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IL-6 antagonists to replace systemic corticosteroids as the preferred anti-inflammatory therapy in patients with COVID-19?
Kow, CS, Zaihan, AF, Ramachandram, DS, Hasan, SS
Cytokine. 2022;:155730
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Adjunctive treatments for the management of septic shock - a narrative review of the current evidence.
Donovan, K, Shah, A, Day, J, McKechnie, SR
Anaesthesia. 2021;(9):1245-1258
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Abstract
Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta-blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta-blocker therapy may have beneficial cardiac and non-cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.
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Intraoperative Applications of Topical Corticosteroid Therapy for Chronic Rhinosinusitis.
Lelegren, MJ, Bloch, RA, Lam, KK
Ear, nose, & throat journal. 2021;(5):320-328
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OBJECTIVES To provide an overview of recent techniques and technologies for the application of topical corticosteroid therapy immediately following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS). METHODS A comprehensive search in the PubMed and Google Scholar databases was conducted to identify publications between January 2000 and December 2019 detailing clinical trials that have evaluated the efficacy and safety of intraoperative applications of topical corticosteroids for CRS. RESULTS A total of 21 articles, all of which highlight a variety of corticosteroid-infused products, including Propel corticosteroid-eluting stents, NasoPore, Merocel, SinuBand, calcium alginate, and bioresorbable gel-type products, are included for review. Propel stents are the only devices that have achieved level 1A evidence in terms of efficacy and have data to support their safety. The remaining products have shown mixed results in terms of efficacy and safety. CONCLUSION A wide range of techniques and technologies have been introduced to enhance the topical delivery of corticosteroids into the neosinuses after ESS for CRS. Regarding efficacy, there is level 1A evidence to support the use of Propel stents. Most of the remaining strategies show some degree of efficacy. Direct comparisons across the different strategies are limited owing to the varied uses of delivery vectors, corticosteroid choices, and doses of corticosteroids. Propel stents and SinuBand have sufficient data to support systemic and ocular safety, whereas the remaining products have limited data to support their safety.
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AIRE Gene Mutation Presenting at Age 2 Years With Autoimmune Retinopathy and Steroid-Responsive Acute Liver Failure: A Case Report and Literature Review.
Sakaguchi, H, Mizuochi, T, Haruta, M, Takase, R, Yoshida, S, Yamashita, Y, Nishikomori, R
Frontiers in immunology. 2021;:687280
Abstract
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare monogenic autosomal recessive disorder caused by mutation in the autoimmune regulator (AIRE) gene. Patients usually are diagnosed at ages between 5 and 15 years when they show 3 or more manifestations, most typically mucocutaneous candidiasis, Addison's disease, and hypoparathyroidism. APECED-associated hepatitis (APAH) develops in only 10% to 40% of patients, with severity varying from subclinical chronic active hepatitis to potentially fatal acute liver failure (ALF). Ocular abnormalities are fairly common, most often keratopathy but sometimes retinopathy. Here we report a 2-year-old Japanese girl with an AIRE gene mutation who developed APAH with ALF, preceded by autoimmune retinopathy associated with anti-recoverin antibody before major symptoms suggested a diagnosis of APECED. Intravenous pulse methylprednisolone therapy followed by a corticosteroid combined with azathioprine treatment resolved ALF and achieved control of APAH. To our knowledge, our patient is the youngest reported to have ALF resulting from an AIRE gene mutation. Pulse methylprednisolone induction therapy followed by treatment with corticosteroid plus azathioprine may well be effective in other children with APAH and AIRE gene mutations.
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Interventions for the prevention of persistent post-COVID-19 olfactory dysfunction.
