-
Frontiers in Immunology 2020Thymoglobulin (THG) and antithymocyte globulin-Fresenius (ATG-F) have not been compared directly as induction therapies in kidney transplantation. We performed a... (Meta-Analysis)
Meta-Analysis
Thymoglobulin (THG) and antithymocyte globulin-Fresenius (ATG-F) have not been compared directly as induction therapies in kidney transplantation. We performed a Bayesian network meta-analysis to compare THG with ATG-F by pooling direct and indirect evidence. Surface under the cumulative ranking curve (SUCRA) values were used to compare the superiority of one method over the other. A total of 27 randomized controlled trials (RCT) were eligible for the network meta-analysis. Efficacy endpoints, as well as safety indicators, were statistically comparable. For efficacy endpoints, THG seemed inferior to ATG-F in preventing delayed graft function [odds ratio (OR): 1.27; SUCRA: 78% vs. 58%], patient deaths (OR: 2.78; SUCRA: 83% vs. 34%), and graft loss (OR: 1.40; SUCRA: 83% vs. 59%), but superior to ATG-F in biopsy-proven acute rejection (BPAR; OR: 0.59; SUCRA: 78% vs. 39%) and steroid-resistant BPAR prevention (OR: 0.61; SUCRA: 76% vs. 49%) within the first year. For safety endpoints, THG was associated with higher risk of infection (OR: 1.49, SUCRA: 79% vs. 54%), cytomegalovirus infection (OR: 1.04; SUCRA: 40% vs. 37%), diabetes (OR: 1.10; SUCRA: 90% vs. 30%), and malignancy (OR: 8.40; SUCRA: 89% vs. 6%) compared to ATG-F. A subgroup analysis of patients at high risk for immunologic complications revealed similar results, but THG performed better for graft loss (OR: 0.82; SUCRA: 68% vs. 54%). ATG-F seemed to be more effective than THG in improving the short-term kidney transplantation outcomes. Prospective head-to-head comparison of THG and ATG-F with larger sample sizes and longer follow-up is still required.
Topics: Antilymphocyte Serum; Bayes Theorem; Delayed Graft Function; Graft Rejection; Immunosuppressive Agents; Kidney Transplantation; Network Meta-Analysis; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome
PubMed: 32318057
DOI: 10.3389/fimmu.2020.00457 -
Clinical Transplantation Jul 2020The role of antithymocyte globulin (ATG) in patients with hematologic diseases undergoing umbilical cord blood transplantation (UCBT) remains controversial. This... (Meta-Analysis)
Meta-Analysis
The role of antithymocyte globulin (ATG) in patients with hematologic diseases undergoing umbilical cord blood transplantation (UCBT) remains controversial. This systematic review and meta-analysis was conducted to comprehensively evaluate this issue. PubMed, Embase, and the Cochrane Library were systematically searched. Clinical studies reporting the impact of ATG- vs non-ATG-containing conditioning regimens on transplantation outcomes were identified. Twenty-five studies were included. ATG significantly prevented grade II-IV and grade III-IV acute graft-vs-host disease (GVHD) (11 studies, 5020 patients, HR: 0.49, 95% CI: 0.42-0.56, P < .001; 5 studies, 5490 patients, HR: 0.60, 95% CI: 0.46-0.80, P < .001) but not chronic GVHD (8 studies, 5952 patients, HR: 0.78, 95% CI: 0.51-1.20, P = .266). However, use of ATG was associated with increased transplantation-related mortality and inferior overall survival (9 studies, 4244 patients, HR: 1.79, 95% CI: 1.38-2.33, P < .001; 8 studies, 5438 patients, HR: 1.96, 95% CI: 1.56-2.46, P < .001). Our study did not recommend routine use of ATG in UCBT. Individualizing the ATG timing and dose based on patient characteristics to retain the prophylactic effects of ATG on GVHD without compromising the survival of UCBT recipients may be reasonable.
Topics: Antilymphocyte Serum; Cord Blood Stem Cell Transplantation; Graft vs Host Disease; Hematologic Diseases; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Transplantation Conditioning
PubMed: 32277839
DOI: 10.1111/ctr.13876 -
International Immunopharmacology Jun 2020The novel coronavirus (2019-nCoV) is an emerging pathogen that was first described in late December 2019 and causes a severe respiratory infection in humans. Since the...
