Background: Allostatic load index (ALI) is often utilized to quantify the physiological response to stress. This study assesses the relationship between ALI and its impact on all-cause, cardiovascular, and stroke mortality in individuals with a self-reported history of stroke and within the general National Health and Nutritional Examination Survey sampled population.
Methods: Using data from the National Health and Nutritional Examination Survey (III, 1988-1994) and the 2015 Linked Mortality File, we selected adults aged ≥25 years with self-reported stroke.
Nusinersen, administered by intrathecal injection at a dose of 12 mg, is indicated across all ages for the treatment of spinal muscular atrophy (SMA). Evidence on real-world healthcare resource use (HRU) and costs among patients taking nusinersen remains limited. This study aimed to evaluate real-world HRU and costs associated with nusinersen use through US claims databases.
View Article and Find Full Text PDFIn the absence of head-to-head trials, indirect treatment comparisons (ITCs) are often used to compare the efficacy of different therapies to support decision-making. Matching-adjusted indirect comparison (MAIC), a type of ITC, is increasingly used to compare treatment efficacy when individual patient data are available from one trial and only aggregate data are available from the other trial. This paper examines the conduct and reporting of MAICs to compare treatments for spinal muscular atrophy (SMA), a rare neuromuscular disease.
View Article and Find Full Text PDFIntroduction: Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by progressive muscular atrophy and weakness. Nusinersen was the first treatment approved for SMA. Per the US label, the nusinersen administration schedule consists of three loading doses at 14-day intervals, a fourth loading dose 30 days later, and maintenance doses every 4 months thereafter.
View Article and Find Full Text PDFBackground: Spinal muscular atrophy (SMA) is a rare genetic disease characterized by progressive muscular weakness and atrophy resulting from motor neuron degeneration. Limited information is available on disease progression among older SMA patients, particularly adults.
Objective: This study sought to characterize the natural history of SMA among adult patients in US hospital settings through the assessment of symptoms, complications, costs, and healthcare resource utilization (HRU) over 3 years before the availability of disease-modifying therapies.
Background: Cure SMA maintains the largest patient-reported database for people affected with spinal muscular atrophy (SMA). In 2017, Cure SMA initiated annual surveys with their membership to collect demographic and disease characteristics, healthcare, and burden of disease information from patients and caregivers.
Objective: To summarize results from two large-scale Cure SMA surveys in 2017 and 2018.
Recurrence rates after breast-conserving therapy may depend on genomic characteristics of cancer-adjacent, benign-appearing tissue. Studies have not evaluated recurrence in association with multiple genomic characteristics of cancer-adjacent breast tissue. To estimate the prevalence of DNA defects and RNA expression subtypes in cancer-adjacent, benign-appearing breast tissue at least 2 cm from the tumor margin, cancer-adjacent, pathologically well-characterized, benign-appearing breast tissue specimens from The Cancer Genome Atlas project were analyzed for DNA sequence, copy-number variation, DNA methylation, messenger RNA (mRNA) sequence, and mRNA/microRNA expression.
View Article and Find Full Text PDFA large percentage of breast cancer patients treated with breast conserving surgery need to undergo multiple surgeries due to positive margins found during post-operative margin assessment. Carcinomas could be removed completely during the initial surgery and additional surgery avoided if positive margins can be determined intraoperatively. Spectrally encoded confocal microscopy (SECM) is a high-speed reflectance confocal microscopy technology that has a potential to rapidly image the entire surgical margin at subcellular resolution and accurately determine margin status intraoperatively.
View Article and Find Full Text PDFInvasive lobular carcinoma (ILC) is the second most prevalent histologic subtype of invasive breast cancer. Here, we comprehensively profiled 817 breast tumors, including 127 ILC, 490 ductal (IDC), and 88 mixed IDC/ILC. Besides E-cadherin loss, the best known ILC genetic hallmark, we identified mutations targeting PTEN, TBX3, and FOXA1 as ILC enriched features.
View Article and Find Full Text PDFThe categorization of intraductal proliferative lesions of the breast based on routine light microscopic examination of histopathologic sections is in many cases challenging, even for experienced pathologists. The development of computational tools to aid pathologists in the characterization of these lesions would have great diagnostic and clinical value. As a first step to address this issue, we evaluated the ability of computational image analysis to accurately classify DCIS and UDH and to stratify nuclear grade within DCIS.
View Article and Find Full Text PDFProblem: Although substantial progress has been made in improving the health of persons in the United States, serious problems remain to be solved. Life expectancy is increasing, and the rates of the leading causes of death are improving in many cases; however, numerous indicators (i.e.
View Article and Find Full Text PDFRapid intraoperative assessment of breast excision specimens is clinically important because up to 40% of patients undergoing breast-conserving cancer surgery require reexcision for positive or close margins. We demonstrate nonlinear microscopy (NLM) for the assessment of benign and malignant breast pathologies in fresh surgical specimens. A total of 179 specimens from 50 patients was imaged with NLM using rapid extrinsic nuclear staining with acridine orange and intrinsic second harmonic contrast generation from collagen.
View Article and Find Full Text PDFLeukemic involvement of the breast is rare, particularly involvement by chronic lymphocytic leukemia (CLL). While concurrent invasive ductal carcinoma and CLL manifesting as a collision tumor in the breast is extremely rare, this association (CLL and carcinoma) has been described in other organs. We report here a case of a 58-year-old woman with concurrent invasive ductal carcinoma and CLL and describe the imaging features of CLL, particularly the differentiation on MRI.
View Article and Find Full Text PDFPurpose: Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the population-based Polish Women's Breast Cancer Study.
Experimental Design: Breast cancer cases were classified on the basis of a previously reported, biologically defined extratumoral gene expression signature with two subtypes: an Active subtype, which is associated with high expression of genes related to fibrosis and wound response, and an Inactive subtype, which has high expression of cellular adhesion genes.
The purpose of this review is to discuss the less common variants and mimics of ductal carcinoma in situ (DCIS). DCIS lesions are heterogeneous in clinical presentation and behavior, morphology, biomarker profile, and identified genetic aberrations. DCIS is most easily recognized when presenting with classical features.
View Article and Find Full Text PDFAneuploidy is common in human tumours and is often indicative of aggressive disease. Aneuploidy can result from cytokinesis failure, which produces binucleate cells that generate aneuploid offspring with subsequent divisions. In cancers, disruption of cytokinesis is known to result from genetic perturbations to mitotic pathways or checkpoints.
View Article and Find Full Text PDFCertain nonmalignant lesions encountered on percutaneous breast biopsies pose dilemmas with regard to the most appropriate clinical management subsequent to needle biopsy (ie, surgical excision vs. follow-up). These lesions include columnar cell lesions, atypical ductal hyperplasia, lobular neoplasia, papillary lesions, radial scars, fibroepithelial lesions, and mucocele-like lesions.
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