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Jornal de Pediatria 2023Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF),... (Review)
Review
OBJECTIVES
Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies.
SOURCES
The articles were selected from PubMed, Web of Science, Scielo and Lilacs.
SUMMARY OF THE FINDINGS
Nine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis.
CONCLUSION
Further studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.
Topics: Humans; Cystic Fibrosis; Leukocyte L1 Antigen Complex; Biomarkers; Inflammation; Intestines; Feces; Randomized Controlled Trials as Topic
PubMed: 35523321
DOI: 10.1016/j.jped.2022.01.006 -
Scientific Reports Mar 2016ABO blood group system, a well-known genetic risk factor, has clinically been demonstrated to be linked with thrombotic vascular diseases. However, the relationship... (Meta-Analysis)
Meta-Analysis Review
ABO blood group system, a well-known genetic risk factor, has clinically been demonstrated to be linked with thrombotic vascular diseases. However, the relationship between ABO blood group and coronary artery disease (CAD) is still controversial. We here performed an updated meta-analysis of the related studies and tried to elucidate the potential role of ABO blood group as a risk factor for CAD. All detectable case-control and cohort studies comparing the risk of CAD in different ABO blood groups were collected for this analysis through searching PubMed, Embase, and the Cochrane Library. Ultimately, 17 studies covering 225,810 participants were included. The combined results showed that the risk of CAD was significantly higher in blood group A (OR = 1.14, 95% CI = 1.03 to 1.26, p = 0.01) and lower in blood group O (OR = 0.85, 95% CI = 0.78 to 0.94, p = 0.0008). Even when studies merely about myocardial infarction (MI) were removed, the risk of CAD was still significantly higher in blood group A (OR = 1.05, 95% CI = 1.00 to 1.10, p = 0.03) and lower in blood group O (OR = 0.89, 95% CI = 0.85 to 0.93, p < 0.00001). This updated systematic review and meta-analysis indicated that both blood group A and non-O were the risk factors of CAD.
Topics: ABO Blood-Group System; Adult; Aged; Coronary Artery Disease; Disease Susceptibility; Female; Humans; Male; Middle Aged; Risk Factors; Young Adult
PubMed: 26988722
DOI: 10.1038/srep23250 -
BMC Infectious Diseases Mar 2023Hepatitis B infection seriously threatens global public health, especially in developing nations. Despite several investigations on HBV incidence, the national pooled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis B infection seriously threatens global public health, especially in developing nations. Despite several investigations on HBV incidence, the national pooled prevalence remains unknown, particularly in populations at-risk at whom interventions should be primarily aimed.
METHODS
A comprehensive literature search of the following databases: Medline [PubMed], Scopus, Google Scholar, and Web of Science was conducted following the PRISMA guidelines. I-squared and Cochran's Q were used to measure the heterogeneity between the studies. Publications that matched the following were included: Primary studies published in Egypt from 2000 to 2022 reported HBV prevalence based on HBsAg. We excluded any studies that were not performed on Egyptians or that were performed on patients suspected of acute viral hepatitis or studies focusing on occult hepatitis or vaccination evaluation studies, or national surveys.
RESULTS
The systematic review included 68 eligible studies reporting a total of 82 incidences of HBV infection based on hepatitis B surface antigen with a total sample size of 862,037. The pooled national prevalence among studies was estimated to be 3.67% [95% CI; 3: 4.39]. Children under 20 with a history of HBV vaccination during infancy had the lowest prevalence of 0.69%. The pooled prevalence of HBV infection among pregnant women, blood donors, and healthcare workers was 2.95%, 1.8%, and 1.1%, respectively. While patients with hemolytic anemia and hemodialysis patients, patients with malignancies, HCC patients, and chronic liver disease patients had the highest prevalences at 6.34%, 25.5%, 18.6%, and 34%, respectively. Studies reporting HBV prevalence in urban settings compared to rural settings revealed a similar HBV prevalence of 2.43% and 2.15%, respectively. Studies comparing HBV prevalence in males and females revealed a higher prevalence among males (3.75%) than females (2.2%).
