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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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  • 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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  • 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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  • Höglund, Arja, et al. (författare)
  • Associations between fluctuations in daytime sleepiness and motor and non-motor symptoms in Parkinson's disease
  • 2021
  • Ingår i: Movement Disorders Clinical Practice. - 2330-1619. ; 8:1, s. 44-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background Non-motor fluctuations (NMF) are a major concern in Parkinson's disease (PD), and they have been categorised into neuropsychiatric, autonomic and sensory fluctuations. However, this categorisation does not include sleep and sleep-related features, and the association between daytime sleepiness and other motor and/or non-motor fluctuations in PD remains to be elucidated. Objective To investigate the relationship between daytime sleepiness and other non-motor and motor fluctuations in people with PD. Methods A three-day home diary recording daytime sleepiness, mood, anxiety, and motor symptoms was used along with the Karolinska Sleepiness Scale (KSS) and six days of accelerometer (Parkinson's KinetiGraph?; PKG?) registration to detect motor fluctuations among people with a DaTSCAN verified clinical PD diagnosis (32 men; mean PD duration, 8.2?years). Participants were categorised as motor fluctuators or non-fluctuators according to the UPDRS part IV and/or the presence of motor and non-motor fluctuations. Results Fifty-two people with PD participated. Daytime sleepiness correlated significantly with motor symptoms, mood and anxiety among those classified as motor fluctuators (n = 28). Motor fluctuators showed stronger correlations between the individual mean level of all diary variables (daytime sleepiness, anxiety, mood and motor symptoms) when compared to the non-fluctuators (n = 24). Stronger positive within-individual correlations were found among fluctuators in comparison to non-fluctuators. In general, PKG data did not correlate with diary data. Conclusion Episodes of daytime sleepiness, as reported by home diaries, were associated with other self-reported non-motor and motor fluctuations, but were not supported by PKG data.
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  • Boskabadi, Arman, et al. (författare)
  • Carbonate alteration of ophiolitic rocks in the Arabian-Nubian Shield of Egypt : sources and compositions of the carbonating fluid and implications for the formation of Au deposits
  • 2017
  • Ingår i: International Geology Review. - : TAYLOR & FRANCIS INC. - 0020-6814 .- 1938-2839. ; 59:4, s. 391-419
  • Forskningsöversikt (refereegranskat)abstract
    • Ultramafic portions of ophiolitic fragments in the Arabian-Nubian Shield (ANS) show pervasive carbonate alteration forming various degrees of carbonated serpentinites and listvenitic rocks. Notwithstanding the extent of the alteration, little is known about the processes that caused it, the source of the CO2 or the conditions of alteration. This study investigates the mineralogy, stable (O, C) and radiogenic (Sr) isotope composition, and geochemistry of suites of variably carbonate altered ultramafics from the Meatiq area of the Central Eastern Desert (CED) of Egypt. The samples investigated include least-altered lizardite (Lz) serpentinites, antigorite (Atg) serpentinites and listvenitic rocks with associated carbonate and quartz veins. The C, O and Sr isotopes of the vein samples cluster between -8.1 parts per thousand and -6.8 parts per thousand for delta C-13, +6.4 parts per thousand and +10.5 parts per thousand for delta O-18, and Sr-87/Sr-86 of 0.7028-0.70344, and plot within the depleted mantle compositional field. The serpentinites isotopic compositions plot on a mixing trend between the depleted-mantle and sedimentary carbonate fields. The carbonate veins contain abundant carbonic (CO2 +/- CH4 +/- N-2) and aqueous-carbonic (H2O-NaCl-CO2 +/- CH4 +/- N-2) low salinity fluid, with trapping conditions of 270-300 degrees C and 0.7-1.1kbar. The serpentinites are enriched in Au, As, S and other fluid-mobile elements relative to primitive and depleted mantle. The extensively carbonated Atg-serpentinites contain significantly lower concentrations of these elements than the Lz-serpentinites suggesting that they were depleted during carbonate alteration. Fluid inclusion and stable isotope compositions of Au deposits in the CED are similar to those from the carbonate veins investigated in the study and we suggest that carbonation of ANS ophiolitic rocks due to influx of mantle-derived CO2-bearing fluids caused break down of Au-bearing minerals such as pentlandite, releasing Au and S to the hydrothermal fluids that later formed the Au-deposits. This is the first time that gold has been observed to be remobilized from rocks during the lizardite-antigorite transition.
