Citations

Abstract Background Breast cancer chemoprevention is underutilized among high-risk women. We examined whether decision support could increase informed decision making. Methods We conducted a cluster randomized controlled trial to evaluate the effect of a patient-facing decision aid (RealRisks) and provider tool (BNAV) compared with standard education on the number of women with high-risk breast lesions making informed choices. Questionnaires were administered at baseline and 6 and 12 months. The primary outcome was chemoprevention informed choice (defined as adequate knowledge and attitudes congruent with decision) at 6 months. Secondary endpoints included breast cancer risk perceptions, worry, chemoprevention knowledge, decision conflict, and chemoprevention decision. Results Across 31 randomized sites, we enrolled 210 providers, who were primarily breast health specialists. Of these, 24 sites (14 intervention, 10 control) enrolled 412 patients. Among 287 patients evaluable for the primary outcome, there were no statistically significant differences in informed choice between the intervention and control arms at 6 months (35% vs 27%, respectively; P = .20) and 12 months (37% vs 25%, respectively; P = .05). At 6 months, women in the intervention compared with control arm were more likely to have accurate breast cancer risk perceptions (31% vs 21%, respectively; P = .03) and adequate chemoprevention knowledge (33% vs 23%, respectively; P = .04). At 12 months, 52% of women in the control and 50% in the intervention arm self-reported initiating chemoprevention. Conclusion Decision support led to modest improvements in accurate risk perceptions and chemoprevention knowledge but not informed choice. Relatively high chemoprevention uptake was achieved among women with high-risk breast lesions managed mainly by breast health specialists. Trial Registration NCT04496739, https://clinicaltrials.gov/study/NCT04496739?cond=NCT04496739&viewType=Card&rank=1

The Omicron variant of SARS-CoV-2 is associated with milder symptoms and lower hospitalization and mortality rates than Delta variants, although the impact of Omicron on immunocompromised patients, especially solid organ transplant (SOT) recipients, is still unclear. This study compares the hospitalization rate and outcomes between immunocompromised, immunocompetent, and SOT patients during the Delta and Omicron periods. We included adult patients who tested positive for SARS-CoV-2 on PCR or nasopharyngeal antigen test between 26 June 2021 to 8 September 2022, at our institution. A total of 12,401 COVID-19 patients were included, of which 11,055 were immunocompetent, and 1346 were immunocompromised (375 SOT recipients). Throughout the Delta and Omicron outbreaks, immunocompromised patients exhibited higher comorbidities and 30-day hospitalizations, but rates of mechanical ventilation and ICU-level care were like immunocompetent patients. During the Omicron wave, immunocompromised patients had higher unadjusted relative risk estimates (RR = 2.37, 95% CI 1.96–2.87, p < 0.05) than Delta (RR = 1.58, 95% CI 1.24–2.01, p < 0.05), with higher adjusted relative risk for hospitalization in Omicron (RR = 1.50, 95% CI 1.10–2.03, p = 0.01). Analyses show increased hospitalization risk in immunocompromised during the Omicron wave compared to the Delta wave, with no significant difference in hospitalization outcomes. The relative risk of hospitalization for SOT patients was higher in both waves.

Purpose To investigate outcomes among patients undergoing total hip arthroplasty after hip arthroscopy (HA‐THA) compared with a matched cohort undergoing primary THA without prior arthroscopy (Only‐THA). Methods Patients who underwent THA after primary hip arthroscopic labral repair from 2009 to 2022 at a single institution were identified. Cases were propensity‐matched 1:4 to primary THA controls by age at THA, sex, body mass index (BMI), surgical approach, and year of surgery. At minimum 2‐year follow‐up, patient‐reported outcomes (PROs)—Forgotten Joint Score (FJS), modified Harris Hip Score (mHHS), and Hip Disability and Osteoarthritis Outcome Score Pain (HOOS‐Pain)—were analyzed. Results Sixty‐two hips (age: 47.5 ± 9.3 years, BMI: 29.7 ± 6.2 kg/m 2 ) were matched to 248 Only‐THA hips (age: 47.9 ± 10 years, BMI: 29.5 ± 5.8 kg/m 2 ). Although both HA‐THA and Only‐THA patients showed significant ( P < .001) postoperative improvements in PROs, HA‐THA patients reported significantly lower postoperative FJS, mHHS, HOOS‐Pain, and inferior Visual Analog Scale pain scores ( P < .001) compared with Only‐THA controls. A cohort‐specific minimal clinical important difference for mHHS was calculated as 9.6 points, with 75.7% of HA‐THA and 87.5% Only‐THA patients achieving this threshold ( P = . 077). At mean 6.6 ± 3.3 years follow‐up, HA‐THA patients with preoperative Tönnis grades 1 reported significantly decreased FJS, mHHS, and HOOS‐Pain compared with HA‐THA patients with preoperative Tönnis grade 2‐3 ( P ≤ .05). HA‐THA patients with Tönnis grade 1 also exhibited worse PROs ( P < .001) compared with Only‐THA controls. Although there were no differences in complication rates between HA‐THA and Only‐THA patients (8% vs. 5%, P = .49), all‐cause reoperation was greater amongst HA‐THA (10% vs. 2%, P = .01). Conclusions Patients undergoing THA after prior hip arthroscopy showed modestly inferior subjective outcomes at mid‐term follow up compared with an age‐matched cohort without prior arthroscopy. Although both groups showed meaningful improvement, a smaller proportion of HA‐THA patients achieved the cohort‐specific MCID for mHHS compared with Only‐THA controls. Level of Evidence Level III, retrospective cohort study.

