Citations

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.

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 < .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 < .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

While most cases of human muscle-invasive bladder cancer (MIBC) are diagnosed as conventional urothelial carcinoma (UC), there is growing recognition of histologic subtypes and divergent differentiation within conventional UC. In this study, 31 dogs with UC (33 slides) were evaluated for histologic subtypes and divergent differentiation, as specified by the recent World Health Organization update on the classification of urinary bladder cancers. Slides were reviewed by a medical uropathologist and 3 board-certified veterinary pathologists and assessed for expression of uroplakin III, vimentin, and E-cadherin. All tumors were classified as UC. Fifteen cases were identified as conventional UC. Among the remainder, 8 displayed glandular differentiation, 4 were classified as sarcomatoid UC, 2 showed squamous differentiation, 1 case was classified as a large nested subtype, and 1 case was classified as a tubular/microcystic subtype. This study found a higher frequency of certain histologic subtypes and divergent differentiation in canine UC, particularly sarcomatoid UC and UC with glandular differentiation, compared to previous reports of both canine UC and human MIBC. The relatively high prevalence of the sarcomatoid UC and UC with glandular differentiation in dogs observed in this study suggests that canine UC may serve as a valuable translational model for evaluating novel therapeutic agents, particularly for these rare and aggressive subtypes in humans.

Abstract Aims The clinical significance of early recurrences during the blanking period following pulmonary vein isolation (PVI) remains uncertain, particularly after pulsed field ablation (PFA). This study aimed to evaluate the prognostic impact of early recurrences at 30-, 60-, and 90-day thresholds on outcomes following PFA for atrial fibrillation (AF). Methods and results Consecutive patients who underwent PFA for AF across multiple centres within the Mayo Clinic health system were included. The primary endpoint was AF-free survival. Kaplan–Meier and multivariate Cox regression analyses were performed to compare outcomes between patients with and without early recurrences using 30-, 60-, and 90-day thresholds. A total of 1162 patients were included. The estimated AF-free survival at 1 year was 70%. Early recurrences within 30-, 60-, and 90-days post-ablation were significantly associated with late recurrences beyond 90 days (hazard ratio [HR] 5.9, 95% confidence interval [CI] 4.4–7.9, P < 0.01; HR 6.6, 95% CI: 5.0–8.6, P < 0.01; and HR 9.1, 95% CI: 7.0–11.7, P < 0.01, respectively). These findings remained significant among patients undergoing continuous rhythm monitoring. Early recurrences within 30 days in this subgroup were significantly associated with a 1-year AF burden >1% or the need for repeat AF ablation (odds ratio 25.0, 95% CI: 6.6–126.8, P < 0.01). Conclusion Early recurrences following PFA are strongly predictive of long-term arrhythmia recurrence and are unlikely to represent transient inflammatory phenomena. Accordingly, the applicability of the conventional blanking interval after PFA should be reconsidered.

Abstract Background Artificial intelligence (AI)–based, mammography breast cancer risk prediction models show improved discriminatory accuracy relative to clinical risk models. However, data on their calibration are limited. This study compared model performance of 3 clinical breast cancer risk models: Gail, Tyrer–Cuzick v8, and Breast Cancer Surveillance Consortium v3 with the MIRAI AI-risk model. Methods Digital mammograms were ascertained from a screening mammography cohort of 12 308 women within the Mayo Clinic Biobank with 250 incident breast cancers (176 invasive) within 5 years. We predicted 5-year breast cancer risk, estimated discriminatory accuracy (C-index), and calibration (observed-to-expected ratio) of both overall and invasive breast cancer and compared estimates using bootstrapping approaches. Results MIRAI demonstrated similar or improved discriminatory accuracy of overall breast cancer (C-index = 0.71, 95% confidence interval [CI] = 0.68 to 0.74) and invasive breast cancer (C-index = 0.71, 95% CI = 0.67 to 0.75) compared with clinical models (overall breast cancer: C-index = 0.59-0.68; invasive breast cancer: C-index = 0.60-0.68). MIRAI’s calibration for risk of overall breast cancer (observed-to-expected ratio = 0.96, 95% CI = 0.85 to 1.08) was improved compared with Gail (observed-to-expected ratio = 1.22, 95% CI = 1.07 to 1.38) and Breast Cancer Surveillance Consortium (observed-to-expected ratio = 1.38, 95% CI = 1.22 to 1.56) but similar to TC with volumetric percent density and polygenic risk score (observed-to-expected ratio = 0.99, 95% CI = 0.87 to 1.13). However, for low-risk women (approximately 50%), MIRAI overestimated risk of overall breast cancer. MIRAI also overestimated risk of invasive breast cancer across the risk spectrum (observed-to-expected ratio = 0.68, 95% CI = 0.58 to 0.78), whereas clinical models had good calibration (observed-to-expected ratio = 0.86–0.99). Conclusion MIRAI demonstrated stronger discriminatory accuracy than clinical models for 5-year overall and invasive breast cancer risk prediction but overestimated risk for both breast cancer endpoints. AI-based risk models should consider discriminatory accuracy and calibration for invasive cancer before implementation.

OBJECTIVE: A definition of refractory septic shock is necessary to guide diagnosis, management, prognostication, research, and future guidelines for this most severe form of the disease. We sought to achieve consensus on clinical criteria that would be used to define refractory septic shock. DESIGN: Review of literature, expert panel position statements, and Delphi rounds with an international expert group. SETTING: Consensus was defined as having at least 75% of panellists in agreement or disagreement on the three highest or lowest levels of a 7-point Likert scale or based on responses to single- or multiple-choice questions, respectively. SUBJECTS: A panel of multinational, multiprofessional and multidisciplinary critical care experts assembled by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine (57 invitations and 56 participants). MEASUREMENTS AND MAIN RESULTS: A five-round Delphi process was conducted for consensus and stability. The steering committee proposed 34 statements, and five of them were rejected by panel experts after round 2. Among 29 statements selected from eight domains, consensus was reached for 13. The panel agreed on the need for a comprehensive consensus set of clinical criteria for refractory septic shock. Markers of organ dysfunction (75%, 2 rounds), tissue perfusion (91.1%, 2 rounds) including lactate (94.6%, 2 rounds) and capillary refill time (76.8%, 2 rounds), assessment of fluid-responsiveness after initial resuscitation (92.9%, 5 rounds), and use of vasoactive drugs at norepinephrine equivalents greater than 0.5 µg/kg/min (75.0%, 3 rounds), were selected as clinical criteria of refractory septic shock. The use of critical care ultrasound (CCUS) (92.9%, 3 rounds) was the single diagnostic modality that reached a consensus-based agreement. CONCLUSIONS: A consensus for 13 criteria to frame the definition of refractory septic shock was reached. Refractory septic shock is characterised by persistently elevated lactate concentrations and or prolonged capillary refill time in patients with septic shock who are fluid unresponsive, require a norepinephrine base equivalent dose greater than 0.5 micrograms per kilogram per minute, and undergo CCUS assessment when mixed shock is suspected.

ABSTRACT Evaluating patients following a COVID‐19 infection with multiple chronic, progressive symptoms can be challenging, but easy to navigate by using the temporal profile obtained from the clinical history, findings from the neurological exam, and screening for red flag symptoms.