CONCLUSION
In Egypt, hepatitis B infection is a significant public health issue. The blocking of mother-to-infant hepatitis B transmission, the scaling up of the scope of the existing vaccination program, and implementing new strategies, including screen-and-treat, may reduce the prevalence of the disease.
Topics: Male; Child; Humans; Female; Pregnancy; Hepatitis B Surface Antigens; Hepatitis B virus; Egypt; Carcinoma, Hepatocellular; Seroepidemiologic Studies; Liver Neoplasms; Hepatitis B; Antigens, Surface; Prevalence
PubMed: 36899311
DOI: 10.1186/s12879-023-08110-5 -
Breast (Edinburgh, Scotland) Oct 2023Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have an extremely important impact on the treatment of hormone-sensitive breast cancer (BC) and have radically changed the first-line treatment for metastatic disease with increased rates of treatment response, overall survival (OS), and progression-free survival (PFS). We performed a pooled analysis of randomized trials to validate or refute the hypothesis that there is a significant survival benefit of adding anti-CDK4/6 inhibitors to standard endocrine therapy (ET) in older patients with advanced BC.
METHODS
We selected only English-language phase II/III randomized controlled trials that compared ET alone with ET with anti-CDK4/6 inhibitors in the treatment of advanced BC, with subgroups reporting the outcomes of elderly patients (usually at least 65 years). The primary endpoint was OS.
RESULTS
The review process led to the inclusion of 12 articles and two meeting abstracts, including a total of 10 trials. The addition of CDK4/6 inhibitors to ET (letrozole or fulvestrant) significantly reduced mortality risk by 20% in younger patients (fixed-effect model; HR 0.80; 95% CI 0.72-0.9; p < 0.01) and 21% in older BC patients (HR 0.79; 95% CI 0.69-0.91; p < 0.01). No OS data were available for patients ≥70 years.
CONCLUSION
This large, pooled analysis is the first to demonstrate that CDK4/6 inhibitors confer OS and PFS benefits in elderly patients (those aged ≥65 years) with advanced ER + BC and to indicate that it should be discussed with and offered to all patients after geriatric assessment and according to the toxicity profile.
Topics: Aged; Humans; Female; Breast Neoplasms; Cyclin-Dependent Kinase 4; Receptor, ErbB-2; Cyclin-Dependent Kinase 6; Fulvestrant; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37198053
DOI: 10.1016/j.breast.2023.05.002 -
Immunotherapy Sep 2017Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a... (Meta-Analysis)
Meta-Analysis Review
Chimeric antigen receptor modified T cells targeting CD19 and CD20 have shown activity in Phase I, II trials of patients with hematological malignancies. We conducted a systematic review and meta-analysis of all published clinical trials studying the role of efficacy as well as safety of CD-19 and CD-20 chimeric antigen receptor-T therapy for B-cell hematologic malignancies. A total of 16 studies with 195 patients were identified. The pooled analysis showed an overall response rate of 61% (118/195) with complete response of 42% (81/195) and partial response of 19% (37/195). Major adverse events were cytokine release syndrome 33%, neurotoxicity 33% and B-cell aplasia 54%. Collectively, the results indicate encouraging response in relapsed/refractory B lymphoma and leukemia, especially in acute lymphoblastic leukemia (ALL) patients.
Topics: Animals; Antigens, CD19; Antigens, CD20; B-Lymphocytes; Cell Count; Genetic Therapy; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Receptors, Antigen; Recombinant Fusion Proteins; Remission Induction; T-Lymphocytes
PubMed: 28971751
DOI: 10.2217/imt-2017-0062 -
Clinical Gastroenterology and... Jul 2020Endoscopic healing, an important target of treatment for Crohn's disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether... (Review)
Review
BACKGROUND & AIMS
Endoscopic healing, an important target of treatment for Crohn's disease (CD), requires ileocolonoscopy, which is costly and burdensome. We investigated whether published noninvasive models (based on symptoms and biomarkers) to evaluate CD activity have sufficient accuracy to replace ileocolonoscopy.
