ACS Chemical Health & Safety最新文献

Limited data exist on the effects of induction treatment in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI), who may also be ineligible for autologous stem cell transplant. This analysis investigated the impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on renal function in patients from the Connect® MM Registry based on transplant status. Eligible patients were aged ≥18 years with symptomatic MM diagnosed ≤2 months before enrollment. Patients in this analysis received front-line RVd for ≥3 cycles and were grouped by transplant status and baseline renal function. As of August 4, 2021, 344 transplanted and 289 non-transplanted patients had received RVd for ≥3 cycles at induction. Improved renal function was observed at 3, 6, and 12 months in patients with all severities of RI at baseline. In patients with >60 and ≤60 creatinine clearance mL/min at baseline, median progression-free survival was 49.4 months and 47.6 months in transplanted patients and 35.7 months and 29.1 months in non-transplanted patients, respectively. These results provide real-world evidence that patients with NDMM and RI who receive front-line RVd for ≥3 cycles may have improved renal function regardless of transplant status, with renal function no longer affecting the long-term outcome. Clinical trial information: NCT01081028.

The Voyager 2 flyby of Uranus in 1986 revealed an unusually oblique and off-centred magnetic field. This single in situ measurement has been the basis of our interpretation of Uranus’s magnetosphere as the canonical extreme magnetosphere of the solar system; with inexplicably intense electron radiation belts and a severely plasma-depleted magnetosphere. However, the role of external forcing by the solar wind has rarely been considered in explaining these observations. Here we revisit the Voyager 2 dataset to show that Voyager 2 observed Uranus’s magnetosphere in an anomalous, compressed state that we estimate to be present less than 5% of the time. If the spacecraft had arrived only a few days earlier, the upstream solar wind dynamic pressure would have been ~20 times lower, resulting in a dramatically different magnetospheric configuration. We postulate that such a compression of the magnetosphere could increase energetic electron fluxes within the radiation belts and empty the magnetosphere of its plasma temporarily. Therefore, the interpretation of Uranus’s magnetosphere as being extreme may simply be a product of a flyby that occurred under extreme upstream solar wind conditions.

A new phase III, randomized, controlled trial was carried out to assess the efficacy of ¹⁷⁷Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer (mCRPC). A total of 468 patients with PSMA⁺ mCRPC who experienced disease progression after receiving an androgen receptor pathway inhibitor (ARPI) were randomly allocated to receive ¹⁷⁷Lu-PSMA-617 or a different ARPI. Treatment with ¹⁷⁷Lu-PSMA-617 resulted in improved median radiographic progression-free survival (PFS) compared with a change of ARPI (11.60 months (95% CI 9.30–14.19) versus 5.59 months (95% CI 4.21–5.95)), with a good safety profile. These results showed that ¹⁷⁷Lu-PSMA-617 prolonged radiographic PFS and could be a valid therapeutic alternative for patients considered for a change of ARPI.

The central role of the endothelial microenvironment in orchestrating bone marrow (BM) homeostasis and hematopoietic support has been confirmed at various developmental stages and in adult life. The BM vasculature is crucial in mediating communication between BM parenchyma and circulating blood, displaying remarkable heterogeneity in structure and function. While vascular cell diversity in other tissues has long been recognized, the molecular basis of this phenomenon in BM is just now emerging. Over the past decade, single-cell approaches and microscopic observations have expanded our understanding of BM vasculature. While solely characterized for their paracrine properties in the past, recent advances have revolutionized our perception of endothelial function, revealing distinct anatomical locations associated with diverse endothelial cell states. The identification of phenotypic differences between normal and pathological conditions has therefore deepened our understanding of vascular dynamics and their impact on hematopoiesis in health and disease. In this review, we highlight key milestones and recent advances in understanding vascular heterogeneity within BM microenvironment during development, adulthood and aging. We also explore how leukemia affects this heterogeneity and how we can take this knowledge forward to improve clinical practices. By synthesizing existing literature, we aim to address unresolved questions and outline future research directions.