scholarly journals Passive immune therapies: another tool against COVID-19

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 628-641
Author(s):  
Lise J. Estcourt
Keyword(s):  
Additional Data ◽  
Respiratory Infections ◽  
Immune Therapy ◽  
The United Kingdom ◽  
High Quality Evidence ◽  
Pandemic Planning ◽  
Hyperimmune Globulin ◽  
Immune Therapies ◽  
Intact Immune System ◽  
Patient Groups

Abstract Passive immune therapy consists of several different therapies, convalescent plasma, hyperimmune globulin, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing monoclonal antibodies. Although these treatments were not part of any pandemic planning prior to coronavirus disease 2019 (COVID-19), due to the absence of high-quality evidence demonstrating benefit in other severe respiratory infections, a large amount of research has now been performed to demonstrate their benefit or lack of benefit in different patient groups. This review summarizes the evidence up to July 2021 on their use and also when they should not be used or when additional data are required. Vaccination against SARS-CoV-2 is the most important method of preventing severe and fatal COVID-19 in people who have an intact immune system. Passive immune therapy should only be considered for patients at high risk of severe or fatal COVID-19. The only therapy that has received full regulatory approval is the casirivimab/imdevimab monoclonal cocktail; all other treatments are being used under emergency use authorizations. In Japan, it has been licensed to treat patients with mild to moderate COVID-19, and in the United Kingdom, it has also been licensed to prevent infection.

Psychiatric services

2017 ◽  
pp. 777-800
Author(s):  
Paul Harrison ◽  
Philip Cowen ◽  
Tom Burns ◽  
Mina Fazel
Keyword(s):  
Historical Development ◽  
Psychiatric Services ◽  
Global Perspective ◽  
Rehabilitation Services ◽  
International Service ◽  
Care Services ◽  
The United Kingdom ◽  
Working Age ◽  
Patient Groups

‘Psychiatric services’ is concerned with the provision of psychiatric care for populations. It deals mainly with the needs of and provisions for people aged 18–65 years (‘adults of working age’), and focuses on the situation in the United Kingdom. (A more global perspective is provided in Chapter 23.) The chapter begins with an account of the historical development of psychiatric services, followed by descriptions of the commonly available psychiatric services and of the problems they encounter. It outlines the components of services, both those within primary care and those within specialized secondary care. These include services for acute disorders and those for complex long-term disorders (rehabilitation services). Service adaptations for patient groups with special needs (e.g. deafness, eating disorders) are also presented. The difficulties encountered by community care services are examined, as are emerging international service principles.

Moving Immune Therapy Forward Targeting TME

2020 ◽  
Author(s):  
Kayla F Goliwas ◽  
Jessy S. Deshane ◽  
Craig A Elmets ◽  
Mohammad Athar
Keyword(s):  
Immune System ◽  
Targeted Therapies ◽  
Immune Therapy ◽  
Clinical Trial Design ◽  
Therapeutic Interventions ◽  
Host Immune System ◽  
Host Immune Responses ◽  
Metabolic Plasticity ◽  
Cancer Pathogenesis ◽  
Immune Therapies

The host immune system shapes the fate of tumor progression. Hence, manipulating patients' immune system to activate host immune responses against cancer pathogenesis is a promising strategy to develop effective therapeutic interventions for metastatic and drug resistant cancers. Understanding the dynamic mechanisms within the tumor microenvironment (TME) that contribute to heterogeneity and metabolic plasticity is essential to enhance the patients' responsiveness to immune targeted therapies. Riera-Domingo et. al. describe the immune landscape within the TME, and highlight the significance of metabolic and hypoxic signatures that impact immune function and response to immunotherapy. Current literature in this field confirms that targeting tumor metabolism and the acidic microenvironment commonly associated with tumors may present as viable strategies to modulate the host immune system in favor of developing highly effective immune targeted therapies. However, development of better tools to understand tumor-immune interactions and identify mechanisms driving non-responders, more innovative clinical trial design, and new therapies will need to be identified to move the field forward. Personalized immune therapies incorporating metabolic and microbiome-based gene signatures to influence the therapeutic response and novel methods to generate immunologically "hot" tumors are at the forefront of immunotherapy currently. The combination of these approaches with clinically approved immunotherapies will also be valuable moving forward.

scholarly journals The Abscopal Effect: Could a Phenomenon Described Decades Ago Become Key to Enhancing the Response to Immune Therapies in Breast Cancer?

