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Diagnostics (Basel, Switzerland) Sep 2021The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower... (Review)
Review
The study's objective was the evaluation of the diagnostic accuracy of the T2-FLAIR mismatch sign in terms of diagnosing IDH-mutant non-codeleted (IDHmut-Noncodel) lower grade gliomas (LGG) of the brain. We searched the MEDLINE, Scopus and Cochrane Central databases. The last database search was performed on 12 April 2021. Studies that met the following were included: MRI scan assessing the presence of T2-FLAIR mismatch sign, and available IDH mutation and 1p/19q codeletion status. The quality of studies was assessed using the QUADAS-2 tool. Twelve studies involving 14 cohorts were included in the quantitative analysis. The diagnostic odds ratio [DOR (95% confidence interval; CI)] was estimated at 34.42 (20.95, 56.56), < 0.01. Pooled sensitivity and specificity (95% CI) were estimated at 40% (31-50%; = 0.05) and 97% (93-99%; < 0.01), respectively. The likelihood ratio (LR; 95% CI) for a positive test was 11.39 (6.10, 21.29; < 0.01) and the LR (95% CI) for a negative test was 0.40 (0.24, 0.65; < 0.01).The T2-FLAIR mismatch sign is a highly specific biomarker for the diagnosis of IDHmut-Noncodel LGGs. However, the test was found positive in some other tumors and had a high number of false negative results. The diagnostic accuracy of the mismatch sign might be improved when combined with further imaging parameters.
PubMed: 34573962
DOI: 10.3390/diagnostics11091620 -
Journal of Clinical Oncology : Official... Dec 2022Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic.
MATERIALS AND METHODS
We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis.
RESULTS
Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50).
CONCLUSION
Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.
Topics: Humans; Genetic Predisposition to Disease; Genetic Counseling; Privacy; Neoplastic Syndromes, Hereditary
PubMed: 35960887
DOI: 10.1200/JCO.22.00303 -
Journal of Controlled Release :... Dec 2020For the past two decades, biomimetic high-density lipoproteins (b-HDL) have been used for various drug delivery applications. The b-HDL mimic the endogenous HDL, and... (Meta-Analysis)
Meta-Analysis Review
For the past two decades, biomimetic high-density lipoproteins (b-HDL) have been used for various drug delivery applications. The b-HDL mimic the endogenous HDL, and therefore possess many attractive features for drug delivery, including high biocompatibility, biodegradability, and ability to transport and deliver their cargo (e.g. drugs and/or imaging agents) to specific cells and tissues that are recognized by HDL. The b-HDL designs reported in the literature often differ in size, shape, composition, and type of incorporated cargo. However, there exists only limited insight into how the b-HDL design dictates their biodistribution. To fill this gap, we conducted a comprehensive systematic literature search of biodistribution studies using various designs of apolipoprotein A-I (apoA-I)-based b-HDL (i.e. b-HDL with apoA-I, apoA-I mutants, or apoA-I mimicking peptides). We carefully screened 679 papers (search hits) for b-HDL biodistribution studies in mice, and ended up with 24 relevant biodistribution profiles that we compared according to b-HDL design. We show similarities between b-HDL biodistribution studies irrespectively of the b-HDL design, whereas the biodistribution of the b-HDL components (lipids and scaffold) differ significantly. The b-HDL lipids primarily accumulate in liver, while the b-HDL scaffold primarily accumulates in the kidney. Furthermore, both b-HDL lipids and scaffold accumulate well in the tumor tissue in tumor-bearing mice. Finally, we present essential considerations and strategies for b-HDL labeling, and discuss how the b-HDL biodistribution can be tuned through particle design and administration route. Our meta-analysis and discussions provide a detailed overview of the fate of b-HDL in mice that is highly relevant when applying b-HDL for drug delivery or in vivo imaging applications.
Topics: Animals; Apolipoprotein A-I; Biomimetics; Drug Delivery Systems; Lipids; Lipoproteins, HDL; Mice; Tissue Distribution
PubMed: 32971201
DOI: 10.1016/j.jconrel.2020.09.038 -
The Cochrane Database of Systematic... Nov 2020Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second...
BACKGROUND
Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review.
OBJECTIVES
The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020.
SELECTION CRITERIA
All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting.
DATA COLLECTION AND ANALYSIS
No trials of gene therapy for sickle cell disease were found.
MAIN RESULTS
No trials of gene therapy for sickle cell disease were reported.
AUTHORS' CONCLUSIONS
No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.
Topics: Anemia, Sickle Cell; Genetic Therapy; Humans
PubMed: 33251574
DOI: 10.1002/14651858.CD007652.pub7 -
Frontiers in Oncology 2020The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for patients with EGFR-mutant non-small cell lung cancer...
