A Scoping Review and Meta-Analysis of the Relations Between Cognition and Cochlear Implant Outcomes and the Effect of Quiet Versus Noise Testing Conditions.

OBJECTIVES: Evidence continues to emerge of associations between cochlear implant (CI) outcomes and cognitive functions in postlingually deafened adults. While there are multiple factors that appear to affect these associations, the impact of speech recognition background testing conditions (i.e., in quiet versus noise) has not been systematically explored. The two aims of this study were to (1) identify associations between speech recognition following cochlear implantation and performance on cognitive tasks, and to (2) investigate the impact of speech testing in quiet versus noise on these associations. Ultimately, we want to understand the conditions that impact this complex relationship between CI outcomes and cognition. DESIGN: A scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed on published literature evaluating the relation between outcomes of cochlear implantation and cognition. The current review evaluates 39 papers that reported associations between over 30 cognitive assessments and speech recognition tests in adult patients with CIs. Six cognitive domains were evaluated: Global Cognition, Inhibition-Concentration, Memory and Learning, Controlled Fluency, Verbal Fluency, and Visuospatial Organization. Meta-analysis was conducted on three cognitive assessments among 12 studies to evaluate relations with speech recognition outcomes. Subgroup analyses were performed to identify whether speech recognition testing in quiet versus in background noise impacted its association with cognitive performance. RESULTS: Significant associations between cognition and speech recognition in a background of quiet or noise were found in 69% of studies. Tests of Global Cognition and Inhibition-Concentration skills resulted in the highest overall frequency of significant associations with speech recognition (45% and 57%, respectively). Despite the modest proportion of significant associations reported, pooling effect sizes across samples through meta-analysis revealed a moderate positive correlation between tests of Global Cognition (r = +0.37, p < 0.01) as well as Verbal Fluency (r = +0.44, p < 0.01) and postoperative speech recognition skills. Tests of Memory and Learning are most frequently utilized in the setting of CI (in 26 of 39 included studies), yet meta-analysis revealed nonsignificant associations with speech recognition performance in a background of quiet (r = +0.30, p = 0.18), and noise (r = -0.06, p = 0.78). CONCLUSIONS: Background conditions of speech recognition testing may influence the relation between speech recognition outcomes and cognition. The magnitude of this effect of testing conditions on this relationship appears to vary depending on the cognitive construct being assessed. Overall, Global Cognition and Inhibition-Concentration skills are potentially useful in explaining speech recognition skills following cochlear implantation. Future work should continue to evaluate these relations to appropriately unify cognitive testing opportunities in the setting of cochlear implantation.

Magnetic Resonance Imaging-based Prostate Cancer Screening in Carriers of Pathogenic Germline Mutations: Interim Results from the Initial Screening Round of the Prostate Cancer Genetic Risk Evaluation and Screening Study.

BACKGROUND: The risk of early-onset and clinically aggressive prostate cancer is elevated in carriers of certain rare pathogenic germline mutations. The utility of augmenting traditional prostate-specific antigen (PSA)-based screening measures with multiparametric magnetic resonance imaging (MRI) in this population is not yet known. OBJECTIVE: To evaluate MRI-based screening in comparison with traditional PSA-based screening among individuals at an elevated genetic risk for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Male germline carriers of pathogenic/likely pathogenic variants in any of 19 prostate cancer risk genes between the ages of 35 and 74 yr with no prior history of prostate cancer were recruited. Intervention Enrolled participants underwent screening with annual PSA, digital rectal examination (DRE), and triennial multiparametric MRI. Individuals with abnormal DRE, elevated age-adjusted PSA (>1.5 ng/ml for 35-49 yr, >2.0 ng/ml for 50-54 yr, and >3.0 ng/ml for 55-74 yr), or suspicious multiparametric MRI (Prostate Imaging Reporting and Data System [PI-RADS] ≥3 lesion) were offered prostate biopsy. Outcome measurements and statistical analysis Endpoints were diagnosis of any and clinically significant prostate cancer, and alternative screening strategies were compared by a decision curve analysis. RESULTS AND LIMITATIONS: To date, 101 males have completed the first round of screening. The greatest proportion of participants are carriers of BRCA2 (n = 44), BRCA1 (n = 35), and ATM (n = 7) variants. Twenty-one have undergone biopsy, resulting in the detection of nine cases of cancer (seven clinically significant). For the detection of clinically significant prostate cancer, abnormal MRI (PI-RADS ≥3) demonstrated 100% sensitivity (7/7) with a negative predictive value (NPV) of 100%, whereas PSA-based screening alone had 57% (4/7) sensitivity with an NPV of 73%. Of six screening strategies evaluated in the decision curve analysis, MRI-based screening alone achieved superior net benefit at all threshold probabilities compared with PSA screening-detecting one additional cancer case per 7.5 patients, while avoiding more unnecessary biopsies at the same threshold probability. CONCLUSIONS: Disease prevalence is high among carriers of prostate cancer-associated pathogenic germline mutations. Early results suggest that MRI-based screening enhances early detection of clinically significant disease beyond PSA screening alone. PATIENT SUMMARY: In this study, we present the interim results from the PROGRESS prostate cancer screening trial. We found that in certain germline carriers of prostate cancer risk mutations, magnetic resonance imaging-based screening enhances detection of prostate cancer while reducing biopsies triggered, in comparison with traditional prostate-specific antigen screening strategies.

