scholarly journals Low-Dose Radiotherapy for Late-Stage COVID-19 Pneumonia?

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582095135
Author(s):  
Michael I. Koukourakis

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 IFNαβ 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.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Massoud Daheshia ◽  
James D. Prahl ◽  
Jacob J. Carmichael ◽  
John S. Parrish ◽  
Gilbert Seda

Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.


2008 ◽  
Vol 86 (3) ◽  
pp. 399-406 ◽  
Author(s):  
Meritxell Arenas ◽  
Fèlix Gil ◽  
Meritxell Gironella ◽  
Víctor Hernández ◽  
Albert Biete ◽  
...  

2020 ◽  
Vol 20 (9) ◽  
pp. 1523-1530
Author(s):  
Murat Dabak ◽  
Durrin O. Dabak ◽  
Tuncay Kuloglu ◽  
Ersoy Baydar ◽  
Hakan Bulut ◽  
...  

Background: Extrarenal 1α,25-dihydroxyvitamin D3 (1,25-D) locally produced by immune cells plays crucial roles in the regulation of the immune system. However, in vivo status of extrarenal 1,25-D and 25-hydroxyvitamin D (25-D) in acute inflammatory conditions are unknown. Objective: The aim of this study was to determine the extrarenal 1,25-D level in circulation in bilaterally nephrectomized rats, induced by low-dose lipopolysaccharide (LPS). Methods: Renal 1,25-D synthesis was terminated through bilateral nephrectomy in rats. The rats received intraperitoneal LPS (50 μg/kg BW) three times and the experiment was ended 24 hours after nephrectomy. Serum 1,25-D, 25-D, calcium, phosphorus, intact parathyroid hormone, and calcitonin levels were measured and immunohistochemistry was applied to detect the sources of extrarenal 1,25- D synthesis. Results: Circulatory 1,25-D concentration remarkably increased in both LPS-treated and non-treated bilaterally nephrectomized rats. Elevated circulatory 1,25-D did not have hypercalcemic endocrinal effects. The increased 1,25-D level also resulted in a concurrent rapid and dramatic depletion of circulatory 25-D. Conclusions: Extrarenal 1,25-D could enter into the systemic circulation and, therefore, might have systemic effects besides its autocrine and paracrine functions.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 457.1-457
Author(s):  
A. Sargsyan ◽  
V. Vardanyan ◽  
K. Ginosyan ◽  
S. Vardanyan ◽  
V. Mukuchyan

