. tularensis subsp. holarctica-positive adult mosquitoes and susceptible mice, none of the animals developed tularaemia. However, we confirmed that there was transmission of the bacterium to blood vials by mosquitoes that had been exposed to the bacterium in the larval stage. Taken together, these results provide evidence that mosquitoes play a role in disease transmission in part of Sweden where tularaemia recurs.
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  • Andren, M., et al. (författare)
  • Coupling between mineral reactions, chemical changes in groundwater, and earthquakes in Iceland
  • 2016
  • Ingår i: Journal of Geophysical Research-Solid Earth. - : American Geophysical Union (AGU). - 2169-9313. ; 121:4, s. 2315-2337
  • 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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  • Becanovic, K, et al. (författare)
  • New loci regulating rat myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis
  • 2003
  • Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 170:2, s. 1062-1069
  • Tidskriftsartikel (refereegranskat)abstract
    • Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in rats that closely mimics many clinical and histopathological aspects of multiple sclerosis. Non-MHC quantitative trait loci regulating myelin oligodendrocyte glycoprotein-induced EAE have previously been identified in the EAE-permissive strain, DA, on rat chromosomes 4,10,15, and 18. To find any additional gene loci in another well-known EAE-permissive strain and thereby to assess any genetic heterogeneity in the regulation of the disease, we have performed a genome-wide linkage analysis in a reciprocal (LEW.1AV1 x PVG.1AV1) male/female F-2 population (n = 185). We examined reciprocal crosses, but no parent-of-origin effect was detected. The parental rat strains share the RT1(av1) MHC haplotype; thus, non-MHC genes control differences in EAE susceptibility. We identified Eae(16) on chromosome 8 and Eae17 on chromosome 13, significantly linked to EAE phenotypes. Two loci, on chromosomes 1 and 17, respectively showed suggestive linkage to clinical and histopathological EAE phenotypes. Eae16 and Eae17 differ from those found in previously studied strain combinations, thus demonstrating genetic heterogeneity of EAE. Furthermore, we detected a locus-specific parent-of-origin effect with suggestive linkage in Eae17. Further genetic and functional dissection of these loci may disclose critical disease-regulating molecular mechanisms.
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  • Broman, Erik, 1977, et al. (författare)
  • Stochastic domination and weak convergence of conditioned Bernoulli random vectors
  • 2012
  • Ingår i: Alea-Latin American Journal of Probability and Mathematical Statistics. - 1980-0436. ; 9:2, s. 403-434
  • 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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  • Broman, J., et al. (författare)
  • Long-term risk of recurrent vascular events and mortality in young stroke patients: Insights from a multicenter study
  • 2023
  • Ingår i: European Journal of Neurology. - 1351-5101. ; 30:9, s. 2675-2683
  • 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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  • Broman, T., et al. (författare)
  • Campylobacter jejuni in black-headed gulls (Larus ridibundus) : prevalence, genotypes, and influence on C. jejuni epidemiology
  • 2002
  • Ingår i: Journal of Clinical Microbiology. - 0095-1137 .- 1098-660X. ; 40:12, s. 4594-4602
  • Tidskriftsartikel (refereegranskat)abstract
    • Campylobacteriosis is a zoonotic disease in which birds have been suggested to play an important role as a reservoir. We investigated the prevalence of Campylobacter jejuni subsp. jejuni in black-headed gulls (Larus ridibundus) in southern Sweden with the aim of examining the nature of C. jejuni infection in this bird species. Birds were sampled in four sampling series each year during 1999 (n = 419) and 2000 (n = 365). Longitudinally sampled C. jejuni isolates from individual gulls were subjected to macrorestriction profiling (MRP) by pulsed-field gel electrophoresis to investigate the genotypical stability during the natural course of infection. Furthermore, a subset (n = 76) of black-headed gull isolates was compared to isolates from broiler chickens (n = 38) and humans (n = 56) originating from the same geographic area. We found a pronounced seasonal variation in C. jejuni carriage, with the highest rates found in late autumn. MRP similarities were higher between isolates of human and broiler chicken origin, than between those of wild bird origin and either of the other two hosts. However, identical MRPs were found in two gull isolates and one human isolate after digestion with two restriction enzymes, strongly indicating that they may have been colonized by the same clone of C. jejuni. The MRPs most prevalent in gull isolates did not occur among isolates from humans and broiler chickens, suggesting the existence of a subpopulation of C. jejuni adapted to species-specific colonization or environmental survival.
