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BioDrugs : Clinical Immunotherapeutics,... Jan 2021Acute graft-versus-host disease (GVHD), the major complication after allogeneic hematopoietic cell transplant (HCT), develops in approximately 50% of patients. The... (Review)
Review
Acute graft-versus-host disease (GVHD), the major complication after allogeneic hematopoietic cell transplant (HCT), develops in approximately 50% of patients. The primary treatment is high-dose systemic steroids, but treatment failure is common, and steroid-refractory (SR) GVHD is the leading cause of non-relapse mortality after allogeneic HCT. Ruxolitinib became the first treatment for SR GVHD to obtain US Food and Drug Administration approval, and other new treatments are actively being studied. We searched the literature using the PubMed database and clinical trials using ClinicalTrials.gov to identify the most promising new treatments for GVHD. In this review, we categorize potential new treatments for GVHD by their mechanism of action (e.g., antibodies that deplete T cells or prevent their trafficking to target tissues, proteasome inhibitors, tyrosine kinase inhibitors, and other agents) and summarize the results from clinical trials.
Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Steroids; United States
PubMed: 33201499
DOI: 10.1007/s40259-020-00454-7 -
Nefrologia : Publicacion Oficial de La... 2016Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular... (Review)
Review
Steroid minimization after kidney transplantation has become more widely practiced as transplant clinicians seek the potential benefits such as reduced cardiovascular risk factors, improved growth in pediatric patients, and improved compliance with the immunosuppression regimen. Steroid avoidance (i.e. no steroids after the first week) is generally favored compared to later withdrawal. Induction therapy is routine in this setting, frequently rabbit antithymocyte globulin (rATG, Thymoglobulin®) or off-license use of alemtuzumab. Direct comparisons of steroid minimization regimens versus standard steroid regimens are rare. However, the available data show that the risk of acute rejection is low when rATG or alemtuzumab induction is given to support steroid-avoidance regimens after kidney transplantation. Steroid avoidance may be inadvisable in patients at high immunological risk or at risk of recurrent glomerular disease. Steroid withdrawal after day 8 may be possible without additional risk of rejection in patients given rATG induction, but while encouraging, the data are too sparse for firm conclusions. In summary, steroid avoidance may be beneficial for patients after renal transplantation, with the potential to avoid or reduce steroid-related comorbidities. Whilst depleting induction therapy could be the treatment of choice, results of prospective randomized, controlled studies are eagerly awaited.
Topics: Alemtuzumab; Animals; Antilymphocyte Serum; Cardiovascular Diseases; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Lymphocyte Depletion; Risk Factors; Steroids
PubMed: 27184648
DOI: 10.1016/j.nefro.2016.03.019 -
Alimentary Pharmacology & Therapeutics Feb 2016Acute severe ulcerative colitis (ASUC) is a life-threatening condition for which optimal management strategies remain ill-defined. (Review)
Review
BACKGROUND
Acute severe ulcerative colitis (ASUC) is a life-threatening condition for which optimal management strategies remain ill-defined.
AIM
To review the evidence regarding the natural history, diagnosis, monitoring and treatment of ASUC to inform an evidence-based approach to management.
METHODS
Relevant articles addressing the management of ASUC were identified from a search of MEDLINE, the Cochrane Library and conference proceedings.
RESULTS
Of ASUC, 31-35% is steroid-refractory. Infliximab and ciclosporin salvage therapies have improved patient outcomes in randomised controlled trials. Short-term response rates (within 3 months) have ranged from 40% - 54% for ciclosporin and 46-83% for infliximab. Long-term clinical response rates (≥1 year) have ranged from 42%-50% for ciclosporin and 50-65% for infliximab. Short-term and long-term colectomy rates have been respectively: 26-47% and 36-58% for ciclosporin, and 0-50% and 35-50% for infliximab. Mortality rates for ciclosporin and infliximab-treated patients have been: 0-5% and 0-2%, respectively. At present, management challenges include the selection, timing and assessment of response to salvage therapy, utilisation of therapeutic drug monitoring and long-term maintenance of remission.