PURPOSE
The role of neoadjuvant epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeted therapy for patients with EGFR-mutant non-small cell lung cancer (NSCLC) has not been clarified. A pooled analysis of prospective clinical trials was conducted to evaluate the efficacy and safety of neoadjuvant EGFR-TKI therapy.
METHODS
The PubMed, Embase, Web of Science, and Cochrane Library databases, as well as meeting abstracts were searched for prospective clinical trials evaluating the efficacy and safety of neoadjuvant EGFR-TKI for treatment of EGFR-mutant NSCLC. The main outcomes included the objective response rate (ORR), downstaging rate, surgical resection rate (SRR), pathologic complete response (pCR) rate, progression-free survival (PFS), and adverse events.
RESULTS
A total of five, phase II, prospective, clinical trials involving 124 patients with resectable or potentially resectable EGFR-mutant NSCLC treated with neoadjuvant erlotinib or gefitinib treatment were included in this pooled analysis. The median neoadjuvant medication time was 42 (range, 21-56) days and the median time of response evaluation was 45 (range, 42-56) days. The pooled ORR was 58.5% [95% confidence interval (CI), 45.5%-71.8%] and the surgical resection and complete resection (R0) rates were 79.9% (95% CI, 65.3%-94.5%) and 64.3% (95% CI, 43.8%-84.8%), respectively. In the stage IIIA subgroup (n = 68), the pooled ORR, SRR, and R0 rate were 51.4%, 72.9%, and 57.0%, respectively, while the downstaging and pCR rates were 14.0% and 0.0%, respectively. The pooled median PFS and overall survival were 13.2 and 41.9 months, respectively. Of the most common grade 3/4 adverse events in the overall group, the incidences of hepatotoxicity and skin rash were 5.3% and 14.7%, respectively. The most commonly reported postoperative complications were lung infection, arrhythmia, and pneumothorax.
CONCLUSION
Neoadjuvant EGFR-TKI therapy provides a feasible treatment modality for patients with resectable or potentially resectable EGFR-mutant NSCLC, with satisfactory surgical outcomes and low toxicity. Although further phase III clinical trials are needed to confirm these findings, it is necessary to explore the feasibility of a more effective EGFR-TKI combination neoadjuvant therapy given the modest downgrade and pCR rates for EGFR-TKI alone.
PubMed: 33511076
DOI: 10.3389/fonc.2020.586596 -
Animals : An Open Access Journal From... Jul 2021Recently, it has been proved that SARS-CoV-2 has the ability to infect multiple species. This work was aimed at identifying the clinical signs of SARS-CoV-2 infection in... (Review)
Review
Recently, it has been proved that SARS-CoV-2 has the ability to infect multiple species. This work was aimed at identifying the clinical signs of SARS-CoV-2 infection in domestic and wild felids. A PRISMA-based systematic review was performed on case reports on domestic and wild cats, reports on experimental infections, case reports in databases, preprints and published press releases. Descriptive statistical analysis of the data was performed. A total of 256 articles, 63 detailed official reports and 2 press articles on SARS-CoV-2 infection in domestic and wild cats were analyzed, of which 19 articles and 65 reports were finally included. In domestic cats, most cats' infections are likely to be asymptomatic, and 46% of the reported infected animals were symptomatic and predominantly presented respiratory signs such as sneezing and coughing. In wild felines, respiratory clinical signs were most frequent, and up to 96.5% of the reported affected animals presented coughing. It is noteworthy that, to date, symptomatic animals with SARS-CoV-2 infection have been reported to belong to two different subfamilies ( and ), with up to five different felid species affected within the family. Reported results evince that the signs developed in felids show similar progression to those occurring in humans, suggesting a relationship between the viral cycle and target tissues of the virus in different species. While viral transmission to humans in contact with animal populations has not been reported, spill-back could result in the emergence of immune-escape mutants that might pose a risk to public health. Despite the clear results in the identification of the typical clinical picture of SARS-CoV-2 infection in felines, the number of detailed academic reports and papers on the subject is scarce. Therefore, further description of these cases will allow for more accurate and statistically robust clinical approaches in the future.
PubMed: 34359182
DOI: 10.3390/ani11072056 -
International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Neuro-oncology Advances 2022Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have...
BACKGROUND
Prognostic factors in adolescent and young adult (AYA) glioma are not well understood. Though clinical and molecular differences between pediatric and adult glioma have been characterized, their application to AYA populations is less clear. There is a major need to develop more robust evidence-based practices for managing AYA glioma patients.
METHODS
A systematic review using PRISMA methodology was conducted using multiple databases with the objective of identifying demographic, clinical, molecular and treatment factors influencing AYA glioma outcomes.
