Evolving the narrative for protecting a rapidly changing ocean, post-COVID-19.

The ocean is the linchpin supporting life on Earth, but it is in declining health due to an increasing footprint of human use and climate change. Despite notable successes in helping to protect the ocean, the scale of actions is simply not now meeting the overriding scale and nature of the ocean's problems that confront us.Moving into a post-COVID-19 world, new policy decisions will need to be made. Some, especially those developed prior to the pandemic, will require changes to their trajectories; others will emerge as a response to this global event. Reconnecting with nature, and specifically with the ocean, will take more than good intent and wishful thinking. Words, and how we express our connection to the ocean, clearly matter now more than ever before.The evolution of the ocean narrative, aimed at preserving and expanding options and opportunities for future generations and a healthier planet, is articulated around six themes: (1) all life is dependent on the ocean; (2) by harming the ocean, we harm ourselves; (3) by protecting the ocean, we protect ourselves; (4) humans, the ocean, biodiversity, and climate are inextricably linked; (5) ocean and climate action must be undertaken together; and (6) reversing ocean change needs action now.This narrative adopts a 'One Health' approach to protecting the ocean, addressing the whole Earth ocean system for better and more equitable social, cultural, economic, and environmental outcomes at its core. Speaking with one voice through a narrative that captures the latest science, concerns, and linkages to humanity is a precondition to action, by elevating humankind's understanding of our relationship with 'planet Ocean' and why it needs to become a central theme to everyone's lives. We have only one ocean, we must protect it, now. There is no 'Ocean B'.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.

The polymorphism IL-1beta T-31C is associated with a longer overall survival in patients with multiple myeloma undergoing auto-SCT.

Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). Therefore, it is possible that inborn genetic variations leading to a modified expression of these cytokines will influence the outcome for these patients. We investigated 348 MM patients undergoing high-dose melphalan treatment followed by Auto-SCT and examined the influence of single nucleotide polymorphisms (SNPs) in genes involved in the inflammatory response. We found that the polymorphism IL-1beta T-31C significantly influenced overall survival (OS; P=0.02) and that carriers of the variant C-allele had a significantly longer survival than homozygous wild-type allele TT-carriers (relative risk 0.6 (95% CI=0.5-0.9); P=0.008). The polymorphisms IL-6 G-174C, IL-10 C592A, PPARgamma2 Pro(12)Ala, COX-2 A-1195G, COX-2 T8473C and NFKB1 ins/del did not influence the OS in this group of patients. Furthermore, homozygous carriers of the variant allele of IL-1beta T-31C were at 1.37-fold (CI=1.05-1.80) increased risk of MM as compared with population-based controls (P=0.02). Our results indicate that IL-1beta is involved in the pathogenesis of MM.

Renal function in 153 manic-depressive patients treated with lithium for more than five years.

Renal function was examined in 153 manic-depressive patients treated with lithium for more than 5 years, mean 10 years. No significant change was detectable in plasma creatinine. Glomerular filtration rate (GFR) decreased slightly, but significantly, and not until after 17 years of treatment did the regression line reach the lower confidence limit in the reference material. GFR was generally only moderately decreased. Renal concentrating capacity was significantly reduced during the whole investigation period and did not change with time. GFR was independent of the dosage pattern. The diuresis did not differ markedly in patients given one or three daily doses. In a two-dose group predominantly treated with slow-release tablets, the diuresis was somewhat higher in 75% of the patients but much higher for the rest of the group. Since the prophylactic effect of lithium was the same in the one-dose group (mean dosage 21 mmol/day) as in the two-dose and three-dose groups (mean dosage 27-28 mmol/day), our data indicate that generally employed lithium doses may be reduced somewhat without loss of prophylactic efficacy.