Citations

ABSTRACT Introduction/Aims Eplontersen is approved in multiple regions for adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv‐PN). This exploratory analysis was conducted to evaluate the treatment effect of eplontersen by sex in patients with ATTRv‐PN from the NEURO‐TTRansform trial (NCT04136184). Methods Participants in NEURO‐TTRansform who received ≥ 1 dose of eplontersen were included in this analysis; participants in the inotersen reference group who switched to eplontersen were excluded. Eplontersen was evaluated in the overall patient population and in a subgroup with cardiomyopathy. Change from baseline in the NEURO‐TTRansform primary endpoints of serum transthyretin (TTR) levels to Week 65, modified Neuropathy Impairment Score +7 (mNIS+7) composite score to Week 66, and Norfolk Quality of Life‐Diabetic Neuropathy (Norfolk QoL‐DN) total score to Week 66 were evaluated. A historical placebo group from the NEURO‐TTR trial (NCT01737398) was included as a control. Results The eplontersen group comprised 100 (69.4%) male and 44 (30.6%) female patients. The placebo group comprised 41 (68.3%) male and 19 (31.7%) female patients. For both sexes, treatment with eplontersen decreased serum TTR levels by > 80% (vs. reductions of 3%–13% with placebo), maintained mNIS+7 scores, and improved Norfolk QoL‐DN scores (vs. deterioration with placebo). The treatment effect of eplontersen was similar in male and female patients with cardiomyopathy. Discussion Eplontersen halted neuropathy impairment and improved quality of life versus placebo to a similar degree in both male and female patients with ATTRv‐PN, including those with cardiomyopathy. These findings support the use of eplontersen as an effective treatment for ATTRv‐PN regardless of sex.

Abstract Background X‐ray Induced Acoustic Computed Tomography (XACT) is an emerging imaging technique that provides 3D volumetric images from a single projection by detecting X‐ray‐induced acoustic (XA) waves with ultrasound (US) transducers. Unlike MRI or CT, XACT enables real‐time 3D imaging without long acquisition times, 2D limitations, or motion artifacts from mechanical rotation. Furthermore, when integrated with conventional pulse‐echo US through time‐sequenced operation, XACT provides complementary soft‐tissue contrast, establishing it as a promising platform for dynamic interventional radiology (IR) guidance. Purpose This study aims to evaluate the feasibility of XACT as a novel imaging tool for IR, specifically for guiding needle placement and monitoring contrast agent dynamics. Methods We developed a 3D XACT imaging system equipped with a 256‐element 2D matrix array and a portable X‐ray tube to visualize needle insertion and contrast agent dynamics. To capture both needle position and soft tissue anatomy, we integrated a dual‐modality system combining XACT with pulse‐echo US using a 128‐element linear US array. Experiments were conducted on both tissue‐mimic phantoms and soft tissue samples. GPU‐accelerated algorithm has been developed for 3D XACT image reconstruction. Results The results demonstrate the 3D capabilities of XACT imaging for interventional procedures, including monitoring of needle placement and tracking of contrast agent dynamics. The imaging speed reached up to 3∼4 s per frame, constrained by the repetition rate of the X‐ray source and signal to noise ratio. The dual‐modality approach provided clear visualization of the needle's position and the surrounding soft tissue structures, achieving imaging resolution around 2 mm. Conclusions This study demonstrates that XACT imaging is feasible to be used for IR. Its 3D imaging capability with faster imaging speed would be an alternative to cone beam CT and its capability to combine US imaging will provide richer information for soft tissue

Despite the increasing prevalence and median severity of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), medical education on the disease is scant, leading to a diagnostic crisis in which the majority of people with ME/CFS are undiagnosed. We created a care process algorithm in AskMayoExpert accessible to all Mayo Clinic medical providers as a source for information on diagnosis and management of ME/CFS. To evaluate whether the algorithm was associated with improved diagnostic accuracy, we compared concordance before versus after the algorithm was introduced, where concordance was defined as agreement between an appropriately coded referral to Mayo Clinic’s Chronic Fatigue Specialty Clinic and the specialty clinic with an expert diagnosis of ME/CFS. Referrals to the Chronic Fatigue Specialty Clinic increased overall and were more likely to show concordance between specialist diagnosis and referral after the introduction of the ME/CFS AskMayoExpert algorithm. Particularly in diseases that are prevalent and poorly understood, a point-of-care clinical tool may offer just-in-time opportunities to improve diagnosis and management.

Summary Frailty is independently associated with significantly higher 1‐year mortality and MACCE following MTEER. Frail patients also demonstrated increased risks of HF exacerbation, major bleeding, and readmission. Incorporating frailty assessment into pre‐procedural evaluation may improve risk stratification and guide personalized management strategies.

