scholarly journals Use of Intravenous Immunoglobulins in Sepsis Therapy—A Clinical View

2020 ◽  
Vol 21 (15) ◽  
pp. 5543
Author(s):  
Dominik Jarczak ◽  
Stefan Kluge ◽  
Axel Nierhaus
Keyword(s):  
Intravenous Immunoglobulins ◽  
Coagulation Cascade ◽  
Optimal Timing ◽  
Evidence Based ◽  
Promising Therapeutic Approach ◽  
Sepsis Therapy ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Anti Inflammation

Sepsis is a life-threatening organ dysfunction, defined by a dysregulated host immune response to infection. During sepsis, the finely tuned system of immunity, inflammation and anti-inflammation is disturbed in a variety of ways. Both pro-inflammatory and anti-inflammatory pathways are upregulated, activation of the coagulation cascade and complement and sepsis-induced lymphopenia occur. Due to the manifold interactions in this network, the use of IgM-enriched intravenous immunoglobulins seems to be a promising therapeutic approach. Unfortunately, there is still a lack of evidence-based data to answer the important questions of appropriate patient populations, optimal timing and dosage of intravenous immunoglobulins. With this review, we aim to provide an overview of the role of immunoglobulins, with emphasis on IgM-enriched formulations, in the therapy of adult patients with sepsis and septic shock.

scholarly journals The Diverse Roles of Heme Oxygenase-1 in Tumor Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Kim Ngan Luu Hoang ◽  
Joanne E. Anstee ◽  
James N. Arnold
Keyword(s):  
Tumor Progression ◽  
Heme Oxygenase ◽  
Cancer Progression ◽  
Biologically Active ◽  
Heme Oxygenase 1 ◽  
Biological Processes ◽  
Intracellular Enzyme ◽  
Promising Therapeutic Approach ◽  
Anti Inflammation

Heme oxygenase-1 (HO-1) is an inducible intracellular enzyme that is expressed in response to a variety of stimuli to degrade heme, which generates the biologically active catabolites carbon monoxide (CO), biliverdin and ferrous iron (Fe2+). HO-1 is expressed across a range of cancers and has been demonstrated to promote tumor progression through a variety of mechanisms. HO-1 can be expressed in a variety of cells within the tumor microenvironment (TME), including both the malignant tumor cells as well as stromal cell populations such as macrophages, dendritic cells and regulatory T-cells. Intrinsically to the cell, HO-1 activity provides antioxidant, anti-apoptotic and cytoprotective effects via its catabolites as well as clearing toxic intracellular heme. However, the catabolites of heme degradation can also diffuse outside of the cell to extrinsically modulate the wider TME, influencing cellular functionality and biological processes which promote tumor progression, such as facilitating angiogenesis and metastasis, as well as promoting anti-inflammation and immune suppression. Pharmacological inhibition of HO-1 has been demonstrated to be a promising therapeutic approach to promote anti-tumor immune responses and inhibit metastasis. However, these biological functions might be context, TME and cell type-dependent as there is also conflicting reports for HO-1 activity facilitating anti-tumoral processes. This review will consider our current understanding of the role of HO-1 in cancer progression and as a therapeutic target in cancer.

scholarly journals Role of Steroid in Adult Patients of Septic Shock - A Critical Analysis

KYAMC Journal ◽  
2017 ◽  
Vol 4 (2) ◽  
pp. 409-414
Author(s):  
Rajib Hasan ◽  
Humayun Kabir ◽  
Taposh Chandra Roy ◽  
Javed Sharoar Chowdhury ◽  
Farzana Yeasmin
Keyword(s):  
Septic Shock ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Critical Analysis ◽  
Adult Patients ◽  
Evidence Based ◽  
Icu Patients ◽  
Evidence Based Practices ◽  
Sepsis And Septic Shock

