COVID-19 and the Vascular Elderly Subject: Illustration of Therapeutic Management with Corticosteroids in an Elderly Diabetic Patient with COVID-19

Introduction: The severity of Sars-Cov-2 infection is associated with the development of acute respiratory distress syndrome (ARDS). The progression to ARDS appears to be driven by a major inflammatory mechanism potentially sensitive to corticosteroids. Observation: This article describes the case of an elderly patient was admitted to emergency departments for intense asthenia, accompanied by motor diarrhoea, dyspnoea with desaturation in ambient air, in a context of strong suspicion of infection linked to COVID-19. The article also reviews the existing literature on the diagnosis and treatment of this severe form of the disease. Conclusion: Corticosteroids, and in particular dexamethasone, have been shown to be effective in the management of patients with COVID-19, an oxygen-releasing disease.

Clinical trials on corticosteroids for diabetic macular edema

Diabetic macular edema(DME)is a common cause of visual impairment in diabetic patients.It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier.The pathogenesis of DME is multifactorial.Several therapeutic modalities have been proposed for the treatment of DME.Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities,due to anti-inflammatory,anti-vascular endothelial growth factor and anti-proliferative effects.Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME.Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease.Steroid-related side effects include elevated intraocular pressure,cataract,and injection related complications such as endophthalmitis,vitreous hemorrhage,and retinal detachment particularly with intravitreal steroid injections.In order to reduce the risks,complications and frequent dosing of intravitreal steroids,intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME.

A clinical study of the efficacy of topical corticosteroids on dry eye

Objective: To evaluate the effect of topical corticosteroid for treatment of moderate or severe dry eye. Methods: Sixty eyes of 30 patients with moderate or severe dry eye, who were not sensitive to artificial tears, were treated with 0.1% fluoro- metholone eye drops. Subjective symptom and objective tests were used to evaluate the efficacy of treatment before and after application of 0.1% fluorometholone eye drops for 1 week and 1 month. Side effects were also evaluated. Results: After 1 week of treatment, subjective symptoms were improved in all dry eye patients; objective tests were improved in all dry eye patients 1 month after treatment, and the difference was significant. Conclusion: Topical corticosteroid drops can rapidly and effectively relieve the symptoms and signs of moderate or severe dry eye.

Corticosteroids or non-corticosteroids: a fresh perspective on alcoholic hepatitis treatment

BACKGROUND: Alcoholic hepatitis (AH) is a necrotizing inflammatory process caused by alcoholic liver injury. It carries a significant short-term mortality. The management of AH is challenging. Although corticosteroids have been demonstrated to exert anti-inflammatory and antifibrotic effects, their efficacy for the treatment of AH remains debatable. DATA SOURCES: A literature search was performed of MEDLINE, ScienceDirect, SpringerLink and Wiley InterScience using the key words 'alcoholic hepatitis', 'alcoholic liver disease', and 'corticosteroids'. The available data reported in the relevant literature were analyzed. RESULTS: More than 17 controlled trials and at least 13 meta-analyses have reported the efficacy of corticosteroids in the treatment of AH in the past 40 years. Many were poorly designed and used different inclusion/exclusion criteria, making it difficult to reach a consensus. In this review, we summarized all the controversial data in the past decade and analyzed the potential causes for the varying therapeutic effects of corticosteroids in AH. The focus of the controversy has changed from 'whether steroids are beneficial or harmful for AH patients' to 'how to accurately identify responders to steroids early and rationalize corticosteroid treatment'. An early response to glucocorticoids, as determined by calculating the Lille score after 7 days of treatment, has been shown to be a clinically useful indicator. Moreover, down-regulation of steroid sensitivity, risk of infection, and a rational therapeutic strategy of corticosteroids in AH patients are all crucial for therapeutic effect.CONCLUSIONS: An early and accurate determination of steroid sensitivity is important. Besides, we need to overcome the down-regulation of steroid sensitivity, reduce the infection risk and rationalize the therapeutic strategy of corticosteroids. A fresh perspective is needed on the use of corticosteroids in AH patients.

Do inhaled corticosteroids increase the risk of Pneumocystis pneumonia in people with lung cancer?