Background:Gouty arthritis is a common, potentially disabling and increasingly prevalent disease [1]. The main goals of treatment are to treat acute arthritis, decrease uric acid (UA) levels and prevent occurrence of further attacks. According to 2016 updated EULAR evidence-based recommendations for the management of gout, the most common and efficient options include prescription of colchicine (up to 6 mg during the first day) and intra-articular injections of glucocorticoids (GC) [2]. First option often causes diarrhea, the latter is extremely traumatic and painful in this group of patients.Objectives:The aim of this study was to determine the efficacy of sustainability of anti-inflammatory effect of combination of low dose colchicine with sporadic intramuscular injections of betamethasone in the treatment of acute gouty arthritis.Methods:41 treatment naïve patients with acute gouty arthritis (27 male /65,9 %/, 14 female /34,1 %/, mean age 55,9 ± 13,7 years, mean disease duration 5,9 ± 4,4 years) were recruited in the study. On the first visit all the patients were prescribed 1.5 mg of colchicine per day and 2 intramuscular injections of betamethasone preparation (7mg-1ml) with an interval of 4 days. On the second visit (30thday) daily dose of colchicine was decreased to 1.0 mg, urate-lowering therapy (ULT) was begun. 21 patients (51,2%) received febuxostat 80 mg/day, 20 patients (48,8%) – allopurinol 100-150 mg/day.Routine investigation included accurate collection of disease history, objective examination with determining the disease activity (Gout Activity Score /GAS/) and visual analogue scale (VAS patient), CBC, CRP, measurement of serum UA and creatinine level, urinalysis and other examinations [4]. GAS, VAS, CRP and uric acid were measured 3 times: at baseline, on 30thand 60thday of follow-up period.Results:Investigation had shown the following results at baseline: sUA1- 9,2 ± 1,5 mg/dl, CRP1- 24,3 ± 21,5 mg/L, VAS1- 8,3 ± 1,3 cm, GAS16,3 ± 0,7. All enrolled patients completed 60 days of treatment. Preparations were well tolerated, no serious adverse events occurred: mild dyspepsia was observed in 4 (9,8%) patients, mild hypertension – in 7 (17,1%), 10 (24,4%) patients had transient diarrhea. Only in 14 out of 41 patients (34,1 %) there was a necessity to add NSAIDs to the main scheme of treatment.On the second visit (30thday) all investigated measures with exception for UA (sUA2- 8,8 ± 1,9 mg/dl, p>0.05) had shown significantly lower results: CRP2- 4,9±3,5 mg/dl, VAS2– 4,2±1,2 cm, GAS2- 4,9 ± 0,7 (p<0.001).On the third visit (60thday) the following results were obtained: sUA3- 4,7 ± 1,3 mg/dl, CRP3- 3,5±2,0 mg/L, VAS3- 3,3±2,1 cm, GAS3- 3,7±0,9. All the measures were significantly lower than at baseline (p<0,001).During all the follow-up period recurrent attacks of arthritis were observed in 6 patients (14,6%), particularly, only 2 patients experienced arthritis after the prescription of ULT.Conclusion:Low dose colchicine in combination with sporadic (1-2) intramuscular injections of betamethasone can present as an efficient, non-traumatic, safe and cost-effective option for the treatment of acute gouty arthritis. Moreover, according to results of our study, anti-inflammatory effect was stable even after the prescription of ULT.References:[1]Kuo C-F, Grainge MJ, Zhang W, et al. Global epidemiology of gout: prevalence, incidence and risk factors. Nat Rev Rheumatol 2015;11:649–62. doi:10.1038/nrrheum.2015.91[2]Richette P, et al. 2016 updated EULAR evidence-based recommendations for the management of gout Ann Rheum Dis 2017;76:29–42. doi:10.1136/annrheumdis-2016-209707[3]Scirè, Carlo A et al. “Development and First Validation of a Disease Activity Score for Gout.” Arthritis care & research vol. 68,10 (2016): 1530-7. doi:10.1002/acr.22844Disclosure of Interests: :None declared


Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 584
Author(s):  
Lars-Olav Harnisch ◽  
Onnen Moerer

(1) Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used for acute respiratory failure with few absolute but many relative contraindications. The provider in charge often has a difficult time weighing indications and contraindications to anticipate if the patient will benefit from this treatment, a decision that often decides life and death for the patient. To assist in this process in coming to a good evidence-based decision, we reviewed the available literature. (2) Methods: We performed a systematic review through a literature search of the MEDLINE database of former and current absolute and relative contraindications to the initiation of ECMO treatment. (3) Results: The following relative and absolute contraindications were identified in the literature: absolute—refusal of the use of extracorporeal techniques by the patient, advanced stage of cancer, fatal intracerebral hemorrhage/cerebral herniation/intractable intracranial hypertension, irreversible destruction of the lung parenchyma without the possibility of transplantation, and contraindications to lung transplantation; relative—advanced age, immunosuppressed patients/pharmacological immunosuppression, injurious ventilator settings > 7 days, right-heart failure, hematologic malignancies, especially bone marrow transplantation and graft-versus-host disease, SAPS II score ≥ 60 points, SOFA score > 12 points, PRESERVE score ≥ 5 points, RESP score ≤ −2 points, PRESET score ≥ 6 points, and “do not attempt resuscitation” order (DN(A)R status). (4) Conclusions: We provide a simple-to-follow algorithm that incorporates absolute and relative contraindications to the initiation of ECMO treatment. This algorithm attempts to weigh pros and cons regarding the benefit for an individual patient and hopefully assists caregivers to make better, informed decisions.


2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.


Sign in / Sign up

Export Citation Format

Share Document