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Transplant Immunology Dec 2023Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis. ABO-incompatible (ABO-I) kidney transplantation relies on two principles: (i) removal of antibodies from a blood group; and (ii) inhibition of reappearance of blood group antibodies by intensifying the induction and maintenance of immunosuppression. This systematic review aimed to analyze the success and safety of ABO-I live-donor kidney transplantation.
METHODS
Databases, including Google Scholar, PubMed, Embase, Web of Science, and Medline were searched. Search duration was from the database establishment to December 2022. A thorough search was performed for relevant studies investigating the success and safety of ABO-I live-donor kidney transplantation. Two investigators independently extracted literature information and assessed the quality of the included studies. Heterogeneity test was performed using Cochrane's Q and chi-squared tests. All statistical analyses were performed using R software (version 4.2.1).
RESULTS
The search for relevant literature in the five electronic databases yielded 1238 articles. Of the 1238 articles, only 15 were included. Meta-analysis of outcomes from five studies showed a survival rate of 0.93 (95% confidence interval [CI]: 0.88 to 0.97, P < 0.001) after ≥3 years, while outcomes from 12 studies revealed a short-term patient survival rate of 0.94 (95% CI: 0.92 to 0.96, P = 0.75). In contrast, long- and short-term graft survival rates were 0.89 (95% CI: 0.75 to 0.96, P < 0.001) and 0.94 (95% CI: 0.90 to 0.97, P < 0.001), respectively. Incidence rates of infectious, surgical, and medical complications were 0.31 (95% CI: 0.22 to 0.41, P < 0.001), 0.12 (95% CI: 0.05 to 0.25, P < 0.001), and 0.38 (95% CI: 0.17 to 0.66, P < 0.001), respectively.
CONCLUSION
Good long- and short-term patient outcomes and graft survival rates were observed after ABO-I kidney transplantation. Similarly, the safety of performing kidney transplantations from living donors with ABO-I blood groups was established by the results of the current meta-analysis. Therefore, ABO-I live-donor kidney transplantations should be encouraged to reduce the time recipients spend on waiting lists and supplement the existing paired-exchange donor program.
Topics: Humans; Kidney Transplantation; ABO Blood-Group System; Living Donors; Quality of Life; Renal Dialysis; Blood Group Incompatibility; Antibodies; Graft Survival; Graft Rejection
PubMed: 37648033
DOI: 10.1016/j.trim.2023.101921 -
Systematic Review of PD-1/PD-L1 Inhibitors in Oncology: From Personalized Medicine to Public Health.The Oncologist Oct 2021To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as... (Review)
Review
BACKGROUND
To review and summarize all U.S. Food and Drug Administration (FDA) approvals of programmed death (PD)-1 and PD-ligand 1 blocking antibodies (collectively referred to as PD-[L]1 inhibitors) over a 6-year period and corresponding companion/complementary diagnostic assays.
MATERIALS AND METHODS
To determine the indications and pivotal trials eligible for inclusion, approval letters and package inserts available on Drugs@FDA were evaluated for approved PD-[L]1 inhibitors to identify all new indications granted from the first approval of a PD-[L]1 inhibitor on September 4, 2014, through September 3, 2020. The corresponding FDA drug and device reviews from the marketing applications for the approved indications were identified through FDA internal records. Two reviewers independently extracted information for the endpoints, efficacy data, basis for approval, type of regulatory approval, and corresponding in vitro diagnostic device test. The results were organized by organ system and tumor type.
RESULTS
Of 70 Biologic Licensing Application or supplement approvals that resulted in new indications, 32 (46%) were granted based on response rate (ORR) and durability of response, 26 (37%) on overall survival, 9 (13%) on progression-free survival, 2 (3%) on recurrence-free survival, and 1 (1%) on complete response rate. Most ORR-based approvals were granted under the accelerated approval provisions and were supported with prolonged duration of response. Overall, 21% of approvals were granted with a companion diagnostic. Efficacy results according to tumor type are discussed.