ABSTRACT Importance Rural-urban disparities in chronic disease prevalence are well established; however, the extent to which individual-level socioeconomic status (SES) contributes to these disparities remains unclear. Objective To examine the associations of rurality and SES with the prevalence of five most burdensome chronic diseases among adults. Design We conducted a retrospective cross-sectional study of adults across 27 Upper Midwest counties using the Expanded Rochester Epidemiology Project (E-REP) medical record data linkage system to evaluate associations between rurality, SES and chronic disease prevalence. Prevalence of clinically diagnosed asthma, diabetes, hypertension, coronary heart disease, and mood disorders was identified from International Classification of Diseases ICD9/10 codes over a five-year period (2014-2019). Setting Population based Participants Adults over 18 years residing in the 27 E-REP counties, excluding those missing rural-urban residence status. Exposure HOUSES index, an individual-level measure of SES, served as the primary measure, while rurality based on Rural Urban Commuting Area (RUCA) codes 4-10 was the secondary measure. Main Outcome Prevalence of the five clinically diagnosed chronic diseases was identified using ICD9/10 codes from 2014–2019. Mixed effect logistic regression models were used and adjusted for demographics and general medical examination receipt, to assess rural-urban and SES differences for prevalence of each chronic disease. Results Among 455,802 adults with available HOUSES index, 42.8% lived in rural areas, 53.8% were female and 87.4% were non-Hispanic White. In the unadjusted analysis, rural and urban populations showed comparable asthma and CHD prevalence, while mood disorders, hypertension, and diabetes were more common in urban areas. After adjusting for demographic factors and healthcare utilization, rural-urban differences were no longer statistically significant, whereas SES remained strongly associated with all diseases in a dose response manner (e.g., adjusted Odds Ratio for hypertension (ref: HOUSES index Q4): 1.14, 1.27, and 1.42 for HOUSES index Q3, Q2, and Q1, respectively). Conclusions and Relevance Individual-level SES measured by the HOUSES index, was more strongly associated with chronic disease prevalence than rurality, supporting its integration into population health assessment and risk stratification.

Acute type A aortic dissection is a life-threatening condition requiring emergency surgery and complex postoperative management. Although survival rates have improved, many patients experience long-term functional impairments, reduced quality of life, and an elevated risk of complications. Despite strong evidence supporting cardiac rehabilitation in other cardiovascular populations, structured programs remain underutilized in patients with surgically resolved acute type A aortic dissection. Exercise-based cardiac rehabilitation appears feasible and can be delivered safely in carefully selected patients when appropriately adapted to individual needs and conducted under close supervision. Postoperative patients are often physically deconditioned, prone to hospital-acquired disability, and may misjudge exercise intensity. Therefore, individualized exercise prescription, guided by exercise testing when available, is important to support safe training thresholds. Early and gradual introduction of physical activity may help prevent complications associated with immobility, support blood pressure control, and contribute to improvements in functional capacity. However, training volume should be purposefully lower than in conventional program settings to reduce hemodynamic stress. Education on safe exercise parameters and self-monitoring plays a central role in enabling long-term adherence and promoting patient autonomy. Cardiac rehabilitation programs should incorporate dietary, nutritional, and psychological support. Although evidence specific to this patient population remains limited, available data suggest the feasibility and potential benefits of cardiac rehabilitation when delivered with appropriate precautions. Our review underscores the need for a tailored, multidisciplinary CR approach aimed at enhancing physical recovery, supporting cardiovascular stability, and improving overall quality of life in patients following surgery. Further research is required to define optimal program protocols.

Homeobox (HOX) transcription factors are encoded within highly organized loci expressed along an anterior–posterior axis through embryogenesis and in a pleiotropic manner in hematopoiesis. HOX expression has been exhaustively studied in the context of oncogenesis and malignancy, but the compensatory substitution of HOX paralogs makes mechanistic annotation in steady-state hematopoiesis challenging. Despite this, HOX genes reflect numerous non-redundant roles in healthy hematopoiesis including HSC self-renewal, development, lymphopoiesis, myelopoiesis, and erythropoiesis. Here, we review historical and current insights into HOX functions in steady-state hematopoiesis and highlight unexplored avenues in their biology that could further elucidate their significance to hematopoietic homeostasis.

