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Journal of Tropical Medicine 2024To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of... (Review)
Review
OBJECTIVE
To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis.
METHODS
PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis.
RESULTS
Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity.
CONCLUSION
Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.
PubMed: 38419946
DOI: 10.1155/2024/1514178 -
Vaccines Jan 2024This systematic review investigated the association between platform type and the clinical efficacy of SARS-CoV-2 vaccines using the meta-regression of randomized... (Review)
Review
Effect of Platform Type on Clinical Efficacy of SARS-CoV-2 Vaccines in Prime Vaccination Settings: A Systematic Review and Meta-Regression of Randomized Controlled Trials.
This systematic review investigated the association between platform type and the clinical efficacy of SARS-CoV-2 vaccines using the meta-regression of randomized controlled trials to compare the rates of the first appearance of symptomatic COVID-19 on the platforms. The trial search was conducted using PubMed, ClinicalTrials.gov, and the EU Clinical Trials Register. The main selection criteria included: non-active control, immunocompetent individuals without previous vaccination, and a low risk of bias. The platform effect was summarized with an incidence rate ratio (IRR) and a 95% confidence interval for every platform category against the reference. IRR was obtained by random-effect meta-regression with adjustment for confounding by effect modifiers. The analysis was conducted in per-protocol (PP) and modified intention-to-treat (mITT) sets. Six vaccine types with 35 trials were included. Vector vaccines were a reference category. In the PP set, rates of symptomatic COVID-19 on mRNA and protein subunit vaccines were significantly lower than on the vector: IRR = 0.30 [0.19; 0.46], = 0.001 and 0.63 [0.46; 0.86], = 0.012, respectively. There was no difference for inactivated and virus-like particle vaccines compared to the vector: IRR = 0.98 [0.71; 1.36], = 0.913 and 0.70 [0.41; 1.20], = 0.197, respectively. The rate of cases on DNA vaccines was significantly higher than that on the vector: IRR = 2.58 [1.17; 5.68], = 0.034. Results for the mITT set were consistent. Platform type is an effect modifier of the clinical efficacy of SARS-CoV-2 vaccines.
PubMed: 38400114
DOI: 10.3390/vaccines12020130 -
Life (Basel, Switzerland) Feb 2024Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined... (Review)
Review
Osteoarthritis is a leading cause of disability in the world. The scientific literature highlights the critical importance of epigenetic regulatory effects, intertwined with biomechanical and biochemical peculiar conditions within each musculoskeletal district. While the contribution of genetic and epigenetic factors to knee OA is well-recognized, their precise role in disease management remains an area of active research. Such a field is particularly heterogeneous, calling for regular analysis and summarizing of the data that constantly emerge in the scientific literature, often sparse and scant of integration. The aim of this study was to systematically identify and synthesize all new evidence that emerged in human and animal model studies published between 2020 and 2023. This was necessary because, to the best of our knowledge, articles published before 2019 (and partly 2020) had already been included in systematic reviews that allowed to identify the ones concerning the knee joint. The review was carried out in accordance with Preferential Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only peer-reviewed articles were considered for inclusion. A total of 40 studies were identified, showing promising results in terms either of biomarker identification, new insight in mechanism of action or potential therapeutic targets for knee OA. DNA methylation, histone modification and ncRNA were all mechanisms involved in epigenetic regulation of the knee. Most recent evidence suggests that epigenetics is a most promising field with the long-term goal of improving understanding and management of knee OA, but a variety of research approaches need greater consolidation.
PubMed: 38398778
DOI: 10.3390/life14020269 -
Cancers Feb 2024Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately... (Review)
Review
Urine-Based Biomarker Test Uromonitor in the Detection and Disease Monitoring of Non-Muscle-Invasive Bladder Cancer-A Systematic Review and Meta-Analysis of Diagnostic Test Performance.
Optimal urine-based diagnostic tests (UBDT) minimize unnecessary follow-up cystoscopies in patients with non-muscle-invasive bladder-cancer (NMIBC), while accurately detecting high-grade bladder-cancer without false-negative results. Such UBDTs have not been comprehensively described upon a broad, validated dataset, resulting in cautious guideline recommendations. Uromonitor, a urine-based DNA-assay detecting hotspot alterations in TERT, FGFR3, and KRAS, shows promising initial results. However, a systematic review merging all available data is lacking. Studies investigating the diagnostic performance of Uromonitor in NMIBC until November 2023 were identified in PubMed, Embase, Web-of-Science, Cochrane, Scopus, and medRxiv databases. Within aggregated analyses, test performance and area under the curve/AUC were calculated. This project fully implemented the PRISMA statement. Four qualifying studies comprised a total of 1190 urinary tests (bladder-cancer prevalence: 14.9%). Based on comprehensive analyses, sensitivity, specificity, positive-predictive value/PPV, negative-predictive value/NPV, and test accuracy of Uromonitor were 80.2%, 96.9%, 82.1%, 96.6%, and 94.5%, respectively, with an AUC of 0.886 (95%-CI: 0.851-0.921). In a meta-analysis of two studies comparing test performance with urinary cytology, Uromonitor significantly outperformed urinary cytology in sensitivity, PPV, and test accuracy, while no significant differences were observed for specificity and NPV. This systematic review supports the use of Uromonitor considering its favorable diagnostic performance. In a cohort of 1000 patients with a bladder-cancer prevalence of ~15%, this UBDT would avert 825 unnecessary cystoscopies (true-negatives) while missing 30 bladder-cancer cases (false-negatives). Due to currently limited aggregated data from only four studies with heterogeneous quality, confirmatory studies are needed.