The novel coronavirus (2019-nCoV) is an emerging pathogen that was first described in late December 2019 and causes a severe respiratory infection in humans. Since the outbreak of COVID-19, international attention has raised to develop treatment and control options such as types of immunotherapies. The immunotherapy is an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. These methods include several types of vaccines, monoclonal antibody candidates, and etc. This systematic review article was designed to evaluate the existing evidence and experience related to immunotherapy for 2019-nCoV. Web of Science (ISI), PubMed, and Scopus databases were used to search for suitable keywords such as 2019-nCoV, novel coronavirus, Immunotherapy, interleukin, vaccine and the related words for relevant publications up to 24.3.2020. The present systematic review was performed based on PRISMA protocol. Data extraction and quality valuation of articles were performed by two reviewers. 51 articles were the results of the search and based on the inclusions and exclusions criteria, 7 articles were included in the final review. As a conclusion of these studies demonstratedthat although no serious research has been done on this subject at the time of writing this article, similar studies on the related viruses showed notable results. So immunotherapy for this virus can also be a suitable option.
Topics: Antibodies, Monoclonal; Antibodies, Viral; Antigens, Viral; Betacoronavirus; COVID-19; COVID-19 Vaccines; Coronavirus Infections; Cytokine Release Syndrome; Cytokines; Humans; Immune Sera; Immunization, Passive; Immunotherapy; Interleukins; Middle East Respiratory Syndrome Coronavirus; Pandemics; Pneumonia, Viral; Receptors, Virus; Severe acute respiratory syndrome-related coronavirus; SARS-CoV-2; Severe Acute Respiratory Syndrome; Spike Glycoprotein, Coronavirus; Viral Vaccines
PubMed: 32272396
DOI: 10.1016/j.intimp.2020.106455 -
International Urology and Nephrology Apr 2020The aim of this meta-analysis is to explore the effect of IL-2RA vs rATG on the rate of acute rejection, post-transplant infections, and graft as well as patient's... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The aim of this meta-analysis is to explore the effect of IL-2RA vs rATG on the rate of acute rejection, post-transplant infections, and graft as well as patient's survival in standard- and high-risk renal transplant patients receiving tacrolimus-based maintenance immunotherapy.
METHODS
Random effects model was the method used for identifying risk difference. Confidence interval including the value 1 was used as evidence for statistically significant risk difference. Heterogeneity was assessed using Der Simonian analysis. Heterogeneity was evident at the level of P value < 0.1 RESULTS: The random effects model showed no significant differences in both acute rejection rates between IL-2RA and rATG induction therapies with relative risk of 1.24 graft survival with relative risk 0.90. Patient survival also did not demonstrate any significant difference with a relative risk of 1.19. Random effects for CMV infection showed a lesser tendency for CMV infection in IL-2RA group compared to ATG group the with a relative risk of 0.73.In subgroup analysis, the random effects model for acute rejection rates in high-risk transplants showed a higher risk of acute rejection in the IL-2RA group compared to rATG (relative risk equals 1.55) In standard-risk transplants, there were no significant differences between both groups with relative risk equals 1.02 CONCLUSIONS: This meta-analysis revealed no significant difference in patient and graft survival when using IL-2RA vs rATG with the tacrolimus-based maintenance immunosuppression era. However, subgroup analysis showed less incidence of rejection in high-risk renal transplant recipient's population using rATG compared to IL-2RA.
Topics: Antilymphocyte Serum; Basiliximab; Cytomegalovirus Infections; Daclizumab; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Induction Chemotherapy; Kidney Transplantation; Maintenance Chemotherapy; Models, Statistical; Receptors, Interleukin-2; Survival Rate; Tacrolimus
PubMed: 32170593
DOI: 10.1007/s11255-020-02418-w -
PLoS Neglected Tropical Diseases Jun 2019Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality...
Reviewing evidence of the clinical effectiveness of commercially available antivenoms in sub-Saharan Africa identifies the need for a multi-centre, multi-antivenom clinical trial.
BACKGROUND
Snakebite envenoming kills more than more than 20,000 people in Sub-Saharan Africa every year. Poorly regulated markets have been inundated with low-price, low-quality antivenoms. This review aimed to systematically collect and analyse the clinical data on all antivenom products now available in markets of sub-Saharan Africa.