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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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  • Billstrom, K., et al. (författare)
  • Geochronological, stable isotopes and fluid inclusion constraints for a premetamorphic development of the intrusive-hosted Bjorkdal Au deposit, northern Sweden
  • 2009
  • Ingår i: International journal of earth sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 98:5, s. 1027-1052
  • Tidskriftsartikel (refereegranskat)abstract
    • The Bjorkdal gold deposit, bound to a quartz vein system which is mainly hosted by a quartz-monzodioritic intrusion, is situated at the easternmost part of the 1.9 Ga Skellefte base metal district in the Fennoscandian shield. Three fluid stages may be distinguished, referred to as a ""barren"" stage, a main gold stage, and a remobilization stage, respectively. From oxygen and hydrogen isotope evidence, it is argued that fluids of different origins (magmatic and surface waters) penetrated the ore zone at the inferred stages, but regional metamorphic fluids appear essentially only to have redistributed elements. Early quartz veining took place during a pre-metamorphic stage at ca. 1.88 Ga, as evidenced by unradiogenic galena data and an Sm-Nd scheelite errorchron of 1,915 +/- A 32 Ma (MSWD = 0.25). Temporarily, the main ore-forming stage was closely related to the first barren stage and took place during a major uplift event close to 1.88 Ga. Although other source rocks cannot be totally ruled out, available isotope data (O, S, Sr and Pb) are seemingly consistent with the view that these elements, and by inference other ore elements, were derived from the host intrusion.
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  • Björk, Yvonne, et al. (författare)
  • Androgens in women after allogeneic hematopoietic cell transplantation : Impact of chronic GvHD and glucocorticoid therapy
  • 2017
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 52:3, s. 431-437
  • Tidskriftsartikel (refereegranskat)abstract
    • Low androgen levels may contribute to sexual dysfunction in women after allogeneic hematopoietic cell transplantation (alloHCT). However, data on serum androgens in women after alloHCT are limited. The aim of this study was to assess androgen levels and their association with chronic GvHD (cGvHD) and glucocorticoid (GC) therapy. Included were 65 allografted women, 33 with cGvHD, and 23 of these were on GC therapy. Controls were 94 healthy, age-matched women. Supportive study groups were women after autologous HCT (autoHCT; n=20) and non-transplanted women on GC therapy (n=26). Compared with controls, free testosterone (free T) and dehydroepiandrosterone sulfate (DHEAS) levels were lower in both the alloHCT group and GC groups; P<0.0001 and P<0.05, respectively. Androgens in the autoHCT group were similar or higher than controls. In the subgroup of alloHCT patients without cGvHD, free T was similar to controls (7.2 vs 8.6 pmol/L; P=0.42), whereas DHEAS levels was lower than controls (1.7 vs 2.5 μmol/L; P=0.008). Compared with controls, cGvHD without GC (n=10) was associated with lower free T and DHEAS; P=0.004 and P=0.0004, respectively). The lowest androgen levels were seen in women with both cGvHD and GC therapy. In conclusion, low serum androgens were associated with cGvHD and GC therapy, prompting for studies assessing a possible association between low androgens and sexual dysfunction and quality of life in allografted women.