PubMed: 38398144
DOI: 10.3390/cancers16040753 -
Cancers Feb 2024Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative... (Review)
Review
Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.
PubMed: 38398089
DOI: 10.3390/cancers16040698 -
Biomedicines Feb 2024The () gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted... (Review)
Review
The () gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between methylation and age, indicating that the degree of methylation of the gene increases with advancing age. Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.
PubMed: 38398047
DOI: 10.3390/biomedicines12020445 -
Tropical Medicine and Infectious Disease Feb 2024spp. are among the few enteric parasites with a prevalence that can reach up to approximately 80% in communities of developing countries. This systematic review updates... (Review)
Review
spp. are among the few enteric parasites with a prevalence that can reach up to approximately 80% in communities of developing countries. This systematic review updates and summarizes available literature on the molecular prevalence and subtype distribution of spp. in Latin American people. This work follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The literature revised covers from 1 January 2015 to 6 October 2023 in seven different scientific databases, and the material was selected through inclusion and exclusion criteria. According to data found in the 36 selected articles, the prevalence of spp. in Latin America ranged between 5.8% (Bolivian rural communities) and 94.0% (Colombian general public). Generally, genomic DNA was extracted from approximately 200 mg fecal sediments using commercial kits, such as the QIAamp Stool Mini Kit (QIAGEN, Hilden, Germany) or the Norgen Stool DNA Isolation Kit (Norgen Biotek Corporation, Thorold, ON, Canada). Subtype-specific primers (such as the couple of primers BhRDr-RD5) developed from unique sequences of the SSU rRNA gene were applied to subtyping. Ten specific subtypes (STs) were found as well as various mixed infections, and the most circulating STs were in the order ST3, ST1, ST2, and ST4. The most recent data about spp. molecular epidemiology and the STs in communities of Latin America are limited to studies from specific countries. Novel scientific data from the other countries are required to obtain a complete picture and truly understand the distribution and prevalence of spp. and the STs.
PubMed: 38393127
DOI: 10.3390/tropicalmed9020038 -
Frontiers in Public Health 2023(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated... (Review)
Review
BACKGROUND
(), a Gram-positive anaerobic bacterium, exhibits colonization tendencies on oral mucosal and skin surfaces, potentially evolving into a pathogenic entity associated with diverse diseases. The diagnostic trajectory for -related diseases encounters delays, often with severe consequences, including fatality, attributed to the absence of symptom specificity and challenges in culture. The absence of a consensus on the diagnostic and therapeutic approaches to exacerbates the complexity of addressing associated conditions. This study aims to elucidate and scrutinize the clinical manifestations linked to , drawing insights from an extensive literature review of pertinent case reports.
CASE PRESENTATION
A 53-year-old male sought medical attention at our institution presenting with recurrent hemoptysis. Empirical treatment was initiated while awaiting pathogen culture results; however, the patient's symptoms persisted. Subsequent metagenomic next-generation sequencing (mNGS) analysis revealed a pulmonary infection attributable to . Resolution of symptoms occurred following treatment with piperacillin sulbactam sodium and moxifloxacin hydrochloride. A comprehensive literature review, utilizing the PubMed database, was conducted to assess case reports over the last decade where was identified as the causative agent.
CONCLUSION
The literature analysis underscores the predilection of for immunocompromised populations afflicted by cardiovascular diseases, diabetes, orthopedic conditions, and tumors. Risk factors, including oral and periodontal hygiene, smoking, and alcohol consumption, were found to be associated with infections. Clinical manifestations encompassed fever, cough, sputum production, and back pain, potentially leading to severe outcomes such as Spondylodiscitis, septic arthritis, lung abscess, bacteremia, sepsis, and mortality. While conventional bacterial culture remains the primary diagnostic tool, emerging technologies like mNGS offer alternative considerations. In terms of treatment modalities, β-lactam antibiotics and nitroimidazoles predominated, exhibiting recovery rates of 56.10% (46/82) and 23.17% (19/82), respectively. This case report and literature review collectively aim to enhance awareness among clinicians and laboratory medicine professionals regarding the intricacies of -associated infections.
Topics: Humans; Male; Middle Aged; Base Composition; Firmicutes; Hemoptysis; Phylogeny; Piperacillin; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Gram-Positive Bacterial Infections
PubMed: 38389952
DOI: 10.3389/fpubh.2023.1307902 -
Biomolecules & Biomedicine Feb 2024Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and... (Meta-Analysis)
Meta-Analysis
Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72-0.88), 0.80 (95% CI, 0.73-0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR.
PubMed: 38386614
DOI: 10.17305/bb.2024.10049 -
Pharmacology & Therapeutics Apr 2024Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of... (Review)
Review
Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.
Topics: Humans; Melanoma; Skin Neoplasms; Immunotherapy; Biomarkers
PubMed: 38367867
DOI: 10.1016/j.pharmthera.2024.108613