Early axonal loss predicts long-term disability in chronic inflammatory demyelinating polyneuropathy

ObjectiveTo investigate early pre-treatment nerve fiber loss as a predictor of long-term clinical outcome in chronic inflammatory demyelinating polyneuropathy (CIDP).MethodsIn 14 patients, motor and sensory conduction studies of the median, fibular, and sural nerves were performed at pre-treatment and follow-up 11–28 years later. Z-scores of amplitudes were combined as biomarkers of axonal loss and Z-scores of conduction properties as demyelination scores. The axonal loss was further examined by electromyography (EMG) and motor unit number estimation. Axonal and demyelination scores were compared to clinical outcomes in the Inflammatory Rasch-built Overall Disability Scale, the Neuropathy Impairment Score, and dynamometry.ResultsAt follow-up 12 patients walked independently, one needed support and one could not walk. The initial and follow-up axonal and demyelination scores were markedly abnormal. The initial axonal loss but not demyelination was strongly associated with both the follow-up axonal loss and the clinical measures. Moreover, delay of treatment initiation negatively influenced the axonal scores and clinical outcomes.ConclusionIn this hypothesis generating limited study, we found that axonal loss at early CIDP was highly predictive for long-term nerve fiber loss and disability.SignificanceThe study indicates that prompt initiation of treatment to prevent nerve fiber loss is necessary for outcome in CIDP.     

Mesenchymal stromal cell secretome in liver failure: Perspectives on COVID-19 infection treatment

Due to their immunomodulatory potential and release of trophic factors that promote healing, mesenchymal stromal cells (MSCs) are considered important players in tissue homeostasis and regeneration. MSCs have been widely used in clinical trials to treat multiple conditions associated with inflammation and tissue damage. Recent evidence suggests that most of the MSC therapeutic effects are derived from their secretome, including the extracellular vesicles, representing a promising approach in regenerative medicine application to treat organ failure as a result of inflammation/fibrosis. The recent outbreak of respiratory syndrome coronavirus, caused by the newly identified agent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has forced scientists worldwide to use all available instruments to fight the infection, including the inflammatory cascade caused by this pandemic disease. The use of MSCs is a valid approach to combat organ inflammation in different compartments. In addition to the lungs, which are considered the main inflammatory target for this virus, other organs are compromised by the infection. In particular, the liver is involved in the inflammatory response to SARS-CoV-2 infection, which causes organ failure, leading to death in coronavirus disease 2019 (COVID-19) patients. We herein summarize the current implications derived from the use of MSCs and their soluble derivatives in COVID-19 treatment, and emphasize the potential of MSC-based therapy in this clinical setting.     

Understanding thoracic surgeons' perceptions of administrative database analyses and guidelines in clinical decision-making

ObjectivesThis study explored cardiothoracic surgeons' perceptions of health services research and practice guidelines, particularly how both influence providers' clinical decision-making.MethodsA trained interviewer conducted open-ended, semistructured phone interviews with cardiothoracic surgeons across the United States. The interviews explored surgeons' experiences with lung cancer treatment and their perceptions of health services research and guidelines. Researchers coded the transcribed interviews using conventional content analysis. Interviews continued until thematic saturation was reached.ResultsThe 27 surgeons interviewed mostly were general thoracic surgeons (23/27) who attend tumor board weekly (21/27). Five themes relating to physician perceptions of health services research and guidelines emerged. Databases analyses' inherent selection bias and perceived deficit of pertinent clinical variables made providers skeptical of using these studies as primary decision drivers; however, providers thought that database analyses are useful to supplement other data and drive future research. Likewise, providers generally felt that although guidelines provide a useful framework, they often have difficulty applying guidelines to individual patients. An analysis of provider characteristics revealed that younger physicians in practice for fewer years appeared more likely to report using guidelines, and physicians who were aged 50 years or more and not purely academic surgeons appeared to find database analyses less impactful.ConclusionsHealth services research, including database analyses, comprise much of the surgical literature; however, this study suggests that perceptions of database analyses and guidelines are mixed and questions whether thoracic surgeons routinely use either to inform their decisions. Researchers must address how to present compelling data to influence clinical practice.     

Prognostic value of red blood cell distribution width in patients with acute pulmonary embolism: A protocol for systematic review and meta-analysis

Background:Prior reports have suggested that the red blood cell distribution width (RDW) parameter could be measured as a prognostic indicator in pulmonary embolism (PE) patients, thereby helping to guide their care. However, no systematic analyses on this topic have been completed to date, and the exact relationship between RDW and PE remains to be fully clarified. We will therefore conduct a systematic literature review with the goal of defining the correlation between RDW and mortality in acute PE cases.Methods:The EMBASE, Web of Knowledge, PubMed, ClinicalTrials.gov, and Cochrane Library databases will be searched for all relevant studies published from inception through March 2021 using the following search strategy: (“red blood cell distribution width”) AND (“pulmonary embolism”). Two authors will independently identify eligible studies and extract data. The Q and I² statistics will be used to judge heterogeneity among studies.Results:This study will establish the relative efficacy of RDW as a metric for predicting PE patient mortality.Conclusions:This study will offer a reliable, evidence-based foundation for the clinical utilization of RDW as a tool for gauging mortality risk in acute PE patients.Ethics and dissemination:As this is a protocol for a systematic review of previously published data, no ethical approval is required. Electronic dissemination of study results will be done through a peer-review publication or represented at a related conference.     

Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor

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circZBTB44通过调控AKT通路促进肾透明细胞癌增殖和迁移的研究

目的 探究circZBTB44在肾透明细胞癌中的表达情况及探讨circZBTB44在肾透明细胞癌中的生物学功能及促进肾透明细胞癌细胞进展的可能机制。方法 通过qRT-PCR法检测circZBTB44在我院21对肾透明细胞癌组织及细胞系786-O、ACHN中的表达水平;通过放线菌素D实验、RNase R实验、核浆分离实验鉴定circZBTB44的特征;通过siRNA下调circZBTB44的表达后,通过MTS细胞增殖实验、克隆形成实验及Transwell迁移实验来探究circZBTB44对肾透明细胞癌786-O、ACHN的生物学功能影响;通过蛋白免疫印迹实验来探究circZBTB44调控的下游通路。结果 circZBTB44在肾透明细胞癌组织和细胞株786-O和ACHN中明显高表达。下调circZBTB44的表达可明显抑制786-O和ACHN的增殖和迁移能力。下调circZBTB44可抑制肾透明细胞癌786-O和ACHN细胞中AKT的磷酸化。结论 circZBTB44在肾透明细胞癌中高表达。circZBTB44可能通过调控AKT信号通路促进肾透明细胞癌的增殖和迁移。     

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging

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