scholarly journals 111 The Systemic Effects of Intra-Articular Steroid Injections- Should COVID-19 Change Our Practice?

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
S Shah ◽  
S Raut ◽  
R Conyers ◽  
S Ahmed
Keyword(s):  
Inflammatory Arthritis ◽  
Low Dose ◽  
Systemic Absorption ◽  
Systemic Effects ◽  
Steroid Injections ◽  
Therapeutic Value ◽  
Endogenous Cortisol ◽  
Coronavirus Infection ◽  
Dose Dependent ◽  
Pituitary Adrenal Axis

Abstract Aim The COVID-19 pandemic prompted us to review and often suspend services, while patients continue to suffer with painful musculoskeletal conditions. The diagnostic and therapeutic value of intra-articular corticosteroid injections (IACSI) cannot be denied. Current BOA guidelines advise giving the lowest effective dose for inflammatory arthritis and limit use in osteoarthritis to patients with high levels of pain and disability. We aimed to evaluate the literature pertaining to the use of IACSI and the potential systemic immunosuppressive effects. Method We searched Medline, using the terms “systemic effects of intra-articular steroid” and “clinical course of Coronavirus infection in patients with steroid use”, between 1997 and 2020. Results No studies specifically looked at the systemic effects of intra-articular steroids in the presence of COVID-19 infection; however, four studies were identified which concluded that intra-articular steroid injections resulted in sufficient systemic absorption to cause suppression of the hypothalamic-pituitary-adrenal axis and endogenous cortisol production. These effects are dose dependent and are more common in patients with inflammatory joint diseases. A further four RCT’s, including one systematic review, showed that suppressed cortisol concentration was associated with a significant increase in mortality. Conclusions There is a lack of evidence in relation to the use of intra-articular steroids in COVID-19. However, evidence suggests that intra-articular steroids can result in systemic absorption and suppression of endogenous cortisol production thus increasing the potential risk of complications of COVID-19. We therefore support cautious use of low dose steroid injections in patients with inflammatory arthritis, where no alternative treatment is available.

scholarly journals The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Immune Tolerance ◽  
Immune Cells ◽  
Low Dose ◽  
Innate Immune ◽  
Immune Memory ◽  
Innate Immune Cells ◽  
Atp Production ◽  
Dose Dependent

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.

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

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582095135
Author(s):  
Michael I. Koukourakis
Keyword(s):  
Respiratory Failure ◽  
Immune Cells ◽  
Late Stage ◽  
Low Dose ◽  
Inflammatory Cells ◽  
Lung Parenchyma ◽  
Death Rates ◽  
Low Dose Radiotherapy ◽  
Therapeutic Value ◽  
Inflammatory Effect

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.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

Overt Glucocorticoid Excess Due to Inhaled Corticosteroid Therapy

PEDIATRICS ◽  
1988 ◽  
Vol 81 (3) ◽  
pp. 452-455
Author(s):  
Gregory A. Hollman ◽  
David B. Allen
Keyword(s):  
Triamcinolone Acetonide ◽  
Inhaled Corticosteroids ◽  
Therapeutic Option ◽  
Serum Cortisol ◽  
Hypothalamic Pituitary Adrenal Axis ◽  
Systemic Absorption ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Axis ◽  
Cortisol Levels ◽  
Pituitary Adrenal Axis

Inhaled corticosteroids have become an important therapeutic option in the treatment of childhood asthma. The preparations currently available for pediatric use (beclomethasone dipropionate and triamcinolone acetonide) do not, in general, cause significant hypothalamic-pituitary-adrenal axis suppression and physical signs of glucocorticoid excess have not been described with their use. We report an 8-year-old girl with asthma in whom obesity, hirsutism, and growth retardation developed during treatment with inhaled triamcinolone acetonide alone. Laboratory studies showed suppression of endogenous cortisol production but did not demonstrate suppression of the hypothalamic-pituitary-adrenal axis. Cessation of inhaled triamcinolone acetonide therapy resulted in resolution of obesity and hirsutism, resumption of normal growth, and a return to normal of serum cortisol levels and urinary 17-hydroxycorticosteroid excretion. Careful monitoring of growth velocity and (if clinically indicated) morning serum cortisol levels in asthmatic children using inhaled corticorsteroids will detect the rare instance of glucocorticoid excess resulting from systemic absorption of these drugs.