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  • Broman, T, et al. (författare)
  • Molecular Detection of Persistent Francisella tularensis Subspecies holarctica in Natural Waters
  • 2011
  • Ingår i: International Journal of Microbiology. - : Hindawi Publishing Corporation. - 1687-918X .- 1687-9198. ; 2011, s. Article ID 851946-
  • 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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  • Di Nardo, M, et al. (författare)
  • A narrative review of the technical standards for extracorporeal life support devices (pumps and oxygenators) in Europe
  • 2018
  • Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 33:7, s. 553-561
  • 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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  • Drake, Henrik, 1979-, et al. (författare)
  • Incorporation of Metals into Calcite in a Deep Anoxic Granite Aquifer
  • 2018
  • Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851 .- 1086-931X .- 1520-6912. ; 52:2, s. 493-502
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding metal scavenging by calcite in deep aquifers in granite is of importance for deciphering and modeling hydrochemical fluctuations and water rock interaction in the upper crust and for retention mechanisms associated With underground, repositories for toxic wastes. Metal scavenging into calcite has generally been established in the laboratory or in natural environments that cannot be unreservedly applied to conditions in deep crystalline rocks, an environment of broad interest, for nuclear waste repositories. Here, we report a microanalytical study: of calcite precipitated over a period of 17 years from anoxic, low-temperature (14 degrees C), neutral (pH: 7.4-7.7), and brackish (Cl: 1700-7100 mg/L) groundwater flowing in fractures at >400 m depth in granite rock. This enabled assessment of the trace metal uptake by calcite under these deep-seated conditions. Aquatic speciation modeling was carried out to assess influence of metal complexation on the partitioning into calcite. The resulting environment-specific partition coefficients were for several divalent ions in line with values obtained in controlled laboratory experiments, whereas for several other ions they differed substantially. High absolute uptake of rare earth elements and U(IV) suggests that coprecipitation into calcite can be an important sink for these metals and analogousactinides in the vicinity of geological repositories.
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  • Fisser, C, et al. (författare)
  • Recirculation in single lumen cannula venovenous extracorporeal membrane oxygenation: A non-randomized bi-centric trial
  • 2022
  • Ingår i: Frontiers in medicine. - : Frontiers Media SA. - 2296-858X. ; 9, s. 973240-
  • Tidskriftsartikel (refereegranskat)abstract
    • Recirculation is a common problem in venovenous (VV) extracorporeal membrane oxygenation (ECMO). The aims of this study were to compare recirculation fraction (Rf) between femoro-jugular and jugulo-femoral VV ECMO configurations, to identify risk factors for recirculation and to assess the impact on hemolysis.MethodsPatients in the medical intensive care unit (ICU) at the University Medical Center Regensburg, Germany receiving VV ECMO with femoro-jugular, and jugulo-femoral configuration at the ECMO Center Karolinska, Sweden, were included in this non-randomized prospective study. Total ECMO flow (QEC), recirculated flow (QREC), and recirculation fraction Rf = QREC/QEC were determined using ultrasound dilution technology. Effective ECMO flow (QEFF) was defined as QEFF = QEC * (1–Rf). Demographics, cannula specifics, and markers of hemolysis were assessed. Survival was evaluated at discharge from ICU.ResultsThirty-seven patients with femoro-jugular configuration underwent 595 single-point measurements and 18 patients with jugulo-femoral configuration 231 measurements. Rf was lower with femoro-jugular compared to jugulo-femoral configuration [5 (0, 11) vs. 19 (13, 28) %, respectively (p &lt; 0.001)], resulting in similar QEFF [2.80 (2.21, 3.39) vs. 2.79 (2.39, 3.08) L/min (p = 0.225)] despite lower QEC with femoro-jugular configuration compared to jugulo-femoral [3.01 (2.40, 3.70) vs. 3.57 (3.05, 4.06) L/min, respectively (p &lt; 0.001)]. In multivariate regression analysis, the type of configuration, distance between the two cannula tips, ECMO flow, and heart rate were significantly associated with Rf [B (95% CI): 25.8 (17.6, 33.8), p &lt; 0.001; 960.4 (960.7, 960.1), p = 0.009; 4.2 (2.5, 5.9), p &lt; 0.001; 960.1 (960.2, 0.0), p = 0.027]. Hemolysis was similar in subjects with Rf &gt; 8 vs. ≤ 8%. Explorative data on survival showed comparable results in the femoro-jugular and the jugulo-femoral group (81 vs. 72%, p = 0.455).ConclusionVV ECMO with femoro-jugular configuration caused less recirculation. Further risk factors for higher Rf were shorter distance between the two cannula tips, higher ECMO flow, and lower heart rate. Rf did not affect hemolysis.