Abstract Aims Prognosis in tricuspid regurgitation (TR) is shaped by complex clinical and haemodynamic interactions, complicating risk stratification. We aimed to use explainable artificial intelligence (EAI) to model these relationships and identify key predictors of outcomes. Methods and results We analysed long-term all-cause mortality in a large prospective registry of patients with native TR across the full severity spectrum. Patients underwent detailed clinical evaluation and quantitative Doppler-echocardiography. Supervised EAI models were applied to identify and rank predictors of mortality under medical therapy, capturing non-linear associations and interactions among baseline characteristics. Among 9761 patients [mean age 73 ± 15 years; 56.9% women; effective regurgitant orifice area (EROA) 40 (30–56) mm2; regurgitant volume 39 (29–53) mL/beat; 42% severe TR], 2676 deaths occurred during 3.8 ± 4.6 years of follow-up. EAI identified and ranked 20 prognostic determinants of survival. Haemodynamic measures, led by elevated pulmonary-artery systolic and right-atrial pressures, were strongest, followed by age and comorbidity. TR-related variables ranked next, led by right ventricular dysfunction and EROA, which outperformed integrative TR grade and TRIScore. Left-ventricular parameters were less influential. Non-linear effects, including those involving ejection fraction, and interactions such as higher EROA-related risk with elevated pulmonary pressures or lower TRIScore (both P &lt; 0.03) were observed. Proportional hazards models confirmed EROA as the strongest TR severity marker (P &lt; 0.0001), with excess mortality beginning at 40 mm2 and increasing further at 60 mm2. Conclusion EAI ranked mortality predictors in TR, highlighting patient factors, haemodynamics, TR-specific measures, and left-ventricular function. Among TR-specific measures, EROA and TRIScore were most prognostic. Recognizing their impact can refine risk stratification, guide intervention timing, and inform long-term management.

Abstract TAR DNA-binding protein 43 (TDP-43) pathology frequently co-occurs with Tau neurofibrillary tangles (NFTs) and amyloid β plaques in Alzheimer’s disease (AD), driving significant clinical heterogeneity. Whether TDP-43 engages autonomous molecular programs or instead amplifies Tau-driven neurodegeneration remains difficult to resolve, largely because these pathologies often co-occur. To separate these overlapping signatures, we generated regionally resolved transcriptomic profiles from cognitively normal controls (Controls), neuropathologically defined cohorts of AD, AD with limbic-predominant age-related TDP-43 encephalopathy (AD/LATE), and frontotemporal lobar degeneration (FTLD-TDP), categorizing them by their distinct TDP-43 subtypes (types α and β for AD/LATE; types A and B for FTLD-TDP). By integrating transcriptomic profiles with quantitative measures of phosphorylated TDP-43 (pTDP-43) and Tau (pTau), we separated pathology-associated signals within mixed disease contexts. We found that TDP-43 is linked to distinct transcriptomic programs in AD/LATE that are largely uncoupled from Tau burden and diverge from those observed in FTLD-TDP. These signatures showed regional specificity, with transcriptomic remodeling occurring in the amygdala across both diseases, whereas frontal cortex alterations were largely restricted to FTLD-TDP. Furthermore, by stratifying cases by TDP-43 morphological subtype, we unmasked specific biological trajectories, from immune activation to unique cellular vulnerabilities, that are not apparent in unstratified cohorts. Together, our findings provide a framework for decoupling mixed proteinopathies and demonstrate that TDP-43 shapes autonomous, subtype-dependent transcriptional landscapes in AD.

Abstract INTRODUCTION Face identification algorithms have increased the risk of study participants being identified through different neuroimaging modalities. De‐facing algorithms can de‐identify neuroimages; however, none are validated in individuals with Down syndrome (DS) – a population at high risk of Alzheimer's disease and the focus of numerous Alzheimer's disease cohort studies. METHODS Overall, 37 adults with DS were parcellated using FreeSurfer before and after de‐facing with mri_reface . A group of neurotypically developed individuals balanced on age, sex, and magnetic resonance imaging scanner manufacturer served as controls. RESULTS De‐facing produced no effect on cortical thickness or volumetrics in adults with DS compared to controls or regional discrimination based on an area under the receiver operating characteristic curve analysis after correcting for multiple comparisons. DISCUSSION FreeSurfer‐derived volumetric and cortical thickness measures changed minimally following de‐facing with mri_reface in adults with DS and are unlikely to influence study outcomes. De‐facing should be considered prior to data sharing in studies of adults with DS.