Breast Care ◽  
2020 ◽  
Vol 15 (5) ◽  
pp. 443-449
Author(s):  
Hans-Christian Kolberg ◽  
Oliver Hoffmann ◽  
René Baumann
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Checkpoint Inhibitors ◽  
Immune Therapy ◽  
Antitumor Immune Response ◽  
Abscopal Effect ◽  
Antitumor Effects ◽  
Effective Combination ◽  
Immunological Mechanisms ◽  
Immune Therapies

Background: The term “abscopal effect” was defined in 1953. In oncology the term is used to describe systemic antitumor effects triggered by local irradiation (nontarget effect). Although the mechanism of the abscopal effect is not completely understood yet, it has been demonstrated that in situ tumor vaccination, and the resulting antitumor immune response, is one of the key factors. Summary: The development of immune therapies has recently led to concepts combining local radiotherapy and immune therapy with the aim of enhancing the response to immune therapy by the immunological mechanisms summarized in the term abscopal effect. This concept has also been investigated in less immunogenic tumors such as breast cancer. Initial data are promising but the hypothesis that the combination of checkpoint inhibitors and local radiotherapy could be an effective combination in breast cancer has to be proven by ongoing trials. Substitution of local radiotherapy by local hyperthermia could be an option in selected cases. Key Messages: Combination of checkpoint inhibitors with local radiation or hyperthermia in breast cancer is a promising approach and could enhance the response rates generated by immune therapy alone through the antitumor immune response initiated by the abscopal effect.

scholarly journals Immune therapy in sepsis: Are we ready to try again?

2018 ◽  
Vol 19 (4) ◽  
pp. 326-344 ◽  
Author(s):  
Roger Davies ◽  
Kieran O’Dea ◽  
Anthony Gordon
Keyword(s):  
Patient Outcomes ◽  
Point Of Care ◽  
Secondary Infection ◽  
Immune Therapy ◽  
Immune Biomarkers ◽  
Immune Therapies ◽  
Point Of Care Technology ◽  
Care Technology ◽  
Past Experiences ◽  
Improve Patient

Immune therapy to ease the burden of sepsis has thus far failed to consistently improve patient outcomes. Advances in cancer immune therapy and awareness that prolonged immune-suppression in sepsis can leave patients vulnerable to secondary infection and death have driven resurgence in the field of sepsis immune-therapy investigation. As we develop and evaluate these novel therapies, we must learn from past experiences where single-mediator targeted immune therapies were blindly delivered to heterogeneous patient cohorts with complex and evolving immune responses. Advances in genomics, proteomics, metabolomics, and point-of-care technology, coupled with a better understanding of sepsis pathogenesis, have meant that personalised immune-therapy is on the horizon. Here, we review the complex immune pathogenesis in sepsis and the contemporary immune therapies that are being investigated to manipulate this response. An outline of the immune biomarkers that may be used to support this approach is also provided.

scholarly journals Competitive Inhibition Flow Analysis Assay for the Non-Culture-Based Detection and Serotyping of Pneumococcal Capsular Polysaccharide

2008 ◽  
Vol 16 (2) ◽  
pp. 222-229 ◽  
Author(s):  
H. Findlow ◽  
G. Laher ◽  
P. Balmer ◽  
C. Broughton ◽  
E. D. Carrol ◽  
...  
Keyword(s):  
Large Scale ◽  
Capsular Polysaccharide ◽  
Competitive Inhibition ◽  
Flow Analysis ◽  
High Risk Patient ◽  
Epidemiologic Studies ◽  
Conjugate Vaccines ◽  
The United Kingdom ◽  
Pneumococcal Serotype ◽  
Patient Groups

ABSTRACT Traditional confirmation procedures for the identification of a pneumococcal serotype require an isolate. Non-culture-based confirmation protocols are available. Some of these confirm only the presence of pneumococci, and others are capable of identifying a limited number of serotypes. The increased use of pneumococcal polysaccharide and conjugate vaccines, especially in high-risk patient groups, and the likely increase in the number of serotypes included in future versions of the conjugate vaccines have necessitated the need for improved enhanced surveillance in order to assess their impact on public health. Since 2006, a multiplexed assay has been used at the Health Protection Agency of the United Kingdom for the detection of 14 pneumococcal serotypes which requires pneumococcal serotype-specific monoclonal antibodies (MAbs). We have developed a microsphere competitive inhibition method capable of detecting 23 pneumococcal capsular polysaccharide serotypes in cerebrospinal fluid (CSF) and urine and serotyping pneumococcal suspensions, utilizing an international reference serum, 89-SF. The assay was shown to be reproducible and specific for homologous polysaccharide. Validation of the assay was performed with a selection of MAbs specific for pneumococcal capsular polysaccharide serotypes, which confirmed the specificity of the assay. Analysis of pneumolysin PCR-positive CSF samples in the competitive inhibition assay determined a serotype for 89% of the samples. The assay developed here is well suited to large-scale epidemiologic studies because the assay is simple, robust, and rapid and utilizes readily available resources.