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  • Holmberg, Carl Jacob, et al. (författare)
  • The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study
  • 2022
  • Ingår i: EUROPEAN JOURNAL OF CANCER. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 40:16
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Guidelines addressing melanoma in-transit metastasis (ITM) recommend immune checkpoint inhibitors (ICI) as a first-line treatment option, despite the fact that there are no efficacy data available from prospective trials for exclusively ITM disease. The study aims to analyze the outcome of patients with ITM treated with ICI based on data from a large cohort of patients treated at international referral clinics. Methods: A multicenter retrospective cohort study of patients treated between January 2015 and December 2020 from Australia, Europe, and the USA, evaluating treatment with ICI for ITM with or without nodal involvement (AJCC8 N1c, N2c, and N3c) and without distant disease (M0). Treatment was with PD-1 inhibitor (nivolumab or pembrolizumab) and/or CTLA-4 inhibitor (ipilimumab). The response was evaluated according to the RECIST criteria modified for cutaneous lesions. Results: A total of 287 patients from 21 institutions in eight countries were included. Immunotherapy was first-line treatment in 64 (22%) patients. PD-1 or CTLA-4 inhibitor monotherapy was given in 233 (81%) and 23 (8%) patients, respectively, while 31 (11%) received both in combination. The overall response rate was 56%, complete response (CR) rate was 36%, and progressive disease (PD) rate was 32%. Median PFS was ten months (95% CI 7.4-12.6 months) with a one-, two-, and five-year PFS rate of 48%, 33%, and 18%, respectively. Median MSS was not reached, and the one-, two-, and five-year MSS rates were 95%, 83%, and 71%, respectively. Conclusion: Systemic immunotherapy is an effective treatment for melanoma ITM. Future studies should evaluate the role of systemic immunotherapy in the context of multimodality therapy, including locoregional treatments such as surgery, intralesional therapy, and regional therapies.
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  • Jung, T. D., et al. (författare)
  • Quality of life in Swedish patients with post-polio syndrome with a focus on age and sex
  • 2014
  • Ingår i: International Journal of Rehabilitation Research. - : Ovid Technologies (Wolters Kluwer Health). - 0342-5282. ; 37:2, s. 173-179
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the health-related quality of life (QOL) in Swedish patients with post-polio syndrome (PPS), with a focus on sex and age. A total of 364 patients were recruited from five Swedish post-polio clinics. Analysis was carried out using SF-36 and data were compared with those of a normal population. QOL was significantly lower in PPS patients for all eight subdomains and the two main scores (physical compound score and mental compound score) when compared with the controls. Male patients had a significantly higher QOL than female patients for all subdomains and also for mental compound score and physical compound score, a phenomenon also observed in the normal population. There was a decrease in QOL in the physical domains and an increase in vitality with age. PPS decreases health-related QOL in both sexes, more in female patients. QOL for physical domains decreases whereas vitality increases with age in both sexes. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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  • Little, Crispin T. S., et al. (författare)
  • A late Paleoproterozoic (1.74 Ga) deep-sea, low-temperature, iron-oxidizing microbial hydrothermal vent community from Arizona, USA
  • 2021
  • Ingår i: Geobiology. - : John Wiley & Sons. - 1472-4677 .- 1472-4669. ; 19:3, s. 228-249