CONCLUSIONS
Optimal management of acute severe ulcerative colitis should be guided by risk stratification using predictive indices of corticosteroid response. Timely commencement and assessment of response to salvage therapy is critical to reducing morbidity and mortality. Emerging pharmacokinetic models and therapeutic drug monitoring may assist clinical decision-making and facilitate a shift towards individualised acute severe ulcerative colitis therapies.
Topics: Acute Disease; Antibodies, Monoclonal; Colitis, Ulcerative; Cyclosporine; Humans; Immunosuppressive Agents; Infliximab; Male; Middle Aged; Randomized Controlled Trials as Topic; Salvage Therapy; Steroids; Treatment Outcome
PubMed: 26725569
DOI: 10.1111/apt.13491 -
Otolaryngologia Polska = the Polish... Jan 2022<b>Introduction:</b> Studies on the pathophysiology of chronic rhinosinusitis have shown an effect of IgE antibodies on the course of the disease, as well as... (Randomized Controlled Trial)
Randomized Controlled Trial
<b>Introduction:</b> Studies on the pathophysiology of chronic rhinosinusitis have shown an effect of IgE antibodies on the course of the disease, as well as the effectiveness of treatment. Steroid therapy remains the most prevailing method of CRS treatment. </br></br> <b>Aim: </b>The aim of our study was to determine the clinical response to systemic and local steroid therapy in patients with CRSsNP depending on the total IgE antibody serum concentration. </br></br> <b>Material and methods:</b> A total of 92 patients with CRSsNP took part in the study, where they were divided randomly into 2 groups. In group I, the patients received fluticasone propionate 800 mcg/day intranasally for 12 weeks. Patients in group II were treated with prednisone at a dose of 0.5 mg/kg/day, given orally, for 7 consecutive days and continued by another week with decreasing dosage. Both groups were evaluated prior to and following treatment using the TSS score of CRS clinical symptoms, the endoscopic Lund-Kennedy scale and the Lund-Mackay CT staging of chronic rhinosinusitis. Statistical analy-sis of the effectiveness of treatment was carried out in subgroups according to the total IgE serum concentrations obtained before treatment. </br></br> <b>Results:</b> Both groups of patients achieved statistically significant improvement in the TSS evaluation, as well as in endosco-pic and CT imaging findings. In patients with a total IgE serum concentration over 100 IU/ml systemic steroid therapy sho-wed significantly greater effect on the relief of CRS symptoms in the TSS score than intranasal steroid therapy. Analogous differences in the effectiveness of both methods were not found in patients with a normal total IgE serum concentration (<100 IU/ml). </br></br> <b>Conclusions:</b> A short course of systemic steroid therapy is more effective than local treatment in relieving of CRS symptoms in patients with CRSsNP with elevated serum concentration of IgE antibodies. Atopy may be considered a specific predictor of response to steroid therapy in the treatment of chronic rhinosinusitis.
Topics: Chronic Disease; Humans; Immunoglobulin E; Immunotherapy; Nasal Polyps; Sinusitis; Steroids
PubMed: 35796392
DOI: 10.5604/01.3001.0015.7082 -
The Cochrane Database of Systematic... Nov 2014Tuberculosis causes approximately 8.6 million disease episodes and 1.3 million deaths worldwide per year. Although curable with standardized treatment, outcomes for some... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculosis causes approximately 8.6 million disease episodes and 1.3 million deaths worldwide per year. Although curable with standardized treatment, outcomes for some forms of tuberculosis are improved with adjunctive corticosteroid therapy. Whether corticosteroid therapy would be beneficial in treating people with pulmonary tuberculosis is unclear.
