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Gemcitabine and cisplatin plus durvalumab with or without tremelimumab in chemotherapy-naive patients with advanced biliary tract cancer: an open-label, single-centre, phase 2 study

The recent revelation that the gut microbiome, home to approximately 100 trillion microorganisms, is implicated in the development of both health and disease has spurred an exponential increase in interdisciplinary research involving gut microbiology. In all this hype, there is a need to better understand and contextualize the emerging evidence for the role of the gut microbiota in neurodegenerative and neurodevelopmental diseases, including central nervous system (CNS) malignancies. In this review, we aim to unravel the complex interactions of the microbiota-gut-brain-axis to pave a better understanding of microbiota-mediated pathogenesis, avenues for noninvasive prognosis, and therapeutic possibilities leveraging microbiota-gut-brain-axis modulations. We further provide insights of the ongoing transition from bench to bedside and discuss limitations of current approaches. Ultimately, we urge the continued development of synergistic therapeutic models with considerable consideration of the many gut-resident bacteria that will enable significant progress for the treatment of many neurological diseases.

Do-Youn Oh, MD, Kyung-Hun Lee, MD, Dae-Won Lee, MD, Jeesun Yoon, MD, Tae-Yong Kim, MD, Ju-Hee Bang, MS, et al

Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS

The recent revelation that the gut microbiome, home to approximately 100 trillion microorganisms, is implicated in the development of both health and disease has spurred an exponential increase in interdisciplinary research involving gut microbiology. In all this hype, there is a need to better understand and contextualize the emerging evidence for the role of the gut microbiota in neurodegenerative and neurodevelopmental diseases, including central nervous system (CNS) malignancies. In this review, we aim to unravel the complex interactions of the microbiota-gut-brain-axis to pave a better understanding of microbiota-mediated pathogenesis, avenues for noninvasive prognosis, and therapeutic possibilities leveraging microbiota-gut-brain-axis modulations. We further provide insights of the ongoing transition from bench to bedside and discuss limitations of current approaches. Ultimately, we urge the continued development of synergistic therapeutic models with considerable consideration of the many gut-resident bacteria that will enable significant progress for the treatment of many neurological diseases.

Longsha Liu, Jun R. Huh, Khalid Shah

© 2022 The Authors. Published by Elsevier B.V.

Nuclear receptors in renal health and disease

As a major social and economic burden for the healthcare system, kidney diseases contribute to the constant increase of worldwide deaths. A deeper understanding of the underlying mechanisms governing the etiology, development and progression of kidney diseases may help to identify potential therapeutic targets. As a superfamily of ligand-dependent transcription factors, nuclear receptors (NRs) are critical for the maintenance of normal renal function and their dysfunction is associated with a variety of kidney diseases. Increasing evidence suggests that ligands for NRs protect patients from renal ischemia/reperfusion (I/R) injury, drug-induced acute kidney injury (AKI), diabetic nephropathy (DN), renal fibrosis and kidney cancers. In the past decade, some breakthroughs have been made for the translation of NR ligands into clinical use. This review summarizes the current understanding of several important NRs in renal physiology and pathophysiology and discusses recent findings and applications of NR ligands in the management of kidney diseases.

 Zhi-Lin Luan, Cong Zhang, Wen-Hua Min, Ying-Zhi Huang, You-Fei Guan, Xiao-Yan Zhang

© 2022 The Authors. Published by Elsevier B.V.

Biliary tract cancer

Biliary tract cancers, including intrahepatic, perihilar, and distal cholangiocarcinoma as well as gallbladder cancer, are low-incidence malignancies in most high-income countries, but represent a major health problem in endemic areas; moreover, the incidence of intrahepatic cholangiocarcinoma is rising globally. Surgery is the cornerstone of cure; the optimal approach depends on the anatomical site of the primary tumour and the best outcomes are achieved through management by specialist multidisciplinary teams. Unfortunately, most patients present with locally advanced or metastatic disease. Most studies in advanced disease have pooled the various subtypes of biliary tract cancer by necessity to achieve adequate sample sizes; however, differences in epidemiology, clinical presentation, natural history, surgical therapy, response to treatment, and prognosis have long been recognised. Additionally, the identification of distinct patient subgroups harbouring unique molecular alterations with corresponding targeted therapies (such as isocitrate dehydrogenase-1 mutations and fibroblast growth factor receptor-2 fusions in intrahepatic cholangiocarcinoma, among others) is changing the treatment paradigm. In this Seminar we present an update of the causes, diagnosis, molecular classification, and treatment of biliary tract cancer.

 Prof Juan W Valle, MD; R Katie Kelley, MD; Bruno Nervi, MD; Prof Do-Youn Oh, PhD; Prof Andrew X Zhu, MD

© 2021 Elsevier Ltd. All rights reserved.