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Mycoses Mar 2017Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional... (Meta-Analysis)
Meta-Analysis Review
Invasive fungal infections, an important cause of mortality, are primarily treated using amphotericin B, which is available in different formulations, both conventional and lipid-based (liposomal, lipid complex, colloidal dispersion and Intralipid infusion). The aim of our study was to determine the efficacy and safety of conventional amphotericin B vs its lipid-based formulations. A systematic review followed by pairwise meta-analysis was performed, including randomised controlled trials (RCTs) that evaluated the use of lipid-based amphotericin B in patients with any degree of immunosuppression and susceptibility to invasive fungal infection. An electronic search was conducted using PubMed, Scopus, Web of Science and Scielo databases. Extracted outcomes were related to efficacy (cure) and safety (incidence of adverse events). Results were evaluated and meta-analyses were performed. Twenty-three RCTs were identified (n=2677 participants) for meta-analysis. No significant differences between conventional amphotericin B and any of the five formulations evaluated were observed, with regard to the efficacy analysis. With respect to the adverse events of nephrotoxicity, fever, chills and vomiting, all lipid formulations presented better profiles than the conventional formulation. The present systematic review and meta-analysis showed that conventional amphotericin B presents the same efficacy profile as lipid-based formulations, although the latter were associated with a safer profile.
Topics: Amphotericin B; Antifungal Agents; Clinical Trials as Topic; Colloids; Drug Compounding; Emulsions; Fever; Humans; Invasive Fungal Infections; Lipids; Phospholipids; Soybean Oil
PubMed: 27878878
DOI: 10.1111/myc.12585 -
Mycoses Apr 2021Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause...
Dermatophyte infections usually present as various types of superficial cutaneous mycoses; on very rare occasions, dermatophytes enter deep into the dermis and cause invasive infections. In this study, we aimed to perform a systematic review of all reported invasive dermatophytosis cases over the past 20 years. We performed systematic searches in PubMed/Medline, EMBASE and Web of Science and identified 123 papers reporting 160 individual cases of invasive dermatophytosis between 2000 and 2020. Our study included 103 (64.4%) males, and the mean age at diagnosis was 43.0 years (range: 3-87 years). The most common predisposing factor was superficial dermatophytosis (56.9%), followed by solid organ transplantation (26.9%), the use of topical immunosuppressants (15.6%), gene mutations (14.4%), diabetes (14.4%) and trauma (6.9%). Trichophyton (T.) rubrum was the most prevalent pathogen (53.1%) responsible for invasive dermatophytosis, followed by T. mentagrophytes (7.5%), Microsporum canis (6.9%), T. tonsurans (5.6%), T. interdigitale (5.0%) and T. violaceum (3.8%). Patients with CARD9 or STAT3 mutations were prone to have mixed infection of two or more dermatophytes, present with eosinophilia and high IgE, and develop disseminated infections. Overall mortality was 7.9%, and the mortality in patients with and without gene mutations was 17.4% and 5.5%, respectively. Most of the normal host patients responded well to oral antifungal agents, while gene-deficient patients usually required lifelong treatment to stabilise their infection status. Our review indicated the importance of preventive treatment of superficial tinea in patients with immunosuppression and gene deficiencies to avoid the development of invasive dermatophytosis.
Topics: Antifungal Agents; Dermatomycoses; Humans; Invasive Fungal Infections; Organ Transplantation; Risk Factors; Skin
PubMed: 33217082
DOI: 10.1111/myc.13212 -
The Journal of Dermatological Treatment Feb 2022For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For severe cases of lichen planopilaris (LPP), unresponsive to first line therapy, systemic or potent agents may be required for disease control. There have been several reports of the off-label use of mycophenolate mofetil (MMF) in patients with LPP or have developed adverse effects to initial agents.
METHODS
A systematic review and meta-analysis was performed according to recommended Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies with ≥5 cases reporting the outcomes of MMF in LPP were pooled and a meta-analysis of proportion was performed. Case reports were excluded from analysis.
