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Expert Opinion on Biological Therapy Sep 2021This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis were performed to explore the association between rabbit thymoglobulin (rATG) doses and transplant-related efficacy and safety outcomes.
METHODS
We searched PubMed and Scopus databases from inception up to June 2020. The primary efficacy and safety endpoints in kidney transplant recipients were evaluated.
RESULTS
Data of 23 cohort studies (3457 patients) and three RCTs (154 patients) were extracted and analyzed. rATG doses of ≤4.5 m/kg was associated with lower rates of biopsy proven acute rejection, cytomegalovirus infection, BK virus infection, and malignancy with a comparable rate of delayed graft function, patients' mortality, and death-censored graft loss compared to rATG total doses of 4.5-6 mg/kg or more than 6 mg/kg. The rATG doses of 3-4.5 mg/kg was associated with better outcomes in dose-response analysis.
EXPERT OPINION
Cumulative rATG induction doses as much as 3-4.5 mg/kg is as effective as higher doses regarding to allograft and patient outcomes while minimizing potential adverse effects in kidney transplant recipients.
Topics: Antilymphocyte Serum; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Retrospective Studies
PubMed: 34304664
DOI: 10.1080/14712598.2021.1960978 -
Reviews in Medical Virology Mar 2022BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory... (Review)
Review
Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.
BNT162b2 and mRNA-1273 are two types of mRNA-based vaccine platforms that have received emergency use authorization. The emergence of novel severe acute respiratory syndrome (SARS-CoV-2) variants has raised concerns of reduced sensitivity to neutralization by their elicited antibodies. We aimed to systematically review the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern. We searched PubMed, Scopus, and Web of Science in addition to bioRxiv and medRxiv with terms including 'SARS-CoV-2', 'BNT162b2', 'mRNA-1273', and 'neutralizing antibody' up to June 29, 2021. A modified version of the Consolidated Standards of Reporting Trials (CONSORT) checklist was used for assessing included study quality. A total 36 in vitro studies meeting the eligibility criteria were included in this systematic review. B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta) are four SARS-CoV-2 variants that have recently been identified as variants of concern. Included studies implemented different methods regarding pseudovirus or live virus neutralization assays for measuring neutralization titres against utilized viruses. After two dose vaccination by BNT162b2 or mRNA-1273, the B.1.351 variant had the least sensitivity to neutralizing antibodies, while B.1.1.7 variant had the most sensitivity; that is, it was better neutralized relative to the comparator strain. P.1 and B.1.617.2 variants had an intermediate level of impaired naturalization activity of antibodies elicited by prior vaccination. Our review suggests that immune sera derived from vaccinated individuals might show reduced protection of individuals immunized with mRNA vaccines against more recent SARS-CoV-2 variants of concern.
Topics: 2019-nCoV Vaccine mRNA-1273; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2
PubMed: 34286893
DOI: 10.1002/rmv.2277 -
Annals of Palliative Medicine May 2021When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
When it comes to the treatment of aplastic anemia fever, the Guidelines for Aplastic Anemia regards Anti-thymocyte globulin (ATG) combined with eltrombopag as the standard immunosuppressive treatment plan, and ATG is the main mode to treat severe aplastic anemia. A large number of prospective studies and clinical trials have confirmed the clinical application value of eltrombopag in aplastic anemia. Although ATG combined with eltrombopag brings satisfactory treatment results, the safety of long-term use is still unclear. Therefore, more clinical trial studies are needed to verify its safety.
METHODS
Literature in the Chinese and English medical databases was searched using the following search terms: "Antithymocyte globulin", "severed aplastic anemia" and "eltrombopag". Patients in the experimental group were administered ATG combined with eltrombopag and patients in the control group received ATG treatment alone. Rev Man5.3 software was used for meta-analysis.
