The Lancet

Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19.

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IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial

Paul M Ridker,Matt Devalaraja,Florian M M Baeres,Mads D M Engelmann,G Kees Hovingh,Milana Ivkovic,Larry Lo,Douglas Kling,Pablo Pergola,Dominic Raj,Peter Libby,Michael Davidsonon behalf of the RESCUE Investigators

doi : 10.1016/S0140-6736(21)00520-1

ARTICLES| VOLUME 397, ISSUE 10289, P2060-2069, MAY 29, 2021

IL-6 has emerged as a pivotal factor in atherothrombosis. Yet, the safety and efficacy of IL-6 inhibition among individuals at high atherosclerotic risk but without a systemic inflammatory disorder is unknown. We therefore addressed whether ziltivekimab, a fully human monoclonal antibody directed against the IL-6 ligand, safely and effectively reduces biomarkers of inflammation and thrombosis among patients with high cardiovascular risk. We focused on individuals with elevated high-sensitivity CRP and chronic kidney disease, a group with substantial unmet clinical need in whom previous studies in inflammation inhibition have shown efficacy for cardiovascular event reduction.

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Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

Brad H Rovin,Y K Onno Teng,Ellen M Ginzler,Cristina Arriens,Dawn J Caster,Juanita Romero-Diaz,Keisha Gibson,Joshua Kaplan,Laura Lisk,Sandra Navarra,Samir V Parikh,Simrat Randhawa,Neil Solomons,Robert B Huizinga

doi : 10.1016/S0140-6736(21)00578-X

ARTICLES| VOLUME 397, ISSUE 10289, P2070-2080, MAY 29, 2021

Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis.

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Immunotactoid glomerulopathy associated with monoclonal gammopathy

Satoshi Inotani,Taro Horino,Masayuki Ishihara,Osamu Ichii,Akinori Matsumori

doi : 10.1016/S0140-6736(21)00477-3

CLINICAL PICTURE| VOLUME 397, ISSUE 10289, P2081, MAY 29, 2021

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Chronic pain: an update on burden, best practices, and new advances

Steven P Cohen,Lene Vase,William M Hooten

doi : 10.1016/S0140-6736(21)00393-7

SERIES|CHRONIC PAIN| VOLUME 397, ISSUE 10289, P2082-2097, MAY 29, 2021

Chronic pain exerts an enormous personal and economic burden, affecting more than 30% of people worldwide according to some studies. Unlike acute pain, which carries survival value, chronic pain might be best considered to be a disease, with treatment (eg, to be active despite the pain) and psychological (eg, pain acceptance and optimism as goals) implications. Pain can be categorised as nociceptive (from tissue injury), neuropathic (from nerve injury), or nociplastic (from a sensitised nervous system), all of which affect work-up and treatment decisions at every level; however, in practice there is considerable overlap in the different types of pain mechanisms within and between patients, so many experts consider pain classification as a continuum. The biopsychosocial model of pain presents physical symptoms as the denouement of a dynamic interaction between biological, psychological, and social factors. Although it is widely known that pain can cause psychological distress and sleep problems, many medical practitioners do not realise that these associations are bidirectional. While predisposing factors and consequences of chronic pain are well known, the flipside is that factors promoting resilience, such as emotional support systems and good health, can promote healing and reduce pain chronification. Quality of life indicators and neuroplastic changes might also be reversible with adequate pain management. Clinical trials and guidelines typically recommend a personalised multimodal, interdisciplinary treatment approach, which might include pharmacotherapy, psychotherapy, integrative treatments, and invasive procedures.

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Nociplastic pain: towards an understanding of prevalent pain conditions

Mary-Ann Fitzcharles,Steven P Cohen,Daniel J Clauw,Geoffrey Littlejohn,Chie Usui,Winfried H?user

doi : 10.1016/S0140-6736(21)00392-5

SERIES|CHRONIC PAIN| VOLUME 397, ISSUE 10289, P2098-2110, MAY 29, 2021

Nociplastic pain is the semantic term suggested by the international community of pain researchers to describe a third category of pain that is mechanistically distinct from nociceptive pain, which is caused by ongoing inflammation and damage of tissues, and neuropathic pain, which is caused by nerve damage. The mechanisms that underlie this type of pain are not entirely understood, but it is thought that augmented CNS pain and sensory processing and altered pain modulation play prominent roles. The symptoms observed in nociplastic pain include multifocal pain that is more widespread or intense, or both, than would be expected given the amount of identifiable tissue or nerve damage, as well as other CNS-derived symptoms, such as fatigue, sleep, memory, and mood problems. This type of pain can occur in isolation, as often occurs in conditions such as fibromyalgia or tension-type headache, or as part of a mixed-pain state in combination with ongoing nociceptive or neuropathic pain, as might occur in chronic low back pain. It is important to recognise this type of pain, since it will respond to different therapies than nociceptive pain, with a decreased responsiveness to peripherally directed therapies such as anti-inflammatory drugs and opioids, surgery, or injections.

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Neuromodulation for chronic pain

Helena Knotkova,Clement Hamani,Eellan Sivanesan,Mar?a Francisca Elgueta Le Beuffe,Jee Youn Moon,Steven P Cohen,Marc A Huntoon

doi : 10.1016/S0140-6736(21)00794-7

SERIES|CHRONIC PAIN| VOLUME 397, ISSUE 10289, P2111-2124, MAY 29, 2021

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables.

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