Pandemic aspect of dexamethasone: Molecular mechanisms and clinical application

Li, Anna F.Y.; Wang, Chia Lin; Tai, Hung-Chi; Fu, Yao‐Shi; Tsai, Fu Ting; Tsai, Yi Ching; Ko, Yu Ling; Li, Mei Jane; Lin, Chiou Chyn; Chang, Tai Jay

doi:10.1097/jcma.0000000000000485

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…Low molecular weight heparin can bind to antithrombin III, resulting in structural changes of antithrombin III, thereby accelerating the inhibitory effect on factor Xa, producing anticoagulant effect, and having less effect on antithrombin, so it can reduce heparin-induced bleeding and other adverse reactions while achieving effective anticoagulant effect [ 44 ]. Dexamethasone is a commonly used steroid hormone with the effects of immunosuppression, anti-endotoxin and enhancing the body's stress response [ 45 ]. It can inhibit the accumulation of inflammatory cells at the site of inflammation, and inhibit phagocytosis, release of lysosomal enzymes, and synthesis and release of inflammatory mediators, thereby reducing the tissue response to inflammation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of heparin plus dexamethasone after partial splenic embolization for liver cirrhosis with massive splenomegaly

Zheng

Xiong

et al. 2022

BMC Gastroenterol

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Purpose The aim of this study was to investigate the efficacy and safety of the combination of low-molecular-weight heparin + dexamethasone after partial splenic embolization in cirrhotic patients with massive splenomegaly. Methods This study included 116 patients with liver cirrhosis complicated with massive splenomegaly who underwent PSE in Union Hospital from January 2016 to December 2019, and they met the criteria. They were divided into two groups: PSE + Hep + Dex group (N = 54) and PSE group (N = 62). We conducted a retrospective study to analyze the efficacy and safety of the two groups of patients. Results The volume of splenic embolization was 622.34 ± 157.06 cm3 in the PSE + Hep + DEX group and 587.62 ± 175.33 cm3 in the PSE group (P = 0.306). There was no statistically difference in the embolization rate of the spleen between the two groups (P = 0.573). WBC peaked 1 week after PSE and PLT peaked 1 month after PSE in both groups; it gradually decreased later, but was significantly higher than the preoperative level during the 12-month follow-up period. The incidences of abdominal pain (46.3% vs 66.1%, P = 0.039), fever (38.9% vs 75.8%, P < 0.001), PVT (1.9% vs 12.9%, P = 0.026), refractory ascites (5.6% vs 19.4%, P = 0.027) were lower in the PSE + Hep + DEX group than in the PSE group. The VAS score of abdominal pain in PSE group was higher than that in PSE + Hep + DEX group on postoperative days 2–8 (P < 0.05). Splenic abscess occurred in 1(1.6%) patient in the PSE group and none (0.0%) in the PSE + Hep + DEX group (P = 0.349). Conclusions The combined use of dexamethasone and low-molecular-weight heparin after PSE is a safe and effective treatment strategy that can significantly reduce the incidence of complications after PSE (such as post-embolization syndrome, PVT, refractory ascites).

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of heparin plus dexamethasone after partial splenic embolization for liver cirrhosis with massive splenomegaly

Zheng

Xiong

et al. 2022

BMC Gastroenterol

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“…Most effects of GCs are via the genomic mechanisms which takes time, while the immediate effects via the non-genomic mechanisms occur at high doses of GCs. 28,29 Given the diversity in the mechanism of action of GCs, systemic plasma concentrations are subject to high variability that can cause a wide array of drug-related problems ranging from mild to severe adverse effects on one hand and treatment failure on the other. Of all the factors influencing the efficacy of GCs, the therapeutic dose is one of the most important independent and well-documented risk factors.…”

Section: Discussionmentioning

confidence: 99%

“…Some authors have reported that the anti‐inflammatory and immunosuppressive effects of GCs are dose‐dependent, with immunosuppressive effects seen mostly at higher doses. Most effects of GCs are via the genomic mechanisms which takes time, while the immediate effects via the non‐genomic mechanisms occur at high doses of GCs 28,29 . Given the diversity in the mechanism of action of GCs, systemic plasma concentrations are subject to high variability that can cause a wide array of drug‐related problems ranging from mild to severe adverse effects on one hand and treatment failure on the other.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone exposure in normal‐weight and obese hospitalized COVID‐19 patients: An observational exploratory trial