Webster, KE, O'Byrne, L, MacKeith, S, Philpott, C, Hopkins, C, Burton, MJ
The Cochrane database of systematic reviews. 2021;(7):CD013877
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Abstract
BACKGROUND Loss of olfactory function is well recognised as a cardinal symptom of COVID-19 infection, and the ongoing pandemic has resulted in a large number of affected individuals with abnormalities in their sense of smell. For many, the condition is temporary and resolves within two to four weeks. However, in a significant minority the symptoms persist. At present, it is not known whether early intervention with any form of treatment (such as medication or olfactory training) can promote recovery and prevent persisting olfactory disturbance. OBJECTIVES To assess the effects (benefits and harms) of interventions that have been used, or proposed, to prevent persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020. SELECTION CRITERIA Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Individuals who had symptoms for less than four weeks were included in this review. Studies compared any intervention with no treatment or placebo. DATA COLLECTION AND ANALYSIS We used standard Cochrane methodological procedures. Our primary outcomes were the presence of normal olfactory function, serious adverse effects and change in sense of smell. Secondary outcomes were the prevalence of parosmia, change in sense of taste, disease-related quality of life and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS We included one study of 100 participants, which compared an intranasal steroid spray to no intervention. Participants in both groups were also advised to undertake olfactory training for the duration of the trial. Data were identified for only two of the prespecified outcomes for this review, and no data were available for the primary outcome of serious adverse effects. Intranasal corticosteroids compared to no intervention (all using olfactory training) Presence of normal olfactory function after three weeks of treatment was self-assessed by the participants, using a visual analogue scale (range 0 to 10, higher scores = better). A score of 10 represented "completely normal smell sensation". The evidence is very uncertain about the effect of intranasal corticosteroids on self-rated recovery of sense of smell (estimated absolute effect 619 per 1000 compared to 520 per 1000, risk ratio (RR) 1.19, 95% confidence interval (CI) 0.85 to 1.68; 1 study; 100 participants; very low-certainty evidence). Change in sense of smell was not reported, but the self-rated score for sense of smell was reported at the endpoint of the study with the same visual analogue scale (after three weeks of treatment). The median scores at endpoint were 10 (interquartile range (IQR) 9 to 10) for the group receiving intranasal corticosteroids, and 10 (IQR 5 to 10) for the group receiving no intervention (1 study; 100 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS There is very limited evidence regarding the efficacy of different interventions at preventing persistent olfactory dysfunction following COVID-19 infection. However, we have identified a small number of additional ongoing studies in this area. As this is a living systematic review, the evidence will be updated regularly to incorporate new data from these, and other relevant studies, as they become available. For this (first) version of the living review, we identified a single study of intranasal corticosteroids to include in this review, which provided data for only two of our prespecified outcomes. The evidence was of very low certainty, therefore we were unable to determine whether intranasal corticosteroids may have a beneficial or harmful effect.
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Early short-course corticosteroids and furosemide combination to treat non-critically ill COVID-19 patients: An observational cohort study.
Kevorkian, JP, Riveline, JP, Vandiedonck, C, Girard, D, Galland, J, Féron, F, Gautier, JF, Mégarbane, B
The Journal of infection. 2021;(1):e22-e24
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Autoimmune encephalitis: proposed best practice recommendations for diagnosis and acute management.
Abboud, H, Probasco, JC, Irani, S, Ances, B, Benavides, DR, Bradshaw, M, Christo, PP, Dale, RC, Fernandez-Fournier, M, Flanagan, EP, et al
Journal of neurology, neurosurgery, and psychiatry. 2021;(7):757-768
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Abstract
The objective of this paper is to evaluate available evidence for each step in autoimmune encephalitis management and provide expert opinion when evidence is lacking. The paper approaches autoimmune encephalitis as a broad category rather than focusing on individual antibody syndromes. Core authors from the Autoimmune Encephalitis Alliance Clinicians Network reviewed literature and developed the first draft. Where evidence was lacking or controversial, an electronic survey was distributed to all members to solicit individual responses. Sixty-eight members from 17 countries answered the survey. Corticosteroids alone or combined with other agents (intravenous IG or plasmapheresis) were selected as a first-line therapy by 84% of responders for patients with a general presentation, 74% for patients presenting with faciobrachial dystonic seizures, 63% for NMDAR-IgG encephalitis and 48.5% for classical paraneoplastic encephalitis. Half the responders indicated they would add a second-line agent only if there was no response to more than one first-line agent, 32% indicated adding a second-line agent if there was no response to one first-line agent, while only 15% indicated using a second-line agent in all patients. As for the preferred second-line agent, 80% of responders chose rituximab while only 10% chose cyclophosphamide in a clinical scenario with unknown antibodies. Detailed survey results are presented in the manuscript and a summary of the diagnostic and therapeutic recommendations is presented at the conclusion.
