| 1. |
- 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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| 2. |
- 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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| 3. |
- Marcote, B., et al.
(författare)
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A repeating fast radio burst source localized to a nearby spiral galaxy
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 577:7789, s. 190-194
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Tidskriftsartikel (refereegranskat)abstract
- Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4–7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9–12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.
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| 4. |
- Scholz, P., et al.
(författare)
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Simultaneous X-Ray and Radio Observations of the Repeating Fast Radio Burst FRB similar to 180916.J0158+65
- 2020
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 901:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on simultaneous radio and X-ray observations of the repeating fast radio burst source FRB 180916.J0158+65 using the Canadian Hydrogen Intensity Mapping Experiment (CHIME), Effelsberg, and Deep Space Network (DSS-14 and DSS-63) radio telescopes and the Chandra X-ray Observatory. During 33 ks of Chandra observations, we detect no radio bursts in overlapping Effelsberg or Deep Space Network observations and a single burst during CHIME/FRB source transits. We detect no X-ray events in excess of the background during the Chandra observations. These non-detections imply a 5 sigma limit of <5 x 10(-10)erg cm(-2)for the 0.5-10 keV fluence of prompt emission at the time of the radio burst and 1.3 x 10(-9)erg cm(-2)at any time during the Chandra observations. Given the host-galaxy redshift of FRB 180916.J0158+65 (z similar to 0.034), these correspond to energy limits of <1.6 x 10(45)erg and <4 x 10(45)erg, respectively. We also place a 5 sigma limit of <8 x 10(-15)erg s(-1) cm(-2)on the 0.5-10 keV absorbed flux of a persistent source at the location of FRB 180916.J0158+65. This corresponds to a luminosity limit of <2 x 10(40)erg s(-1). Using an archival set of radio bursts from FRB 180916.J0158+65, we search for prompt gamma-ray emission in Fermi/GBM data but find no significant gamma-ray bursts, thereby placing a limit of 9 x 10(-9)erg cm(-2)on the 10-100 keV fluence. We also search Fermi/LAT data for periodic modulation of the gamma-ray brightness at the 16.35 days period of radio burst activity and detect no significant modulation. We compare these deep limits to the predictions of various fast radio burst models, but conclude that similar X-ray constraints on a closer fast radio burst source would be needed to strongly constrain theory.
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| 5. |
- Demirkan, Ayse, et al.
(författare)
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Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations
- 2012
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:2, s. e1002490-
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Tidskriftsartikel (refereegranskat)abstract
- Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88 x 10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10 x 10(-57)). After a correction for multiple comparisons (P-value, 2.2 x 10(-9)), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study identified nine novel phospho- and sphingolipid loci, substantially increasing our knowledge of the genetic basis for these traits.
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| 6. |
- Danilenko, A., et al.
(författare)
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Deep optical imaging of the gamma-ray pulsar J1048-5832 with the VLT
- 2013
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552, s. A127-
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Tidskriftsartikel (refereegranskat)abstract
- Context. PSR J1048-5832 is a young radio-pulsar that has recently been detected in gamma-rays with Fermi, and also in X-rays with Chandra and XMM-Newton. It powers a compact pulsar wind nebula visible in X-rays and is in many ways similar to the Vela pulsar. Aims. We present deep optical observations made with the ESO Very Large Telescope to search for optical counterparts of the pulsar and its nebula and to explore their multi-wavelength emission properties. Methods. The data were obtained in the V and R bands and were compared with archival data in other spectral domains. Results. We do not detect the pulsar in the optical and derive informative upper limits of R greater than or similar to 28(.)(m) 1 and V less than or similar to 28(.)(m) 4 for its brightness. Using a red-clump star method, we estimate an interstellar extinction towards the pulsar of A(V) approximate to 2 mag, which is consistent with the absorbing column density derived from X-rays. The respective distance agrees with the dispersion measure distance. We reanalysed the Chandra X-ray data and compared the dereddened upper limits with the unabsorbed X-ray spectrum of the pulsar. We find that regarding its optical-X-ray spectral properties this gamma-ray pulsar is not distinct from other pulsars detected in both ranges. However, like the Vela pulsar, it is very inefficient in the optical and X-rays. Among a dozen optical sources overlapping with the pulsar X-ray nebula we find one with V approximate to 26(.)(m)9 and R approximate to 26. m 3, whose colour is slightly bluer than that of the field stars and is consistent with the peculiar colours typical for pulsar nebula features. It positionally coincides with a relatively bright feature of the pulsar X-ray nebula, resembling the Crab wisp and is located in similar to 2 '' from the pulsar. We suggest this source as a counterpart candidate to the feature. Conclusions. Based on the substantial interstellar extinction towards the pulsar and its optical inefficiency, additional optical studies should be carried out at longer wavelengths.
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