Pneumocystis pneumonia(PCP) is a life-threatening infection in immunocompromised patients. It is relatively uncommon in patients with lung cancer. We report a case of PCP in a 59-year-old man with a past medical history of chronic obstructive pulmonary disease treated with formoterol and a moderate daily dose of inhaled budesonide. He had also advanced stage non-small lung cancer treated with concurrent chemo-radiation with a cisplatin-etoposide containing regimen. The diagnosis of PCP was suspected based on the context of rapidly increasing dyspnea, lymphopenia and the imaging findings. Polymerase chain reaction testing on an induced sputum specimen was positive for Pneumocystis jirovecii. The patient was treated with oral trimethoprim-sulfamethoxazole and systemic corticotherapy and had showed clinical and radiological improvement. Six months after the PCP diagnosis, he developed a malignant pleural effusion and expired on hospice care. Through this case, we remind the importance of screening for PCP in lung cancer patients under chemotherapeutic regimens and with increasing dyspnea. In addition, we alert to the fact that long-term inhaled corticosteroids may be a risk factor for PCP in patients with lung cancer. Despite intensive treatment, the mortality of PCP remains high, hence the importance of chemoprophylaxis should be considered.

Corticosteroids and pentoxifylline for the treatment of alcoholic hepatitis:Current status

The treatment of choice for patients with severe alcoholic hepatitis (AH) is use of corticosteroids.Many randomized well designed studies have been reported from all over the world on the use of corticosteroids in the treatment of AH.However,the data on the efficacy of corticosteroids in these patients have been conflicting.Initial meta-analyses also failed to show beneficial effects of corticosteroids.Based on individual data meta-analysis showing clear benefit of corticosteroids amongst patients with severe AH (modified discriminant function of 32 or more),led American College of Gastroenterology to recommend use of corticosteroids as the first line treatment option amongst patients with severe AH.However,corticosteroids are relatively contraindicated amongst patients with severe AH and coexistent sepsis,gastrointestinal bleeding,and acute pancreatitis.These patients may be candidates for second line treatment with pentoxifylline.Further,specific treatment of AH with corticosteroids far from satisfactory with as many as 40%-50% of patients failing to respond to steroids,thus classified as nonresponsive to steroids.The management of these patients is a continuing challenge for physicians.Better treatment modalities need to be developed for this group of patients in order to improve the outcome of patients with severe AH.This article describes at length the available trials on use of corticosteroids and pentoxifylline with their current status.Route of administration,dosage,adverse effects,and mechanisms of action of these two drugs are also discussed.Finally,an algorithm with clinical approach to management of patients who present with clinical syndrome of AH is described.

Efficacy and safety of corticosteroids in immunocompetent patients with septic shock

BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.

Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis:A global survey of physicians'practice

AIM To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates(5ASA) with corticosteroids(CS) versus corticosteroids alone for patients with active ulcerative colitis(UC). METHODS A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. RESULTS Six hundred and sixty-four questionnaires were distributed and 349 received(52.6% response rate). Of 340 eligible respondents, 221(65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108(32%) would stop the 5ASA(P < 0.001), and 11(3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340(41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most(94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. CONCLUSION Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.

Insight into the interaction of inhaled corticosteroids with human serum albumin: A spectroscopic-based study

It is well known that the safety and efficacy profile of an inhaled cortocosteroid(ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating,protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin(HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van't Hoff analysis of the binding constants(negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes.

Corticosteroids and ICU Course of Community Acquired Pneumonia in Egyptian Settings

Background: Pneumonia is the most common cause of community-acquired infection requiring ICU admission. 60-87% of patients with severe community acquired pneumonia (CAP) admitted to the ICU develops respiratory failure and require mechanical ventilation (MV). Objectives: To assess the efficacy and safety of adjunctive low dose hydrocortisone infusion treatment in Egyptian ICU patients with CAP. Methods: Hospitalized patients, clinically and radiologically diagnosed with CAP, were randomized to receive hydrocortisone 12.5 mg/h IV infusion for 7 days or placebo, along with antibiotics. The end-points of the study were improvement in PaO2:FIO2 (PaO2:FIO2 > 300 or ≥100 increase from study entry) and SOFA score by study day 8 and the development of delayed septic shock. Results: 80 patients were recruited, 40 of them received hydrocortisone and the remaining 40 received placebo. By study day 8, hydrocortisone treated patients showed a significant improvement in PaO2:FIO2 and chest radiograph score, and a significant reduction in C-reactive protein (CRP) levels, Sepsis-related Organ Failure Assessment (SOFA) score, and delayed septic shock compared to the control group. Hydrocortisone treatment was associated with a significant reduction in the duration of MV. However, hydrocortisone infusion did not show significant difference in the ICU mortality. Conclusions: adjunctive 7-day course of low dose hydrocortisone IV in patients with CAP hastens recovery of pneumonia and prevents the development of sepsis related complications with a significant reduction in duration of the mechanical ventilation.