METHODOLOGY/PRINCIPAL FINDINGS
Our market analysis identified 12 polyspecific and 4 monospecific antivenom products in African markets. Our search strategy was first based on a systematic search of publication databases, followed by manual searches and discussions with experts. All types of data, including programmatic data, were eligible. All types of publications were eligible, including grey literature. Cohorts of less than 10 patients were excluded. 26 publications met the inclusion criteria. Many publications had to be excluded because clinical outcomes were not clearly linked to a specific product. Our narrative summaries present product-specific clinical data in terms of safety and effectiveness against the different species and envenoming syndromes. Three products (EchiTabPlus, EchiTabG, SAIMR-Echis-monovalent) were found to have been tested in robust clinical studies and found effective against envenoming caused by the West African carpet viper (Echis ocellatus). Four products (Inoserp-Panafricain, Fav-Afrique, SAIMR-Polyvalent, Antivipmyn-Africa) were found to have been evaluated only in observational single-arm studies, with varying results. For nine other products, there are either no data in the public domain, or only negative data suggesting a lack of effectiveness.
CONCLUSIONS/SIGNIFICANCE
Clinical data vary among the different antivenom products currently in African markets. Some products are available commercially although they have been found to lack effectiveness. The World Health Organization should strengthen its capacity to assess antivenom products, support antivenom manufacturers, and assist African countries and international aid organizations in selecting appropriate quality antivenoms.
Topics: Africa South of the Sahara; Antivenins; Clinical Trials as Topic; Humans; Multicenter Studies as Topic; Snake Bites; Treatment Outcome
PubMed: 31233536
DOI: 10.1371/journal.pntd.0007551 -
Expert Review of Clinical Immunology Aug 2019: Innate immune response and bone remodeling are key factors contributing to the pathogenesis of psoriatic arthritis (PsA). Moreover, the evidence of autoantibodies in...
: Innate immune response and bone remodeling are key factors contributing to the pathogenesis of psoriatic arthritis (PsA). Moreover, the evidence of autoantibodies in patients' sera suggests an autoimmune side in PsA. Besides the immune pathways, studies strongly support the role of genetic risk alleles in affecting the clinical heterogeneity of PsA as well as the response to therapy. A good clinical response to treatment, indeed, represents a challenge in PsA patients and the identification of patient-targeted therapies is still a critical issue. : We performed a systematic review aiming at describing new evidence on PsA pathogenesis and treatments. Reported items for systematic reviews (PRISMA checklist) were analyzed. Studies included from the PubMed database addressed the following items: innate immunity, autoimmunity, bone remodeling, and therapeutic targets in PsA; time frame of research 1970-2019. Specifically, we reviewed data on IL-17 inhibitors, abatacept, JAK inhibitors, ABT 122, and A (3) adenosine receptors agonist, CF101. : In PsA an intriguing pathogenetic network has been documented. Several biological and synthetic drugs are promising in terms of efficacy and safety profile.
Topics: Abatacept; Adenosine; Alleles; Arthritis, Psoriatic; Genetic Predisposition to Disease; HLA Antigens; Humans; Immunoglobulins; Immunosuppressive Agents; Treatment Outcome
PubMed: 31177868
DOI: 10.1080/1744666X.2019.1627876 -
Haematologica Jan 2020Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different... (Meta-Analysis)
Meta-Analysis
Immunosuppressive therapy (IST) is one therapy option for treatment of patients with lower-risk myelodysplastic syndromes (MDS). However, the use of several different immunosuppressive regimens, the lack of high-quality studies, and the absence of validated predictive biomarkers pose important challenges. We conducted a systematic review and meta-analysis according to the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and searched MEDLINE PubMed, Ovid EMBASE, COCHRANE registry of clinical trials (CENTRAL), and the Web of Science without language restriction from inception through September 2018, as well as relevant conference proceedings and abstracts, for prospective cohort studies or clinical trials investigating IST in MDS. Fixed and Random-effects models were used to pool response rates. We identified nine prospective cohort studies and 13 clinical trials with a total of 570 patients. Overall response rate was 42.5% [95% confidence interval (CI): 36.1-49.2%] including a complete remission rate of 12.5% (95%CI: 9.3-16.6%) and red blood cell transfusion independence rate of 33.4% (95% CI: 25.1-42.9%). The most commonly used forms of IST were anti-thymocyte globulin alone or in combination with cyclosporin A with a trend towards higher response rates with combination therapy. Progression rate to acute myeloid leukemia was 8.6% per patient year (95%CI: 3.3-13.9%). Overall survival and adverse events were only inconsistently reported. We were unable to validate any biomarkers predictive of a therapeutic response to IST. IST for treatment of lower-risk MDS patients can be successful to alleviate transfusion burden and associated sequelae.
