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Background: Sinonasal malignancies (SNM) are rare cancers associated with poor prognosis and impaired quality of life (QOL). The 22-question Sino-Nasal Outcome Test (SNOT-22) has been used to assess QOL in patients with SNM. Objective: To determine the minimal clinically important difference (MCID) for the SNOT-22 in patients with SNM. Methods: About 264 patients with SNM were drawn from a prospective, longitudinal, multi-institutional study. SNOT-22 scores were collected at pre-treatment baseline and follow-up through 5 years post-treatment. Cronbach’s alpha was used to assess the internal consistency of the SNOT-22. Distribution-based approaches were used to estimate the MCID. Multivariable regression identified factors associated with SNOT-22 improvement exceeding the determined MCID. Results: Cronbach’s alpha was >.85. The estimated MCIDs were: 1.44 (Cohen’s effect size), 1.32 (standard error of the mean), 10.45 (1/2 of baseline standard deviation), and 3.67 (minimum detectable change). The mean MCID across methods was 4.22. Multivariable regression demonstrated higher odds of clinically meaningful improvement from baseline in patients with early-stage disease (odds ratio (OR) 3.510, P = .035), no neck irradiation (OR 11.050, P = .014), and neoadjuvant therapy (OR 16.667, P = .047). Conclusions: The SNOT-22 MCID was estimated as 4.22 in a large multi-center cohort of patients with SNM, suggesting that relatively small QOL changes are clinically relevant. When applying the MCID to the current cohort, advanced stage, treatment of neck disease, and not requiring neoadjuvant therapy were predictive of worse QOL.

PURPOSE Gastroesophageal carcinoma (GEC) is increasingly managed using biomarker-guided therapies. Although both tissue DNA (tDNA) and circulating tumor DNA (ctDNA) testing are used clinically, the concordance of genomic alterations between primary tumors, metastatic sites, and liquid biopsy remains incompletely understood. METHODS We retrospectively analyzed 345 patients with GEC who underwent ctDNA testing at Mayo Clinic. tDNA next-generation sequencing and immunohistochemistry (IHC) for human epidermal growth factor receptor 2 (HER2)/erb-b2 receptor tyrosine kinase 2 ( ERBB2 ) and mismatch repair (MMR) were collected. Concordance was evaluated between ctDNA and tDNA, ctDNA and IHC, and across all three modalities, using 60-day and 30-day intervals. RESULTS Among 345 patients with ctDNA testing, 186 had tDNA testing, and 310 underwent IHC. ctDNA testing showed a shorter turnaround time than tDNA (median 6 v 13 days). The most frequent alteration in ctDNA, primary tDNA, and metastatic tDNA was TP53. Concordance between ctDNA and primary tDNA was ≥78.8% for key genes; between ctDNA and metastatic tDNA, it was ≥84.8%. IHC-ctDNA concordance was higher in metastatic tumors, with 91.1% for HER2/ ERBB2 and 97.7% for mismatch repair (MMR)/microsatellite instability (MSI) compared with 81.1% and 95.8%, respectively, in primary tumors. Triplet concordance for MSI/MMR was 97.6% in primary tumors and 100% in metastatic tumors, while ERBB2 /HER2 showed 84.4% and 93.9% concordance, respectively. ctDNA temporal heterogeneity analysis revealed 14 patients with fluctuating ERBB2 status and 3 with fluctuating MSI-H status. CONCLUSION ctDNA testing demonstrates high concordance with tDNA and IHC and offers faster turnaround. Given its minimally invasive nature and strong concordance with tissue-based testing, ctDNA is a reliable tool for genomic profiling and longitudinal monitoring in GEC.

