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The purpose of this study was to investigate the perspectives of Deaf students attending a large "hearing" university regarding their use of assistive technology (AT). Individual, semi-structured interviews were conducted with nine participants and responses were videotaped and transcribed from sign language to English. A collective case study approach was used to analyze the data. Three primary categories concerning perspectives of AT emerged from the qualitative analysis: (a) self-reported use of assistive technology and overall benefits, (b) barriers to AT use, and (c) facilitators to AT use. Discussion centers on the struggle to balance the triad of information that deaf students encounter in the university classroom and offers recommendations to assist deaf students in "hearing" classrooms at the university level. (Contains 2 tables and 1 figure.)

Background: Germline pathogenic variants in CHEK2 are associated with a moderate increase in the lifetime risk for breast cancer. Increased risk for other cancers, including non-medullary thyroid cancer (NMTC), has also been suggested. To date, data implicating CHEK2 variants in NMTC predisposition primarily derive from studies within Poland, driven by a splice site variant (c.444 + 1G>A) that is uncommon in other populations. In contrast, the predominant CHEK2 variants in non-Polish populations are c.1100del and c.470T>C/p.I157T, representing 61.1% and 63.8%, respectively, of all CHEK2 pathogenic variants in two large U.S.-based commercial laboratory datasets. To further delineate the impact of common CHEK2 variants on thyroid cancer, we aimed to investigate the association of three CHEK2 founder variants (c.444 + 1G>A, c.1100del, and c.470T>C/p.Ile157Thr) on NMTC susceptibility in three groups of unselected NMTC patients. Methods: The presence of three CHEK2 founder variants was assessed within three groups: (1) 1544 NMTC patients (and 1593 controls) from previously published genome-wide association study (GWAS) analyses, (2) 789 NMTC patients with germline exome sequencing (Oncology Research Information Exchange Network [ORIEN] Avatar), and (3) 499 NMTC patients with germline sequence data available in The Cancer Genome Atlas (TCGA). A case-control study design was utilized with odds ratios (ORs) calculated by comparison of all three groups with the Ohio State University GWAS control group. Results: The predominant Polish variant (c.444 + 1G>A) was present in only one case. The proportion of patients with c.1100del was 0.92% in the GWAS group, 1.65% in the ORIEN Avatar group, and 0.80% in the TCGA group. The ORs (with 95% confidence intervals [CIs]) for NMTC associated with c.1100del were 1.71 (0.73-4.29), 2.64 (0.95-7.63), and 2.5 (0.63-8.46), respectively. The proportion of patients with c.470T>C/p.I157T was 0.91% in the GWAS group, 0.76% in the ORIEN Avatar group, and 0.80% in the TCGA group, respectively. The ORs (with CIs) for NMTC associated with c.470T>C/p.I157T were 1.75 (0.74-4.39), 1.52 (0.42-4.96), and 2.31 (0.58-7.90), respectively. Conclusions: Our analyses of unselected patients with NMTC suggest that CHEK2 variants c.1100del and c.470T>C/p.I157T have only a modest impact on thyroid cancer risk. These results provide important information for providers regarding the relatively low magnitude of thyroid cancer risk associated with these CHEK2 variants.

A germline pathogenic variant may be present even if the results of tumor genomic sequencing do not suggest one. There are key differences in the assay design and reporting of variants between germline and somatic laboratories. When appropriate, both tests should be completed to aid in therapy decisions and determining optimal screening and risk-reduction interventions., (© 2023. Springer Nature Limited and Centre of Excellence in Genomic Medicine Research, King Abdulaziz University.)

In the era of precision medicine, genomic interrogation for identification of both germline and somatic genetic alterations has become increasingly important. While such germline testing was usually undertaken via a phenotype-driven single-gene approach, with the advent of next-generation sequencing (NGS) technologies, the widespread utilization of multigene panels, often agnostic of cancer phenotype, has become a commonplace in many different cancer types. At the same time, somatic tumor testing in oncology performed for the purpose of guiding therapeutic decisions for targeted therapies has also rapidly expanded, recently starting to incorporate not just patients with recurrent or metastatic cancer but even patients with early-stage disease. An integrated approach may be the best approach for the optimal management of patients with different cancers. The lack of complete congruence between germline and somatic NGS tests does not minimize the power or importance of either, but highlights the need to understand their limitations so as not to overlook an important finding or omission. NGS tests built to more uniformly and comprehensively evaluate both the germline and tumor simultaneously are urgently required and are in development. In this article, we discuss approaches to somatic and germline analyses in patients with cancer and the knowledge gained from integration of tumor-normal sequencing. We also detail strategies for the incorporation of genomic analysis into oncology care delivery models and the important emergence of poly(ADP-ribose) polymerase and other DNA Damage Response inhibitors in the clinic for patients with cancer with germline and somatic BRCA1 and BRCA2 mutations.

