Citations

ABSTRACT Background: Esophageal cancer remains one of the most aggressive malignancies of the gastrointestinal tract, with high rates of recurrence and mortality despite curative-intent surgery and adjuvant therapies. Identifying factors associated with recurrence is crucial for improving outcomes and guiding personalized treatment. Aims: The aim of this study was to evaluate pretreatment and treatment-related variables associated with recurrence in patients with esophageal cancer undergoing surgical resection. Methods: This retrospective study analyzed data from patients with stage I–III esophageal carcinoma who underwent esophagectomy between 2000 and 2025, using the Fundação Oncocentro de São Paulo (FOSP) database. Clinical, histological, and treatment-related variables were evaluated. Disease-free survival and recurrence patterns were assessed using Cox proportional hazards models and Fine–Gray subdistribution hazard models. Results: A total of 2,057 patients were included, with a mean follow-up of 36.5 months (±44.8). In the multivariate analysis, advanced tumor stage (stage II: HR 1.68, 95%CI 1.21–2.33; stage III: HR 3.23, 95%CI 2.29–4.56; both p<0.01), location (middle esophagus: HR 1.31, 95%CI 1.11–1.54; p=0.001; upper esophagus: HR 1.54, 95%CI 1.21–1.96; p<0.001), and histological subtype (rare histologies: HR 2.17, 95%CI 1.35–3.49; p=0.001) were associated with worse disease-free survival. Multimodal therapy improved disease-free survival (HR 0.40, 95%CI 0.24–0.66) in stage III tumors. Squamous cell carcinoma was independently associated with locoregional recurrence (SHR 1.52, 95%CI 1.05–2.20; p=0.027). For distant recurrence, squamous cell carcinoma showed a protective effect (SHR 0.52, 95%CI 0.31–0.88; p=0.015), while high tumor grade (grade II: SHR 3.65, 95%CI 1.98–6.72; p<0.001) was associated with an increased risk. Multimodal treatments influenced recurrence patterns but did not independently predict outcomes after adjustment. Conclusions: Tumor stage, location, and histology were strong predictors of disease-free survival after surgery for esophageal cancer. Histological subtypes significantly influenced recurrence patterns. Squamous cell carcinoma was associated with a higher risk of locoregional recurrence but a lower risk of distant metastasis compared to adenocarcinoma. Multimodal therapy demonstrated a protective effect in stage III disease.

Abstract OBJECTIVE AND SCOPE A panel of clinicians, subject‐matter experts, and guideline methodologists convened by the Alzheimer's Association conducted a systematic review and formulated evidence‐based recommendations for using blood‐based biomarkers (BBMs) in the diagnostic workup of suspected Alzheimer's disease (AD) within specialized care settings. The scope focuses on individuals with objective cognitive impairment, including those with mild cognitive impairment (MCI) or dementia, who are undergoing evaluation by providers trained and experienced in memory disorders, where AD is the suspected underlying etiology. METHODS The panel conducted a systematic review to assess the diagnostic accuracy of BBMs in detecting AD pathology. The BBMs of interest included plasma phosphorylated‐tau (p‐tau) and amyloid‐beta (Aβ) tests measuring the following analytes: p‐tau217, ratio of p‐tau217 to non‐p‐tau217 ×100 (%p‐tau17), p‐tau181, p‐tau231, and ratio of Aβ42 to Aβ40. The reference standard tests included cerebrospinal fluid (CSF) AD biomarkers, amyloid positron emission tomography (PET), or neuropathology. The panel applied the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of the evidence and the GRADE evidence‐to‐decision (EtD) Framework to develop its recommendations. RECOMMENDATIONS The key recommendations in this Clinical Practice Guideline (CPG) are: (1) BBM tests with ≥90% sensitivity and ≥75% specificity can be used as a triaging test and (2) BBM tests with ≥90% sensitivity and specificity can serve as a substitute for amyloid PET imaging or CSF AD biomarker testing in patients with cognitive impairment presenting to specialized care for memory disorders. The panel cautions users of this guideline that there is significant variability in diagnostic test accuracy and many commercially available BBM tests do not meet these thresholds, especially using a single cutoff. Additionally, these tests do not serve as a substitute for comprehensive clinical evaluation by a healthcare professional and should be used only as part of a full diagnostic workup of patients with cognitive impairment presenting to specialized care settings, and with careful consideration of pretest probability of AD pathology. CONCLUSIONS AND PRACTICAL IMPLICATIONS This CPG provides performance‐based, brand‐agnostic recommendations for the use of BBMs in the diagnostic workup of suspected AD within specialized care settings. By linking recommendations to a systematic review and associated living updates, and using a robust and transparent methodology, the guideline ensures scientific rigor, adaptability, and sustained relevance as evidence evolves. Clinicians are encouraged to stay informed about emerging paradigms—such as biomarker combinations or ratios and multi‐threshold testing—that may further refine the diagnostic accuracy of BBMs as the field evolves.

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.