Corticosteroids for severe influenza pneumonia: A critical appraisal

Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit(ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in s evere influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials.

Infection does not increase long-term mortality in patients with acute severe alcoholic hepatitis treated with corticosteroids

AIM To determine whether infection in patients with acute severe alcoholic hepatitis(AAH) treated with corticosteroids is associated with increased mortality.METHODS Consecutive patients with AAH were treated with steroids and recruited to the study. Clinically relevant infections(body temperature > 38 ℃ or < 36 ℃ for more than 4 h, ascitic neutrophil count > 0.25 ×109/L, consolidation on chest radiograph or clinically relevant positive microbiological culture of bodily fluid) were recorded prospectively. Clinical and laboratory parameters were recorded and survival at 90 d and 6 mo was determined. Univariate analysis of factors associated with 90-d mortality was performed and significant variables included in a multivariate analysis.RESULTS Seventy-two patients were included in the final analysis(mean age 47.9 years, 26% female, mean discriminant function 53.0). Overall mortality in the group occurred in 15(21%), 23(32%) and 31(43%) at day 28, day 90 and 1 year respectively. 36(50%) had a clinically relevant infection during their hospitalisation(23 after initiation of steroids). The median time to development of incident infection after commencement of steroids was 10 d. The commonest site of infection was ascites(31%) and bacteraemia(31%) followed by urinary tract(19%) and respiratory tract(8%). Forty-one separate organisms were isolated in 33 patients; the most frequent genus was Escherichia(22%) and Enterococcus(20%). Infection was not associated with 90-d or 1 year mortality but was associated with higher creatinine, model for end-stage liver disease and Lille score. Baseline urea was the only independent predictor of 90-d mortality.CONCLUSION Clinically relevant infections are common in patients with AAH but are not associated with increased 90-d or 1 year mortality.

Treatment of eosinophlic esophagitis with swallowed topical corticosteroids

Eosinophilic esophagitis(EoE)is an emerging chronic local immune-mediated disease of the esophagus.Beside proton pump inhibitors and food-restrictiondiets swallowed topical corticosteroids(STC)can be offered as a first line therapy according to current guidelines.This review describes the background and practical management of STCs in EoE.So far,mainly asthma inhalers containing either budesonide or fluticasone have been administered to the esophagus by swallowing these medications“off label”.Recently esophagus-targeted formulations of topical steroids have been developed showing clinicopathological response rates up to 85%-an orodispersible tablet of budesonide has been approved as the first“in label”medication for EoE in Europe in June 2018.Whereas it was shown that disease remission induction of EoE by STCs is highly effective,there is still a lack of data regarding long-term and maintenance therapy.However,current studies on STC maintenance therapy add some movement into the game.

Acute and recurring pericarditis: More colchicine,less corticosteroids

Acute and recurring pericarditis are frequently encountered clinical entities.Given that severe complications such as tamponade and constrictive pericarditis occur rarely,the majority of patients suffering from acute pericarditis will have a benign clinical course.However,pericarditis recurrence,with its painful symptoms,is frequent.In effect,recent studies have demonstrated a beneficial role of colchicine in preventing recurrence,while also suggesting an increase in recurrences with the use of corticosteroids,the traditional first-line agent.

Use of corticosteroids during acute phase of Kawasaki disease

In spite of initial intravenous immunoglobulin(IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, havebeen considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids- the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary.

Evaluation of the Effects of Corticosteroids on Histamine Release by ex Vivo Cutaneous Microdialysis

The purpose of the study was to evaluate the effects of corticosteroids on histamine release and to compare their potency with the MacKenzie classification based on their vasoconstrictor effects. Thanks to ex Vivo cutaneous microdialysis, we studied histamine-induced release over a period of time on excised abdominal skin from women. Eight corticosteroids were topically applied with occlusive dressing onto the skin, above probes, before anti-IgE injection. Histamine levels were assessed by an EIA method. In order to compare the different corticosteroids, AUC was calculated allowing an estimation of the amount of released histamine for 60 min of ex vivo cutaneous microdialysis. Diflucortolone 0.1% and micronized betamethasone dipropionate 0.05% are considered as corticosteroids with high potency in MacKenzie classification. Betamethasone dipropionate associated with propylene glycol 0.05%, belongs to a stronger class in Mackenzie classification. Our results showed that the decrease in histamine release was more important with difluocortolone than with both of these corticosteroids. Therefore there was no correlation between the vasoconstrictor potency of topical corticosteroids and their ability to inhibit histamine release.