Next-generation sequencing of circulating tumor DNA (ctDNA) is a non-invasive method to guide therapy selection for cancer patients. ctDNA variant allele frequency (VAF) is commonly reported and may aid in discerning whether a variant is germline or somatic. We report on the fidelity of VAF in ctDNA as a predictor for germline variant carriage. Two patient cohorts were studied. Cohort 1 included patients with known germline variants. Cohort 2 included patients with any variant detected by the ctDNA assay with VAF of 40-60%. In cohort 1, 36 of 91 (40%) known germline variants were identified through ctDNA analysis with a VAF of 39-87.6%. In cohort 2, 111 of 160 (69%) variants identified by ctDNA analysis with a VAF between 40 and 60% were found to be germline. Therefore, variants with a VAF between 40 and 60% should induce suspicion for germline status but should not be used as a replacement for germline testing.

Purpose: Identification of incidental germline mutations in the context of next-generation sequencing is an unintended consequence of advancing technologies. These data are critical for family members to understand disease risks and take action., Patients and Methods: A retrospective cohort analysis was conducted of 1,028 adult patients with metastatic cancer who were sequenced with tumor and germline whole exome sequencing (WES). Germline variant call files were mined for pathogenic/likely pathogenic (P/LP) variants using the ClinVar database and narrowed to high-quality submitters., Results: Median age was 59 years, with 16% of patients ≤ 45 years old. The most common tumor types were breast cancer (12.5%), colorectal cancer (11.5%), sarcoma (9.3%), prostate cancer (8.4%), and lung cancer (6.6%). We identified 3,427 P/LP variants in 471 genes, and 84% of patients harbored one or more variant. One hundred thirty-two patients (12.8%) carried a P/LP variant in a cancer predisposition gene, with BRCA2 being the most common (1.6%). Patients with breast cancer were most likely to carry a P/LP variant (19.2%). One hundred ten patients (10.7%) carried a P/LP variant in a gene that would be recommended by the American College of Medical Genetics and Genomics to be reported as a result of clinical actionability, with the most common being ATP7B (2.7%), BRCA2 (1.6%), MUTYH (1.4%), and BRCA1 (1%). Of patients who carried a P/LP variant in a cancer predisposition gene, only 53% would have been offered correct testing based on current clinical practice guidelines. Of 471 mutated genes, 231 genes had a P/LP variant identified in one patient, demonstrating significant genetic heterogeneity., Conclusion: The majority of patients undergoing clinical cancer WES harbor a pathogenic germline variation. Identification of clinically actionable germline findings will create additional burden on oncology clinics as broader WES becomes common.

The identification of cancer-predisposing germline variants has potentially substantial clinical impact for patients and their families. Although management guidelines have been proposed for some genes, guidelines for other genes are lacking. This review focuses on the current surveillance and management guidelines for the most common hereditary cancer syndromes and discusses some of the most pivotal studies supporting the available guidelines. We also highlight the gaps in the identification of germline carriers, the cascade testing of at-risk relatives, and the challenges impeding the proper follow-up and optimal management of pathogenic germline carriers. The anticipated surge in the number of identified germline carriers, deficient management guidelines, poor cascade testing uptake, and long-term follow-up necessitate the development of multidisciplinary clinics as an obligatory step toward the improvement of cancer prevention.

Context: The Center for Public Health Quality and its partner, North Carolina State University Industrial Extension Service, used 2 existing, yet similar quality improvement (QI) programs to provide technical assistance to conduct return on investment (ROI) and economic impact (EI) analyses so that they could estimate their QI projects' financial impacts., Objectives: The objectives of this article are to describe the approach and ongoing learning from applying ROI and EI analyses to public health QI projects and analyze the results in order to illustrate ROI potential in public health., Design: We used a before-after study design for all ROI and EI analyses, spanning a 3-year time period., Setting: The study was conducted as part of 2 existing public health QI training programs that included webinars, face-to-face workshops, on-site facilitation, and longitudinal coaching and mentoring., Participants: The QI training programs included multidisciplinary teams from local and state public health programs in North Carolina., Main Outcome Measure: Return on investment and EI calculations., Results: Numerous adaptations were made over the 3 years of the ROI program to enhance participant's understanding and application. Results show an average EI of $149 000, and a total EI in excess of $5 million for the 35 projects studied. The average ROI per QI project was $8.56 for every $1 invested in the project., Conclusions: Adapting the ROI approach was important in helping teams successfully conduct their ROI analyses. This study suggests that ROI analyses can be effectively applied in public health settings, and the potential for financial return is substantial.

Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura, is a rare bleeding disorder caused by increased peripheral platelet destruction. The laboratory and clinical criteria for establishing the diagnosis of acute ITP in children and adolescents are widely accepted. Treatment options for ITP remain controversial. Retrospective data analysis of patients with acute ITP referred to the pediatric Hematology/Oncology Clinic at Sioux Valley Children's Specialty Clinic, seen from August 1998 to December 2004. Fourteen patients out of 25 presented with acute ITP, and had platelet count < or = 10 x 10(9)/L. Life threatening hemorrhage did not occur with any of these patients. Eleven of the analyzed 25 (44%) patients had thrombocytopenia resolve within six months of diagnosis. Nine patients (9/25, 36%) continue to be thrombocytopenic at one year from diagnosis, but without significant bleeding episodes. The clinical presentation, duration and severity of disease in patients with acute ITP seen in our Center are similar to those described in recently published studies. Our approach to treatment differed when compared with other studies. The difference in treatment may be due to patients' significant geographic distance from a tertiary care center, combined with unavailability of necessary treatment in local health institutions.