RESULTS
A total of 16 references were included in this meta-analysis. Heterogeneity tests examining total effective rate demonstrated that Chi2 =4.48, df =15, I2=0%<50%, and P=1.00>0.01. The effective rate of the experimental group was higher than that of the control group, with odds ratio (OR) =1.90 and 95% confidence interval (CI) 1.35 to 2.68 (Z=3.70, P=0.0002). The heterogeneity test results of the survival rate within 2 years were Chi2 =3.09, df =7, I2=0%<50%, and P=0.88>0.01. The survival rate of the experimental group was higher than that of the control group, with OR =2.54, and 95% CI: 1.58 to 4.09 (Z=3.84, P=0.0001). The heterogeneity test results of the mortality rate were Chi2 =3.49, df =6, I2=0%<50%, and P=0.75>0.01. The mortality rate of the experimental group was lower than that of the control group, with OR =0.48 and 95% CI: 0.33 to 0.70 (Z=3.84, P=0.0001). The heterogeneity test results of the occurrence of side effects were Chi2 =0.12, df =3, I2=0%<50%, P=0.99>0.01. The incidence of side effects in the experimental group was lower than that in the control group, with OR =0.74, 95% CI: 0.48 to 1.17 (Z=1.29, P=0.20).
DISCUSSION
This meta-analysis demonstrated that the combination of ATG with eltrombopag in the treatment of SAA is safer and more effective than ATG alone.
Topics: Anemia, Aplastic; Antilymphocyte Serum; Benzoates; Humans; Hydrazines; Prospective Studies; Pyrazoles; Treatment Outcome
PubMed: 34107711
DOI: 10.21037/apm-21-1049 -
Transplantation and Cellular Therapy Aug 2021With the increasing number of non-matched donor hematopoietic stem cell transplantations (HSCTs) has come increasing evidence regarding factors affecting graft outcomes.... (Meta-Analysis)
Meta-Analysis
With the increasing number of non-matched donor hematopoietic stem cell transplantations (HSCTs) has come increasing evidence regarding factors affecting graft outcomes. One factor affecting graft outcomes currently being evaluated is anti-HLA donor-specific antibodies (DSAs). In this, we analyzed the clinical relevance of anti-HLA DSAs in patients who have undergone HSCT at a population level by conducting a systematic review of existing literature. A comprehensive search was conducted through PubMed, Embase, the Cochrane library, and Web of Science from inception to January 1, 2021. A meta-analysis was performed of the association between anti-HLA DSAs and primary graft failure (PGF) with further subgroup analyses. The search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 920 eligible citations were identified, out of which 15 studies were included in the final meta-analyses after application of rigorous selection criteria and independent review. A total of 2436 patients were included in these 15 studies. Patients with anti-HLA DSAs prior to undergoing HSCT had a 7.47-fold increased risk of PGF failure compared with patients without anti-HLA DSAs (odds ratio, 7.47; 95% confidence interval, 4.54 to 12.28, P < .001; I= 28.91%, P = .1315). In subgroup and meta-regression analyses, area, Newcastle Ottawa Scale score, mean fluorescence intensity cutoff, primary disease, HSCT type, graft source, and pretransplantation desensitization did not affect the impact of anti-HLA DSAs on PGF. There also was no significant difference in impact between HLA class I and II on PGF. We conclude that the prior presence of anti-HLA DSAs has a negative impact on graft outcomes in recipients of haploidentical and umbilical cord blood HSCT.
Topics: Antibodies; Antilymphocyte Serum; HLA Antigens; Hematopoietic Stem Cell Transplantation; Humans; Tissue Donors
PubMed: 33989833
DOI: 10.1016/j.jtct.2021.04.030 -
Frontiers in Immunology 2020There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological...
There is an urgent need to strengthen the implementation of the 3Rs principle (Replacement, Reduction and Refinement) in the use of experimental animals in toxinological research and in the assessment of the neutralizing efficacy of snake antivenoms. This is a challenging task owing to the inherent complexity of snake venoms. The state of the art on this topic is hereby reviewed, with emphasis on the studies in which a correlation has been observed between toxicity tests and surrogate assays, particularly in the study of lethal activity of venoms and its neutralization. Correlations have been described with some venoms-antivenoms when using: (a) enzyme immunoassays, (b) hemagglutination, (c) enzyme assays (proteinase, phospholipase A), (d) coagulant effect on plasma, (e) cell culture assays for cytotoxicity, (f) functional assays for assessing neurotoxicity , (g) use of hens' eggs, and (h) antivenomics. Additionally, the routine introduction of analgesia in these assays and the design of more 'humane' protocols for the lethality test are being pursued. It is expected that the next years will witness a growing awareness of the relevance of the 3Rs principles in antivenom testing, and that new alternatives and more 'humane' experimental designs will emerge in this field.
