6594. Chronic kidney disease.
作者: Kamyar Kalantar-Zadeh.;Tazeen H Jafar.;Dorothea Nitsch.;Brendon L Neuen.;Vlado Perkovic.
来源: Lancet. 2021年398卷10302期786-802页
Chronic kidney disease is a progressive disease with no cure and high morbidity and mortality that occurs commonly in the general adult population, especially in people with diabetes and hypertension. Preservation of kidney function can improve outcomes and can be achieved through non-pharmacological strategies (eg, dietary and lifestyle adjustments) and chronic kidney disease-targeted and kidney disease-specific pharmacological interventions. A plant-dominant, low-protein, and low-salt diet might help to mitigate glomerular hyperfiltration and preserve renal function for longer, possibly while also leading to favourable alterations in acid-base homoeostasis and in the gut microbiome. Pharmacotherapies that alter intrarenal haemodynamics (eg, renin-angiotensin-aldosterone pathway modulators and SGLT2 [SLC5A2] inhibitors) can preserve kidney function by reducing intraglomerular pressure independently of blood pressure and glucose control, whereas other novel agents (eg, non-steroidal mineralocorticoid receptor antagonists) might protect the kidney through anti-inflammatory or antifibrotic mechanisms. Some glomerular and cystic kidney diseases might benefit from disease-specific therapies. Managing chronic kidney disease-associated cardiovascular risk, minimising the risk of infection, and preventing acute kidney injury are crucial interventions for these patients, given the high burden of complications, associated morbidity and mortality, and the role of non-conventional risk factors in chronic kidney disease. When renal replacement therapy becomes inevitable, an incremental transition to dialysis can be considered and has been proposed to possibly preserve residual kidney function longer. There are similarities and distinctions between kidney-preserving care and supportive care. Additional studies of dietary and pharmacological interventions and development of innovative strategies are necessary to ensure optimal kidney-preserving care and to achieve greater longevity and better health-related quality of life for these patients.
6595. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.
作者: Jesus G Berdeja.;Deepu Madduri.;Saad Z Usmani.;Andrzej Jakubowiak.;Mounzer Agha.;Adam D Cohen.;A Keith Stewart.;Parameswaran Hari.;Myo Htut.;Alexander Lesokhin.;Abhinav Deol.;Nikhil C Munshi.;Elizabeth O'Donnell.;David Avigan.;Indrajeet Singh.;Enrique Zudaire.;Tzu-Min Yeh.;Alicia J Allred.;Yunsi Olyslager.;Arnob Banerjee.;Carolyn C Jackson.;Jenna D Goldberg.;Jordan M Schecter.;William Deraedt.;Sen Hong Zhuang.;Jeffrey Infante.;Dong Geng.;Xiaoling Wu.;Marlene J Carrasco-Alfonso.;Muhammad Akram.;Farah Hossain.;Syed Rizvi.;Frank Fan.;Yi Lin.;Thomas Martin.;Sundar Jagannath.
来源: Lancet. 2021年398卷10297期314-324页
CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis.
6596. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions.
The sphingosine 1-phosphate (S1P) signalling pathways have important and diverse functions. S1P receptors (S1PRs) have been proposed as a therapeutic target for various diseases due to their involvement in regulation of lymphocyte trafficking, brain and cardiac function, vascular permeability, and vascular and bronchial tone. S1PR modulators were first developed to prevent rejection by the immune system following renal transplantation, but the only currently approved indication is multiple sclerosis. The primary mechanism of action of S1PR modulators in multiple sclerosis is through binding S1PR subtype 1 on lymphocytes resulting in internalisation of the receptor and loss of responsiveness to the S1P gradient that drives lymphocyte egress from lymph nodes. The reduction in circulating lymphocytes presumably limits inflammatory cell migration into the CNS. Four S1PR modulators (fingolimod, siponimod, ozanimod, and ponesimod) have regulatory approval for multiple sclerosis. Preclinical evidence and ongoing and completed clinical trials support development of S1PR modulators for other therapeutic indications.
6598. A strategy to reduce the carbon footprint of clinical trials.
作者: Fiona Adshead.;Rustam Al-Shahi Salman.;Simon Aumonier.;Michael Collins.;Kerry Hood.;Carolyn McNamara.;Keith Moore.;Richard Smith.;Matthew R Sydes.;Paula R Williamson.
来源: Lancet. 2021年398卷10297期281-282页 6599. Contemporary radiotherapy: present and future.
作者: Ravi A Chandra.;Florence K Keane.;Francine E M Voncken.;Charles R Thomas.
来源: Lancet. 2021年398卷10295期171-184页
Oncology care is increasingly a multidisciplinary endeavour, and radiation therapy continues to have a key role across the disease spectrum in nearly every cancer. However, the field of radiation oncology is still one of the most poorly understood of the cancer disciplines. In this Review, we attempt to summarise and contextualise developments within the field of radiation oncology for the non-radiation oncologist. We discuss advancements in treatment technologies and imaging, followed by an overview of the interplay with advancements in systemic therapy and surgical techniques. Finally, we review new frontiers in radiation oncology, including advances within the metastatic disease continuum, reirradiation, and emerging types of radiation therapy.
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