Abstract：
:Sepsis is life-threatening organ dysfunction due to dysregulated response to infection. Patients with sepsis exhibit wide heterogeneity stemming from genetic, molecular, and clinical factors as well as differences in pathogens, creating challenges for the development of effective treatments. Several gaps in knowledge also contribute: (i) biomarkers that identify patients likely to benefit from specific treatments are unknown; (ii) therapeutic dose and duration is often poorly understood; and (iii) short-term mortality, a common outcome measure, is frequently criticized for being insensitive. To date, the majority of sepsis trials use traditional design features, and have largely failed to identify new treatments with incremental benefit over standard of care. Traditional trials are also frequently conducted as part of a drug evaluation process that is segmented into several phases, each requiring separate trials, with a long time delay from inception through design and execution to incorporation of results into clinical practice. By contrast, adaptive clinical trial designs facilitate the evaluation of several candidate treatments simultaneously, learn from emergent discoveries during the course of the trial, and can be structured efficiently to lead to more timely conclusions compared to traditional trial designs. Adoption of new treatments in clinical practice can be accelerated if these trials are incorporated in electronic health records as part of a learning health system. In this review, we discuss challenges in the evaluation of treatments for sepsis, and explore potential benefits and weaknesses of recent advances in adaptive trial methodologies to address these challenges.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Talisa VB,Yende S,Seymour CW,Angus DCdoi
10.3389/fimmu.2018.01502subject
Has Abstractpub_date
2018-06-28 00:00:00pages
1502issn
1664-3224journal_volume
9pub_type
杂志文章,评审abstract：:Bovine neonatal pancytopenia (BNP) was a vaccine-induced alloimmune disease observed in young calves and characterized by hemorrhages, pancytopenia, and severe destruction of the hematopoietic tissues. BNP was induced by alloreactive maternal antibodies present in the colostrum of certain cows vaccinated with a highly...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.01902
更新日期：2018-08-14 00:00:00
abstract：:The clinical experience gathered throughout the years has raised awareness of primary immunodeficiency diseases (PIDD). T cell receptor excision circles (TREC) and kappa-deleting recombination excision circles (KREC) assays for thymic and bone marrow outputs measurement have been widely implemented in newborn screenin...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.01411
更新日期：2020-07-16 00:00:00
abstract：:The mechanistic requirements of antigen recognition by T cells expressing a γδ TCR has revealed important differences with those of αβ TCR cells and, despite impressive new data generated in the very recent years, they remain poorly understood. Based on the structure of the TCR chains and the tissue distribution, γδ c...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2014.00679
更新日期：2015-01-15 00:00:00
abstract：:Human cytomegalovirus (HCMV) is under constant selective pressure from the immune system in vivo. Study of HCMV genes that have been lost in the absence of, or genetically altered by, such selection can focus research toward findings of in vivo significance. We have been particularly interested in the most pronounced ...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2018.02214
更新日期：2018-10-01 00:00:00
abstract：:The small GTPase Rab5 is one of the master regulators of vesicular trafficking that participates in early stages of the endocytic pathway, such as endocytosis and endosome maturation. Three Rab5 isoforms (a, b, and c) share high sequence identity, and exhibit complex functions. However, the role of Rab5c in virus infe...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.02133
更新日期：2020-09-02 00:00:00
abstract：:The neonatal Fc receptor (FcRn) plays key roles in IgG and albumin homeostasis, maternal IgG transport, and antigen presentation of IgG-opsonized antigens. Previously, we reported that transgenic (Tg) mice that overexpress the bovine FcRn (bFcRn) have augmented T-dependent humoral immune response with increased IgG pr...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2015.00357
更新日期：2015-07-20 00:00:00
abstract：:Background and Aims: Despite the negative results of blocking IL-17 in Crohn's disease (CD) patients, selective modulation of Th17-dependent responses warrants further study. Inhibition of retinoic acid-related orphan receptor gamma (RORγt), the master regulator of the Th17 signature, is currently being explored in in...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.02307
更新日期：2018-10-22 00:00:00
abstract：:Acute infection of bovine viral diarrhea virus (BVDV) is associated with immune dysfunction and can cause peripheral blood lymphopenia and lymphocyte apoptosis. Our previous study has confirmed that programmed death-1 (PD-1) blockade inhibits peripheral blood lymphocyte (PBL) apoptosis and restores proliferation and a...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.00467
更新日期：2020-03-17 00:00:00
abstract：Objective:To examine the utility of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) as biomarkers of prognosis in seropositive autoimmune encephalitis (AE). Methods:In this multicenter study, we retrospectively analyzed 57 cases of seropositive AE with hospital admissio...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.597858
更新日期：2021-01-14 00:00:00
abstract：:Type 2 diabetes is a metabolic disorder characterized by persistently elevated glucose levels. There is no effective treatment strategy for this condition, and it poses a massive economic burden globally. Schistosoma soluble egg antigen (SEA)-induced immunomodulatory mechanisms have been reported in the treatment of a...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2019.01471
更新日期：2019-06-26 00:00:00
abstract：:The heat-labile toxins (LT) produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is know...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2017.01175
更新日期：2017-09-25 00:00:00
abstract：Background:CD1d restricted invariant natural killer T (iNKT) cells are important in the activation and regulation of immune responses. Limited information is available regarding the functional role of iNKT cells in the human immunodeficiency virus (HIV) disease progression. Methodology:α-GalCer stimulated iNKT cells w...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.01152
更新日期：2018-05-24 00:00:00