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern marine hydrothermal vents occur in a wide variety of tectonic settings and are characterized by seafloor emission of fluids rich in dissolved chemicals and rapid mineral precipitation. Some hydrothermal systems vent only low-temperature Fe-rich fluids, which precipitate deposits dominated by iron oxyhydroxides, in places together with Mn-oxyhydroxides and amorphous silica. While a proportion of this mineralization is abiogenic, most is the result of the metabolic activities of benthic, Fe-oxidizing bacteria (FeOB), principally belonging to the Zetaproteobacteria. These micro-organisms secrete micrometer-scale stalks, sheaths, and tubes with a variety of morphologies, composed largely of ferrihydrite that act as sacrificial structures, preventing encrustation of the cells that produce them. Cultivated marine FeOB generally require neutral pH and microaerobic conditions to grow. Here, we describe the morphology and mineralogy of filamentous microstructures from a late Paleoproterozoic (1.74 Ga) jasper (Fe-oxide- silica) deposit from the Jerome area of the Verde mining district in central Arizona, USA, that resemble the branching tubes formed by some modern marine FeOB. On the basis of this comparison, we interpret the Jerome area filaments as having formed by FeOB on the deep seafloor, at the interface of weakly oxygenated seawater and low-temperature Fe-rich hydrothermal fluids. We compare the Jerome area filaments with other purported examples of Precambrian FeOB and discuss the implications of their presence for existing redox models of Paleoproterozoic oceans during the “Boring Billion.”
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  • Nfon, Erick, et al. (författare)
  • Biomagnification of organic pollutants in benthic and pelagic marine food chains from the Baltic Sea
  • 2008
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 397:1-3, s. 190-204
  • Tidskriftsartikel (refereegranskat)abstract
    • The trophic transfer of organic pollutants with varying physical chemical properties was determined in both a pelagic and benthic food chain using delta N-15 as a continuous variable for assessing trophic levels. The trophic transfer of organic pollutants through the entire food chain in terms of food chain magnification factors (FCMFs) was quantified from the slope of the regression between In [concentration] and delta N-15. Organic pollutants with statistically significant FCMFs >1 were considered to biomagnify within the food chain, whereas those with FCMFs < 1 were considered to trophically dilute. Statistically significant FCMFs >1 were found for PCB congeners and organochlorine pesticides in the Baltic food chains whereas statistically significant FCMFs <1 were found for PAHs and PCNs due to trophic dilution resulting from metabolism. FCMFs were generally greater in the pelagic food chain than in the benthic food chain. However, estimated FCMFs for the benthic food chain are likely in error, as the delta N-15 method suggested a food chain structure which was not consistent with the known dietary patterns of the species. Biomagnification factors (BMFs) were additionally calculated as the ratio of the lipid normalized concentrations in the predator and prey species with adjustment for trophic level and were generally consistent with the FCMFs with BMF >1 for PCBs and organochlorines.
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37.
  • Nfon, Erick, et al. (författare)
  • Trophodynamics of mercury and other trace elements in a pelagic food chain from the Baltic Sea
  • 2009
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 407:24, s. 6267-74
  • Tidskriftsartikel (refereegranskat)abstract
    • Mercury (Hg) and 13 other trace elements (Al, Ti, V, Cr, Fe, Mn, Co, Ni, Cu, Zn, As, Cd, and Pb) were measured in phytoplankton, zooplankton, mysis and herring in order to examine the trophodynamics in a well-studied pelagic food chain in the Baltic Sea. The fractionation of nitrogen isotopes (delta(15)N) was used to evaluate food web structure and to estimate the extent of trophic biomagnification of the various trace elements. Trophic magnification factors (TMFs) for each trace element were determined from the slope of the regression between trace element concentrations and delta(15)N. Calculated TMFs showed fundamental differences in the trophodynamics of the trace elements in the pelagic food chain studied. Concentrations of Al, Fe, Ni, Zn, Pb and Cd showed statistically significant decreases (TMF<1) with increasing trophic levels and thus these trace elements tropically dilute or biodilute in this Baltic food chain. Cu, As, Cr, Mn, V, Ti and Co showed no significant relationships with trophic levels. Hg was unique among the trace elements studied in demonstrating a statistically significant increase (TMF>1) in concentration with trophic level i.e. Hg biomagnifies in this Baltic food chain. The estimated TMF for Hg in this food chain was comparable to TMFs observed elsewhere for diverse food chains and locations.