CONCLUSION
PD-[L]1 inhibitors are an effective anticancer therapy in a subset of patients. This class of drugs has provided new treatment options for patients with unmet need across a wide variety of cancer types. Yet, the modest response rates in several tumor types signal a lack of understanding of the biology of these diseases. Further preclinical and clinical investigation may be required to identify a more appropriate patient population, particularly as drug development continues and additional treatment alternatives become available.
IMPLICATIONS FOR PRACTICE
The number of PD-[L]1 inhibitors in drug development and the associated companion and complementary diagnostics have led to regulatory challenges and questions regarding generalizability of trial results. The interchangeability of PD-L1 immunohistochemical assays between PD-1/PD-L1 drugs is unclear. Furthermore, robust responses in some patients with low levels of PD-L1 expression have limited the use of PD-L1 as a predictive biomarker across all cancers, particularly in the setting of diseases with few alternative treatment options. This review summarizes the biomarker thresholds and assays approved as complementary and companion diagnostics and provides regulatory perspective on the role of biomarkers in oncology drug development.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Neoplasms; Precision Medicine; Programmed Cell Death 1 Receptor; Public Health
PubMed: 34196068
DOI: 10.1002/onco.13887 -
American Journal of Obstetrics and... Aug 2022This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.
OBJECTIVE
This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus.
DATA SOURCES
Medline, Cochrane, and Scopus databases were searched up to October 28, 2020.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included.
METHODS
Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status.
RESULTS
Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance.
CONCLUSION
A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.
Topics: Antiviral Agents; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Immunoglobulins; Infant; Infectious Disease Transmission, Vertical; Network Meta-Analysis; Pregnancy; Pregnancy Complications, Infectious; Tenofovir; Viral Load
PubMed: 35263648
DOI: 10.1016/j.ajog.2022.02.042 -
Annals of Medicine Dec 2023We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.
MATERIALS AND METHODS
We systematically searched three databases (PubMed, Web of Science and Embase) up to 20 February 2023. Extracting the effect size and 95% confidence intervals for overall survival (OS), progression-free survival (PFS) and the objective response rate (ORR).
RESULTS
A total of 65 articles were included. We identified the following factors that benefit ICI therapy: smoking status (PFS: 0.72 [0.62, 0.84], < .001), chemotherapy (PFS: 0.68 [0.58, 0.79], < .001), expression of programmed cell death ligand 1(PD-L1) (≥1%, ≥5%, or ≥10%) (≥1%: 0.76 [0.71,0.82], < .001; ≥5%: 0.62 [0.52, 0.74], < .001; ≥10%: 0.42 [0.30, 0.59], < .001). We also identified three adverse factors: epidermal growth factor receptor mutations (OS: 1.57 [1.06, 2.32], = .02), with liver metastases (OS: 1.16 [1.02,1.32], = .02) and antibiotics (OS: 3.13 [1.25,7.84], < .001; PFS: 2.54 [1.38, 4.68], = .003).
CONCLUSION
The results of this umbrella meta-analysis first supported pre-existing understandings of the relationship between beneficial and adverse factors with the efficacy of ICI therapy. In addition, the overexpression of PD-L1 may adversely affect patients.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Immune Checkpoint Inhibitors; Antineoplastic Agents, Immunological; Randomized Controlled Trials as Topic
PubMed: 37212453
DOI: 10.1080/07853890.2023.2215543 -
Malaria Journal Apr 2017Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature... (Review)
Review
BACKGROUND
Naturally acquired immunity can reduce parasitaemia and potentially influence anti-malarial treatment outcomes; however, evidence for this in the current literature provides conflicted results. The available evidence was synthesized to determine and quantify the association between host immunity and anti-malarial treatment failure.
METHODS
Four databases were searched to identify studies investigating malaria antibody levels in patients receiving anti-malarial treatment for symptomatic malaria with treatment failure recorded according to the World Health Organization classification. Odds ratios or hazard ratios were extracted or calculated to quantify the association between malarial antibody levels and treatment failure, and findings from different studies were visualized using forest plots.