RESULTS
A total of six studies were identified and included for meta-analysis, comprising 94 LPP patients. The pooled proportion of any good response (partial or complete) was 69.2% (95% confidence interval (CI): 47.8-77). The pooled proportion of complete response was 20% (95% CI: 10.1-36.3). The pooled proportion of partial responses was 49.2% (95% CI: 30.5-63.7). Side effects occurred in 16.9% (95% CI: 17.6-33.2). of cases, which included elevated LFTs, edema, hyperlipidemia, anemia, herpes zoster infection, photosensitivity, and urinary tract infection.
CONCLUSION
The current evidence for MMF remains limited. However, it appears to be a potential treatment option for patients with severe or recalcitrant LPP who have failed hydroxychloroquine and other immunosuppressants.
Topics: Humans; Hydroxychloroquine; Immunosuppressive Agents; Lichen Planus; Mycophenolic Acid; Remission Induction
PubMed: 32281437
DOI: 10.1080/09546634.2020.1755416 -
Transplant Immunology Dec 2022Existing guidelines recommend a triple immunosuppressive regimen with calcineurin inhibitors, antimetabolites, and corticosteroids for postoperative immunosuppression in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Existing guidelines recommend a triple immunosuppressive regimen with calcineurin inhibitors, antimetabolites, and corticosteroids for postoperative immunosuppression in renal transplant patients. However, few studies have compared cyclosporine and tacrolimus for long-term outcomes. In this study, the meta-analysis was used to compare long-term outcomes in renal transplant patients to evaluate the use of cyclosporine vs. tacrolimus. The pros and cons of suppression programs have been analyzed.
METHODS
Cyclosporine, tacrolimus, and kidney transplantation, were used as search terms to retrieve relevant publications in PubMed, Embase, and The Cochrane library. Two independent researchers screened and evaluated the relevant results of each search using the RevMan5.4 program to make relevant charts for the meta-analysis. Odds ratios (OR) and 95% confidence intervals (CI) were used to report dichotomous variables, while mean differences (MD) and 95% confidence intervals (CI) were used to report continuous variables. The study took tacrolimus- and cyclosporine-based maintenance immunosuppression as experimental and control groups, respectively. The graft and patient survival outcomes were followed for 5 or more years.
RESULTS
Overall, thirteen studies were included in the meta-analysis, including nine randomized controlled trials and four non-randomized controlled trials. Compared with the cyclosporine group, the incidence of rejection, drug conversion, and dyslipidemia were significantly lower in the tacrolimus group. Furthermore, there was higher glomerular filtration rates and graft survival rates in the tacrolimus group than in the cyclosporine group. In contrast, there were no significant differences between the two groups in terms of patient survival, incidence of infection, hypertension and new tumors. However, the use of tacrolimus was associated with a high risk of a new onset of diabetes.
CONCLUSION
The meta-analysis showed that, compared with cyclosporine, tacrolimus increases the risk of a new-onset diabetes. However, tacrolimus had higher graft survival rate and better creatinine clearance than cyclosporine.
Topics: Humans; Calcineurin Inhibitors; Tacrolimus; Kidney Transplantation; Graft Rejection; Cyclosporine; Prognosis; Diabetes Mellitus
PubMed: 36372141
DOI: 10.1016/j.trim.2022.101741 -
Autoimmunity Reviews Jun 2016Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and... (Review)
Review
Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders.
Topics: Animals; Autoimmune Diseases; Cannabinoids; Humans; Inflammation; Mice; Multiple Sclerosis; Neuralgia
PubMed: 26876387
DOI: 10.1016/j.autrev.2016.02.008 -
Mycopathologia Aug 2023Endemic systemic mycoses such as blastomycosis, coccidioidomycosis, histoplasmosis, talaromycosis, paracoccidioidomycosis are emerging as an important cause of morbidity... (Review)
Review
Endemic systemic mycoses such as blastomycosis, coccidioidomycosis, histoplasmosis, talaromycosis, paracoccidioidomycosis are emerging as an important cause of morbidity and mortality worldwide. We conducted a systematic review on endemic systemic mycoses reported in Italy from 1914 to nowadays. We found out: 105 cases of histoplasmosis, 15 of paracoccidioidomycosis, 10 of coccidioidomycosis, 10 of blastomycosis and 3 of talaromycosis. Most cases have been reported in returning travelers and expatriates or immigrants. Thirtytwo patients did not have a story of traveling to an endemic area. Fortysix subjects had HIV/AIDS. Immunosuppression was the major risk factor for getting these infections and for severe outcomes. We provided an overview on microbiological characteristics and clinical management principles of systemic endemic mycoses with a focus on the cases reported in Italy.
