scholarly journals Role of Lopinavir/Ritonavir in the Treatment of Covid-19: A Review of Current Evidence, Guideline Recommendations, and Perspectives

2020 ◽  
Vol 9 (7) ◽  
pp. 2050 ◽  
Author(s):  
Simone Meini ◽  
Alberto Pagotto ◽  
Benedetta Longo ◽  
Igor Vendramin ◽  
Davide Pecori ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Respiratory Illness ◽  
Organ Damage ◽  
Current Evidence ◽  
Laboratory Studies ◽  
Scientific Societies ◽  
Pathogenetic Role ◽  
Proven Efficacy ◽  
Life Threatening

A life-threatening respiratory illness (COVID-19) due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus was first described in December 2019 in Wuhan (China), rapidly evolving into a pandemic. In the first phase, when the viral replication plays a pivotal pathogenetic role, antiviral drugs could be crucial in limiting viral-induced organ damage. Unfortunately, there are no specific antivirals of proven efficacy for COVID-19, and several drugs have been repurposed to face this dramatic pandemic. In this paper we review the studies evaluating lopinavir/ritonavir association (LPV/r) use in COVID-19, and previously in SARS and Middle East respiratory syndrome (MERS). We searched PubMed to identify all relevant clinical and laboratory studies published up to 15 May 2020; the guidelines on the use of LPV/r in COVID-19 were further directly searched on the website of the main international scientific societies and agencies. Available evidence is currently scarce and of low quality. The recommendations issued for COVID-19 vary from positions clearly against the use of LPV/r to other positions that are more favorable. In our opinion, despite the controversial results of an important randomized clinical trial, and some recommendations, clinicians should not abandon the use of LPV/r for the treatment of COVID-19, possibly using this drug inside a prospective randomized trial, waiting for the results of the numerous ongoing trials evaluating its efficacy.

scholarly journals Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  
Keyword(s):  
Review Article ◽  
Lung Damage ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Cytokine Storm ◽  
Future Perspectives ◽  
Pathogenic Role ◽  
Refractory Rheumatoid Arthritis ◽  
Life Threatening

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

Cancer and COVID-19: A proposed mechanism with therapeutic interventions.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3135-3135
Author(s):  
Yan Leyfman ◽  
Nancy Emmanuel ◽  
Aleksey Tentler ◽  
Jared Cappelli ◽  
Timothy K Erick ◽  
...  
Keyword(s):  
Respiratory Illness ◽  
Organ Damage ◽  
Multiple Organ ◽  
Therapeutic Interventions ◽  
Actual Number ◽  
Data Registry ◽  
Number Of Patients ◽  
Increased Risk ◽  
Life Threatening ◽  
Active Cancer

3135 Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus that causes the respiratory illness coronavirus disease 2019 (COVID-19). COVID-19 ranges in severity from an asymptomatic viral infection to life-threatening cases of pneumonia, acute respiratory distress syndrome (ARDS), multi-organ damage and sepsis. Cancer patients are at an increased risk of severe SARS-CoV-2 infection due to their immunocompromised status. We propose a mechanism by which SARS-CoV-2 infection causes multiple organ damage through IL-6-mediated inflammation and hypoxia-induced cellular metabolic alterations leading to cell death. Hypoxia is also induced by malignancy due to alterations in metabolism, resulting in greater IL-6 secretion. Methods: To highlight the possible effect of active cancer on the likelihood of hypoxia in COVID-19, we analyzed the correlation between cancer status and the severity of COVID-19 from the COVID-19 and Cancer Consortium data registry. For cancer status, we looked at progressive cancer and remission of cancer only -- those being the two extremes of presence and absence of uncontrolled cancer. Similar to prior studies, the severity of COVID-19 was used as an indication of hypoxia. Results: We observed a 24% positive deviation between expected and actual number of patients with actively progressing cancer who had hypoxic COVID-19 (moderate to severe), and a 26.9% negative deviation between expected and actual number of patients with active cancer who had no hypoxia with COVID-19 (p<0.0001). Conversely, for patients with cancer in remission, there was only a +5.8% and -5.1% deviation between expected and actual number of patients who did not have hypoxia and who had hypoxia, respectively. Conclusions: These results suggest that in the presence of poorly controlled malignancy, there is an increased likelihood of hypoxia in patients with COVID-19, thereby exacerbating downstream cytokine release syndrome and contributing to prolonged systemic inflammatory injury. Appreciating this pathway, future therapies can be developed to target the pathogenesis of both diseases and prevent progression, as seen with mesenchymal stem cells, which demonstrated a 91% overall survival and 100% survival in patients younger than 85 years old at one month after a single treatment.[Table: see text]

scholarly journals Role of Environmental Chemicals in Obesity: A Systematic Review on the Current Evidence

