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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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[Immunoglobulin A nephropathy].
Seikrit, C, Rauen, T, Floege, J
Der Internist. 2019;(5):432-439
Abstract
Immunoglobulin A nephropathy (IgAN) is the most prevalent primary form of glomerulopathy in the western world. The pathogenetic relevance of autoimmune mechanisms, genetics and environmental or nutritional factors is not fully established. The majority of IgAN patients present with mild symptoms; however, the exact prognosis of the individual IgAN course is often difficult to predict. In approximately one third of the patients the disease remains on a stable benign course, whereas approximately 30% may develop end-stage renal disease. Risk factors for disease progression are a persistent microhematuria and proteinuria >1 g/day, arterial hypertension and the extent of tubulointerstitial fibrosis at the time of diagnosis. Recent genome-wide association studies (GWAS) identified numerous risk alleles, which can contribute to the pathophysiology of IgAN. The so-called gut-kidney axis as well as the complement system and genes that are linked to mucosal immunity appear to be important for the manifestation of the disease. Intensive supportive care should be initiated as first-line treatment and only rare cases with progressive features require treatment with corticosteroids. Other immunosuppressive treatment strategies have currently no indications for IgAN. Future approaches might be the use of local budesonide or the inhibition of lymphocyte activation.
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Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and catecholamine molecules on lactoperoxidase.
Sheikh, IA, Jiffri, EH, Ashraf, GM, Kamal, MA, Beg, MA
Life sciences. 2018;:412-419
Abstract
AIM: Lactoperoxidase (LPO) is an essential protein with broad spectrum antimicrobial activity present in mammalian milk. It imparts immunity to infants against wide range of pathogenic infections. Several in vitro studies have shown inhibition of LPO activity by pharmaceutical compounds including commonly used antibiotics such as ampicillin and gentamicin, and molecules like prednisolone, norepinephrine, etc. Prescription of such drugs to lactating mothers might have adverse health effects on infants. The aim of our study was the elucidation of the structural aspects of the inhibitory mechanism of ampicillin, gentamicin, amoxicillin, prednisolone and norepinephrine on LPO. MATERIAL AND METHODS Three dimensional structure of camel LPO (cLPO) was developed using homology modeling and used for in silico experimental studies. The Schrödinger induced fit docking along with binding affinity estimation experiments were performed. The cLPO and Ligands were prepared using Protein Preparation Wizard and Ligprep modules available in Schrodinger suite. For estimating Binding affinity Prime Molecular Mechanics with Generalized Born and Surface Area (MMGB-SA) module was used. KEY RESULTS The five drug ligands formed three to five hydrogen bonding interactions with cLPO. Amino acids Arg-231, Asp-232, Ser-370, Arg-371 and Glu-374 of cLPO were crucial for these interactions. The binding affinity values for gentamicin were highest and for norepinephrine were the lowest. SIGNIFICANCE This study concludes that the five drug molecules show potential ability to inhibit the LPO activity. Further, a very high sequence similarity of cLPO with human LPO imparts high significance to these conclusions in relation to human health especially in new born infants.
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4.
Diagnosis and Management of Immune-Mediated Myopathies.
Milone, M
Mayo Clinic proceedings. 2017;(5):826-837
Abstract
Immune-mediated myopathies (IMMs) are a heterogeneous group of acquired muscle disorders characterized by muscle weakness, elevated creatine kinase levels, and myopathic electromyographic findings. Most IMMs feature the presence of inflammatory infiltrates in muscle. However, the inflammatory exudate may be absent. Indeed, necrotizing autoimmune myopathy (NAM), also called immune-mediated necrotizing myopathy, is characterized by a necrotizing pathologic process with no or minimal inflammation in muscle. The recent discovery of antibodies associated with specific subtypes of autoimmune myopathies has played a major role in characterizing these diseases. Although diagnostic criteria and classification of IMMs currently are under revision, on the basis of the clinical and muscle histopathologic findings, IMMs can be differentiated as NAM, inclusion body myositis (IBM), dermatomyositis, polymyositis, and nonspecific myositis. Because of recent developments in the field of NAM and IBM and the controversies around polymyositis, this review will focus on NAM, IBM, and dermatomyositis.
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Eosinophilic esophagitis: update on management and controversies.
Chen, JW, Kao, JY
BMJ (Clinical research ed.). 2017;:j4482
Abstract
Eosinophilic esophagitis is a chronic allergen driven immune mediated disease that is increasingly recognized as a leading cause of dysphagia and foregut symptoms in children and adults. Much knowledge has been gained in recent years on the genetic and environmental risk factors for this disease, the associated inflammatory milieu, and the long term complications from esophageal remodeling. In this review we will highlight recent progress made in research into this disease, focusing on adults. We will discuss ongoing efforts to develop a minimally invasive technique that may obviate the need for repeated endoscopic assessment of disease activity. Moreover, we will review studies using novel tools such as mucosal impedance and functional lumen imaging as potential surrogate markers for mucosal integrity and esophageal remodeling. With regard to the treatment of eosinophilic inflammation, we will discuss the controversies surrounding responsiveness to proton pump inhibitors in some patients. Therapeutic trials continue to support the use of topical glucocorticoids and empiric food elimination diets as first line treatments. We will discuss ongoing efforts to optimize the elimination diet protocol to decrease the level and duration of food restrictions. Looking ahead, our growing knowledge on the pathogenesis of eosinophilic esophagitis has enabled further advancement of promising targeted biologic therapies.