Topics: Humans; Histoplasmosis; Coccidioidomycosis; Blastomycosis; Paracoccidioidomycosis; Mycoses
PubMed: 37294504
DOI: 10.1007/s11046-023-00735-z -
Frontiers in Immunology 2023To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR). (Meta-Analysis)
Meta-Analysis
AIM
To systematically compare the efficacy and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) in children with allergic rhinitis (AR).
METHODS
PubMed, Embase, Cochrane Library, and Web of Science were searched from inception to March 2, 2023. Outcomes included symptom scores (SSs), medication scores (MSs), symptom and medication scores (SMSs), new sensitizations, development of asthma, improvement, and treatment-related adverse events (TRAEs). The quality of the included studies was assessed by the modified Jadad scale and Newcastle-Ottawa scale (NOS). Meta-regression was carried out to explore the source of heterogeneity. Subgroup analysis was further conducted in terms of study design [randomized controlled trials (RCTs), cohort studies], allergen [house dust mites (HDMs), grass pollen], treatment duration (≥ 24, 12-23 or < 12 months), allergen immunotherapy (AIT) modality (drops or tablets), and AIT protocol [continuous, pre-seasonal, co-seasonal, or after the grass pollen season (GPS)]. Sensitivity analysis was conducted for all outcomes. A Bayesian framework and a Monte Carlo Markov Chain (MCMC) model were developed for indirect comparison.
RESULTS
Totally 50 studies with 10813 AR children were included, with 4122 treated with SLIT, 1852 treated with SCIT, and 4839 treated with non-SLIT or non-SCIT therapy. For direct comparison, the SLIT group had a similar SS to the SCIT group [pooled standardized mean difference (SMD): 0.41, 95% confidence interval (CI): -0.46, 1.28, = 0.353]. Comparable MSs were observed in the SLIT and SCIT groups (pooled SMD: 0.82, 95%CI: -0.88, 2.53, = 0.344). For indirect comparison, no significant differences were found in SSs (pooled SMD: 1.20, 95% credibility interval (CrI): -1.70, 4.10), MSs (pooled SMD: 0.57, 95%CrI: -1.20, 2.30), SMSs (pooled SMD: 1.80, 95%CrI: -0.005, 3.60), new sensitizations [pooled relative risk (RR): 0.34, 95%CrI: 0.03, 3.58], and development of asthma (pooled RR: 0.68, 95%CrI: 0.01, 26.33) between the SLIT and SCIT groups; the SLIT group illustrated a significantly lower incidence of TRAEs than the SCIT group (pooled RR: 0.17, 95%CrI: 0.11, 0.26).
CONCLUSION
Considering both efficacy and safety, SLIT might be a more favorable AIT than SCIT in the treatment of pediatric AR, which may serve as a decision-making reference for clinicians.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42023460693).
Topics: Child; Humans; Allergens; Asthma; Desensitization, Immunologic; Pollen; Rhinitis, Allergic; Immunotherapy; Sublingual Immunotherapy
PubMed: 38162647
DOI: 10.3389/fimmu.2023.1274241 -
Reviews in Medical Virology Jan 2023Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic... (Meta-Analysis)
Meta-Analysis Review
Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03-1.32; HR: 1.05, 95% CI: 0.97-1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87-0.94; HR: 0.74, 95% CI: 0.71-0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.
Topics: Humans; Torque teno virus; Retrospective Studies; Prospective Studies; Organ Transplantation; Immunosuppression Therapy; Viral Load; DNA, Viral
PubMed: 36056751
DOI: 10.1002/rmv.2393 -
Transplantation Reviews (Orlando, Fla.) Dec 2021Successful maintenance of a heart transplant (HTx) graft requires adherence to a triple-drug regimen of immunosuppression. However, achieving adequate adherence can be... (Review)
Review
BACKGROUND
Successful maintenance of a heart transplant (HTx) graft requires adherence to a triple-drug regimen of immunosuppression. However, achieving adequate adherence can be difficult secondary to complicated dosing regimens, side effects, and mental/emotional barriers. A detailed review of current patterns of adherence to immunosuppression in adult HTx recipients is lacking.
