Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Quantitative analysis of apoptosis and bcl-2 in Sjögren's syndrome

Resources All ResourcesChemicals & BioassaysBioSystemsPubChem BioAssayPubChem CompoundPubChem Structure SearchPubChem SubstanceAll Chemicals & Bioassays Resources...DNA & RNABLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)E-UtilitiesGenBankGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome WorkbenchInfluenza VirusNucleotide DatabasePopSetPrimer-BLASTProSplignReference Sequence (RefSeq)RefSeqGeneSequence Read Archive (SRA)SplignTrace ArchiveUniGeneUniSTSAll DNA & RNA Resources...Data & SoftwareBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)Cn3DConserved Domain Search Service (CD Search)E-UtilitiesGenBank: BankItGenBank: SequinGenBank: tbl2asnGenome ProtMapGenome WorkbenchPrimer-BLASTProSplignPubChem Structure SearchSNP Submission ToolSplignVector Alignment Search Tool (VAST)All Data & Software Resources...Domains & StructuresBioSystemsCn3DConserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Structure (Molecular Modeling Database)Vector Alignment Search Tool (VAST)All Domains & Structures Resources...Genes & ExpressionBioSystemsDatabase of Genotypes and Phenotypes (dbGaP)E-UtilitiesGeneGene Expression Omnibus (GEO) Database Gene Expression Omnibus (GEO) DatasetsGene Expression Omnibus (GEO) ProfilesGenome WorkbenchHomoloGeneMap ViewerOnline Mendelian Inheritance in Man (OMIM)RefSeqGeneUniGeneAll Genes & Expression Resources...Genetics & MedicineBookshelfDatabase of Genotypes and Phenotypes (dbGaP)Genetic Testing RegistryInfluenza VirusMap ViewerOnline Mendelian Inheritance in Man (OMIM)PubMedPubMed Central (PMC)PubMed Clinical QueriesRefSeqGeneAll Genetics & Medicine Resources...Genomes & MapsDatabase of Genomic Structural Variation (dbVar)GenBank: tbl2asnGenomeGenome ProjectGenome ProtMapGenome WorkbenchInfluenza VirusMap ViewerNucleotide DatabasePopSetProSplignSequence Read Archive (SRA)SplignTrace ArchiveUniSTSAll Genomes & Maps Resources...HomologyBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)Genome ProtMapHomoloGeneProtein ClustersAll Homology Resources...LiteratureBookshelfE-UtilitiesJournals in NCBI DatabasesMeSH DatabaseNCBI HandbookNCBI Help ManualNCBI NewsPubMedPubMed Central (PMC)PubMed Clinical QueriesAll Literature Resources...ProteinsBioSystemsBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Database (CDD)Conserved Domain Search Service (CD Search)E-UtilitiesProSplignProtein ClustersProtein DatabaseReference Sequence (RefSeq)All Proteins Resources...Sequence AnalysisBLAST (Basic Local Alignment Search Tool)BLAST (Stand-alone)BLAST Link (BLink)Conserved Domain Search Service (CD Search)Genome ProtMapGenome WorkbenchInfluenza VirusPrimer-BLASTProSplignSplignAll Sequence Analysis Resources...TaxonomyTaxonomyTaxonomy BrowserTaxonomy Common TreeAll Taxonomy Resources...Training & TutorialsNCBI Education PageNCBI HandbookNCBI Help ManualNCBI NewsScience PrimerAll Training & Tutorials Resources...VariationDatabase of Genomic Structural Variation (dbVar)Database of Genotypes and Phenotypes (dbGaP)Database of Single Nucleotide Polymorphisms (dbSNP)SNP Submission ToolAll Variation Resources...How To All How ToChemicals & BioassaysDNA & RNAData & SoftwareDomains & StructuresGenes & ExpressionGenetics & MedicineGenomes & MapsHomologyLiteratureProteinsSequence AnalysisTaxonomyTraining & TutorialsVariationSkip to main contentSkip to navigationAbout NCBI AccesskeysMy NCBISign InSign OutPubMedUS National Library of Medicine National Institutes of Health Search termSearch databaseAll DatabasesPubMedProteinNucleotideGSSESTStructureGenomeAssemblyBioProjectBioSampleBioSystemsBooksConserved DomainsClonedbGaPdbVarEpigenomicsGeneGEO DataSetsGEO ProfilesHomoloGeneMeSHNCBI Web SiteNLM CatalogOMIAOMIMPMCPopSetProbeProtein ClustersPubChem BioAssayPubChem CompoundPubChem SubstancePubMed HealthSNPSRATaxonomyToolKitToolKitAllUniGeneUniSTSSearch AdvancedHelp Result FiltersDisplay Settings:AbstractFormatSummarySummary (text)AbstractAbstract (text)MEDLINEXMLPMID ListApply Send to:Choose DestinationFileClipboardCollectionsE-mailOrderMy BibliographyCitation manager FormatSummary (text)Abstract (text)MEDLINEXMLPMID ListCSVCreate File 1 selected item: 9263150FormatSummarySummary (text)AbstractAbstract (text)MEDLINEXMLPMID ListMeSH and Other DataE-mailSubjectAdditional textE-mail"SPAM" filtering software notice Add to Clipboard Add to CollectionsOrder articles Add to My BibliographyGenerate a file for use with external citation management software. Create File J Rheumatol. 1997 Aug;24(8):1552-7. Quantitative analysis of apoptosis and bcl-2 in Sjögren's syndrome. Manganelli P, Quaini F, Andreoli AM, Lagrasta C, Pilato FP, Zuccarelli A, Monteverdi R, D'Aversa C, Olivetti G. SourceRheumatic Disease Unit, Hospital of Parma, Italy. Abstract OBJECTIVE: To determine whether apoptosis plays a significant role in tissue damage of Sjögren's syndrome (SS). METHODS: We performed a quantitative analysis of programmed cell death on salivary glands of 11 patients. Ten age matched women with sicca syndrome served as controls. Morphometric measurement of the fractional volume of acini and ducts showing DNA strand breaks was performed in sections stained by deoxynucleotidyl transferase assay. The extent of bcl-2 expression was determined in sections labeled with monoclonal antibody. The different cell populations infiltrating the glands were examined in tissues stained with anti-leukocyte common antigen and OPD4 monoclonal antibodies. RESULTS: In patients with SS, 68% of the ductal epithelium was occupied by apoptotic structures, whereas only 12% of acini showed DNA strand breaks. Corresponding values in control salivary glands were 3 and 0.13%. bcl-2 labeling was higher in ducts than in acini of both control and pathologic glands. However, in SS a 43% (p < 0.001) and 75% (p < 0.001) reduction in bcl-2 expression was observed in ductal and acinar epithelium, respectively. In comparison with controls, the numerical density of CD4+ cells and plasma cells scattered throughout the interstitium was 323% and 203% higher (p < 0.001) in SS. Moreover, T helper/inducer lymphocytes represented 52% of the inflammatory foci. CONCLUSION: Apoptosis occurs in minor salivary glands of patients with SS with a prevailing localization on the ductal epithelium in association with downregulation of bcl-2 and a large number of infiltrating CD4+ lymphocytes. Thus, the destruction of glandular tissue and the loss of secretory function in SS is dependent on the activation of the suicide program of epithelial cell

