Citations

Abstract Cerium oxide (CeO 2 ) nanozymes have emerged as a novel class of nanozyme materials distinguished by their tunable valence states (Ce 3+ /Ce 4+ ) and abundant surface oxygen vacancies (OVs), demonstrating exceptional chemical stability, cost‐effectiveness, and scalable manufacturability. Precise control of reaction temperature or implementation of carrier‐mediated crystal growth strategies effectively enhances nanoparticle dispersion and mitigates aggregation. This review systematically summarizes recent advancements in CeO 2 nanozymes: First, it elaborates on cutting‐edge synthetic methodologies, encompassing self‐supported strategies (calcination, hydrothermal, and sol–gel) and carrier‐mediated approaches (small‐molecule compounds, macromolecular compounds, and nanomaterials), with comparative analysis of their respective merits and limitations. Second, the catalytic mechanism is comprehensively elucidated, particularly focusing on the modulation of electron transfer kinetics and surface adsorption energies in metal/nonmetal hybrid systems. By optimizing oxygen vacancy concentration to regulate Ce 3+ /Ce 4+ redox cycling dynamics, significant enhancement in redox efficiency and catalytic stability can be achieved, enabling precise enzyme‐like activity regulation. Furthermore, the review comprehensively summarizes breakthrough applications in multidimensional biomedical fields, including precision tumor therapy, intelligent antibacterial systems, inflammatory microenvironment regulation, and ultrasensitive biosensing. This work establishes a theoretical framework for structure‐activity relationship‐guided rational design of high‐performance CeO 2 nanozymes and delineates their potential translational applications in precision medicine.

Radioiodine ablation therapy is commonly used for patients with well-differentiated thyroid cancer. False-positive radioiodine uptake in benign cystic lesions on post-therapy SPECT/CT presents a recognized diagnostic challenge. Here, we present the case of a 33-year-old woman who underwent total thyroidectomy, followed by I-131 radioiodine therapy. Her post–I-131 therapy SPECT/CT revealed incidental radioiodine uptake in a diaphragmatic mesothelial cyst, prompting further investigation. She subsequently underwent a dedicated liver MRI and excision biopsy, both of which were negative for thyroid cancer metastasis. This case highlights the importance of identifying benign sources of radioiodine uptake to avoid unnecessary interventions.

Background/Objectives: Abnormal brain glycerolipid metabolism has been reported for Alzheimer’s disease (AD). This includes both diacylglycerols (DGs) and monogalactosyl-DGs (MGDGs), which are elevated in AD subjects. While DGs are also elevated in subjects with mild cognitive impairment (MCI), MGDGs have not yet been examined at this early stage of cognitive impairment. Methods: MGDG, triacylglycerol (TG), and ether glycerolipid levels in the cerebral cortex gray matter of controls, MCI, and non-demented Alzheimer’s neuropathology (NDAN) subjects were monitored by high-resolution mass spectrometry (<2 ppm mass error). Results: MGDG, MGDG ether, DG ether, and TG levels were elevated in the cerebral cortex of MCI but not NDAN subjects. Conclusions: A diverse array of glycerolipids was elevated in MCI subjects, suggesting a role in cognitive dysfunction. This suggestion is further supported by the maintenance of normal glycerolipid levels in NDAN subjects with amyloid accumulation but not cognitive deficits. Our data clearly indicate that while complex lipid alterations occur in MCI subjects, relative to controls 20 years younger, no such lipid alterations occur in NDAN subjects. While amyloid deposition in MCI is not involved in the observed lipid alterations, other ongoing neuropathologies may contribute to changes in lipid dynamics and vice versa.

Background Early onset Parkinson's disease (EOPD), defined as Parkinson's disease (PD) diagnosed before age 50, often presents unique challenges compared to late-onset PD, particularly with regard to non-motor symptoms. Psychosis in EOPD is associated with increased functional impairment and may lead to a higher mortality risk. Objective Our study is aimed to determine the prevalence of psychosis in EOPD patients and its impact on all-cause mortality, along with examining the effects of antipsychotic medications and Selective Serotonin Reuptake Inhibitors (SSRIs) on mortality in EOPD patients. Methods Our retrospective cohort included EOPD patients diagnosed between 1990 and 2022 at Mayo Clinic, Rochester, Minnesota. Psychosis was defined using the National Institute of Neurological Disorders and Stroke/the National Institute of Mental Health (NINDS/NIMH) Work Group criteria. Cox proportional hazards models were used to analyze the association of psychosis and medications with mortality. Results Of 829 patients with EOPD, 158 (19.1%) developed psychosis at a median of 12.1 years after PD motor symptom onset. Psychosis was significantly associated with increased mortality in unadjusted (HR = 4.31, 95% CI: 2.59–7.18, p < 0.001) and adjusted (HR = 3.55, 95% CI: 2.10–6.01, p < 0.001) models. No significant difference in mortality risk was observed between patients treated with antipsychotics or SSRIs versus those who were not. Conclusions Psychosis is a possible complication in EOPD and is associated with a significant increase in all-cause mortality. The use of antipsychotics and SSRIs did not significantly alter the mortality risk in these patients. Further research is needed to understand the mechanisms driving this association and to develop tailored interventions.