Topics: Antilymphocyte Serum; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Myelodysplastic Syndromes; Prospective Studies
PubMed: 31004015
DOI: 10.3324/haematol.2019.219345 -
Anaerobe Feb 2019Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and...
Bezlotoxumab use as adjunctive therapy with the third fecal microbiota transplant in refractory recurrent Clostridium difficile colitis; a case report and concise literature review.
Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlights the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.
Topics: Antibodies, Monoclonal; Antibodies, Neutralizing; Antitoxins; Broadly Neutralizing Antibodies; Clostridioides difficile; Clostridium Infections; Combined Modality Therapy; Fecal Microbiota Transplantation; Female; Humans; Middle Aged; Treatment Outcome
PubMed: 30521856
DOI: 10.1016/j.anaerobe.2018.11.010 -
Bone Marrow Transplantation Jul 2019Graft-versus-host disease (GVHD) remains a limiting factor for successful allogeneic hematopoietic cell transplantation (allo-HCT). Conflicting data exist on the benefit... (Meta-Analysis)
Meta-Analysis
Graft-versus-host disease (GVHD) remains a limiting factor for successful allogeneic hematopoietic cell transplantation (allo-HCT). Conflicting data exist on the benefit of ATG on post-transplant survival. We performed a systematic review of randomized controlled trials (RCTs) to assess benefits and harms of thymoglobulin and Fresenius (re-branded as Grafalon) ATG formulations in patients undergoing allo-HCT for a variety of hematologic malignancies and bone marrow failure syndromes. A comprehensive search of MEDLINE, EMBASE, and Cochrane Library was performed. Data on methodological quality, benefits, and harms were extracted for each trial and pooled under a random-effects model. Eight RCTs (1134 patients) met the inclusion criteria. Methodological quality ranged from moderate to very low. Pooled results showed no difference in overall survival (OS) with the use of ATG (hazard ratio (HR) = 0.97; 95% confidence interval (CI) = 0.74-1.28; P = 0.83). ATG reduced grade II/III acute GVHD (risk ratio (RR) = 0.61; 95% CI = 0.48-0.77; P < 0.0001), grade III/IV acute GVHD (RR = 0.52; 95% CI = 0.34-0.81; P = 0.004), and chronic GVHD (RR = 0.52; 95% CI = 0.40-0.69; P < 0.00001) without an increase in non-relapse mortality (NRM) (RR = 0.91; 95% CI = 0.74-1.13; P = 0.40). Future studies with better methodological quality are needed to provide conclusive answers related to optimal dosing and timing of ATG for prevention of GVHD.
Topics: Acute Disease; Allografts; Antilymphocyte Serum; Disease-Free Survival; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; MEDLINE; Male; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 30446739
DOI: 10.1038/s41409-018-0393-0 -
Toxicon : Official Journal of the... Sep 2018Bothrops snakebite treatment is antivenom therapy, which is ineffective in neutralizing the severe local effects caused by these envenomations. There are evidence that...
Bothrops snakebite treatment is antivenom therapy, which is ineffective in neutralizing the severe local effects caused by these envenomations. There are evidence that photobiomodulation therapy (PBMT) has emerged as a promising tool to counteract the venom-induced local effects. The purpose was to write a narrative review of the literature about PBMT as a treatment for Bothrops snakebites. We reviewed articles indexed in PubMed, SCOPUS and Scientif Direct database with filter application. Included studies had to investigate local effects induced by Bothrops snake venom in any animal model using any type of photobiomodulation irradiation and at least one quantitative measure of local effects of Bothrops envenomation. Sixteen studies were selected from 54 original articles targeted PBMT (low-level laser or light emitting diode) as a complementary tool for local effects treatment induced by snakebites, and all its assessments. Articles were critically assessed by two independent raters with a structured tool for rating the research quality. PBMT demonstrate to be a promising tool for local treatment effects caused by snakebite by reducing local edema, hyperalgesia, leukocyte influx and myonecrosis and accelerating tissue regeneration related to myotoxicity. However, the mechanism is not well understood and additional studies are needed.
Topics: Animals; Antivenins; Bothrops; Crotalid Venoms; Disease Models, Animal; Low-Level Light Therapy; Muscle, Skeletal; Snake Bites
PubMed: 30025889
DOI: 10.1016/j.toxicon.2018.07.006