abstract：:Regulatory T cells play an important role in the control of autoimmune diseases and maintenance of tolerance. In the context of transplantation, regulatory T cells (Tregs) have been proposed as new therapeutic tools that may induce allospecific tolerance toward the graft, avoiding the side effects induced by generaliz...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.00375
更新日期：2020-04-02 00:00:00
abstract：:Mesenchymal stromal cells (MSCs) exert immunosuppressive effects on immune cells including dendritic cells (DCs). However, many details of the bidirectional interaction of MSCs with DCs are still unsolved and information on key molecules by which DCs can modulate MSC functions is limited. Here, we report that osteopon...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.01207
更新日期：2018-06-01 00:00:00
abstract：:Epstein Barr virus (EBV) is a gamma herpes virus associated with certain malignancies and autoimmune diseases. EBV maintains latency in B cells with occasional reactivation, in part by overcoming the host immune response with viral homologs of several human proteins. EBV interleukin 10 (vIL-10), a lytic phase protein,...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.02198
更新日期：2018-10-09 00:00:00
abstract：:Regulatory T cells (Tregs) are considered key players in the prevention of allograft rejection in transplanted patients. Belatacept (BLT) is an effective alternative to calcineurin inhibitors that appears to preserve graft survival and function; however, the impact of this drug in the homeostasis of Tregs in transplan...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2017.00219
更新日期：2017-03-03 00:00:00
abstract：:The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life's increased susceptibility to severe infections or until active immunity is achieved following infant's...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2016.00338
更新日期：2016-08-31 00:00:00
abstract：:Obstructive nephropathy constitutes a major cause of pediatric renal progressive disease. The mechanisms leading to disease progression are still poorly understood. Kidney fibrotic lesions are reproduced using a model of partial unilateral ureteral obstruction (pUUO) in newborn mice. Based on data showing significant ...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2017.00450
更新日期：2017-05-04 00:00:00
abstract：:The mucin gene, MUC5AC, is highly expressed both in chronic respiratory inflammatory diseases and inflammatory bowel disease where mucin secretion is regulated by members of the interleukin IL-20 subfamily. This study was conducted to determine the roles and mechanisms of IL-19, a member of the IL-20 subfamily, in reg...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2019.01682
更新日期：2019-07-17 00:00:00
abstract：:Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies w...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2020.01673
更新日期：2020-07-29 00:00:00
abstract：:Human Campylobacter infections are progressively rising and of high socioeconomic impact. In the present preclinical intervention study we investigated anti-pathogenic, immuno-modulatory, and intestinal epithelial barrier preserving properties of vitamin D applying an acute campylobacteriosis model. Therefore, seconda...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2019.02094
更新日期：2019-09-03 00:00:00
abstract：:Early clearance of tuberculosis is the successful eradication of inhaled bacteria before the development of an adaptive immune response. We previously showed, by utilizing a non-virulent mycobacteria infection model, that C57BL/6 mice are more efficient than BALB/c in their control of bacterial growth in the lungs dur...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.01939
更新日期：2018-09-03 00:00:00
abstract：:Recent genome-wide studies have revealed the presence of thousands of long non-protein-coding RNAs (lncRNAs), some of which may play critical roles in the cell. We have previously shown that a large number of lncRNAs show differential expression in response to interferon (IFN)α stimulation in primary human cells. Here...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2014.00676
更新日期：2015-01-30 00:00:00
abstract：:The lung is a primary organ for gas exchange in mammals that represents the largest epithelial surface in direct contact with the external environment. It also serves as a crucial immune organ, which harbors both innate and adaptive immune cells to induce a potent immune response. Due to its direct contact with the ou...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2020.01722
更新日期：2020-08-04 00:00:00
abstract：:Dendritic cells (DCs) are antigen-presenting cells essential for the induction of adaptive immune responses. Their unprecedented ability to present antigens to T cells has made them excellent targets for vaccine development. In the last years, a new technology based on antigen delivery directly to different DC subsets...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2017.01727
更新日期：2017-12-04 00:00:00
abstract：:The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V(D)J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N-region addition. Although the diversity is great, close inspection has revealed distinct and unique characteri...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2014.00096
更新日期：2014-03-19 00:00:00
abstract：:The role of inflammation in atherosclerosis has been recognized several decades ago and existing treatments provide benefits in part through non-specific anti-inflammatory actions. Compared with other cytokines, interleukin-1β (IL-1β) is associated with acute and chronic inflammation. Anti-inflammatory therapy with ca...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2020.589654
更新日期：2020-12-10 00:00:00
abstract：:Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship bet...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2018.01948
更新日期：2018-08-28 00:00:00
abstract：:Infections take their greatest toll in early life necessitating robust approaches to protect the very young. Here, we review the rationale, current state, and future research directions for one such approach: neonatal immunization. Challenges to neonatal immunization include natural concern about safety as well as a d...
journal_title：Frontiers in immunology
pub_type： 杂志文章,评审
doi：10.3389/fimmu.2018.00532
更新日期：2018-04-04 00:00:00
abstract：:This study aimed to investigate the adipokine and cytokine profiles of adipocytes from epicardial and subcutaneous adipose tissues in interconnection with the visceral adipose tissue area and the biochemical and clinical characteristics of patients with coronary artery disease. We assessed 84 patients with coronary ar...
journal_title：Frontiers in immunology
pub_type： 杂志文章
doi：10.3389/fimmu.2019.02163
更新日期：2019-09-19 00:00:00