Management of unstable upper lumbar fractures with corpectomy and posterior fixation is technically demanding, and conventional workflows may require intraoperative repositioning, increasing operative complexity. Lateral mini-open upper lumbar corpectomy (LMULC) paired with robotic-assisted (RA) posterior percutaneous pedicle screw fixation (PPPSF) can be performed in a single position to facilitate ventral spinal decompression and stabilization in the anatomically constrained upper lumbar spine. In this study, we describe the operative technique and report four illustrative cases of unstable L1 or L2 fractures treated with single-position LMULC, RA-PPPSF, and short-segment fusion. Clinical, radiological, intraoperative variables and postoperative outcomes were evaluated. The mean age was 52.3 ± 17.7 years. The median operation time was 314 min (range 268–361 min); the median estimated blood loss (EBL) was 225 mL (range 100–400 mL). The median preoperative kyphosis was 10.15° (range 8.4–14.6°), the median postoperative kyphosis measured 6.65° (range 1.7–10.8°) and the median correction achieved was 3.5° (range −2.4–12.9°). The median visual analog scale (VAS) pain score reduced from 7 (range 7–9) preoperatively to 4.5 (range 2–6) postoperatively at discharge. At a median follow-up of 12 months (range 6–15 months), all patients had uncomplicated recoveries, demonstrated solid fusion on imaging, and reported favorable MacNab outcomes. Single-position LMULC with RA-PPPSF was technically feasible in this preliminary illustrative series and resulted in favorable clinical and radiographic outcomes. However, further studies in larger cohorts are warranted to help confirm these findings and better define the potential advantages and limitations of this technique.

Background/Objectives: Machine learning (ML) models can predict hospital admission from emergency department (ED) triage data with areas under the receiver operating characteristic curve (AUC) exceeding 0.85. Whether incorporating the assigned provider’s identity—as a proxy for unmeasured practice variation—improves prediction has not been systematically studied. We aimed to compare 10 supervised ML classifiers for predicting hospital admission at ED triage, with and without provider identity, and to characterize model reasoning using SHapley Additive exPlanations (SHAP). Methods: We conducted a retrospective cohort study of 186,094 ED visits (2020–2023, training) and 58,151 visits (2024, temporal holdout test) at one academic tertiary-care ED. Ten classifiers spanning linear, distance-based, tree-based, ensemble, probabilistic, and neural network families were each trained in two conditions: baseline (23 triage features) and with provider identity appended. SHAP TreeExplainer was applied to the top-performing models (CatBoost and XGBoost). Results: The admission rate was 31.3% (training) and 31.7% (test). CatBoost achieved the highest baseline AUC of 0.8906 (0.8878–0.8933). Adding provider identity produced negligible AUC changes across all models (ΔAUC range: −0.0029 to +0.0015; all DeLong p > 0.05). SHAP analysis identified ESI level, respiratory rate, temperature, complaint category, and age as the dominant predictors, with clinically intuitive directionality. Conclusions: Provider identity does not meaningfully improve ML prediction of hospital admission beyond standard triage variables. The observed 28-percentage-point variation in provider admission rates is explained by patient case-mix differences than with independent practice pattern effects on prediction. SHAP provides transparent, clinically interpretable explanations suitable for bedside decision support.

Objective Gain‐of‐function variants in IDH1 and IDH2 are enriched among individuals with coexisting myeloid neoplasms and autoimmune diseases. However, the association between IDH1 / IDH2 variants and rheumatic diseases independent of hematologic neoplasms remains unclear. We investigated the association between rare gain‐of‐function and loss‐of‐function genetic variants in IDH1 and IDH2 and immune‐mediated rheumatic diseases. Methods Individuals with gain‐of‐function and loss‐of‐function variants in IDH1/IDH2 were identified by whole genome sequencing in the UK Biobank and the All of Us Research Program. These individuals were matched 1:10 to controls without IDH1 or IDH2 variants by age, sex, and ancestry. The frequency of immune‐mediated rheumatic diseases in the presence and absence of IDH1/IDH2 variants was compared using chi‐square or Fisher exact tests. Results Fifty‐five individuals with IDH1 or IDH2 gain‐of‐function variants without pre‐existing hematologic neoplasms were identified in the UK Biobank. These individuals had a significantly higher frequency of incident immune‐mediated rheumatic diseases compared to matched controls (11 of 55 [20%] vs 20 of 550 [4%], odds ratio [OR] = 6.6, P = 2.7 × 10 −5 ), mainly polymyalgia rheumatica (6 of 11) and rheumatoid arthritis (5 of 11). Replication in the All of Us cohort identified 65 individuals with gain‐of‐function variants and confirmed an increased odds of incident immune‐mediated rheumatic diseases compared to controls (OR = 7.7, P < 5 × 10 −4 ), predominantly rheumatoid arthritis. There was no association between loss‐of‐function variants in IDH1/IDH2 and immune‐mediated rheumatic diseases in either cohort. Conclusion Rare gain‐of‐function variants in IDH1 / IDH2 are associated with increased risk of immune‐mediated rheumatic diseases, particularly rheumatoid arthritis and polymyalgia rheumatica. image