Citations

Background/Objectives: Traditional hearing aid noise reduction algorithms offer no additional benefit in noisy situations for bimodal cochlear implant (CI) users with a CI in one ear and a hearing aid (HA) in the other. Recent breakthroughs in deep neural network (DNN)-based noise reduction have improved speech understanding for hearing aid users in noisy environments. These advancements could also boost speech perception in noise for bimodal CI users. This study investigated the effectiveness of DNN-based noise reduction in the HAs used by bimodal CI patients. Methods: Eleven bimodal CI patients, aged 71–89 years old, were fit with a Phonak Audéo Sphere Infinio 90 HA in their non-implanted ear and were provided with a Calm Situation program and Spheric Speech in Loud Noise program that uses DNN-based noise reduction. Sentence recognition scores were measured using AzBio sentences in quiet and in noise with the CI alone, hearing aid alone, and bimodally with both the Calm Situation and DNN HA programs. Results: The DNN program in the hearing aid significantly improved bimodal performance in noise, with sentence recognition scores reaching 79% compared to 60% with Calm Situation (a 19% average benefit, p < 0.001). When compared to the CI-alone condition in multi-talker babble, the DNN HA program offered a 40% bimodal benefit, significantly higher than the 21% score seen with the Calm Situation program. Conclusions: DNN-based noise reduction in HA significantly improves speech understanding in noise for bimodal CI users. Utilization of this technology is a promising option to address patients’ common complaint of speech understanding in noise.

BACKGROUND: Older adults value the maintenance of function as an outcome of surgery, which can be evaluated by subjective perception and objective performance. The aims of this study were to explore whether these perceptions correlate with a decline in function, as measured by decreased ability to perform activities of daily living (ADLs), and to identify risk factors associated with worsened 30-day postoperative perceived physical function (PPF) in patients aged 80 years and older. STUDY DESIGN: American College of Surgeons NSQIP Geriatric Surgery Verification Pilot Program data (2015 to 2017) were used for patients aged 80 years and older. Chi-square tests were used to examine the concordance between 30-day outcomes of PPF and the quantified performance of ADLs. Multivariable logistic regression models identified risks associated with worsened PPF 30 days postoperatively. RESULTS: A total of 5,464 patients from 16 hospitals were included. The mean age was 85.7 years and 63% of participants were women. At 30 days postoperatively, 33% reported functional decline, whereas 28% had worsened quantified ADL performance (K = 0.25). Twenty-one percent of patients without quantified decline reported worsened PPF. Risk factors for worsened PPF were found for patient (eg American Society of Anesthesiologists class IV and V (odds ratio [OR] 2.2, 95% CI 1.5 to 3.2)), procedure (eg orthopaedic [OR 1.7, 95% CI 1.2 to 2.4]), and older adult-specific characteristics (eg preoperative fall [OR 1.9, 95% CI 1.2 to 2.9]). CONCLUSIONS: At 30 days postsurgery, there was discordance between quantified ADL performance and PPF in patients aged 80 years and older. Although assessing ADLs is a common approach to detect functional decline and loss of independence, directly asking patients about their PPF can serve as an additional important method for identifying functional decline, ensuring that the evaluation remains patient centered.

Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer, with a higher risk of recurrence in the early-stage setting compared to other subtypes. While TNBC is defined as breast cancer that lacks estrogen receptor and progesterone receptor expression and is without human epidermal growth factor receptor 2 (HER2) overexpression, it is increasingly recognized as a very heterogeneous disease. Utilization of neoadjuvant chemotherapy (NAC), with or without immunotherapy (depending on the clinical stage), has significantly improved clinical outcomes in early-stage TNBC (particularly in Stage II and III disease). Use of NAC offers the opportunity to de-escalate surgical treatment and evaluate treatment response, allowing for improved prognostication and further tailoring of post-operative systemic therapy. However, there continues to be a need for the personalization of systemic therapy strategies according to recurrence risk. More effective systemic therapies are still needed for patients who have poor response to NAC. Conversely, there remains a need for the identification of appropriate candidates for systemic therapy de-escalation, particularly given the potentially life-altering toxicities of current chemo-immunotherapy strategies. In this review the authors outline the current neoadjuvant paradigm for early-stage TNBC and emerging therapeutic strategies in this challenging disease state, along with questions that remain unanswered in the field.

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (&lt;30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Abstract Molecular characterization of high-grade B-cell lymphoma, not otherwise specified (HGBCL-NOS), is hindered by its rarity, evolving definition, and poor diagnostic reproducibility. To address this challenge, we analyzed 92 HGBCL-NOS tumors collected across Lymphoma/Leukemia Molecular Profiling Project sites. Leveraging comparison cohorts of diffuse large B-cell lymphoma, NOS (DLBCL-NOS) and Burkitt lymphoma (BL), and molecular frameworks described in these entities, our analysis revealed a heterogenous molecular landscape, reminiscent of DLBCL-NOS but with an enrichment of BL features. By cell-of-origin classification, 59% were germinal center B-cell–like (GCB), and 25% were activated B-cell–like (ABC). LymphGen, a genetic classifier for DLBCL-NOS, assigned a genetic subtype to 34% of HGBCL-NOS. Although classification rate was lower than in DLBCL-NOS (66%), assigned subtypes spanned the spectrum of LymphGen classes, including 31% of ABCs classified as MCD. Features differentiating HGBCL-NOS from DLBCL-NOS included MYC rearrangement (47% vs 6%); dark zone signature (DZsig) expression (45% vs 7%); and more frequent mutation of ID3, MYC, CCND3, and TP53, all common to BL. A genetic classifier that differentiates DLBCL-NOS from BL classified 53% of DZsig+ tumors as BL-like, and those classified as DLBCL-like were frequently BCL2-rearranged. Among DZsig− GCB tumors, 95% were DLBCL-like. Centralized pathology review reclassified almost half of tumors as DLBCL-NOS but did not identify a more homogenous HGBCL-NOS population, with no difference in features between confirmed and reclassified tumors. In conclusion, molecular testing enables a subset of HGBCL-NOS to be assigned to established categories. Based on rarity and diagnostic challenges, broader inclusion of HGBCL-NOS should be considered in biomarker-driven DLBCL trials.