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38.
  • Palmgren, Helena, 1955-, et al. (författare)
  • Salmonella Aamager, Campylobacter jejuni, and urease-positive thermophilic Campylobacter found in free-flying peregrine falcons (Falco peregrinus) in Sweden
  • 2004
  • Ingår i: Journal of Wildlife Diseases. - : Wildlife Disease Association. - 0090-3558 .- 1943-3700. ; 40:3, s. 583-587
  • Tidskriftsartikel (refereegranskat)abstract
    • Rare species with small population sizes are vulnerable to perturbations such as disease, inbreeding, or random events. The threat arising from microbial pathogens could be large and other species could act as reservoirs for pathogens. We report finding three enteric bacterial species, Salmonella Amager, Campylobacter jejuni, and urease-positive thermophilic Campylobacter, in nestling free-flying peregrine falcons (Falco peregrinus) in Sweden in 2000. Cainpylobacterfied inarked genetic similarities to an isolate froin a human, providing a possible association between a human-associated strain of this bacterinin and peregrine falcons.
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39.
  • Persson, Stefan, et al. (författare)
  • Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract.
  • 2006
  • Ingår i: Journal of Comparative Neurology. - : John Wiley & Sons. - 0021-9967 .- 1096-9861. ; 497:5, s. 683-701
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate whether the organization of glutamatergic fibers systems in the lumbar cord is also evident at other spinal levels, we examined the immunocytochemical distribution of vesicle glutamate transporters 1 and 2 (VGLUT1, VGLUT2) at several different levels of the rat spinal cord. We also examined the expression of VGLUTs in an ascending sensory pathway, the spinocervical tract, and colocalization of VGLUT1 and VGLUT2. Mainly small VGLUT2-immunoreactive varicosities occurred at relatively high densities in most areas, with the highest density in laminae I-II. VGLUT1 immunolabeling, including small and medium-sized to large varicosities, was more differentiated, with the highest density in the deep dorsal horn and in certain nuclei such as the internal basilar nucleus, the central cervical nucleus, and the column of Clarke. Lamina I and IIo displayed a moderate density of small VGLUT1 varicosities at all spinal levels, although in the spinal enlargements a uniform density of such varicosities was evident throughout laminae I-II in the medial half of the dorsal horn. Corticospinal tract axons displayed VGLUT1, indicating that the corticospinal tract is an important source of small VGLUT1 varicosities. VGLUT1 and VGLUT2 were cocontained in small numbers of varicosities in laminae III-IV and IX. Anterogradely labeled spinocervical tract terminals in the lateral cervical nucleus were VGLUT2 immunoreactive. In conclusion, the principal distribution patterns of VGLUT1 and VGLUT2 are essentially similar throughout the rostrocaudal extension of the spinal cord. The mediolateral differences in VGLUT1 distribution in laminae I-II suggest dual origins of VGLUT1-immunoreactive varicosities in this region.
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  • Wiktorsson, Magnus, 1971-, et al. (författare)
  • A note on the specification of assembly systems
  • 2000
  • Ingår i: International Journal of Production Research. - : Taylor & Francis. - 0020-7543 .- 1366-588X. ; 38:16, s. 3997-4002
  • Tidskriftsartikel (refereegranskat)abstract
    • Although the characteristics and cost of any technical system are highly influenced by the early design phases, little focus has been on the structure and use of the specification in manufacturing system design, in this paper exemplified by assembly systems for large, high-volume products. This paper proposes a framework for elaborating such specifications. The framework is based on a division in qualifying and winning criteria, and is structured into four classes: functional requirements; internal design constraints; external design constraints; and winning criteria. Defining the specification by these terms is justified and explained by comparing standard mathematical formulation for this kind of problem to the framework. Future research efforts are pointed out where the framework is used throughout the development project for goal-focus, as the specification is used and refined in an iterative manner.
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