OBJECTIVE Patients with growth hormone (GH)–secreting pituitary adenomas (PAs) experience various symptoms and comorbidities, which can ultimately lead to increased mortality. This study aimed to develop and validate a machine learning (ML) model for predicting long-term outcomes in patients with GH-secreting PAs following endonasal transsphenoidal surgery (ETS). METHODS The authors conducted a retrospective three-institution cohort study that included patients with GH-secreting PAs treated with ETS between 2013 and 2023. Clinical, radiological, and biochemical data were collected. The main outcome of interest was the intervention-free rate (IFR) after primary ETS. Supervised ML algorithms, including decision trees and random forests, were developed to predict the IFR. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC) and Shapley Additive Explanations (SHAP) values. RESULTS The median follow-up for 100 patients with GH-secreting PAs (53% female) was 64 months (range 1–130 months). Additional intervention for persistent or recurrent acromegaly was required in 32% of patients. Following primary ETS alone, the 3-year IFR was 70% and the 5-year IFR was 67%. Multiple ML models were developed and evaluated using AUROCs. The decision tree analysis achieved an accuracy of 81% and emphasized the importance of both gross-total resection (GTR) and patient age in determining the long-term IFR. To better understand the factors that contributed to model performance, SHAP analysis was applied to the best-performing model. The SHAP dependence plots showed that key factors associated with a longer IFR included tumor size < 9 mm, GTR, patient age > 65 years, and Knosp grade 0. CONCLUSIONS This ML model offers a more nuanced and potentially more accurate approach to identify patients more likely to develop recurrent or persistent acromegaly following primary ETS and require additional treatment. Following external validation, this ML model could improve personalized treatment planning and follow-up strategies and enhance patient care and resource allocation in clinical practice.

OBJECTIVE Coexisting medical conditions are increasingly prevalent in surgical populations. The impact of multiple comorbidities on patient-reported outcomes (PROs) and endotypes of frequently co-occurring conditions for cervical spondylotic myelopathy (CSM) remain unclear. This study explores whether CSM patients with multimorbidity have worse baseline and postoperative PROs and less functional improvement after surgery compared to those with few or no comorbidities. The authors also investigated whether distinct comorbidity endotypes exist among CSM surgical patients and whether they influence postoperative outcomes. METHODS The prospective Quality Outcomes Database (QOD) was used to assess patients undergoing surgery for CSM. Multimorbidity was defined as ≥ 2 chronic conditions, including diabetes, coronary artery disease, peripheral vascular disease, arthritis, chronic renal disease, chronic obstructive pulmonary disease, Parkinson’s disease, multiple sclerosis, depression, and anxiety. Baseline characteristics and 24-month PROs were assessed across multiple-comorbidity status, including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), visual analog scale for neck and arm pain, EQ-5D, and patient satisfaction scores. Clusters were identified from the full cohort using k-medoids, revealing subgroups with similar comorbidity endotypes. RESULTS The final cohort included 1141 CSM patients (83.1% reaching 24-month follow-up), with 761 (66.7%) having 0 or 1 comorbidity and 380 (33.3%) ≥ 2 comorbidities. The multimorbidity cohort was older (mean age 62.6 ± 11.2 vs 59.5 ± 12.0 years, p < 0.001), more likely to be female (52.9% vs 44.7%, p = 0.011), and had a higher BMI (mean 31.1 ± 6.7 vs 29.7 ± 6.2 kg/m 2 , p < 0.001). Multimorbidity patients exhibited worse mJOA, NDI, and EQ-5D scores at baseline and 24 months (p < 0.05). On multivariable analysis, the total number of comorbidities was not significantly associated with any PRO measures. Four comorbidity clusters were identified: low burden, arthritis, diabetes, and high burden. On one-way ANOVA, the baseline mJOA score was significantly different across clusters (p = 0.003). At 24 months, the mJOA score was significantly lower in the diabetes and high-burden endotypes. Twenty-four-month score change and minimal clinically important difference (MCID) achievement of all PROs remained similar across clusters (p > 0.05). CONCLUSIONS While patients with multimorbidity have worse baseline and postoperative PROs, they achieve similar functional and pain-related improvements following CSM surgery. Similarly, the comorbidity endotypes identified in this QOD cohort suggest that certain patterns of coexisting chronic conditions, such as overlapping diabetes and arthritis, are associated with different levels of disability but may not diminish the effectiveness of surgical intervention.