PURPOSE The primary objective of this randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was to screen two doses of duloxetine for preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN). METHODS Participants were randomly assigned 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine, or placebo. Eligible participants had stage II to III colorectal cancer and no baseline neuropathy, had Eastern Cooperative Oncology Group performance status 0-2, were age 25 years and older, and received oxaliplatin via one of the following doses and schedules: 85 mg/m 2 every 2 weeks (6 or 12 doses) or 130 mg/m 2 every 3 weeks (4 doses). Duloxetine/placebo was taken once daily beginning day 1 of cycle 1 and continued for 17 weeks. The primary end point, a composite response reflecting sensory OIPN symptom severity and onset, was measured in weeks 19-21 using a validated participant-reported outcome survey assessing extremity numbness, tingling, and pain. Response was defined as a participant-reported highest score of ≤2 (ie, 1 = not at all; 2 = a little) on survey items. To be evaluable for the response end point, eligible participants must have initiated oxaliplatin and submitted ≥1 postbaseline OIPN survey. RESULTS Of the 199 participants (n = 66, 30 mg duloxetine; n = 66, 60 mg duloxetine; n = 67, placebo), 46, 47, and 50 (N = 143, 71.8%), respectively, were evaluable for primary end point analysis based on modified intention-to-treat criteria. Participant mean age was 55.1 years (standard deviation = 10.4). Most were White (n = 113, 80.7%) and male (n = 82, 58.6%). The proportion of responders among those receiving placebo (68.0%) was similar to those receiving duloxetine 30 mg (65.2%) or 60 mg (66.0%). Duloxetine adherence rates, measured via pill counts—30 mg (54%), 60 mg (57%), and placebo (59%) groups—were low (<75%). CONCLUSION Duloxetine is not more promising than placebo for preventing sensory OIPN.

Abstract Purpose: This multicenter, single-arm, phase II trial evaluated the safety and efficacy of cabazitaxel and carboplatin followed by abiraterone, plus androgen deprivation therapy (ADT), in patients with high-volume metastatic castration-sensitive prostate cancer (mCSPC). Patients and Methods: Eligible patients had high-volume mCSPC and ≤3 months of prior ADT. Patients received six 21-day cycles of cabazitaxel (20 mg/m2) and carboplatin (AUC 4) with continuous ADT, followed by maintenance abiraterone (1,000 mg daily) and prednisone (5 mg daily). The primary endpoint was the proportion of patients free of prostate-specific antigen (PSA) or radiographic progression at 12 months. Secondary endpoints included complete PSA response (≤0.2 ng/mL), objective response, progression-free survival (PFS), and safety. Overall survival (OS) was also reported. Results: Sixty-one participants were enrolled at eight sites. The median age was 64 years, median baseline PSA was 6.6 ng/mL (0.07–745.7 ng/mL), 73.3% had Gleason grade group 5, 69.5% had 10 or more metastases, and 19.6% had a homologous recombination repair (HRR) mutation. PSA PFS at 12 months was 84.6% [95% confidence interval (CI), 72.5%–91.7%], and OS at 12 months was 94.8% (84.7%–98.3%). Complete PSA response was 66.7%, and complete objective response was 30.7%. Contrary to our hypothesis, relative to HRR wild-type patients, HRR-mutated patients (19.6%) had numerically fewer complete PSA responses (33.3% vs. 70.3%) and inferior PFS (HR, 2.43; 95% CI, 0.93–6.39). Common side effects of this quadruplet regimen included fatigue, nausea, and diarrhea. Conclusions: Cabazitaxel and carboplatin followed by abiraterone, together with ADT, were feasible, safe, and efficacious in patients with high-volume mCSPC and warrant further study in larger randomized trials.

Abstract Purpose: Standard care for high-grade gliomas (HGG) involves maximal surgical resection followed by radiation and temozolomide. Postoperative adjuvant therapy frequently causes lymphopenia, which is associated with poor prognosis. Interleukin 7 (IL7) is essential for lymphocyte development, homeostasis, and survival. NT-I7 (efineptakin alfa), a long-acting recombinant IL7, reverses lymphopenia and improves survival in murine glioma models. However, the safety, maximum tolerated dose (MTD), and impact of NT-I7 on immune cells in patients with HGG remain unknown. Patients and Methods: We conducted a phase I trial (NCT03687957) examining the MTD and effect of NT-I7 on lymphocytes in patients with newly diagnosed HGG. The primary endpoint was dose-limiting toxicity; secondary endpoints included absolute lymphocyte count (ALC) changes over time, overall response, progression-free survival, and overall survival. Exploratory endpoints included immune profiling at different time points using single-cell RNA sequencing (scRNA-seq) in a subset of patients. Results: NT-I7 was well tolerated with a MTD of 720 µg/kg. Moreover, NT-I7 significantly increased ALCs for more than 12 weeks in duration. Early elevations in CD4+, CD8+ T cells and NK cells further coincided with increased TNF and CXCL9 cytokine levels. Comprehensive immune profiling of peripheral blood T cells revealed selective clonotype expansion within CD8+, but not CD4+, T cells following NT-I7 administration. Finally, a subset of our patients with MGMT promoter–unmethylated glioblastoma, which are typically associated with a poorer prognosis, demonstrated promising clinical responses. Conclusions: NT-I7 has the potential to maintain and increase lymphocyte counts in patients with HGG and warrants further investigation, particularly in combination with immune-based therapies.