OBJECTIVES
To evaluate whether adjunctive corticosteroid therapy reduces mortality, accelerates clinical recovery or accelerates microbiological recovery in people with pulmonary tuberculosis.
SEARCH METHODS
We identified studies indexed from 1966 up to May 2014 by searching: Cochrane Infectious Diseases Group's trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS using comparative search terms. We handsearched reference lists of all identified studies and previous reviews and contacted relevant researchers, organizations and companies to identify grey literature.
SELECTION CRITERIA
Randomized controlled trials and quasi-randomized control trials of recognized antimicrobial combination regimens and corticosteroid therapy of any dose or duration compared with either no corticosteroid therapy or placebo in people with pulmonary tuberculosis were included.
DATA COLLECTION AND ANALYSIS
At least two investigators independently assessed trial quality and collected data using pre-specified data extraction forms. Findings were reported as narrative or within tables. If appropriate, Mantel-Haenszel meta-analyses models were used to calculate risk ratios.
MAIN RESULTS
We identified 18 trials, including 3816 participants, that met inclusion criteria. When compared to taking placebo or no steroid, corticosteroid use was not shown to to reduce all-cause mortality, or result in higher sputum conversion at 2 months or at 6 months (mortality: RR 0.77, 95%CI 0.51 to 1.15, 3815 participants, 18 studies, low quality evidence; sputum conversion at 2 months RR 1.03, 95%CI 0.97 to 1.09, 2750 participants, 12 studies; at 6 months; RR1.01, 95%CI 1.01, 95%CI 0.98 to 1.04, 2150 participants, 9 studies, both low quality evidence). However, corticosteroid use was found to increase weight gain (data not pooled, eight trials, 1203 participants, low quality evidence), decrease length of hospital stay (data not pooled, three trials, participants 379, very low quality of evidence) and increase clinical improvement within one month (RR 1.16, 95% CI 1.09 to 1.24; five trials, 497 participants, low quality evidence).
AUTHORS' CONCLUSIONS
It is unlikely that adjunctive corticosteroid treatment provides major benefits for people with pulmonary tuberculosis. Short term clinical benefits found did not appear to be maintained in the long term. However, evidence available to date is of low quality. In order to evaluate whether adjunctive corticosteroids reduce mortality, or accelerate clinical or microbiological recovery in people with pulmonary tuberculosis further large randomized control trials sufficiently powered to detect changes in such outcomes are needed.
Topics: Adrenal Cortex Hormones; Cause of Death; Chemotherapy, Adjuvant; Fever; Humans; Length of Stay; Randomized Controlled Trials as Topic; Steroids; Tuberculosis, Pulmonary; Weight Gain
PubMed: 25387839
DOI: 10.1002/14651858.CD011370 -
Frontiers in Immunology 2023Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results,...
INTRODUCTION
Extracorporal Photophoresis (ECP) is in clinical use for steroid-refractory and steroid-dependent acute GVHD (SR-aGVHD). Based on recent Phase-III study results, ruxolitinib has become the new standard of care for SR-aGVHD. Our aim was to collect comparative data between ruxolitinib and ECP in SR-aGVHD in order to improve the evidence base for clinical decision making.
METHODS
We asked EBMT centers if they were willing to participate in this study by completing a data form (Med-C) with detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient.
RESULTS
31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or ruxolitinib for SR-aGVHD grades II-IV from these centers. We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP and ruxolitinib, respectively. We performed multivariate analyses adjusted on grading and type of SR-aGVHD (steroid dependent vs. refractory). At day+90 after initiation of treatment for SR-aGVHD we found no statistically significant differences in overall response. The odds ratio in the ruxolitinib group to achieve overall response vs. the ECP group was 1.13 (95% CI = [0.41; 3.22], p = 0.81). In line, we detected no statistically significant differences in overall survival, progression-free survival, non-relapse mortality and relapse incidence.