Abouir

Gosselin

Guerrier

et al. 2022

Clinical Translational Sci

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During the latest pandemic, the RECOVERY study showed the benefits of dexamethasone (DEX) use in COVID-19 patients. Obesity has been proven to be an independent risk factor for severe forms of infection, but little information is available in the literature regarding DEX dose adjustment according to body weight.We conducted a prospective, observational, exploratory study at Geneva University Hospitals to assess the impact of weight on DEX pharmacokinetics (PK) in normalweight versus obese COVID-19 hospitalized patients. Two groups of patients were enrolled: normal-weight and obese (body mass index [BMI] 18.5-25 and >30 kg/ m 2 , respectively). All patients received the standard of care therapy of 6 mg DEX orally. Blood samples were collected, and DEX concentrations were measured.The mean DEX AUC 0-8 and C max were lower in the obese compared to the normalweight group (572.02 ± 258.96 vs. 926.92 ± 552.12 ng h/ml and 138.67 ± 68.03 vs.203.44 ± 126.30 ng/ml, respectively). A decrease in DEX AUC 0-8 of 4% per additional BMI unit was observed, defining a significant relationship between weight and DEX AUC 0-8 (p = 0.004, 95% CI 2-7%). In women, irrespective of the BMI, DEX AUC 0-8 increased by 214% in comparison to men (p < 0.001, 95% CI 154-298%).Similarly, the mean C max increased by 205% in women (p < 0.001, 95% CI 141-297%).Conversely, no significant difference between the obese and normal-weight groups was observed for exploratory treatment outcomes, such as the length of hospitalization. BMI, weight, and gender significantly affected DEX AUC. We conclude that dose adjustment would be needed if the aim is to achieve the same exposures in normal-weight and obese patients. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?COVID-19 is a disease caused by SARS-CoV-2 virus capable of causing mild to severe infections in humans up to pneumonia and acute respiratory distress

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“…Dexamethasone is a widespread immunosuppressive and antiinflammatory drug, used in numerous applications in medicine. 49 However, a recent (previously mentioned) double-blinded randomized trial showed no improvement in combining dexamethasone injections with oral PDE5 inhibitors compared with verapamil injections in terms of penile curvature, and both size and amount of fibrous plaques. 33 That said, the trial excluded patients in the acute phase of the disease, which could arguably be the target group for anti-inflammatory agents considering the inflammatory component of the acute phase in PD.…”

Section: Dexamethasonementioning

confidence: 98%

“…Dexamethasone is a widespread immunosuppressive and anti‐inflammatory drug, used in numerous applications in medicine 49 . However, a recent (previously mentioned) double‐blinded randomized trial showed no improvement in combining dexamethasone injections with oral PDE5 inhibitors compared with verapamil injections in terms of penile curvature, and both size and amount of fibrous plaques 33 .…”

Section: Intralesional Injectionsmentioning

confidence: 99%

Current trends in non‐surgical management of Peyronie's disease—A narrative review

Kozub,

Suleja,

Chłosta

et al. 2023

Andrology

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Peyronie's disease (PD) is a connective tissue disorder affecting the tunica albuginea. It can cause pain and penile deformation, and its prevalence increases with age. Although surgery is the gold standard for the chronic phase of the disease, there are several conservative treatment methods available, and the optimal management of the acute phase of the disease remains a matter of debate. In this article, we aim to summarize the recent trends in research on the subject of non‐surgical treatment of PD. The search was performed in PubMed, Scopus, and Web of Science databases and included studies in English published between 2012 and 2022 investigating the clinical outcomes of non‐surgical PD management in humans. We have identified 20 distinct conservative treatment strategies. Among the oral therapeutics, only the use of phosphodiesterase type 5 inhibitors is currently recommended for clinical use in patients with concomitant erectile dysfunction. The use of collagenase from Clostridium histolyticum is supported by the best quality evidence in terms of intralesional injections for patients suffering from significant penile curvature; however, interferon alpha‐2b can also be an option in such patients. Among other non‐invasive methods, extracorporeal shockwaves can be useful for pain reduction, and penile traction therapy can lead to a reduction in penile curvature and plaque size. Despite a wide range of non‐surgical methods available for PD treatment, the majority are not supported by sufficient scientific evidence, and the treatment efficacy is underwhelming. Further research on the subject of non‐surgical management of PD is highly warranted.

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Pandemic aspect of dexamethasone: Molecular mechanisms and clinical application

Cited by 5 publications

References 21 publications

Efficacy and safety of heparin plus dexamethasone after partial splenic embolization for liver cirrhosis with massive splenomegaly

Efficacy and safety of heparin plus dexamethasone after partial splenic embolization for liver cirrhosis with massive splenomegaly

Dexamethasone exposure in normal‐weight and obese hospitalized COVID‐19 patients: An observational exploratory trial

Current trends in non‐surgical management of Peyronie's disease—A narrative review

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