ABSTRACT
Accurate measurement of clonal genotypes, mutational processes, and replication states from individual tumor-cell genomes will facilitate improved understanding of tumor evolution. We have developed DLP+, a scalable single-cell whole-genome sequencing platform implemented using commodity instruments, image-based object recognition, and open source computational methods. Using DLP+, we have generated a resource of 51,926 single-cell genomes and matched cell images from diverse cell types including cell lines, xenografts, and diagnostic samples with limited material. From this resource we have defined variation in mitotic mis-segregation rates across tissue types and genotypes. Analysis of matched genomic and image measurements revealed correlations between cellular morphology and genome ploidy states. Aggregation of cells sharing copy number profiles allowed for calculation of single-nucleotide resolution clonal genotypes and inference of clonal phylogenies and avoided the limitations of bulk deconvolution. Finally, joint analysis over the above features defined clone-specific chromosomal aneuploidy in polyclonal populations.
Subject(s)
DNA Replication/genetics , Genome, Human , High-Throughput Nucleotide Sequencing , Single-Cell Analysis , Aneuploidy , Animals , Cell Cycle/genetics , Cell Line, Tumor , Cell Shape , Cell Survival , Chromosomes, Human/genetics , Clone Cells , DNA Transposable Elements/genetics , Diploidy , Female , Genotype , Humans , Male , Mice , Mutation/genetics , Phylogeny , Polymorphism, Single Nucleotide/geneticsABSTRACT
Despite widespread use of bendamustine and rituximab (BR) as frontline therapy for advanced-stage follicular lymphoma (FL), little is known about the risk of early progression or incidence of histological transformation. We performed a retrospective analysis of a population-based cohort of 296 patients with advanced-stage FL treated with frontline BR and maintenance rituximab. As previously demonstrated, outcomes with this regimen are excellent, with 2-year event-free survival estimated at 85% (95% confidence interval [95% CI], 80-89) and 2-year overall survival 92% (95% CI, 88-95). Progression of disease within 24 months (POD24) occurred in 13% of patients and was associated with a significantly inferior outcome with 2-year overall survival of 38% (95% CI, 20-55). The only significant risk factor for POD24 at baseline was elevated lactate dehydrogenase (P < .001). Importantly, the majority of POD24 patients (76%) had transformed disease. Compared with a historical cohort treated with rituximab, cyclophosphamide, vincristine, and prednisone, event-free survival has improved and the risk of POD24 has decreased, but a higher proportion of patients with POD24 harbor transformation. The overall incidence of transformation appears unchanged. The presence of occult or early transformation is the main driver of POD24 in FL patients treated with frontline BR. Identification of biomarkers and improved management strategies for transformation will be crucial to improving outcomes.
Subject(s)
Antineoplastic Agents/therapeutic use , Bendamustine Hydrochloride/therapeutic use , Lymphoma, Follicular/drug therapy , Rituximab/therapeutic use , Adult , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Lymphoma, Follicular/pathology , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Noncontrast CT (NCCT) has become the standard Imaging study in the emergency department (ED) diagnosis of nephro- and ureterolithiasis. We undertook to audit the results from the first 500 NCCTs performed for patients presenting to the ED with suspected renal colic. PATIENTS AND METHODS: In a retrospective study at one institution from October 2003 to February 2006, 500 patients with suspected stone disease were investigated. In the study, NCCT findings, patient clinical records, and urinary microscopy results were evaluated for 166 women and 334 men. RESULTS: Renal or ureteral calculi were identified in 279 (56%) of NCCTs performed. Of the 500, 112 (19%) NCCTs performed identified unexpected intra-abdominal pathology. When the findings deemed to be of low clinical significance were excluded, the number of scans with additional pathology amounted to 67 (13%). These included vascular emergencies, new cancer diagnoses, and gastrointestinal conditions. CONCLUSIONS: The variety of diagnoses found unexpectedly on the NCCT that alter a patient's treatment demonstrates the pivotal role of NCCT in the triage of these patients rapidly toward optimal therapy. The rapid acquisition time of NCCT has enabled definitive ED patient diagnosis and less bed occupancy for clinically insignificant calculi.
Subject(s)
Colic/diagnostic imaging , Contrast Media , Emergency Service, Hospital , Kidney Diseases/diagnostic imaging , Medical Audit , Tomography, X-Ray Computed , Adolescent , Adult , Aged , Aged, 80 and over , Blood Vessels/pathology , Colic/therapy , Female , Follow-Up Studies , Gynecology , Humans , Image Processing, Computer-Assisted , Incidence , Kidney Calculi/diagnostic imaging , Kidney Calculi/epidemiology , Kidney Calculi/pathology , Kidney Diseases/pathology , Kidney Diseases/therapy , Male , Middle Aged , Retrospective Studies , Ureteral Calculi/diagnostic imaging , Ureteral Calculi/epidemiology , Ureteral Calculi/pathologyABSTRACT
This point-prevalence study was conducted to establish rates of meticillin-resistant Staphylococcus aureus (MRSA) nasal carriage in GPs in three counties in the West of Ireland. One hundred and twenty GPs were randomly selected for the study and 78 participated. The prevalence rate of nasal carriage of MRSA in these participants was 7.7%. A number of GPs in the West of Ireland have nasal carriage of MRSA. The results emphasise the need for high standards of infection control in primary care.