27) Different patterns of myocardial iron distribution by whole-heart T2* Magnetic Resonance as risk markers for heart complications in thalassemia major.

Background: The multislice multiecho T2* cardiovascular magnetic resonance (CMR) technique allows to detect different patterns of myocardial iron overload (MIO). The aim of this cross-sectional study was to verify the association between cardiac complications (heart failure and arrhythmias), biventricular dysfunction and myocardial fibrosis with different patterns of MIO in thalassemia major (TM) patients. Methods: We considered 812 TM patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) Network. The T2* value in all the 16 cardiac segments was evaluated. Results:We identified 4 groups of patients: 138with homogeneous MIO (all segments with T2* b 20 ms), 97with heterogeneousMIO (some segments with T2* b 20 ms, others with T2* 6520 ms) and significant global heart iron (global heart T2* b 20 ms), 238 with heterogeneous MIO and no significant global heart iron, and 339 with no MIO (all segments with T2* 65 20 ms). Compared to patients with no MIO, patients with homogeneous MIO were more likely to have cardiac complications (odds ratio\u2014OR = 2.67), heart failure (OR = 2.54), LV dysfunction (OR = 5.59), and RV dysfunction (OR = 2.26); patients with heterogeneous MIO and significant global heart iron were more likely to have heart failure (OR = 2.38) and LV dysfunction (OR = 2.39). Conclusions: Cardiac complications, heart failure and dysfunction were correlated with MIO distribution with an increasing risk from the TM patientswith no MIO to thosewith homogeneousMIO. Using a segmental approach, early iron deposit or homogeneous MIO patterns can be characterized to better tailor chelation therapy