Topics: Animals; Antivenins; Humans; In Vitro Techniques; Neutralization Tests; Snake Venoms
PubMed: 33505403
DOI: 10.3389/fimmu.2020.617429 -
Annals of Hematology Feb 2021Graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in allogeneic hematopoietic... (Comparative Study)
Comparative Study Meta-Analysis
Graft-versus-host disease (GVHD) prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantations (allo-HCT). The differential impacts of PTCy and ATG on transplantation outcomes are not well characterized. Here we report a meta-analysis of PTCy versus ATG in allo-HCT. Ten studies were eligible, and a total of 1871 patients were included. The incidence of II-IV aGVHD, III-IV aGVHD, and NRM were significantly lower in PTCy arm (HR = 0.63, 95% CI 0.45-0.89; HR = 0.35, 95% CI 0.16-0.77; HR = 0.59, 95% CI 0.48-0.73). PTCy was associated with a better OS and PFS (HR = 0.62, 95% CI = 0.53-0.73; HR = 0.76, 95% CI 0.62-0.93). The relapse rate and cGVHD incidence were not significantly different between PTCy and ATG (HR = 0.85, 95% CI 0.68-1.07; HR = 0.65, 95% CI 0.38-1.12). Thus, compared with ATG, PTCy has a better aGVHD control and OS benefit, without increasing relapse risk, which needs further validation in prospective randomized trials.
Topics: Allografts; Antilymphocyte Serum; Cyclophosphamide; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Recurrence; Risk Factors
PubMed: 33420575
DOI: 10.1007/s00277-021-04399-x -
PLoS Neglected Tropical Diseases Dec 2020Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication...
Snakebite is a neglected tropical disease with significant morbidity and mortality. Thrombotic microangiopathy (TMA) is an important but poorly understood complication of snakebite associated with acute kidney injury (AKI). Numerous treatments have been attempted based on limited evidence. We conducted a systematic review of TMA following snakebite using a pre-determined case definition of blood film red cell schistocytes or histologically diagnosed TMA. The search strategy included major electronic databases and grey literature. We present a descriptive synthesis for the outcomes of AKI, dialysis free survival (DFS), other end-organ damage, overall survival, and interventions with antivenom and therapeutic plasmapheresis (TPE). This study was prospectively registered with PROSPERO (CRD42019121436). Seventy-two studies reporting 351 cases were included, predominantly small observational studies. Heterogeneity for study selection, design, reporting and outcomes were observed. The commonest envenoming species were hump-nosed vipers (Hypnale spp.), Russell's viper (Daboia russelii) and Australian brown snakes (Pseudechis spp.). The prevalence of TMA was at least 5.4% in proven and probable Hypnale bites, and 10-15% of Australian elapid envenomings, AKI occurred in 94% (293/312) of TMA cases, excluding case reports. The majority of cases with AKI required dialysis. Included prospective and retrospective cohort studies reporting interventions and renal outcomes showed no evidence for benefit from antivenom or TPE with respect to DFS in dialysis dependant AKI. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment for quality of accumulated evidence for interventions was low. The major complication of TMA following snakebite is AKI. AKI improves in most cases. We found no evidence to support benefit from antivenom in snakebite associated TMA, but antivenom remains the standard of care for snake envenoming. There was no evidence for benefit of TPE in snakebite associated TMA, so TPE cannot be recommended. The quality of accumulated evidence was low, highlighting a need for high quality larger studies.