scholarly journals Crisis teams: systematic review of their effectiveness in practice

2013 ◽  
Vol 37 (7) ◽  
pp. 232-237 ◽  
Author(s):  
Rebecca A. Carpenter ◽  
Jara Falkenburg ◽  
Thomas P. White ◽  
Derek K. Tracy
Keyword(s):  
Systematic Review ◽  
Cost Effective ◽  
Evidence Base ◽  
Clinical Implications ◽  
Crisis Resolution ◽  
Longitudinal Outcomes ◽  
Patient Admissions ◽  
High Quality Evidence ◽  
Crisis Resolution Teams ◽  
Patient Groups

Aims and methodCrisis resolution and home treatment teams (variously abbreviated to CRTs, CRHTTs, HTTs) were introduced to reduce the number and duration of in-patient admissions and better manage individuals in crisis. Despite their ubiquity, their evidence base is challengeable. This systematic review explored whether CRTs: (a) affected voluntary and compulsory admissions; (b) treat particular patient groups; (c) are cost-effective; and (d) provide care patients value.ResultsCrisis resolution teams appear effective in reducing admissions, although data are mixed and other factors have also influenced this. Compulsory admissions may have increased, but evidence that CRTs are causally related is inconclusive. There are few clinical differences between ‘gate-kept’ patients admitted and those not. Crisis resolution teams are cheaper than in-patient care and, overall, patients are satisfied with CRT care.Clinical implicationsHigh-quality evidence for CRTs is scarce, although they appear to contribute to reducing admissions. Patient-relevant psychosocial and longitudinal outcomes are under-explored.

scholarly journals Application of bacterial therapeutic vaccine Immunovac-VP4 in the treatment of pollinosis

2018 ◽  
Vol 90 (3) ◽  
pp. 16-20
Author(s):  
M P Kostinov ◽  
A M Poddubikova ◽  
O O Magarshak ◽  
A V Poddubikov
Keyword(s):  
Respiratory Infections ◽  
Immune Therapy ◽  
Therapeutic Vaccine ◽  
Allergic Diseases ◽  
Molecular Structures ◽  
Control Group ◽  
Natural Ligand ◽  
Th2 Immune Response ◽  
Aqueous Salt Solutions ◽  
Depth Study

In-depth study of the function and structure of the lymphoid tissue of the gastrointestinal tract and respiratory tract opens wide opportunities for the use of mucosal vaccines to improve immunity to various infectious agents. One such drug is The immunovac-VP4 vaccine containing pathogen-associated molecular structures (PAMSs) of microorganisms. They are the antigens of Klebsiella pneumoniae, Proteus vulgaris, Escherichia coli, Staphylococcus aureus. Discovered in many studies and experiments, the ability of the vaccine to induce innate immunity provides opportunities for prevention and treatment of both infections and allergic diseases, because it promotes the switching of Th2 immune response to Th1. The aim of the study was to study the effectiveness of the complex use of bacterial therapeutic vaccine Immunovac-VP4 and allergen-specific immune therapy (ASIT) in pollinosis in children and adults. Materials and methods. Bacterial therapeutic vaccine Immunovac-VP4 was used annually, nasal and oral administration in patients before the course of ASIT standardized aqueous-salt solutions of allergens. Results. The therapeutic application of bacterial vaccines, Immunoac-ВП4 before the course ASIT has helped to reduce the frequency of acute respiratory infections in 8,5 times in comparison with the control group. Clinical efficacy of complex treatment according to the results of the survey of patients in 7 years after the start of therapy was 90%. There was a significant decrease In IgG4 to causally significant allergens, General immnunoglobulin E (IgE) and a tendency to decrease IgE. Conclusion. The use of bacterial therapeutic vaccine Immunovac-VP4, which is a natural ligand of toll-like receptors in combination with ASIT, seems to be an effective and promising direction in the treatment of allergic diseases.

scholarly journals Corticosteroids and Other Anti-Inflammatory Strategies in Pediatric Heart Surgery: A National Survey of Practice