METHODS
We performed a systematic review of published noninvasive diagnostic models to evaluate CD activity that used endoscopic features of activity (endoscopic activity) or healing as the reference standard. We externally validated these models for the outcome endoscopic activity (CD endoscopic index of severity scores, ≥3) using data from the a randomized controlled trial investigating tailored treatment with infliximab for active luminal Crohn's disease (TAILORIX) study (346 ileocolonoscopies in 155 patients) and the Utrecht Activity Index (UAI) study (93 ileocolonoscopies in 82 patients). We calculated the area under the receiver operating characteristic curves (AUROCs) for the models using data from these studies, and compared the performance of these models against measurements of fecal calprotectin (FC) and C-reactive protein (CRP).
RESULTS
We screened 5303 articles and identified 27 models (from 21 studies) for our analysis. Seven models could be validated externally; in the TAILORIX data set, these models identified patients with endoscopic activity with AUROC values ranging from 0.61 (95% CI, 0.51-0.70) to 0.81 (95% CI, 0.76-0.86). In this data set, the AUROC value for FC concentration was 0.79 (95% CI, 0.74-0.85) and the AUROC value for CRP level was 0.72 (95% CI, 0.66-0.77). The AUROC values for the validation in the UAI data set were similar. In the TAILORIX and/or UAI data set, 4 of the 7 models, as well as the FC and CRP assays, were able to identify patients with endoscopic activity with positive predictive values of 90% or more. Two of the 7 models (but not the FC or CRP values) identified patients without endoscopic activity with a negative predictive value (NPV) of 90% or more, leading to correct prediction of endoscopic healing in 3.2% to 11.3% of all patients. For example, applying the Herranz-Bachiller model (1 of 7 models) at a NPV of 92.1% and a positive predictive value of 91.9% correctly identified 35.7% of all patients in whom ileocolonoscopy could be avoided for expected endoscopic activity or healing but incorrectly identified 3.2% of all patients. Most ileocolonoscopies (66.5% in TAILORIX and 72.6% in the UAI of all ileocolonoscopies) could be avoided correctly based on concentrations of FC of 100 μg/g or less and 250 μg/g or higher. However, using this range of FC concentrations to identify patients who do not require ileocolonoscopy caused 18.7% of all patients in the TAILORIX cohort and 19.8% of all patients in the UAI cohort to be predicted incorrectly to have endoscopic activity or healing.
CONCLUSIONS
In a systematic review and external validation of noninvasive models to identify patients with endoscopic activity of CD, we found only 2 of 7 models evaluated to have NPVs of 90% or more, however, leading to correctly predicted EH in only a small proportion of patients. Ileocolonoscopy therefore remains the mainstay to evaluate CD mucosal disease activity and healing.
Topics: Biomarkers; C-Reactive Protein; Colonoscopy; Crohn Disease; Feces; Humans; Leukocyte L1 Antigen Complex; Randomized Controlled Trials as Topic; Severity of Illness Index
PubMed: 31881273
DOI: 10.1016/j.cgh.2019.12.014 -
International Journal of Molecular... Sep 2022Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid... (Review)
Review
Several studies, although with conflicting results, have sought to determine the concentration of soluble CTLA4 antigens in peripheral blood plasma and peritoneal fluid in patients with endometriosis-related infertility. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) through a search of the following databases: MEDLINE, EMBASE, Global Health, The Cochrane Library, Health Technology Assessment Database and Web of Science, and Clinical Trials research register. We included observational or prospective human and animal studies with any features related to endometriosis and/or infertility studies involving CTLA4-related pathogenesis published in English. The results of studies in which the size and characteristics of the observed groups were not stated were excluded. From the initial pool of 73 publications identified and screened, we finally included 5 articles to summarize the most recent knowledge about CTLA4-linked autoimmunity in the pathogenesis of endometriosis and related infertility. Evidence from clinical studies shows that CTLA4-based autoimmunity is involved in the maintenance of chronic inflammation in the peritoneal environment, with pre-clinical evidence of anti-CTLA antibodies as a potential novel target therapy for endometriosis. However, CTLA4 gene analyses do not support findings of CTLA4-linked autoimmunity as a primary determinant of the pathogenesis of endometriosis. These findings underlie the role of complex interactions within the family of immune checkpoint molecules involved. Further studies are needed to investigate the clinical relevance of anti-CTLA target therapy, taking into account the potential adverse events and repercussions of novel immunologic therapy modalities. However, with the general scarcity of studies investigating this topic, the clinical importance of CTLA4 autoimmunity still remains unclear.