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  • Broman, Aimee Teo, et al. (författare)
  • Estimating the rate of progressive visual field damage in those with open-angle glaucoma, from cross-sectional data
  • 2008
  • Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 49:1, s. 66-76
  • 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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  • Broman, Curt, et al. (författare)
  • Deposition conditions for the indium-bearing polymetallic quartz veins at Sarvlaxviken, south-eastern Finland
  • 2018
  • Ingår i: Mineralogical magazine. - : Mineralogical Society. - 0026-461X .- 1471-8022. ; 82, s. S43-S59
  • Tidskriftsartikel (refereegranskat)abstract
    • Polymetallic quartz veins, with up to 1500ppm indium, have been discovered recently in the Sarvlaxviken area within the 1.64Ga anorogenic multiphase Wiborg rapakivi batholith and adjacent 1.90Ga Svecofennian crust in SE Finland. Evidence from primary fluid inclusions in the Sarvlaxviken area provides new information on the hydrothermal transport and depositional processes of metals in anorogenic granites. Fluid inclusions with variable aqueous liquid and vapour proportions (5-90vol.% vapour) occur in quartz, cassiterite and fluorite belonging to three generations of polymetallic quartz veins. Microthermometry indicates that the veins were deposited at temperatures that range from similar to 500 degrees C down to <100 degrees C and salinities from 0 to 16 eq. mass% NaCl. Fluid inclusion data show that the depositional conditions were similar regardless of vein generation. The interpreted depositional processes involve phase separation with a combination of condensation, cooling and boiling of an initially low-salinity (<3 eq. mass% NaCl) aqueous magmatic vapour phase enriched in CO2-F-Cl-S and metals. Fluid inclusions with low salinities dominate, but higher salinities are recorded in metal-rich parts of the veins. The turbulent fluid flow, with complex geometry and temperature-salinity patterns, may explain why sulfide and/or oxide opaque minerals occur irregularly, and are locally the dominating vein minerals, but disappear completely into barren parts of the quartz veins. All fluids are considered to have been generated by the F-rich Marviken granite (and related granite dykes), which show all geochemical criteria for an ore-fertile granite. The quartz veins investigated in the adjacent Svecofennian country rocks are considered to represent the very last stage of a fluid with similar characteristics to the fluid responsible for the ore formation in the Sarvlaxviken area, but that had cooled to <100 degrees C.
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  • Broman, J., et al. (författare)
  • Association of post-stroke-initiated antidepressants with long-term outcomes in young adults with ischaemic stroke
  • 2022
  • Ingår i: Annals of Medicine. - : Informa UK Limited. - 0785-3890 .- 1365-2060. ; 54:1, s. 1757-1766
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective We examined the association between initiation of antidepressants within the first year after ischaemic stroke (IS) in young adults and long-term fatal and non-fatal cardiovascular events, as well as all-cause mortality. Patients and methods The Helsinki Young Stroke Registry (HYSR) includes patients aged 15-49 years with their first-ever IS occurring 1994-2007. From nationwide registers, we obtained data on prescriptions (1993-2011) and outcomes of interest (1994-2011). Time of initiating post-stroke antidepressants (PSADs) was defined as time of the first filled prescription for antidepressants within the first year from IS. To account for non-random assignment of PSADs, we performed propensity score matching and studied the relationship between PSAD initiation and outcomes using Cox regression models with time-varying coefficients. Results Of all patients (n = 888), 206 (23.2%) initiated PSADs within the first year, of which 203 (98.5%) could be matched to 406 non-initiators. In this matched sample of 609 patients, the median follow-up time was 8.1 (interquartile range [IQR] 5.0-12.6) years and 169 (28.9%) patients had any cardiovascular events, 95 (15.8%) had recurrent ischaemic or haemorrhagic strokes and 106 (17.4%) died. Adjusted for sociodemographics and cardiovascular comorbidities, PSAD initiation was associated with recurrent ischaemic or haemorrhagic stroke 5-10 years after IS (hazard ratio [HR] 3.07, 95% confidence interval [CI] 1.32-7.12). No association emerged between PSAD initiation and other outcomes. Conclusions In young adults, PSAD initiation within the first year after IS was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Future studies are needed to verify the results and to further study the nature of this finding. KEY MESSAGES Initiation of post-stroke antidepressants (PSADs) within the first year after ischaemic stroke (IS) was associated with a heightened hazard of recurrent ischaemic or haemorrhagic stroke in the long term. Patients starting antidepressants after IS should be followed up more closely in case of recurrent events. Future studies are needed to verify the results and to further study the nature of this finding.