Importance Left atrial appendage occlusion (LAAO) is used in patients with contraindications to oral anticoagulation, who are at increased risk for major bleeding (MB). Objective To evaluate the incidence, predictors, management, and clinical outcomes of MB after LAAO in the Amulet IDE trial. Design, Setting, and Participants The randomized clinical Amulet IDE trial enrolled patients from 2016 through 2019 with 5-year follow-up. Procedures were performed at specialized LAAO centers. Of 1878 randomized patients (1:1 Amulet vs Watchman), 1833 underwent attempted LAAO implantation. These data were analyzed from May 2025 through November 2025. Main Outcomes and Measures Pooled (Amulet and Watchman) patients with vs without MB (Bleeding Academic Research Consortium [BARC] score ≥3: overt bleeding with transfusion and ≥3 g/dL hemoglobin drop) were compared. Results This study included a total of 1833 patients (57.7% male and 42.3% female; mean [SD] age, 75.8 [7.5] years). MB occurred in 331 patients (18.1%) over 5 years (annualized rate 5.9% per year). Patients with MB were older (76.8 vs 74.7 years) and had higher CHA 2 DS 2 -VASc (4.8 vs 4.6) and HAS-BLED (3.4 vs 3.2) scores, as well as greater prevalence of diabetes (38.7% vs 34.1%), prior MB (45.3% vs 28.0%), and kidney disease (9.4% vs 4.5%). MB risk was highest in the first 6 months after LAAO (20.5% per year), then decreased to 3.9% per year through 5 years. Most MB events were nonprocedural (88.8%) with gastrointestinal bleeding accounting for 252 of 438 events. Independent predictors of MB included increasing age (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06), female sex (HR, 1.25; 95% CI, 1.01-1.56), diabetes (HR, 1.26; 95% CI, 1.01-1.58), prior MB (HR, 1.93; 95% CI, 1.55-2.40), and kidney disease (HR, 2.15; 95% CI, 1.48, 3.12). At first MB event, 47.1% of patients were not receiving antithrombotic therapy and 92 patients had recurrent events. Patients with MB had significantly higher rates of the composite of stroke, systemic embolism, or cardiovascular death (32.5% vs 18.0%; P &amp;lt; .001), driven by higher stroke (14.7% vs 6.6%) and cardiovascular death (24.4% vs 12.9%) rates. All-cause mortality was also higher (49.2% vs 25.4%; P &amp;lt; .001). MB was fatal (BARC score of 5) in 25 patients (1.4%). Conclusions and Relevance In this study, MB was common in this high-risk population and largely related to underlying patient factors. Early MB risk was highest 6 months post-LAAO, then dropped considerably. Most events were gastrointestinal and occurred even in patients on minimal or no antithrombotic therapy. MB after LAAO was strongly associated with increased stroke and mortality. Trial Registration ClinicalTrials.gov Identifier: NCT02879448

Aim To determine whether there is a difference in the time to complete a rapid number naming task during the interictal state compared to prodrome, migraine headache, postdrome phases of migraine and non-migraine headache, and characterize non-headache symptoms experienced during these phases. Methods This prospective longitudinal cohort study evaluated 30 adults with migraine with or without aura who completed diary entries and a timed rapid number naming task at least three times daily for up to four months from October 2020 to July 2022 at a tertiary headache center. Diary entries included self-report of current migraine phase (having a migraine headache, non-migraine headache, prodrome, postdrome, or interictal baseline) and detailed symptoms experienced. The outcome of interest for the timed rapid number naming task was the time to complete the task with zero errors. Results Compared to the interictal baseline, the time with zero errors for the rapid number naming task was significantly slower during the prodrome (median (Q1, Q3) 1.0 s slower (0.4, 2.9), p -value 0.010), migraine headache (median (Q1, Q3) 3.8 s slower (2.6, 7.5), p -value <0.001), and postdrome (median (Q1, Q3) 0.9 s slower (0.2, 2.1), p -value 0.011) phases of migraine, and non-migraine headache attacks (median (Q1, Q3) 1.2 s slower (0.1, 3.1), p -value 0.006). For those with migraine with aura (N = 15), the time with zero errors was significantly slower during all phases compared to interictal phase. For those with migraine without aura (N = 15), the time with zero errors was significantly slower only during the migraine headache, but not other phases compared to the interictal phase. The top 5 most reported non-headache symptoms during any phase of migraine and non-migraine headache attacks included fatigue, neck stiffness, light sensitivity, blurred vision/vision changes, and difficulty concentrating. Conclusions Among the overall participant cohort, the time with zero errors to complete a rapid number naming task was significantly slower during all ictal phases compared to interictal phase. This was also the case in the migraine with aura cohort but in the migraine without aura cohort there was only a significant difference during the migraine headache phase versus interictal phase. There is overlap in non-headache symptoms between the prodrome, migraine headache, postdrome, and non-migraine headache phases, which may make distinguishing between these phases difficult. Combining subjective data, such as symptom diaries, with objective measures, such as rapid number naming tasks, may allow for more refined assessment of migraine phases and distinguishing migraine from non-migraine headache attacks.