OBJECTIVE Mechanical complications are a vexing occurrence after adult spinal deformity (ASD) surgery. While achieving ideal spinal alignment in ASD surgery is critical, alignment alone may not fully explain all mechanical complications. The authors sought to determine which combination of inputs produced the most sensitive and specific machine learning model to predict mechanical complications using postoperative alignment, bone quality, and soft tissue data. METHODS A retrospective cohort study was performed in patients undergoing ASD surgery from 2009 to 2021. Inclusion criteria were a fusion ≥ 5 levels, sagittal/coronal deformity, and at least 2 years of follow-up. The primary exposure variables were 1) alignment, evaluated in both the sagittal and coronal planes using the L1–pelvic angle ± 3°, L4–S1 lordosis, sagittal vertical axis, pelvic tilt, and coronal vertical axis; 2) bone quality, evaluated by the T-score from a dual-energy x-ray absorptiometry scan; and 3) soft tissue, evaluated by the paraspinal muscle–to–vertebral body ratio and fatty infiltration. The primary outcome was mechanical complications. Alongside demographic data in each model, 7 machine learning models with all combinations of domains (alignment, bone quality, and soft tissue) were trained. The positive predictive value (PPV) was calculated for each model. RESULTS Of 231 patients (24% male) undergoing ASD surgery with a mean age of 64 ± 17 years, 147 (64%) developed at least one mechanical complication. The model with alignment alone performed poorly, with a PPV of 0.85. However, the model with alignment, bone quality, and soft tissue achieved a high PPV of 0.90, sensitivity of 0.67, and specificity of 0.84. Moreover, the model with alignment alone failed to predict 15 complications of 100, whereas the model with all three domains only failed to predict 10 of 100. CONCLUSIONS These results support the notion that not every mechanical failure is explained by alignment alone. The authors found that a combination of alignment, bone quality, and soft tissue provided the most accurate prediction of mechanical complications after ASD surgery. While achieving optimal alignment is essential, additional data including bone and soft tissue are necessary to minimize mechanical complications.

Aims The use of jumbo femoral heads, defined as those with a diameter of ≥ 40 mm, in primary total hip arthroplasty (THA) has gained popularity, to mitigate dislocation. The aim of this study was to determine the risk of dislocation, implant survival, and clinical outcomes of a large cohort of primary THAs with jumbo femoral heads. Methods We conducted a retrospective analysis of 1,828 primary THAs with jumbo femoral heads, which were undertaken for osteoarthritis, in 1,578 patients between January 2000 and December 2022, at a single academic medical centre. The femoral head diameter was 40 mm in 1,584 THAs (87%) and 44 mm in 244 THAs (13%). The outer diameter of the acetabular component ranged from 52 mm to 72 mm in those with 40 mm heads, and from 54 mm to 78 mm in those with 44 mm heads. The types of bearing included ceramic-on-highly cross-linked polyethylene (1,229 THAs; 67%) and metal-on-polyethylene (599 THAs; 33%). Elevated liners were used in 472 THAs (26%) and 1,083 (59%) were lateralized. The most common operative approach was posterior (1,388 THAs; 76%). Outcomes of interest included the rate of dislocation, revision for dislocation, any revision, any reoperation, and the Harris Hip Score (HHS). The mean age of the patients at the time of THA was 64 years (8 to 94); 1,477 (81%) were male, and their mean BMI was 28 kg/m² (5 to 55). The mean follow-up was six years (2 to 14). Results The ten-year survival free of dislocation was 97% (95% CI 96 to 98; 97% for 40 mm heads (95% CI 95 to 98) and 99% for 44 mm heads (95% CI 97 to 100) (hazard ratio 3 (95% CI 1 to 14); p = 0.106)). The ten-year survival free of revision for dislocation was 99.6% (95% CI 99 to 100) (99.5% for 40 mm heads (95% CI 98 to 100) and 100% for 44 mm heads (p = 0.546)). The ten-year survival free of any revision and any reoperation was 95% (95% CI 94 to 97) and 93% (95% CI 91 to 95), respectively. There were no significant differences in survival free of any revision (p = 0.746) or any reoperation (p = 0.762) between the two groups. Conclusion In this large single-centre study of the use of jumbo femoral heads in primary THAs, the ten-year survival free of dislocation was 97%, with extremely few revisions for dislocation. These results highlight the potential for jumbo femoral heads to reduce the risk of dislocation and enhance implant longevity without compromising other clinical outcomes. Cite this article: Bone Joint J 2025;107-B(7):698–706.