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  • Broman, J., et al. (författare)
  • Initiation of antidepressants in young adults after ischemic stroke: a registry-based follow-up study
  • 2022
  • Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 269, s. 956-965
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Data on post-stroke use of antidepressants in young individuals are scarce. We examined pattern and factors associated with initiating post-stroke antidepressants (PSAD) after ischemic stroke (IS) in young adults. Methods: Helsinki Young Stroke Registry includes patients aged 15–49years with first-ever IS, 1994–2007. Data on prescriptions, hospitalizations and death came from nationwide registers. We defined time of initiating PSAD as time of the first filled prescription for antidepressants within 1year from IS. We assessed factors associated with initiating PSAD with multivariable Cox regression models, allowing for time-varying effects when appropriate. Results: We followed 888 patients, of which 206 (23.2%) initiated PSAD. Higher hazard of starting PSAD within the first 100days appeared among patients with mild versus no limb paresis 2.53 (95% confidence interval 1.48–4.31) and during later follow-up among those with silent infarcts (2.04; 1.27–3.28), prior use of antidepressants (2.09; 1.26–3.46) and moderate versus mild stroke (2.06; 1.18–3.58). The relative difference in the hazard rate for moderate–severe limb paresis persisted both within the first 100days (3.84, 2.12–6.97) and during later follow-up (4.54; 2.51–8.23). The hazard rate was higher throughout the follow-up among smokers (1.48; 1.11–1.97) as well as lower (1.78; 1.25–2.54) and upper white-collar workers (2.00; 1.24–3.23) compared to blue-collar workers. Conclusion: One-fourth of young adults started PSADs within 1year from IS. We identified several specific clinical characteristics associated with PSAD initiation, highlighting their utility in assessing the risk of post-stroke depression during follow-up. © 2021, The Author(s).
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  • Bullarbo, Maria, 1958, et al. (författare)
  • Magnesium Supplementation and Blood Pressure in Pregnancy: A Double-Blind Randomized Multicenter Study
  • 2018
  • Ingår i: Journal of Pregnancy. - : Hindawi Limited. - 2090-2727 .- 2090-2735.
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To investigate the effect of magnesium (Mg) supplementation in healthy pregnant women for prevention of blood pressure increase. Secondary outcomes were comparison of biomarkers for hypertensive disorders and labour and fetal outcomes between the groups. Methods. Two hundred nulliparous healthy pregnant women were double-blind randomized to receive Mg daily or placebo. Results. There were no differences in blood pressure increase. However, among the Mg-treated women, there was a significant negative correlation between increase in blood levels of magnesium and increase in systolic blood pressure (p = 0.042). Magnesium supplementation seems to be safe for both mother and infant. Conclusion. Magnesium supplementation in healthy first-time pregnant women is not to be recommended for prevention of blood pressure increase. Supplementation in risk pregnancies needs to be further investigated.