scholarly journals Low-Dose Radiation Therapy for COVID-19 Pneumonia: review

2020 ◽  
pp. 30-34
Author(s):  
N. Kolotilov
Keyword(s):  
Radiation Therapy ◽  
Low Dose ◽  
Ore Deposits ◽  
Molecular Targeting ◽  
Positive Experience ◽  
Low Dose Radiation ◽  
Coronavirus Infection ◽  
Positive Results ◽  
Dose Radiation ◽  
Radiolabeled Antibodies

The use of low-dose radiation therapy (LDRT) in patients with pneumonia from 1905 to 1943 provided positive results in 83.08 % of cases. Interest in LDRT is supported by researchers of radiation hormesis in the 21st century. Attention is drawn to the dynamics of coronavirus infection in the regions of Ukraine and the Kirovograd region with a minimum incidence. It is known that 95 % of uranium ore deposits in Ukraine are concentrated in the Kirovograd region. The positive experience of LDRT in Iran, India, USA, Spain for the treatment of patients with COVID-19 is described. LDRT (<100 cGy) is known to be anti-inflammatory, and therefore pulmonary LDRT has the potential to reduce the severity of pneumonia and reduce mortality. LDRT deserves a clinical study. A new direction in radiation therapy – Auger therapy based on radiolabeled antibodies – is planned to be used as a molecular targeting radiotherapy agent directly to the SARS-CoV-2.

scholarly journals Major Depressive Disorder (MDD) and Antidepressant Medication Are Overrepresented in High-Dose Statin Treatment

2021 ◽  
Vol 8 ◽  
Author(s):  
Leutner Michael ◽  
Matzhold Caspar ◽  
Kautzky Alexander ◽  
Kaleta Michaela ◽  
Thurner Stefan ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Inpatient Care ◽  
Low Dose ◽  
Antidepressant Medication ◽  
Statin Treatment ◽  
High Dose ◽  
Major Depressive ◽  
Dependent Relationship ◽  
Different Types ◽  
Dose Dependent

Objective: To examine the dose-dependent relationship of different types of statins with the occurrence of major depressive disorder (MDD) and prescription of antidepressant medication.Methods: This cross-sectional study used medical claims data for the general Austrian population (n = 7,481,168) to identify all statin-treated patients. We analyzed all patients with MDD undergoing statin treatment and calculated the average defined daily dose for six different types of statins. In a sub-analysis conducted independently of inpatient care, we investigated all patients on antidepressant medication (statin-treated patients: n = 98,913; non-statin-treated patients: n = 789,683). Multivariate logistic regression analyses were conducted to calculate the risk of diagnosed MDD and prescription of antidepressant medication in patients treated with different types of statins and dosages compared to non-statin-treated patients.Results: In this study, there was an overrepresentation of MDD in statin-treated patients when compared to non-statin-treated patients (OR: 1.22, 95% CI: 1.20–1.25). However, there was a dose dependent relationship between statins and diagnosis of MDD. Compared to controls, the ORs of MDD were lower for low-dose statin-treated patients (simvastatin&gt;0– &lt; =10 mg:OR: 0.59, 95% CI: 0.54–0.64; atorvastatin&gt;0– &lt; =10 mg:OR:0.65, 95%CI: 0.59–0.70; rosuvastatin&gt;0– &lt; =10 mg:OR: 0.68, 95% CI: 0.53–0.85). In higher statin dosages there was an overrepresentation of MDD (simvastatin&gt;40– &lt; =60 mg:OR: 2.42, 95% CI: 2.18–2.70, &gt;60–80 mg:OR: 5.27, 95% CI: 4.21–6.60; atorvastatin&gt;40– &lt; =60 mg:OR: 2.71, 95% CI: 1.98–3.72, &gt;60– &lt; =80 mg:OR: 3.73, 95% CI: 2.22–6.28; rosuvastatin&gt;20– &lt; =40 mg:OR: 2.09, 95% CI: 1.31–3.34). The results were confirmed in a sex-specific analysis and in a cohort of patients taking antidepressants, prescribed independently of inpatient care.Conclusions: This study shows that it is important to carefully re-investigate the relationship between statins and MDD. High-dose statin treatment was related to an overrepresentation, low-dose statin treatment to an underrepresentation of MDD.