DISCUSSION
The clinical significance is limited by the retrospective study design and the current data can't replace prospective studies on ECP in SR-aGVHD. However, the present results contribute to the accumulating evidence on ECP as an effective treatment option in SR-aGVHD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Prospective Studies; Steroids; Graft vs Host Disease
PubMed: 38149251
DOI: 10.3389/fimmu.2023.1283034 -
Annals of the Royal College of Surgeons... Sep 2011
Topics: Anesthesia, Local; Anti-Inflammatory Agents, Non-Steroidal; Arthroscopy; Humans; Injections, Intra-Articular; Physical Therapy Modalities; Platelet-Rich Plasma; Splints; Steroids; Tennis Elbow; Treatment Outcome
PubMed: 21929911
DOI: 10.1308/rcsann.2011.93.6.432 -
Molecular and Cellular Endocrinology Jun 2015Steroidogenesis begins with cholesterol transfer into mitochondria through the transduceosome, a complex composed of cytosolic proteins that include steroidogenesis... (Review)
Review
Steroidogenesis begins with cholesterol transfer into mitochondria through the transduceosome, a complex composed of cytosolic proteins that include steroidogenesis acute regulatory protein (STAR), 14-3-3 adaptor proteins, and the outer mitochondrial membrane proteins Translocator Protein (TSPO) and Voltage-Dependent Anion Channel (VDAC). TSPO is a drug- and cholesterol-binding protein found at particularly high levels in steroid synthesizing cells. Its aberrant expression has been linked to cancer, neurodegeneration, neuropsychiatric disorders and primary hypogonadism. Brain steroids serve as local regulators of neural development and excitability. Reduced levels of these steroids have been linked to depression, anxiety and neurodegeneration. Reduced serum testosterone is common among subfertile young men and aging men, and is associated with depression, metabolic syndrome and reduced sexual function. Although testosterone-replacement therapy is available, there are undesired side-effects. TSPO drug ligands have been proposed as therapeutic agents to regulate steroid levels in the brain and testis.
Topics: Animals; Biological Transport; Cholesterol; Humans; Models, Biological; Molecular Targeted Therapy; Receptors, GABA; Steroids
PubMed: 25818881
DOI: 10.1016/j.mce.2015.03.014 -
Memorias Do Instituto Oswaldo Cruz 1991Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent... (Review)
Review
Glycosides are the bioactive components of many famous Chinese medicines. Here reported are some bioactive glycosides we discovered from Chinese medicines in recent years. (1) Phenolic glycosides from Chinese medicines: Gastrodia elata, Aconitum austroyunanense and Helicia erratica, three bioactive phenolic glycosides were discovered and two of them have been developed into new drugs. (2) Terpenoidal glycosides: a) Monoterpenoid: the sweroside from Swertia moleensis has been developed into an anti-hepatitis drug; b) Diterpenoid: Phlomis betonicoides contains sweet glycosides; c) Triterpenoid: many biologically active triterpenoid glycosides were isolated from Panax plants and Siraitia grosvenorii. (3) Steroidal glycosides: a) C21-steroid: Cynanchum otophyllum and C. atratrum contain anti-epilepsy and anti-tumor glycosides; b) C27-steroid Hemostatic saponins were found in Paris polyphylla.
Topics: Animals; Anticonvulsants; Antineoplastic Agents, Phytogenic; Drugs, Chinese Herbal; Glycosides; Hepatitis; Humans; Saponins; Steroids; Sweetening Agents; Terpenes
PubMed: 1842007
DOI: 10.1590/s0074-02761991000600051 -
Current Pain and Headache Reports Oct 2022Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an... (Review)
Review
PURPOSE OF REVIEW
Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education.
RECENT FINDINGS
A small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case-control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease. Currently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management.
Topics: Humans; Pain Management; Low Back Pain; Regenerative Medicine; Biological Products; Anti-Inflammatory Agents, Non-Steroidal; Steroids
PubMed: 36074255
DOI: 10.1007/s11916-022-01078-y