OBJECTIVE
This systematic review aims to detail the current landscape of adherence to immunosuppression in adult heart transplant patients, including the measurement of adherence, correlates to adherence, health outcomes associated with nonadherence, as well as strategies to improve adherence in HTx patients.
METHODS
We conducted searches in PubMed MEDLINE, Embase, CENTRAL register of Controlled Trials (Wiley), and Scopus, from inception to March 2020. Studies were eligible if they outlined an aspect of adherence (as noted above in the objective) to immunosuppression in adult HTx patients. The HTx cohort had to contain at least 10 patients and measurement of adherence had to be done with an objective or otherwise validated measure of adherence (e.g. drug levels, automated pill bottles or adherence questionnaires). Two authors independently screened the articles for inclusion, then subsequently reviewed the full texts of the included articles. Data was extracted into standardized forms and bias evaluations were done using the Newcastle-Ottawa or modified Newcastle-Ottawa tools, depending on the study type. The authors followed all guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
The titles/abstracts of 880 articles were reviewed. Ultimately, 23 articles were included in the final review. The median number of participants was 101, with a range of 19 to 1397. Studies provided information on baseline levels of adherence (17 studies), correlates to adherence (14 studies), health outcomes related to nonadherence (3 studies) and interventions to improve adherence (3 studies). Baseline adherence estimates varied greatly depending on the adherence measure. Multiple significant correlates to nonadherence exist and appear to affect patients with certain sociodemographic backgrounds, those with psychological/psychiatric comorbidities and those with poor support structures. Nonadherence is associated with transplant coronary artery disease and acute late rejection; it may also be associated with long-term mortality. Finally, a simplified dosing regimen with once-a-day tacrolimus as well as use of a mobile phone-based intervention were associated with improved adherence. Bias scores were most deficient due to self-reported outcomes in 18 studies, and lack of controls/adjustments for confounders, in 7 studies.
CONCLUSIONS
Adherence to immunosuppression in transplant patients varies, but is associated with observable and modifiable factors which are worth addressing. Further high-quality studies regarding strategies to improve adherence are needed in the literature.
Topics: Adult; Heart Transplantation; Humans; Immunosuppression Therapy; Self Report; Tacrolimus
PubMed: 34592641
DOI: 10.1016/j.trre.2021.100651 -
Transplantation Reviews (Orlando, Fla.) Jul 2021Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer... (Review)
Review
INTRODUCTION
Cancer is the second most common cause of mortality and morbidity in Kidney Transplant Recipients (KTRs). Immunosuppression can influence the efficacy of cancer treatment and modification of the immunosuppressive regimen may restore anti-neoplastic immune responses improving oncologic prognosis. However, patients and transplant physicians are usually reluctant to modify immunosuppression, fearing rejection and potential graft loss. Due to the lack of extensive and recognised data supporting how to manage the immunosuppressive therapy in KTRs, in the context of immunotherapy, chemotherapy, radiotherapy and loco-regional treatments, a Consensus Conference was organised under the auspices of the European Society of Organ Transplantation and the Italian Society of Organ Transplantation. The conference involved a multidisciplinary group of transplant experts in the field across Europe.
METHODS
The overall process included a) the formulation of 12 specific questions based on the PICO methodology, b) systematic literature review and summary for experts for each question, c) a two-day conference celebration and the collection of experts' agreements. The conference was articulated in three sessions: "Immunosuppressive therapy and immunotherapy", "Systemic therapy", "Integrated Therapy", while the final experts' agreement was collected with a televoting procedure and defined according to the majority criterion.
RESULTS
Twenty-six European experts attended the conference and expressed their vote. A total of 14 statements were finally elaborated and voted. Strong agreement was found for ten statements, moderate agreement for two, moderate disagreement for one and uncertainty for the last one.
CONCLUSIONS
The consensus statements provide guidance to transplant physicians caring for kidney transplant recipients with cancer and indicate key aspects that need to be addressed by future clinical research.
Topics: Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Neoplasms; Organ Transplantation
PubMed: 34237586
DOI: 10.1016/j.trre.2021.100636