Background Kidney transplantation offers substantial clinical and economic benefits for patients with end-stage kidney disease (ESKD), yet organ shortages persist. Enhancing public awareness and health literacy regarding kidney donation is essential for effective donor recruitment. While online patient education materials are primary drivers of public perception, their readability, digital engagement, and accessibility remain underexplored barriers. Methods We analyzed the most prominent kidney donation websites identified through U.S.-based Google searches, including 11 primary organizations and 16 affiliated subdomains, for a total of 27 websites. Readability was benchmarked using Flesch-Kincaid, SMOG, and Gunning Fog indices. To assess qualitative metrics, we deployed a generative AI framework utilizing a Large Language Model (Claude) to conduct automated sentiment analysis and tone evaluation, validated by human review. We systematically mapped digital engagement features, including multimedia, interactive tools, and multilingual support, to determine content comprehensiveness. Results Websites consistently provided accurate information with a generally positive or neutral tone. Average readability exceeded recommended levels, with a combined mean grade of 12.3; 34% of websites were written at a college-level reading standard. Consensus across content was high. Multimedia elements were widely used, but engagement features were limited; only 30% of sites included extensive testimonials, and interactive tools were absent. AI-based analysis enabled standardized and reproducible evaluation, highlighting opportunities to improve accessibility, tone, and inclusivity. Conclusion Current U.S. kidney donation digital resources present a barrier to health equity due to excessive reading complexity and static engagement models. AI provides a scalable, reproducible framework to audit and optimize patient education materials. Future initiatives must leverage AI-guided content optimization to bridge the literacy gap, potentially increasing donor registration and access to transplantation.

Abstract We aim to compare the benefits, harms, and costs of multiple plastic stents (MPS) versus covered self-expandable metallic stents (CSEMS) in the treatment of benign biliary strictures (BBS). A comprehensive database search through June 6, 2024 identified randomized controlled trials (RCT) involving adult patients with BBS comparing MPS to CSEMS in terms of stricture resolution, recurrence, technical success, number of required procedures and stents, treatment duration, all-cause mortality, adverse events, and stent migration. We utilized the Cochrane Risk of Bias (RoB) tool2 for study quality assessment. Meta-analysis following the random effects model was performed. After screening 365 references, we included 7 RCTs (high RoB) involving 594 patients. Most reported stricture etiology is chronic pancreatitis (52.4%), followed by orthotopic liver transplant (40.5%). Compared with MPS, CSEMS achieved similar efficacy and safety. However, CSEMS required fewer procedures (mean difference [MD]: −1.84 [−2.56 to −1.11]; I2 = 76%) and stents (MD: −6.04 [−9.55 to −2.52]; I2 = 93%), amounting for shorter duration of treatment (MD: −119.02 days [−137.41 to −100.62]; I2 = 96%) and savings in costs between 41 and 57% with absolute savings of 4,019$ to 9,192$ favoring CSEMS. All outcomes had a low to very low certainty of evidence (CoE), except for technical success and stricture resolution (moderate CoE). Our analysis suggests that CSEMSs are comparable to MPSs in terms of efficacy and safety. However, it shows that CSEMSs are more cost-effective. Sample size calculations from our analyses can guide the design of future studies to validate the safety profiles and determine the feasibility of the two modalities.

Abstract Coronary artery bypass graft (CABG) surgery is one of the most commonly performed surgeries in the United States. It remains the gold standard of coronary artery revascularization despite the introduction of percutaneous coronary interventions and advancements in medical therapy. First conceptualized in the 1900s, CABG underwent decades of trials, experimentation, innovations, and even failures. Despite the challenges, CABG continued to innovate, overcoming the complexities of coronary artery disease and improving patient outcomes. This manuscript aims to discuss the beginnings, evolution, and future of CABG.