The spectrum of Myelin Oligodendrocytes Glycoprotein (MOG) antibody disease constitutes a recently described challenging entity, referring to a relatively new spectrum of autoimmune disorders with ...antibodies against MOG predominantly involving the optic nerve and spinal cord. The purpose of this article is to describe MRI features of MOG-AD involvement in the optic nerves, spinal cord and the brain of adults.
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.
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.
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).
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.
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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.
In an international cohort of more than 1000 patients with sentinel node‐positive melanoma treated at 21 melanoma centers since the publication of landmark trials supporting active regional nodal basin surveillance using ultrasound as an alternative to completion lymph node dissection, there has been high adoption of active surveillance. Compared with patients who undergo completion lymph node dissection, those who undergo active surveillance have more nodal recurrences but comparable recurrence‐free and disease‐specific survival at this early assessment, including those who receive adjuvant therapy without undergoing prior completion lymph node dissection.
The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node ...(SLN)-positive melanoma.
Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization.
We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics.
Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients.
There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.
Expertise psychiatrique et sexualité (1850-1930) Ancibure, Francis; Cornut, Étienne; Danou, Gérard ...
Droit et cultures : cahiers du Centre de recherche de l'U.E.R. de sciences juridiques,
2010
Journal Article
Nicotiana protoplasts and Arabidopsis leaf discs or roots were co‐cultivated with two Agrobacterium strains each carrying a different T‐DNA. Co‐transformed plants were selected and the integration of ...the different T‐DNAs was analysed at the genetic and genomic level. Genetic analysis showed that the T‐DNAs derived from different bacteria were frequently integrated at the same locus, independent of the plant species or transformation method used. Southern analysis revealed that 12 out of 27 Arabidopsis transformants contained the co‐transferred T‐DNAs linked to each other in all possible configurations but with a preference for those with at least one right border involved in linkage. Overall, our data support the hypothesis that ligation of separate T‐DNAs is a dominant mechanism in formation of the frequently observed repeats of identical T‐DNAs. We propose a scheme which could explain the formation of T‐DNA repeats and the preferential involvement of right borders in T‐DNA linkages.
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