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Vitamin D3 treatment of vitamin D-insufficient asthmatic patients does not alter immune cell function.
Reid, B, Girodet, PO, Boomer, JS, Abdel-Gadir, A, Zheng, K, Wechsler, ME, Bacharier, LB, Kunselman, SJ, King, TS, Israel, E, et al
The Journal of allergy and clinical immunology. 2016;(1):286-289.e9
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Advances in clinical management of eosinophilic esophagitis.
Dellon, ES, Liacouras, CA
Gastroenterology. 2014;(6):1238-54
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Abstract
Eosinophilic esophagitis (EoE) is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsy specimens, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia. We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histological features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and proton pump inhibitor-responsive esophageal eosinophilia. It is also important to consider the epidemiology of EoE (with a current incidence of 1 new case per 10,000 per year and prevalence of 0.5 to 1 case per 1000 per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids, such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and nondirected empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenotic complications of EoE. There are a number of unresolved issues in EoE, including phenotypes, optimal treatment end points, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines; EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians.
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Efficacy of honey in comparison to topical corticosteroid for treatment of recurrent minor aphthous ulceration: a randomized, blind, controlled, parallel, double-center clinical trial.
El-Haddad, SA, Asiri, FY, Al-Qahtani, HH, Al-Ghmlas, AS
Quintessence international (Berlin, Germany : 1985). 2014;(8):691-701
Abstract
BACKGROUND Recurrent aphthous ulceration represents a very common mucosal disorder that general dentists may encounter on a daily basis, and for which there is no curative treatment. The best treatment that can be achieved is to avoid local traumatic precipitants, lessen the pain and duration of ulceration by suppressing the local immune response, and prevent secondary infection. OBJECTIVE The objective of this study was to clinically determine the efficacy of honey as a topical treatment of recurrent minor aphthous ulceration in a Saudi cohort. METHOD AND MATERIALS A randomized, blind, controlled, parallel, double-center clinical trial was carried out. Honey was applied by patients four times a day for 5 days. Clinical parameters (ulcer size, pain scale, and degree of erythema and healing) were recorded both at baseline and during the follow-up period. RESULTS There were 94 subjects, with 180 minor recurrent aphthous ulcerations. The ulcers were distributed as 67, 57, and 56 ulcers for honey, topical corticosteroid, and Orabase treatment, respectively. There was a statistically significant difference between the honey group and the other two groups in terms of reduction of ulcer size, days of pain, and degree of erythema. No side effects were reported in any group. CONCLUSION Honey was found to be effective and safe in reducing minor aphthous ulcer pain, size, and erythema in a Saudi cohort.
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An overview of eosinophilic esophagitis.
Park, H
Gut and liver. 2014;(6):590-7
Abstract
Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated esophageal disease affecting both children and adults. The condition is characterized by an eosinophilic infiltration of the esophageal epithelium. Symptoms of esophageal dysfunction include dysphagia, food impaction and symptoms mimicking gastroesophageal reflux disease. Endoscopic examination typically reveals mucosal fragility, ring or corrugated mucosa, longitudinal furrows, whitish plaques or a small caliber esophagus. Histologic findings of >15 eosinophils per high-power field is the diagnostic hallmark of EoE. An elimination diet, topical corticosteroids or endoscopic dilation for fibrostenotic disease serve as effective therapeutic option.
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Systemic sclerosis - focus on dermatological aspects. Part 2: diagnostics, therapy.
Sticherling, M
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG. 2012;(11):783-91
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Abstract
Systemic sclerosis is a chronic inflammatory multiorgan disease which may involve the skin and internal organs to a varying extent. Pathogenetically the vasculature, connective tissue and the immune system are involved in a yet to be defined sequence and impact. Case history and results of physical as well as laboratory examinations will determine individually adapted further organ imaging or invasive procedures. Based on their results therapy is initiated which may include supportive measures such as physiotherapy as well as basic skin care and avoidance of any trauma. Many agents are available for the circulatory problems including Raynaud phenomenon and digital ulcers such as calcium channel blockers, ACE inhibitors and intravenous prostacyclin derivatives, as well as endothelin receptor blockers and phosphodiesterase inhibitors. Immunosuppressive and immunomodulatory agents are of varying efficacy depending on organ involvement. Though various therapeutic measures are available, beneficial effects are limited and associated with various unwanted effects. In any case, the therapy has to be individually adapted to the disease stage and course of the disease.