" Sepsis and septic shock is the condition which has been with intensive care units from long before. In fact, it is one of the highly ranked diseases causing mortality in ICU patients. There are currently many evidence based practices in the management of septic shock and use of steroid is one of them. The aim of this article is to critically evaluate the evidences regarding the role of steroids in adult patients of septic shock. This article has also evaluated all the current evidences regarding details of the role of steroids including their formulation, dosage, duration and route of administration in patients of septic shock.KYAMC Journal Vol. 4, No.-2, Jan 2014, Page 409-414

scholarly journals The pathophysiology of sepsis—2021 update: Part 1, immunology and coagulopathy leading to endothelial injury

2021 ◽  
Author(s):  
Judith Jacobi
Keyword(s):  
Treatment Options ◽  
Endothelial Injury ◽  
Coagulation Cascade ◽  
Secondary Infections ◽  
Sepsis And Septic Shock ◽  
Risk And Benefit ◽  
Insight Into ◽  
Related Mortality

Abstract Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To provide an overview of current literature on the pathophysiology of sepsis, with a focus on mediators of endothelial injury and organ dysfunction. Summary Sepsis is a dysregulated response to infection that triggers cascades of interconnected systems. Sepsis has been a significant cause of mortality worldwide, and the recent viral pandemic that may produce severe sepsis and septic shock has been a major contributor to sepsis-related mortality. Understanding of the pathophysiology of sepsis has changed dramatically over the last several decades. Significant insight into the components of the inflammatory response that contribute to endothelial injury and trigger coagulation pathways has been achieved. Similarly, characterization of anti-inflammatory pathways that may lead to secondary infections and poor outcome has illustrated opportunities for improved therapies. Description of an increasing number of important mediators and pathways has occurred and may point the way to novel therapies to address immune dysregulation. Pharmacists will need a fundamental understanding of the overlapping pathways of the immune response to fully prepare for use of novel treatment options. While pharmacists typically understand coagulation cascade how to utilize anticoagulants, the issues in sepsis related coagulopathy and role of mediators such as cytokines and complement and role of activated platelets and neutrophils require a different perspective. Conclusion Pharmacists can benefit from understanding both the cellular and organ system issues in sepsis to facilitate assessment of potential therapies for risk and benefit.

scholarly journals Sepsis: source control

2021 ◽  
Vol 18 (5) ◽  
pp. 89-96
Author(s):  
V. V. Kulabukhov ◽  
N. A. Zubareva ◽  
P. A. Yartsev
Keyword(s):  
Successful Treatment ◽  
Randomized Trials ◽  
Source Control ◽  
Optimal Timing ◽  
Source Of Infection ◽  
Threatening Condition ◽  
Life Threatening ◽  
The Moment ◽  
Sepsis And Septic Shock ◽  
Time Of Intervention

Sepsis is a life-threatening condition, which is manifested by the development of organ dysfunction due to generalized inflammation caused by the infection of various nature. Timely lesion debridement combined with adequate antibiotic therapy are important components of the successful treatment of sepsis. At the moment, there is no consensus about the volume and time of intervention in the development of surgical sepsis. The article discusses modern approaches to solving the problem of adequate sanitation of the source of infection. The results of few randomized trials in this area are presented.Source control is absolutely essential for the successful treatment of sepsis. However, it is difcult to create a unifed algorithm for surgical control for all cases due to different approaches depending on the infection location. Properly designed clinical trials are necessary to determine the optimal timing of surgery for sepsis and septic shock as least.

scholarly journals Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel E. Pleguezuelo ◽  
Raquel Díaz-Simón ◽  
Oscar Cabrera-Marante ◽  
Antonio Lalueza ◽  
Estela Paz-Artal ◽  
...  
Keyword(s):  
Anticoagulant Therapy ◽  
Safety Profile ◽  
Plasma Cells ◽  
Intravenous Immunoglobulins ◽  
Coagulation Cascade ◽  
Optimal Timing ◽  
Significant Drop ◽  
Humoral Immune ◽  
Venous Thromboembolic Events ◽  
Anti Phospholipid Syndrome

IntroductionMonoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels.Clinical caseWe present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy.ConclusionsThe treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.

