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1.
Calcif Tissue Int ; 108(4): 452-460, 2021 04.
Article in English | MEDLINE | ID: covidwho-1509222

ABSTRACT

Bone is not only a mineralized and apparently non-vital structure that provides support for locomotion and protection to inner organs. An increasing number of studies are unveiling new biologic functions and connections to other systems, giving the rise to new fields of research, such as osteoimmunology. The bone marrow niche, a new entity in bone physiology, seems to represent the site where a complex crosstalk between bone and immune/inflammatory responses takes place. An impressive interplay with the immune system is realized in bone marrow, with reciprocal influences between bone cells and haematopoietic cells. In this way, systemic chronic inflammatory diseases realize a crosstalk with bone, resulting in bone disease. Thus, pathogenetic links between chronic kidney disease-mineral bone disorders and osteoporosis, cardiovascular disease, and ageing are common. The aim of this narrative review is to provide a general view of the progresses in the field of bone research and their potential clinical implications, with emphasis on the links with inflammation and the connections to osteoimmunology and chemokines.


Subject(s)
Bone and Bones , Renal Insufficiency, Chronic , Bone Marrow , Humans , Inflammation , Oxidative Stress
2.
Brain Behav Immun ; 91: 649-667, 2021 01.
Article in English | MEDLINE | ID: covidwho-1064858

ABSTRACT

For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research.


Subject(s)
Stroke Rehabilitation/methods , Stroke/immunology , Stroke/physiopathology , Animals , Brain Ischemia/drug therapy , Comorbidity , Disease Models, Animal , Humans , Immunity/immunology , Immunity/physiology , Inflammation/immunology , Neuroprotection/immunology , Neuroprotection/physiology , Outcome Assessment, Health Care , Reperfusion/methods , Reperfusion/trends
3.
Semin Respir Crit Care Med ; 42(2): 308-315, 2021 04.
Article in English | MEDLINE | ID: covidwho-1064166

ABSTRACT

Venous thromboembolism (VTE) is the leading preventable cause of death in hospitalized patients and data consistently show that acutely ill medical patients remain at increased risk for VTE-related morbidity and mortality in the post-hospital discharge period. Prescribing extended thromboprophylaxis for up to 45 days following an acute hospitalization in key patient subgroups that include more than one-quarter of hospitalized medically-ill patients represents a paradigm shift in the way hospital-based physicians think about VTE prevention. Advances in the field of primary thromboprophylaxis in acutely-ill medical patients using validated VTE and bleeding risk assessment models have established key patient subgroups at high risk of VTE and low risk of bleeding that may benefit from both in-hospital and extended thromboprophylaxis. The direct oral anticoagulants betrixaban and rivaroxaban are now U.S. Food and Drug Administration-approved for in-hospital and extended thromboprophylaxis in medically ill patients and provide net clinical benefit in these key subgroups. Coronavirus disease-2019 may predispose patients to VTE due to excessive inflammation, platelet activation, endothelial dysfunction, and hemostasis. The optimum preventive strategy for these patients requires further investigation. This article aims to review the latest concepts in predicting and preventing VTE and discuss the new era of extended thromboprophylaxis in hospitalized medically ill patients.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/therapy , Duration of Therapy , Hospitalization , Pulmonary Embolism/prevention & control , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Benzamides/therapeutic use , COVID-19/blood , COVID-19/complications , Critical Care , Decision Support Systems, Clinical , Humans , Medical Informatics , Patient Discharge , Pulmonary Embolism/etiology , Pyridines/therapeutic use , Risk Assessment , Rivaroxaban/therapeutic use , SARS-CoV-2 , Venous Thromboembolism/etiology , Venous Thrombosis/etiology
4.
Br J Cancer ; 124(7): 1183, 2021 03.
Article in English | MEDLINE | ID: covidwho-1007651

ABSTRACT

The use of granulocyte colony-stimulating factor (G-CSF) in patients with haematological malignancies is associated with less febrile neutropenia episodes. But in the presence of COVID-19 infection, the administration of G-CSF is challenging as it may trigger a robust inflammatory reaction resulting in cytokine storm, respiratory failure and severe outcomes.


Subject(s)
COVID-19/epidemiology , Granulocyte Colony-Stimulating Factor/administration & dosage , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , COVID-19/complications , COVID-19/virology , Cytokine Release Syndrome/chemically induced , Granulocyte Colony-Stimulating Factor/adverse effects , Hematologic Neoplasms/complications , Humans , Prognosis , Respiratory Insufficiency/chemically induced , SARS-CoV-2/isolation & purification
5.
Dose Response ; 18(3): 1559325820951357, 2020.
Article in English | MEDLINE | ID: covidwho-768335

ABSTRACT

Low dose radiotherapy has been used in the pre-antibiotic era for the treatment of all kind of pneumonia, with relative success. The unimaginable daily death toll of thousands of victims dying from COVID-19 pneumonia and the marginal therapeutic value of agents tested, brings forward the re-evaluation of the position of radiotherapy in the treatment of late stage lethal COVID-induced respiratory failure. A sound biological rationale supports this idea. Immunopathology studies show that excessive inflammation and infiltration of the lung parenchyma by immune cells is the cause of death. Mice lacking IFNαß receptors remain unaffected by the virus. Radiotherapy at doses of 50-200cG may exert an intense anti-inflammatory effect and reduce the burden of inflammatory cells infiltrating the lungs. Whether radiotherapy, in conjunction with remdesivir and/or macrolides can reduce the dramatic death rates related to COVID-19 is an open challenge, under the absence of an alternative solution.

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