2018 ◽  
Vol 9 (3) ◽  
pp. 289-293 ◽  
Author(s):  
Daniel P. Fudulu ◽  
Alvin Schadenberg ◽  
Ben Gibbison ◽  
Ian Jenkins ◽  
Stafford Lightman ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Heart Surgery ◽  
Pediatric Cardiac Surgery ◽  
Pediatric Heart Surgery ◽  
The United Kingdom ◽  
Wide Variability ◽  
Patient Groups ◽  
Anti Inflammatory ◽  
Almost All

Background: The role of steroids to mitigate the deleterious effects of pediatric cardiopulmonary bypass (CPB) remains a matter of debate; therefore, we aimed to assess preferences in administering corticosteroids (CSs) and the use of other anti-inflammatory strategies in pediatric cardiac surgery. Methods: A 19-question survey was distributed to consultants in pediatric cardiac anesthesia from 12 centers across the United Kingdom and Ireland. Results: Of the 37 respondents (37/60, 62%), 24 (65%) use CSs, while 13 (35%) do not use steroids at all. We found variability within 5 (41%) of the 12 centers. Seven consultants (7/24, 29%) administer CSs in every case, while 17 administer CSs in selected cases only (17/24, 71%). There was variability in the dose of steroid administration. Almost all consultants (23/24, 96%) administer a single dose at induction, and one administers a two-dose regimen (1/24, 4%). There was variability in CS indications. Most consultants (24/37, 66%) use modified ultrafiltration at the conclusion of CPB. Fifteen consultants (15/32, 47%) report the use of aprotinin, while only 3 use heparin-coated circuits (3/24, 9%). Conclusions: We found wide variability in practice in the administration of CSs for pediatric cardiac surgery, both within and between units. While most anesthetists administer CSs in at least some cases, there is no consensus on the type of steroid, the dose, and at which patient groups this should be directed. Modified ultrafiltration is still used by most of the centers. Almost half of consultants use aprotinin, while heparin-coated circuits are infrequently used.

Immune Therapy Opportunities in Ovarian Cancer

2020 ◽  
pp. e228-e240 ◽  
Author(s):  
Lana E. Kandalaft ◽  
Kunle Odunsi ◽  
George Coukos
Keyword(s):  
Ovarian Cancer ◽  
Immune Therapy ◽  
Parp Inhibitors ◽  
Immune Checkpoint Blockade ◽  
Clinical Activity ◽  
Small Subset ◽  
T Cell Therapy ◽  
Rational Combination ◽  
Major Direction ◽  
Immune Therapies

Immunotherapy has emerged as a highly promising approach in the treatment of epithelial ovarian cancer (EOC). Immune checkpoint blockade (ICB) therapy, PARP inhibitors (PARPis), neoantigen vaccines, and personalized T-cell therapy have been associated with encouraging clinical activity in a small subset of patients. To increase the proportion of patients who are likely to derive benefit, it will be important not only to generate sufficient numbers of antitumor T cells but also to overcome multiple inhibitory networks in the ovarian tumor microenvironment (TME). Therefore, a major direction is to develop biomarkers that would predict responsiveness to different types of immunotherapies and allow treatment selection based on the results. Moreover, such biomarkers would allow rational combination of immunotherapies while minimizing toxicities. In this review, we provide progress on immune therapies and future directions for maximally exploiting immune-based strategies for the treatment of ovarian cancer.

scholarly journals Localized CD47 blockade enhances immunotherapy for murine melanoma

2017 ◽  
Vol 114 (38) ◽  
pp. 10184-10189 ◽  
Author(s):  
Jessica R. Ingram ◽  
Olga S. Blomberg ◽  
Jonathan T. Sockolosky ◽  
Lestat Ali ◽  
Florian I. Schmidt ◽  
...  
Keyword(s):  
Immune Therapy ◽  
Regulatory Protein ◽  
Cell Types ◽  
Life Extension ◽  
Endogenous Expression ◽  
Receptor Signal ◽  
Melanoma Model ◽  
Immune Therapies ◽  
Xenograft Models ◽  
Antitumor Antibody

CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47–SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies. We generated a nanobody, A4, that blocks the CD47–SIRPα interaction. A4 synergizes with anti–PD-L1, but not anti-CTLA4, therapy in the syngeneic B16F10 melanoma model. Neither increased dosing nor half-life extension by fusion of A4 to IgG2a Fc (A4Fc) overcame the issue of an antigen sink or, in the case of A4Fc, systemic toxicity. Generation of a B16F10 cell line that secretes the A4 nanobody showed that an enhanced response to several immune therapies requires near-complete blockade of CD47 in the tumor microenvironment. Thus, strategies to localize CD47 blockade to tumors may be particularly valuable for immune therapy.

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