scholarly journals Current controversies in infective endocarditis

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1287 ◽  
Author(s):  
Thomas J. Cahill ◽  
Bernard D. Prendergast
Keyword(s):  
Infective Endocarditis ◽  
Multimodality Imaging ◽  
Evidence Base ◽  
Optimal Timing ◽  
Cardiac Device ◽  
Device Infection ◽  
Focus Of Infection ◽  
Life Threatening ◽  
Cardiac Device Infection

Infective endocarditis is a life-threatening disease caused by a focus of infection within the heart. For clinicians and scientists, it has been a moving target that has an evolving microbiology and a changing patient demographic. In the absence of an extensive evidence base to guide clinical practice, controversies abound. Here, we review three main areas of uncertainty: first, in prevention of infective endocarditis, including the role of antibiotic prophylaxis and strategies to reduce health care-associated bacteraemia; second, in diagnosis, specifically the use of multimodality imaging; third, we discuss the optimal timing of surgical intervention and the challenges posed by increasing rates of cardiac device infection.

scholarly journals Gas6/TAM Axis in Sepsis: Time to Consider Its Potential Role as a Therapeutic Target

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Livia Salmi ◽  
Francesco Gavelli ◽  
Filippo Patrucco ◽  
Marina Caputo ◽  
Gian Carlo Avanzi ◽  
...  
Keyword(s):  
Potential Role ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Protein S ◽  
Pathological Conditions ◽  
Potential Therapeutic Role ◽  
Life Threatening ◽  
Sepsis And Septic Shock ◽  
Clinical Conditions

Tyrosine kinase receptors are transmembrane proteins involved in cell signaling and interaction. Among them, the TAM family (composed by Tyro 3, Axl, and Mer) represents a peculiar subgroup with an important role in many physiological and pathological conditions. Despite different mechanisms of activation (e.g., protein S and Galactin-3), TAM action is tightly related to their common ligand, a protein named growth arrest-specific 6 (Gas6). Since the expression of both TAM and Gas6 is widely distributed among tissues, any alteration of one of these components can lead to different pathological conditions. Moreover, as they are indispensable for homeostasis maintenance, in recent years a growing interest has emerged regarding their role in the regulation of the inflammatory process. Due to this involvement, many authors have demonstrated the pivotal role of the Gas6/TAM axis in both sepsis and the sepsis-related inflammatory responses. In this narrative review, we highlight the current knowledge as well as the last discoveries on TAM and Gas6 implication in different clinical conditions, notably in sepsis and septic shock. Lastly, we underline not only the feasible use of Gas6 as a diagnostic and prognostic biomarker in certain systemic acute conditions but also its potential therapeutic role in these life-threatening diseases.

scholarly journals The Role of Osteopontin as a Diagnostic and Prognostic Biomarker in Sepsis and Septic Shock

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 174 ◽  
Author(s):  
Luigi Mario Castello ◽  
Marco Baldrighi ◽  
Luca Molinari ◽  
Livia Salmi ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Extracellular Matrix Protein ◽  
Suspected Infection ◽  
Significant Difference ◽  
Life Threatening ◽  
Sepsis And Septic Shock

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002–1.039, P = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.

Self-Regulatory Aspects of Bullshitting and Bullshit Detection

2020 ◽  
Vol 51 (4) ◽  
pp. 239-253
Author(s):  
John V. Petrocelli ◽  
Haley F. Watson ◽  
Edward R. Hirt
Keyword(s):  
Evidence Based ◽  
Regulatory Aspects

Abstract. Two experiments investigate the role of self-regulatory resources in bullshitting behavior (i.e., communicating with little to no regard for evidence, established knowledge, or truth; Frankfurt, 1986 ; Petrocelli, 2018a ), and receptivity and sensitivity to bullshit. It is hypothesized that evidence-based communication and bullshit detection require motivation and considerably greater self-regulatory resources relative to bullshitting and insensitivity to bullshit. In Experiment 1 ( N = 210) and Experiment 2 ( N = 214), participants refrained from bullshitting only when they possessed adequate self-regulatory resources and expected to be held accountable for their communicative contributions. Results of both experiments also suggest that people are more receptive to bullshit, and less sensitive to detecting bullshit, under conditions in which they possess relatively few self-regulatory resources.

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