Topics: Animals; Autoimmunity; CTLA-4 Antigen; Endometriosis; Female; Humans; Immune Checkpoint Proteins; Infertility; Prospective Studies
PubMed: 36142815
DOI: 10.3390/ijms231810902 -
International Journal of Molecular... Nov 2023Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's... (Review)
Review
Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's pathogenesis, focusing on established genetic factors. Studies reveal that is the primary genetic risk factor, but non-HLA genes (, , ), as well as innate immunity genes (, , ), also contribute. Genome-wide studies emphasize the significance of and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD's complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.
Topics: Humans; Behcet Syndrome; Antigen Presentation; Genetic Predisposition to Disease; HLA-B Antigens; Risk Factors; Aminopeptidases; Minor Histocompatibility Antigens
PubMed: 38003572
DOI: 10.3390/ijms242216382 -
Systematic Reviews Dec 2022Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Trastuzumab, as the gold standard for HER2-positive BC treatment, was the first-line HER2 targeted drug. However, some studies reported patients benefited more from lapatinib and lapatinib plus trastuzumab therapy than standard trastuzumab therapy. This study presents an update of a systematic review and meta-analysis involving comparison of lapatinib and lapatinib plus trastuzumab therapy versus trastuzumab therapy.
AIM
We determined whether trastuzumab plus lapatinib or lapatinib therapy is not inferior to trastuzumab therapy in HER2-positive breast cancer patients.
METHODS
Relevant trials were searched in CNKI, Wanfang, VIP, Sinomed, PubMed, Embase, and Cochrane CENTRAL databases from inception until October 25, 2021. Primary outcomes were OS, DFS/EFS, and PFS while secondary outcomes were pCR (ypT0/is ypN0), pCR (ypT0/is ypN0/+), ORR, DCR, rate of BCS, RFS, cardiac toxicities, and other toxicities.
RESULTS
Thirteen randomized controlled trials were included in this study. Trastuzumab combined with lapatinib therapy was found to be superior to standard trastuzumab therapy alone with regard to overall survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0), pathologic complete response (ypT0/is ypN0/+), recurrence-free survival, higher incidences of diarrhea, and rash/skin toxicity. Lapatinib therapy was established to be inferior to trastuzumab therapy in overall survival, progression-free survival, disease-free survival/event-free survival, pathologic complete response (ypT0/is ypN0) and pathologic complete response (ypT0/is ypN0/+), diarrhea, and rash/skin toxicity and had a low incidence of left ventricular ejection fraction decline.
CONCLUSIONS
The efficacy of trastuzumab combined with lapatinib therapy is superior to standard trastuzumab therapy alone; however, it has more non-cardiac grade III/IV toxicities. Moreover, the efficacy of lapatinib therapy is inferior to that of standard trastuzumab therapy alone.
Topics: Humans; Female; Trastuzumab; Lapatinib; Breast Neoplasms; Receptor, ErbB-2; Stroke Volume; Antineoplastic Combined Chemotherapy Protocols; Ventricular Function, Left; Randomized Controlled Trials as Topic
PubMed: 36496473
DOI: 10.1186/s13643-022-02134-9 -
Transfusion Feb 2022
Meta-Analysis Review
Topics: ABO Blood-Group System; Blood Grouping and Crossmatching; COVID-19; Humans; Risk Factors; SARS-CoV-2
PubMed: 34773411
DOI: 10.1111/trf.16748