RESULTS
40 Studies met inclusion criteria. Overall survival was highly variable across studies depending on glioma grade, anatomic compartment and cohort characteristics. Thirty-five studies suffered from high risk of bias in at least one domain. Several studies included older adults within their cohorts; few captured purely AYA groups. Despite study heterogeneity, identified favorable prognosticators included younger age, higher functional status at diagnosis, low-grade pathology, oligodendroglioma histology and increased extent of surgical resection. Though isocitrate dehydrogenase (IDH) mutant status was associated with favorable prognosis, validity of this finding within AYA was compromised though may studies including older adults. The prognostic influence of chemotherapy and radiotherapy on overall survival varied across studies with conflicting evidence.
CONCLUSION
Existing literature is heterogenous, at high risk of bias, and rarely focused solely on AYA patients. Many included studies did not reflect updated pathological and molecular AYA glioma classification. The optimal role of chemotherapy, radiotherapy, and targeted agents cannot be determined from existing literature and should be the focus of future studies.
PubMed: 36479061
DOI: 10.1093/noajnl/vdac168 -
Human Antibodies 2021Metastatic or recurrent colorectal cancer (MRCRC) has a poor prognosis. The aim of the present meta-analysis was to assess the prevalence of different subtypes of KRAS... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Metastatic or recurrent colorectal cancer (MRCRC) has a poor prognosis. The aim of the present meta-analysis was to assess the prevalence of different subtypes of KRAS mutation and BRAF mutation in metastatic CRC patients, and evaluate the relationship between the tumor sidedness and prevalence of KRAS and BRAF mutation.
METHODS
We searched MEDLINE/PubMed, the Cochrane Library, and ClinicalTrials.gov from January 2010 to July 2020. The data were extracted independently according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The statistical analysis was done using STATA and Meta-Disk 1.4 applications.
RESULTS
Overall, 6699 colorectal cancer patients were included. KRAS and BRAF mutation was reported in 28% and 6% of patients, respectively. The overall prevalence of right primary and left primary metastatic CRC patients with mutated KRAS was 40% and 60%. However, the prevalence BRAF mutated right primary and left primary metastatic CRC patients was 37% and 63%. The overall HR was 2.38 for patients with metastatic CRC who had a mutated type of KRAS. Our study showed a mean overall survival of 35.4 month for KRAS mutant and a 10.12 month survival for BRAF mutant patients with metastatic colorectal cancer patients.
CONCLUSION
The prevalence of KRAS and BRAF mutations varied significantly according to the location of the tumor. BRAF mutations are more commonly found in metastatic colorectal cancers on the right side. Liver was the most common site of metastases in patients with mutant KRAS and the mortality of patients with mutant KRAS was 2.3 times higher than the patients with wild types. These results help to better describe the population of mCRC patients and can have implications for improving and organizing anti-EGFR therapies. Further research is needed to assess differences in survival through mutation status and primary tumor location.
Topics: Colorectal Neoplasms; Humans; Mutation; Neoplasm Recurrence, Local; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34334388
DOI: 10.3233/HAB-210451 -
Neuroradiology Jul 2022To summarize the predictive value of MRI for H3 K27M-mutant in midline gliomas using meta-analysis. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To summarize the predictive value of MRI for H3 K27M-mutant in midline gliomas using meta-analysis.
METHODS
Systematic electronic searches of the PubMed, Embase, ISI Web of Science, and Cochrane Library up to Jun 31, 2021, were conducted by two experienced neuroradiologists with the keywords of "MRI," "Glioma," and "H3 K27M." The hierarchical summary receiver-operating characteristic (HSROC) model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (LR +), negative likelihood ratio (LR -), and diagnostic odds ratio (DOR). Coupled forest plots were used to evaluate the heterogeneity of the included studies.
RESULTS
Of seven original studies with a total of 593 patients, 240 glioma patients were included, with 45.5-70.6% H3 K27M-mutant gliomas. Using MRI, a pooled sensitivity of 0.78 (95% CI, 0.66-0.87), specificity of 0.85 (95% CI, 0.76-0.91), LR + of 5.07 (95% CI, 3.19-8.08), LR - of 0.26 (95% CI, 0.16-0.42), and DOR of 19.80 (95% CI, 9.28-42.28) were achieved for H3 K27M-mutant prediction. Significant heterogeneity was observed among the studies in terms of sensitivity (Q = 16.83, df = 7, p = 0.02; I = 58.40 [95% CI, 25.83-90.97]), LR - (Q = 16.61, df = 7, p = 0.02; I = 57.87 [95% CI, 24.81-90.93]), and DOR (Q = 14.05, df = 7, p = 0.05; I = 50.18 [95% CI, 10.06-90.31]).
CONCLUSIONS
This meta-analysis demonstrated a clinical value of MRI to predict H3 K27M-mutant in midline gliomas with a pooled sensitivity of 0.78 and specificity of 0.85.
Topics: Brain Neoplasms; Glioma; Histones; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Mutation
PubMed: 35416485
DOI: 10.1007/s00234-022-02947-4