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Association of Antenatal Corticosteroids and Magnesium Sulfate Therapy With Neurodevelopmental Outcome in Extremely Preterm Children.
Gentle, SJ, Carlo, WA, Tan, S, Gargano, M, Ambalavanan, N, Chawla, S, Bell, EF, Bann, CM, Hintz, SR, Heyne, RJ, et al
Obstetrics and gynecology. 2020;(6):1377-1386
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OBJECTIVE To test the primary hypothesis that extremely preterm children antenatally exposed to both magnesium sulfate and antenatal corticosteroids have a lower rate of severe neurodevelopmental impairment or death compared with those exposed to antenatal corticosteroids alone. METHODS This was a prospective observational study of children born at 22 0/7-26 6/7 weeks of gestation from 2011 to 2014 at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network hospitals (N=3,093). The primary outcome was severe neurodevelopmental impairment or death at 18-26 months of corrected age follow-up based on exposure to antenatal corticosteroids and magnesium sulfate or antenatal corticosteroids alone. Secondary outcomes included components of severe neurodevelopmental impairment by exposure group and comparisons of severe neurodevelopmental impairment or death between children exposed to both antenatal corticosteroids and magnesium sulfate with those exposed to magnesium sulfate alone or to neither antenatal corticosteroids nor magnesium sulfate. Logistic regression models adjusted for background characteristics. RESULTS Children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of severe neurodevelopmental impairment or death (813/2,239, 36.3%) compared with those exposed to antenatal corticosteroids alone (225/508, 44.3%; adjusted odds ratio [aOR] 0.73; 95% CI 0.58-0.91), magnesium sulfate alone (47/89, 53%; aOR 0.49; 95% CI 0.29-0.82), or neither therapy (121/251; 48.2%; aOR 0.66, 95% CI 0.49-0.89). Similarly, children exposed to both antenatal corticosteroids and magnesium sulfate had a lower rate of death compared with either or neither therapy, but the rate of severe neurodevelopmental impairment among survivors did not differ between exposure groups. CONCLUSION In children born between 22 0/7 and 26 6/7 weeks of gestation, exposure to both antenatal corticosteroids and magnesium sulfate was associated with lower rates of severe neurodevelopmental impairment or death and death compared with exposure to antenatal corticosteroids alone. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00063063.
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Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective.
Singh, AK, Majumdar, S, Singh, R, Misra, A
Diabetes & metabolic syndrome. 2020;(5):971-978
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BACKGROUND AND AIMS Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.
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Extracorporeal shock wave therapy versus corticosteroid injection for chronic plantar fasciitis: A protocol of randomized controlled trial.
Zhao, J, Luo, WM, Li, T
Medicine. 2020;(19):e19920
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BACKGROUND The outcomes of corticosteroid injection (CSI) and extracorporeal shock wave therapy (ESWT) as primary treatment of plantar fasciitis have been debated. This study was conducted to compare and evaluate the therapeutic effects of ultrasound-guided CSI versus medium frequency ESWT in the treatment of plantar fasciitis among Chinese population. METHODS This study was a single-center, randomized, and double-blinded trial. The study protocol was approved by local ethics committee board and subsequently registered in Research Registry. Eighty patients with unilateral plantar fasciitis were randomized to receive either ESWT (3 times once per week) (n = 40) or CSI treatment (a single 1-mL dose of betamethasone sodium plus 0.5 mL of prilocaine under ultrasound guidance by injection into the plantar fascia) (n = 40). The primary outcome measures were visual analog scale and Foot Function Index scores. Secondary outcome measures included the heel tenderness index score and plantar fascia thickness as obtained by ultrasound examination. All of the assessments were performed at baseline and 1, 3, and 6 months after treatment. RESULTS This is a randomized controlled trial evaluating the efficacy of CSI versus ESWT in the treatment of plantar fasciitis. This study has limited inclusion and exclusion criteria and a well-controlled intervention. CONCLUSIONS The results of this trial will provide more evidence on which method can better treat plantar fasciitis. TRIAL REGISTRATION This study protocol was registered in Research Registry (researchregistry5428).