Heparin inhalation in patients with new coronavirus infection (review)

2020 ◽  
Author(s):  
Н.А. Воробьева ◽  
Е.В. Ройтман ◽  
Е.Ю. Мельничук
Keyword(s):  
Lipoprotein Lipase ◽  
Medical Staff ◽  
Systemic Effects ◽  
Microvascular Thrombosis ◽  
Prevention And Treatment ◽  
Individual Protection ◽  
Coronavirus Infection ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Гепарин используется в клинической практике преимущественно как антикоагулянт. Однако спектр его эффектов значительно шире: противовоспалительный, антипролиферативный, гиполипидемический (как прямой, так и посредством повышения активности липопротеинлипазы), антикоагулянтный, противоотечный и др. Именно на противовоспалительное действие гепарина сделан акцент при терапии COVID-19. Одним из патогенетически обоснованных методов профилактики и терапии микрососудистого тромбоза в тканях легких может быть использование ингаляций нефракционированного гепарина, что позволяет реализовать как местное, так и системное действие этого препарата. Терапия ингаляциями гепарина не будет значительно увеличивать риск контаминации вирусом SARS-CoV-2 медицинского персонала при неукоснительном соблюдении стандартов и рекомендуемых мер индивидуальной защиты. Heparin is considered traditionally as an anticoagulant although it has anti-inflammatory, antiproliferative, hypolipidemic (both direct and by increasing the activity of lipoprotein lipase), anticoagulative, anti-edema effects as well. The anti-inflammatory effect of heparin is in the focus of COVID-19 therapy. Inhaled (nebulized) heparin performs local and systemic effects. This way is pathogenetically justified for the prevention and treatment of microvascular thrombosis in lung tissues. Procedures of heparin inhalation should not significantly increase the risk for medical staff to become infected with SARS-CoV-2 when individual protection is fully observed.

Calcitriol Exerts Prophylactic Anti-Mycobacterium Effect In A Dose-Dependent Manner

2021 ◽  
Author(s):  
Jianguo Li ◽  
Zhen Li ◽  
Zefeng Gao ◽  
Juan Xia ◽  
Jia Cui ◽  
...  
Keyword(s):  
Vitamin D ◽  
1H Nmr ◽  
Low Dose ◽  
Bacterial Load ◽  
High Dose ◽  
Dependent Manner ◽  
Prophylactic Effect ◽  
Moderate Dose ◽  
Metabolism Pathway ◽  
Dose Dependent

Abstract Vitamin D was empirically applied for Tuberculosis (TB) treatment in the past, and is currently used as an adjuvant for TB therapy. Although an increasing pile of evidences suggests that vitamin D has no therapeutic effect against TB infection, the prophylactic effect of vitamin D in preventing TB remains largely undetermined. To experimentally valuate the potential prophylactic effect of calcitriol (the active form of vitamin D) against mycobacterium infection, we performed dose-gradient calcitriol soaking in 30-day-old zebrafish before Mycobacterium marinum (M. marinum) challenge through tail vein injection. 1H-NMR metabolomics analysis was further performed for illustration of potential mechanisms underlying the prophylactic effect of calcitriol against M. marinum. The results suggested that calcitriol exerts dose-dependent prophylactic anti-mycobacterium effects, i.e., the bacterial load and the corresponding inflammatory factors (IL-1β, TNF-α, and IFN-γ) expressions in M. marinum challenged zebrafish were reduced by low-dose (25 µg/L) or high-dose (2500 µg/L) calcitriol soaking, rather than by moderate-dose (250 µg/L) calcitriol soaking. Body weight of the M. marinum challenged zebrafish was recovered by high-dose prophylactic calcitriol soaking rather than by low-dose or moderate-dose calcitriol. The 1H-NMR metabolomic profiling identified 29 metabolites with altered abundance among the dose-gradient calcitriol groups, among which 22 metabolites were co-varied with the dose of calcitriol, the rest 7 metabolites were co-varied with the bacterial load and the inflammatory response in term of cytokine expression. Further pathway analysis indicated that the glycine, serine, and threonine metabolism pathway was the activated in both of the two metabolite groups, indicating that the pathway was altered by dose-gradient of calcitriol and was in response to M. marinum infection in zebrafish. The results of the present study suggested that the activation of glycine, serine and threonine metabolism pathway may play a potential role for the dose-dependent anti-mycobacterium effect induced by prophylactic calcitriol soaking.

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