RESULTS
Eight studies, including patients with falciparum malaria treated with mono- and combination therapy of artemisinin derivatives, sulfadoxine, pyrimethamine and chloroquine, were identified. Reported and calculated effect estimates varied greatly between studies, even those assessing the same antigens and treatments. An association between blood-stage IgG responses and treatment efficacy was observed. The greatest magnitudes of effect were observed for artemisinin [OR/HR (95% CI) range 0.02 (0.00, 0.45)-1.08 (0.57, 2.06)] and chloroquine [0.24 (0.04, 1.37)-0.32 (0.05, 1.96)] treatments, and larger magnitudes of effect were observed for variant surface antigen responses [0.02 (0.00, 0.45)-1.92 (0.94, 3.91)] when compared with merozoite specific responses [0.24 (0.04, 1.37)-2.83 (1.13, 7.09)].
CONCLUSIONS
Naturally acquired malarial immunity is associated with reduced anti-malarial treatment failure in malaria endemic populations. Anti-malarial IgG effects treatment outcome differently for different anti-malarial drugs and antigen targets, and had the greatest impact during treatment with the current first-line treatments, the artemisinins. This has implications for the assessment of the therapeutic efficacy of anti-malarials, particularly in the context of emerging artemisinin resistance.
Topics: Antibodies, Protozoan; Antimalarials; Humans; Immunoglobulin G; Malaria, Falciparum; Plasmodium falciparum; Treatment Failure
PubMed: 28427418
DOI: 10.1186/s12936-017-1815-y -
Anais Da Academia Brasileira de Ciencias May 2016The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive... (Meta-Analysis)
Meta-Analysis Review
The objective of this work was to estimate the accuracy of mesothelin as a biomarker for ovarian cancer. A quantitative systematic review was performed. A comprehensive search of the Medline, LILACS, SCOPUS, Embase, Cochrane Central Register of Controlled Trials, Biomed Central, and ISI Web of Science databases was conducted from January 1990 to June 2015. For inclusion in this systematic review, the papers must have measured mesothelin levels in at least two histological diagnoses; ovarian cancer (borderline or ovarian tumor) vs. benign or normal ovarian tissue. For each study, 2 x 2 contingency tables were constructed. We calculated the sensitivity, specificity and diagnostic odds ratio. The verification bias was performed according to QUADAS-2. Statistical analysis was performed with the software Stata 11, Meta-DiSc(r) and RevMan 5.2. Twelve studies were analyzed, which included 1,561 women. The pooled sensitivity was 0.62 (CI 95% 0.58 - 0.66) and specificity was 0.94 (CI 95% 0.92 - 0.95). The DOR was 38.92 (CI 95% 17.82 - 84.99). Our systematic review shows that mesothelin cannot serve alone as a biomarker for the detection of ovarian cancer.
Topics: Biomarkers, Tumor; Female; GPI-Linked Proteins; Humans; Mesothelin; Ovarian Neoplasms; Ovary; Sensitivity and Specificity
PubMed: 27254448
DOI: 10.1590/0001-3765201620150107 -
BMC Infectious Diseases Nov 2017Chronic Hepatitis B Virus (HBV) infection is characterised by the persistence of hepatitis B surface antigen (HBsAg). Expanding HBV diagnosis and treatment programmes... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic Hepatitis B Virus (HBV) infection is characterised by the persistence of hepatitis B surface antigen (HBsAg). Expanding HBV diagnosis and treatment programmes into low resource settings will require high quality but inexpensive rapid diagnostic tests (RDTs) in addition to laboratory-based enzyme immunoassays (EIAs) to detect HBsAg. The purpose of this review is to assess the clinical accuracy of available diagnostic tests to detect HBsAg to inform recommendations on testing strategies in 2017 WHO hepatitis testing guidelines.
METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines using 9 databases. Two reviewers independently extracted data according to a pre-specified plan and evaluated study quality. Meta-analysis was performed. HBsAg diagnostic accuracy of rapid diagnostic tests (RDTs) was compared to enzyme immunoassay (EIA) and nucleic-acid test (NAT) reference standards. Subanalyses were performed to determine accuracy among brands, HIV-status and specimen type.