It's all about timing, early treatment with hyperbaric oxygen therapy and corticosteroids is essential in acute acoustic trauma

Background: Acute acoustic trauma (AAT) is an acute hearing impairment caused by intense noiseimpact. The current management strategy for AAT with substantial hearing loss in the Dutch militaryis the combination therapy with corticosteroids and hyperbaric oxygen therapy (HBOT). In a previousstudy, early initiation of the combination therapy was associated with better outcomes. Therefore, weperformed a new analysis to assess the difference in hearing outcome between patients in whomcombination therapy was started within two days, versus after more than two days.Methods: A retrospective analysis was performed on military patients diagnosed with AAT with substantial hearing loss who presented between February 2018 and March 2020. Absolute and relativehearing improvement between first and last audiograms were calculated for all affected frequencies(defined as loss of 20 dB on initial audiogram). We also determined the amount of patients whorecovered to the level of Dutch military requirement, and performed speech discrimination tests.Results: In this analysis, 30 male patients (49 ears) with AAT were included. The median age was 24.5years (IQR 23e29). The median time to initiation of therapy with corticosteroids and HBOT were one andtwo days, respectively. HBOT was started within two days in 31 ears, and after more than two days in 18ears. The mean absolute and relative hearing gains were 18.8 dB (SD 14.6) and 46.8% (SD 31.3) on allaffected frequencies. The 100% discrimination/speech perception level improved from 64.0 dB to 51.7 dB(gain 12.3 dB ± 14.1). There was significantly more improvement in absolute and relative hearingimprovement when HBOT was started in 2 days, compared to >2 days.Conclusion: Our analysis shows results in favor of early initiation ( 2 days) of the combination treatmentof HBOT and corticosteroids in patients with AAT.

Corticosteroids Treatment of Patients with Coronavirus Disease 2019:A Propensity Score Matching Study

The role of corticosteroids in the treatment of coronavirus disease 2019(COVID-19)is controversial.In the present study,we evaluated the effects of adjuvant corticosteroids treatment on the outcome of patients with COVID-19(n=966),using Propensity Score Matching to adjust for potential differences between the corticosteroids group(n=289)and the non-corticosteroids group(n=677).Analysis of data without adjusting differences in baseline characteristics indicated that the proportion of mechanical ventilation and the mortality was higher in the corticosteroids treatment group in total or severe/critical patients.The duration of viral shedding was longer in the non-corticosteroids treatment group in total or general/mild patients.After adjusting the difference between the corticosteroids and non-corticosteroids treatment group,the analysis revealed that the use of corticosteroids had no effect on the duration of viral shedding,in-hospital mortality or 28-day mortality.

How do corticosteroids influence myelin genesis in the central nervous system?

Clinical use of corticosteroid （CS） therapy and links with adverse neurological effects CS therapy is widely used in clinical practice worldwide, with ad- ministration of high and multiple doses prescribed for a range of disease and injury. Notably, CS have been used since the 1950＇s for the treatment of suspected respiratory distress syndrome, in order to accelerate lung maturation in premature babies, as also in antenatal therapy to pregnant women at risk of preterm birth （Haddad et al., 1956; Shinwell and Eventov-Friedman, 2009; Bonanno and Wapner, 2012）. High dose immunosuppressive CS therapy is also widely used in the treatment of multiple sclerosis （MS） and spinal cord injury （Bracken, 2012; Burton et al., 2012）. However,

Postmenopausal Bleeding and Changing Bleeding Patterns after Parental Use of Corticosteroids: A Prospective Cohort Study

Objective: To study whether there is a relation between the application of corticosteroids and occurrence of postmenopausal bleeding. Also we want to determine whether corticosteroids can cause an irregularity in a previously regular menstruation cycle. Design and Setting: Prospective cohort study in the department of anesthesiology. Patients: 209 women who received a single dosage of corticosteroids as treatment for pain. Interventions: None, observational cohort study;all women received standard care. Main outcome measures: Postmenopausal blood loss or disruption of menstruation cycle. Result: Postmenopausal blood loss or disruption of menstruation cycle were both more common 6 weeks after administration of corticosteroids, but were sometimes also reported 2 weeks after administration of corticosteroids. Conclusion: After administration of corticosteroids in a postmenopausal woman an episode of menstruation like bleeding can be expected. This is probably due to a transient drop of androstenedione. In premenopausal women a transient change in menstruation cycle can be observed.