Topics: Acute Kidney Injury; Animals; Antivenins; Australia; Female; Humans; Male; Plasmapheresis; Prevalence; Prospective Studies; Retrospective Studies; Daboia; Snake Bites; Thrombotic Microangiopathies; Viper Venoms
PubMed: 33290400
DOI: 10.1371/journal.pntd.0008936 -
Transactions of the Royal Society of... Nov 2020Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom....
Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom. This systematic review analyses the evidence from randomised controlled trials (RCTs) on the efficacy of adjunct treatment administered with antivenom. PubMed, EMBASE, Scopus, Cochrane library and CINAHL were searched for RCTs enrolling patients with snakebite envenoming where a treatment other than antivenom has been assessed for its efficacy within the last 25 y. Fifteen studies met the inclusion criteria. The interventions assessed were categorised as adjunct therapies (heparin or fresh frozen plasma) to reverse haemotoxicity (three studies), antibiotics to prevent local infections (three studies), steroids to reduce local swelling (one study), premedication (adrenaline, steroids and antihistamines, either alone or in combination) to reduce hypersensitivity reactions to antivenom (five studies) and other interventions (three studies). Apart from a beneficial effect of low-dose adrenaline (1:1000, 0.25 ml administered subcutaneously) in preventing antivenom-induced hypersensitivities (OR: 0.54, 95% CI 0.32 to 0.93, two RCTs, 354 participants, moderate certainty evidence) in Sri Lanka, evidence for any other adjunct therapy is either non-existent or needs confirmation by larger better designed trials.
Topics: Anti-Bacterial Agents; Antivenins; Humans; Plasma; Randomized Controlled Trials as Topic; Snake Bites; Sri Lanka
PubMed: 32780827
DOI: 10.1093/trstmh/traa062 -
Journal of the European Academy of... Oct 2020In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles... (Review)
Review
In 2009, snakebites were included in the list of the World Health Organization (WHO) neglected diseases. Dermatological literature lacks current and up-to-date articles about snakebites and their management, despite the fact that dermatologists, especially from rural hospitals, can be called into the emergency room to consult the management of suspected snakebites. In this systematic review, we highlighted the main clinical and laboratory aspects of snakebites from Vipera spp. in Europe, by reviewing 3574 studies initially retrieved from PubMed, Embase and Cochrane CENTRAL databases. Of these, 78 were finally included in the systematic review. We found that the most involved taxon was V. berus in 63.3% and the most involved anatomic site of the bite was the upper limbs 53.1% with fang marks reported in 90.5%. The mean age of the patients was 32.9 years, and bites were slightly more common among males (58.2%). A wound washing was performed in 86.9% of cases before the hospitalization. The most frequently reported grade of envenomation was G2 (42.2%). In addition to local dermatological symptoms (extended erythema, oedema, cutaneous necrosis, hives, purpura, petechiae, acute compartment syndrome), numerous systemic symptoms have also been reported, including fatigue (14.4%), pain (75.3%), fever (49.2%), direct anaphylactoid reaction (5.3%), anxiety (60.8%), cranial nerve neurotoxicity (14.8%), dysesthesia/paraesthesia (7.9%), vomiting (33.7%), abdominal pain (23.3%), diarrhoea (15.4%), dyspnoea (6.3%), proteinuria (10.6%) and haematuria (9.3%). Secondary infections were present in 3.5% and disseminated intravascular coagulation in 3.1% of cases, and fasciotomy was performed in 4.2% cases, while an amputation in 6.9%. Only 0.9% of patients died. Antivenom was administered in 3053 cases. In conclusion, there is a pressing need for robust multi-centre randomized control trials, standardized protocol for snakebite management and antivenom administration across Europe and a National snakebite register for each European country.
Topics: Adult; Antivenins; Emergency Service, Hospital; Europe; Humans; Male; Neglected Diseases; Snake Bites
PubMed: 32530549
DOI: 10.1111/jdv.16722 -
MedRxiv : the Preprint Server For... Apr 2020The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks...
A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease.
The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.
PubMed: 32511434
DOI: 10.1101/2020.04.14.20065771