RESULTS
Of the 40 studies that met the inclusion criteria, 33 compared RDTs and/or EIAs against EIAs and 7 against NATs as reference standards. Thirty studies assessed diagnostic accuracy of 33 brands of RDTs in 23,716 individuals from 23 countries using EIA as the reference standard. The pooled sensitivity and specificity were 90.0% (95% CI: 89.1, 90.8) and 99.5% (95% CI: 99.4, 99.5) respectively, but accuracy varied widely among brands. Accuracy did not differ significantly whether serum, plasma, venous or capillary whole blood was used. Pooled sensitivity of RDTs in 5 studies of HIV-positive persons was lower at 72.3% (95% CI: 67.9, 76.4) compared to that in HIV-negative persons, but specificity remained high. Five studies evaluated 8 EIAs against a chemiluminescence immunoassay reference standard with a pooled sensitivity and specificity of 88.9% (95% CI: 87.0, 90.6) and 98.4% (95% CI: 97.8, 98.8), respectively. Accuracy of both RDTs and EIAs using a NAT reference were generally lower, especially amongst HIV-positive cohorts.
CONCLUSIONS
HBsAg RDTs have good sensitivity and excellent specificity compared to laboratory immunoassays as a reference standard. Sensitivity of HBsAg RDTs may be lower in HIV infected individuals.
Topics: Databases, Factual; Hepatitis B; Hepatitis B Surface Antigens; Humans; Immunoenzyme Techniques; Quality Control; Reagent Kits, Diagnostic; Sensitivity and Specificity
PubMed: 29143619
DOI: 10.1186/s12879-017-2772-3 -
Cancer Medicine Oct 2023Immune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of immune checkpoint inhibitors in recurrent or metastatic head and neck squamous cell carcinoma: A systematic review and meta-analysis of randomized clinical trials.
BACKGROUND
Immune checkpoint inhibitors (ICIs) showed antitumor activity for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, the results from different studies were controversial.
METHODS
Online databases were searched for randomized clinical trials (RCTs) evaluating ICIs for R/M HNSCC. The characteristics of the studies and the results of overall survival (OS), progression-free survival (PFS), objective response rate (ORR), treatment-related adverse events (TRAEs) were extracted.
RESULTS
A total of 4936 patients from eight studies were included. Anti-PD1/PDL1 monotherapy significantly improved OS in total population (hazard ratio, HR, 0.87, 95% CI, 0.79-0.95, p = 0.003) and PD-L1 high expression patients (HR, 0.71, 95% CI, 0.55-0.90, p = 0.006) with significant lower incidence of any grade TRAEs (odds ratio, OR, 0.16, 95% CI, 0.07-0.37, p < 0.00001) and Grades 3-5 TRAEs (OR, 0.18, 95% CI, 0.10-0.33, p < 0.0001) compared with standard of care (SOC); however, the pooled results of PFS and ORR were not significant different. PD1/PDL1 inhibitors plus CTLA4 inhibitors did not improve OS, PFS, ORR compared with SOC or ICIs monotherapy; however, the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy (OR, 1.80, 95% CI, 1.34-2.41, p = 0.0001).
CONCLUSIONS
Anti-PD1/PDL1 monotherapy could improve OS for R/M HNSCC with significant lower incidence of TRAEs compared with SOC. PD1/PDL1 inhibitors plus CTLA4 inhibitors showed no more benefit compared with both SOC and ICIs monotherapy, but the incidence of Grades 3-5 TRAEs was significant higher compared with ICIs monotherapy.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Immune Checkpoint Inhibitors; CTLA-4 Antigen; Randomized Controlled Trials as Topic; Carcinoma; Head and Neck Neoplasms
PubMed: 37814950
DOI: 10.1002/cam4.6564 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Frontiers in Immunology 2023PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.
AIM
To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.
METHODS
As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.
RESULTS
A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I= 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I= 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I= 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05).
CONCLUSION
ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Triple Negative Breast Neoplasms; B7-H1 Antigen; Control Groups
PubMed: 37377959
DOI: 10.3389/fimmu.2023.1206689