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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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  • Knutsson, Eva Smith, et al. (författare)
  • A prospective study of female genital chronic graft-versus-host disease symptoms, signs, diagnosis and treatment
  • 2018
  • Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:9, s. 1122-1129
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionFemale genital chronic graft-versus-host disease (cGvHD) is a complication of allogeneic hematopoietic cell transplantation (alloHCT) for blood malignancies. Unattended inflammation and fibrosis in the vulva andvagina may lead to total vaginal stenosis. The course and treatment of genital cGvHD was observed in this population-based prospective study. Material and methodsWomen (n=41) receiving alloHCT in 2005-10 were examined before and at 3, 6, 9, 12, 18, 24, 30 and 36months post-transplant. Vulvovaginal signs were documented, National Institutes of Health clinical scores were calculated, and women completed questionnaires on symptoms, the Female Sexual Distress Scale and the Beck Depression Inventory. Local immunosuppressive treatment was given weekly. ResultsGenital cGvHD was diagnosed in 27 women (incidence 56% at 12months; 66% at 36months); extragenital cGvHD was found in 21/27. The most common signs at diagnosis were red and white spots, reticular white lines, fissures, synechiae and telangiectasia; symptoms included dryness, itching, dyspareunia, pain or no symptoms. Thirteen women were treated on a schedule of tacrolimus and clobetazol ointments. Although some signs progressed during treatment, only two women developed total stenosis. At 36months, 12 women still had genital cGvHD. ConclusionsGenital cGvHD develops mainly in the first year after alloHCT. Early intervention may halt its progress to severe fibrosis, but despite correct diagnosis and treatment, symptoms and signs may become chronic. Women who develop genital cGvHD following alloHCT require life-long gynecological supervison and care.
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  • Malfertheiner, SF, et al. (författare)
  • Extracorporeal membrane oxygenation during pregnancy and peripartal. An international retrospective multicenter study
  • 2023
  • Ingår i: Perfusion. - : SAGE Publications. - 1477-111X .- 0267-6591. ; 38:5, s. 966-972
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracorporeal Membrane Oxygenation (ECMO) may be used in the setting of pregnancy or the peripartal period, however its utility has not been well-characterized. This study aims to give an overview on the prevalence of peripartel ECMO cases and further assess the indications and outcomes of ECMO in this setting across multiple centers and countries. Methods A retrospective, multicenter, international cohort study of pregnant and peripartum ECMO cases was performed. Data were collected from six ECMO centers across three continents over a 10-year period. Results A total of 60 pregnany/peripartal ECMO cases have been identified. Most frequent indications are acute respiratory distress syndrome ( n = 30) and pulmonary embolism ( n = 5). Veno-venous ECMO mode was applied more often (77%). ECMO treatment during pregnancy was performed in 17 cases. Maternal and fetal survival was high with 87% ( n = 52), respectively 73% ( n = 44). Conclusions Various emergency scenarios during pregnancy and at time of delivery may require ECMO treatment. Peripartal mortality in a well-resourced setting is rare, however emergencies in the labor room occur and knowledge of available rescue therapy is essential to improve outcome. Obstetricians and obstetric anesthesiologists should be aware of the availability of ECMO resource at their hospital or region to ensure immediate contact when needed.
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30.
  • Nordin, Steven, 1960-, et al. (författare)
  • A longitudinal descriptive study of self-reported abnormal smell and taste perception in pregnant women
  • 2004
  • Ingår i: Chemical Senses. - : Oxford University Press. - 0379-864X .- 1464-3553. ; 29:5, s. 391-402
  • Tidskriftsartikel (refereegranskat)abstract
    • Self-reported abnormal sensitivity, qualitative distortions and phantom sensations with respect to smell and taste was assessed with a longitudinal design, based on questions referring to gestational weeks 13–16 and 31–34 of pregnancy in comparison with 9–12 weeks post partum and with non-pregnant women with corresponding time durations and intervals. The results show that abnormal smell and/or taste perception was reported by 76% of the pregnant women, typically believed to be caused by their pregnancy. Increased smell sensitivity was found to be very common at the early stage of pregnancy (67% of all pregnant respondents) and occasionally accompanied by qualitative smell distortions (17%) and phantom smells (14%). The smell abnormalities were less common at the late pregnancy stage and almost absent post partum. Abnormal taste sensitivity was fairly commonly reported (26%), often described as increased bitter sensitivity and decreased salt sensitivity. These results, suggesting that abnormal smell and/or taste perception is experienced by a large majority of pregnant women, imply that further research is needed to understand to what extent these chemosensory changes may underlie food aversions and craving with implications for food intake during pregnancy.
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31.
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34.
  • 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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