Incorporating Genetic Risk Into Prostate Cancer Care: Implications for Early Detection and Precision Oncology.

The availability and cost of germline and somatic genetic testing have dramatically improved over the past two decades, enabling precision medicine approaches in oncology, with significant implications for prostate cancer (PCa) care. Roughly 12% of individuals with advanced disease are carriers of rare pathogenic germline variants that predispose to particularly aggressive and earlier-onset disease. Several of these variants are already established as clinically actionable by modern precision oncology therapeutics, while others may come to aid the selection of active surveillance, definitive local therapies, and systemic therapies. Concurrently, the number of common variants (ie, incorporated into polygenic risk scores) associated with PCa risk has continued to grow, but with several important considerations both at the intersection of race and ancestry and for early detection of aggressive disease. Family history has historically been used as a proxy for this inherited genetic risk of PCa, but recently emerging evidence examining this relation has shifted our understanding of how best to leverage this tool in PCa care. This review seeks to clarify and contextualize the existing and emerging precision oncology paradigms that use inherited genetic risk in PCa care, for both early detection and localized disease management.

Emerging Relations among Cognitive Constructs and Cochlear Implant Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Hearing loss has a detrimental impact on cognitive function. However, there is a lack of consensus on the impact of cochlear implants on cognition. This review systematically evaluates whether cochlear implants in adult patients lead to cognitive improvements and investigates the relations of cognition with speech recognition outcomes. DATA SOURCES: A literature review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies evaluating cognition and cochlear implant outcomes in postlingual, adult patients from January 1996 to December 2021 were included. Of 2510 total references, 52 studies were included in qualitative analysis and 11 in meta-analyses. REVIEW METHODS: Proportions were extracted from studies of (1) the significant impacts of cochlear implantation on 6 cognitive domains and (2) associations between cognition and speech recognition outcomes. Meta-analyses were performed using random effects models on mean differences between pre- and postoperative performance on 4 cognitive assessments. RESULTS: Only half of the outcomes reported suggested cochlear implantation had a significant impact on cognition (50.8%), with the highest proportion in assessments of memory & learning and inhibition-concentration. Meta-analyses revealed significant improvements in global cognition and inhibition-concentration. Finally, 40.4% of associations between cognition and speech recognition outcomes were significant. CONCLUSION: Findings relating to cochlear implantation and cognition vary depending on the cognitive domain assessed and the study goal. Nonetheless, assessments of memory & learning, global cognition, and inhibition-concentration may represent tools to assess cognitive benefit after implantation and help explain variability in speech recognition outcomes. Enhanced selectivity in assessments of cognition is needed for clinical applicability.

Brief report: Areolar melanosis in a girl with precocious puberty.

We report a case of melanosis of the areola in a 7-year-old girl with early thelarche. Areolar melanosis is a rare condition previously only described in women over 25 years of age, often in the setting of pregnancy. This case supports a theory that hyperpigmentation may be associated with increased sensitivity to hormonal stimulation in areas with greater populations of melanocytes.