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Roya Kelishadi ◽  
Parinaz Poursafa ◽  
Fahimeh Jamshidi
Keyword(s):  
Environmental Chemicals ◽  
Human Studies ◽  
Current Evidence ◽  
Laboratory Studies ◽  
Crucial Importance ◽  
Obesity Epidemic ◽  
Complex Disorder ◽  
Developmental Phases ◽  
Systemic Responses

The purpose of this paper is to systematically review the experimental and human studies on obesogenic chemicals and their mechanisms of action to provide a comprehensive view on the multifactorial aspects of obesity. The literatures were searched in available databases. The relevant papers were selected in three phases. After quality assessment, two reviewers extracted the data while another checked their extracted data. In this review, we summarized information regarding environmental chemicals that can be associated with obesity. Most evidence comes from experimental and laboratory studies; however a growing number of human studies also support the role of obesogenic chemicals. The current evidence proposes that the systemic responses to exposure to environmental factors could potentially increase the risk of excess weight. The effects of exposure to these chemicals are of crucial importance during developmental phases of life, when preprogramming for an adipogenic outcome may occur. By considering the adverse transgenerational effects of obesogen chemicals on human health, the global obesity epidemic should be considered as a multifactorial complex disorder necessitating the emphasis of public health interventions for environmental protection.

scholarly journals Vitamin C to Improve Organ Dysfunction in Cardiac Surgery Patients—Review and Pragmatic Approach

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 974 ◽  
Author(s):  
Aileen Hill ◽  
Sebastian Wendt ◽  
Carina Benstoem ◽  
Christina Neubauer ◽  
Patrick Meybohm ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Vitamin C ◽  
Acute Stress ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Organ Damage ◽  
Current Evidence ◽  
Organ Systems

The pleiotropic biochemical and antioxidant functions of vitamin C have sparked recent interest in its application in intensive care. Vitamin C protects important organ systems (cardiovascular, neurologic and renal systems) during inflammation and oxidative stress. It also influences coagulation and inflammation; its application might prevent organ damage. The current evidence of vitamin C’s effect on pathophysiological reactions during various acute stress events (such as sepsis, shock, trauma, burn and ischemia-reperfusion injury) questions whether the application of vitamin C might be especially beneficial for cardiac surgery patients who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of vitamin C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between vitamin C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence on the administration of vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage, and appropriate application strategy.

scholarly journals Angioedema and Fatty Acids

2021 ◽  
Vol 22 (16) ◽  
pp. 9000
Author(s):  
Akane Wada ◽  
Yu Sawada ◽  
Hitomi Sugino ◽  
Motonobu Nakamura
Keyword(s):  
Fatty Acids ◽  
Blood Vessels ◽  
Vascular Permeability ◽  
Therapeutic Options ◽  
Specific Receptor ◽  
Cell Component ◽  
Pathogenetic Role ◽  
Emergency Event ◽  
Life Threatening

Angioedema is a life-threatening emergency event that is associated with bradykinin and histamine-mediated cascades. Although bradykinin-mediated angioedema currently has specific therapeutic options, angioedema is sometimes intractable with current treatments, especially histamine-mediated angioedema, suggesting that some other mediators might contribute to the development of angioedema. Fatty acids are an essential fuel and cell component, and act as a mediator in physiological and pathological human diseases. Recent updates of studies revealed that these fatty acids are involved in vascular permeability and vasodilation, in addition to bradykinin and histamine-mediated reactions. This review summarizes each fatty acid’s function and the specific receptor signaling responses in blood vessels, and focuses on the possible pathogenetic role of fatty acids in angioedema.

scholarly journals Neutrophil in Reverse Migration: Role in Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingjing Ji ◽  
Jie Fan
Keyword(s):  
Host Response ◽  
Immune Reaction ◽  
Innate Immune ◽  
Polymorphonuclear Neutrophils ◽  
Current Evidence ◽  
Protective Response ◽  
Reverse Migration ◽  
Inflammatory Site ◽  
Life Threatening

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. During the development and progression of sepsis, polymorphonuclear neutrophils (PMNs) are the most abundantly recruited innate immune cells at sites of infection, playing critical roles in the elimination of local infection and healing of the injury. PMN reverse migration (rM) describes the phenomenon in which PMNs migrate away from the inflammatory site back into the vasculature following the initial PMN infiltration. The functional role of PMN rM within inflammatory scenarios requires further exploration. Current evidence suggests that depending on the context, PMN rM can be both a protective response, by facilitating an efficient resolution to innate immune reaction, and also a tissue-damaging event. In this review, we provide an overview of current advancements in understanding the mechanism and roles of PMN rM in inflammation and sepsis. A comprehensive understanding of PMN rM may allow for the development of novel prophylactic and therapeutic strategies for sepsis.

scholarly journals Importance and role of independent data monitoring committees (IDMCs) in oncology clinical trials

BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e047294
Author(s):  
P Schöffski
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Adverse Events ◽  
Stopping Rules ◽  
Data Monitoring ◽  
Independent Data ◽  
Oncology Clinical Trials ◽  
Life Threatening ◽  
Study Participants

The role and use of independent data monitoring committees (IDMCs) has evolved over the past decades. The Food and Drug Administration and European Medicines Agency have issued guidelines on the role and functioning of such committees. In general, data monitoring committees are recommended for large, often randomised clinical trials involving life-threatening diseases, studies performed in vulnerable populations or where the experimental intervention can potentially harm the trial participant. Such committees play an important role in trials evaluating treatments with the potential to prolong life or reduce the risk of major adverse health outcomes.Typically, oncology clinical trials fall within these recommendations, as they are often large, randomised, multicentric protocols aiming at improving survival outcomes by exploring the use of study treatments that may be associated with a significant risk of serious, even life-threatening adverse events. IDMCs are required for National Cancer Institute phase III randomised trials, European Organisation for Research and Treatment of Cancer phase II/III trials with formal interim analyses, early-stopping rules or adaptive studies. The primary role of an IDMC of ensuring the safety of study participants and maintaining clinical trial integrity is particularly important in oncology trials, due to the nature of the disease, the potential for treatment toxicity and for instilling confidence that the clinical trial data are reliable. A clear understanding by IDMC members of the natural course of the disease, treatment landscape, importance and relevance of certain adverse events in trial participants, clinical trial methodology in general and stopping rules for oncology trials in particular, is crucial for the functioning of an IDMC.It is recommended that IDMC members should be experienced trialists, have a track record of strong clinical, statistical and/or methodological expertise and the required level of independence, as they play a highly important role in the protection of study participants, and in commercially and strategically important go/no decisions. Ideally, IDMC members should have relevant experience or have some training, mentorship or guidelines.

scholarly journals The Controversies Surrounding Tocilizumab Administration Following Pathogen-Associated Molecular Pattern (PAMP) Induced by COVID-19

2020 ◽  
Author(s):  
Shayesteh Gheibi ◽  
Farhad Najmeddin ◽  
Bita Shahrami ◽  
Kourosh Sadeghi ◽  
Mojtaba Mojtahedzadeh
Keyword(s):  
Viral Infections ◽  
Virus Disease ◽  
Organ Damage ◽  
Immune Dysregulation ◽  
Global Pandemic ◽  
Molecular Pattern ◽  
Life Threatening ◽  
Molecular Patterns ◽  
Valuable Role

A new corona virus disease (COVID-19) has affected more than 17 million people worldwide so far, and has become a global pandemic. Since there is no definitive cure for this life threatening disease, many clinical studies are in progress in this regard. Pathogen-associated molecular patterns (PAMP) prompting by coronavirus seems to generate cellular, structural, and functional derangements induced by immune dysregulation as well as many biological abnormalities including cytokine storm. The role of IL-6 in viral pneumonia and also its inhibition impact on the prevention of organ damage are still unknown.IL-6 seems to behave as a double blade evil cytokine, by playing a valuable role in cell to cell natural physiological communication. Tocilizumab, as an inhibitor of interleukin (IL)-6, may interrupt the paracrine system while causing dissemination of bacterial, fungal, and other viral infections, especially COVID-19, who are at a high-risk for development of sepsis and life-threatening superinfection.

ROLE OF HEALTH-SEEKING BEHAVIOUR IN CHILD MORTALITY IN THE SLUMS OF KARACHI, PAKISTAN

2002 ◽  
Vol 35 (1) ◽  
pp. 131-144 ◽  
Author(s):  
RENNIE M. D’SOUZA
Keyword(s):  
Child Mortality ◽  
Maternal Education ◽  
Family Health ◽  
Respiratory Illness ◽  
Population Based ◽  
Health Seeking Behaviour ◽  
Health Seeking ◽  
Under Five ◽  
Life Threatening

The role of family health-seeking behaviour in under-five-year child mortality was explored through the combined approach of examining health-seeking behaviour regarding treatment generally, and in specific in relation to illness before death. A population-based case control study was carried out during the period 1993–1994 using 222 deaths from diarrhoea and acute respiratory illness (ARI) in children under five years of age in six slums of Karachi as cases, and 419 controls matched on age, disease (diarrhoea and ARI) and slum. Factors significantly associated (p<0·05) with child mortality in the multivariate analysis were: mothers changing healers quickly, using a traditional healer or an unqualified doctor and mothers to whom doctors did not explain the treatment, even when maternal education was controlled for. Seeking effective medical services is highly influential on whether the child survives or succumbs to ARI or diarrhoea. As mothers are the first providers of care, an attempt should be made to try and improve their skills through health education so that they can use simple and effective treatments for minor illnesses. They should also be taught to recognize potentially life-threatening conditions, to seek care early and to persist with treatment.

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