Citations

Abstract Background The isocitrate dehydrogenase (IDH) mutation status is a key molecular marker in diagnosing and treating brain tumors. Currently, it is determined via invasive tissue biopsy. Recent advances in deep learning (DL) have offered promising non-invasive alternatives for determining IDH status. However, their clinical translation is hindered by a significant gap between DL predictions and their clinical applicability. The limited transparency of many DL-networks and inadequate evaluation metrics hinders trust and adoption, as clinicians require clear and validated insights for determining IDH status. These challenges highlight the need for robust validation and measures of predictive reliability to make DL-predictions clinically actionable. Methods We developed a unique approach for non-invasive prediction of IDH status using MRI. We combine a voxel-wise-segmentation network(MC-net) with Bayesian logistic regression (BLR) to provide an IDH status and estimate confidence scores. We utilized a comprehensive dataset of 2,481 glioma cases from eight institutions. Results Our framework(MC-net + BLR) demonstrated robust performance achieving 96.4% and 95.1% classification accuracies on diverse databases, with an AUC of 0.98. The BLR was implemented exclusively on held-out test data, ensuring that the derived confidence scores are independent of the training or validation phases. The derived confidence scores showed a low Brier score of 0.0125, highlighting its superior calibration and uncertainty quantification. Conclusion The developed framework provides an IDH status and a confidence score, offering clinicians an additional layer of assurance in prediction reliability. It bridges the gap between high-performing DL models and their clinical applicability by addressing the challenges in prediction reliability. Our framework is a significant advancement in non-invasive determination of IDH-status and confidence-informed therapeutic decision-making in neuro-oncology.

Background: Home telemetry has been shown to reduce 30-day readmissions in patients at high risk for readmission. It remains unclear whether this finding is due to the telemetry itself or the nurse contact that follows detection of an abnormal parameter. Purpose: This study was a subgroup analysis from a prior trial comparing patients on home telemetry for 30 days to usual care after discharge to determine if nurse contact affected readmission rates. Methods: Patients randomized to telemetry who had at least 1 nurse contact were compared to those who had none to see if the contact reduced the rate of readmissions. Results: Of 449 home telemetry patients, 292 (65.0%) received 1 or more nurse contacts. Single and multivariable logistic regression models exploring the association of contact with 30-day readmission did not find any statistically significant associations of nurse contact with readmission (all unadjusted P ≥ .13, all adjusted P ≥ .18). Conclusion: Our subset analysis did not show that the nurse contact was the factor that reduced readmission in patients on home telemetry.

Abstract Purpose It remains unclear whether increasing the frequency of administration of 0.01% atropine improves its effectiveness in slowing axial elongation or refractive progression. This study compared twice‐daily 0.01% atropine administration and traditional once‐nightly administration. Methods A hybrid design was adopted incorporating both retrospective and prospective elements, with participants observed for 1 year. The control group (received saline eye drops) and once‐daily 0.01% atropine group (Atropine‐1 group) were derived from two previous trials, while the twice‐daily 0.01% atropine group (Atropine‐2 group) was enrolled prospectively. A total of 163 participants were included in the intention‐to‐treat set, with 51, 70 and 42 participants in the control, Atropine‐1 and Atropine‐2 groups, respectively. The primary outcome was the change in axial length (AL), and the secondary outcome was the change in cycloplegic spherical equivalent refraction (SER). Results Compared with the control group (0.48 ± 0.22 mm), both Atropine‐1 (0.26 ± 0.17 mm) and Atropine‐2 (0.15 ± 0.18 mm) groups showed significantly reduced AL elongation ( p < 0.001). Notably, Atropine‐2 significantly improved slowing of AL elongation compared with Atropine‐1 ( p = 0.008). The result of the secondary outcome (adjusted SER change) was consistent. Atropine‐2 was significantly more effective in slowing SER progression (−0.15 ± 0.37 D) than Atropine‐1 (−0.41 ± 0.50 D) ( p = 0.02). Based on a multivariable model, age was identified as the key covariate to perform subgroup analyses. In the younger subgroup (8–10 years), AL elongation was significantly reduced in the Atropine‐2 group (0.16 ± 0.17 mm) compared with the Atropine‐1 group (0.36 ± 0.22 mm; p = 0.002). In the older subgroup (10–12 years), there was no significant difference in progression. Consistent results were observed in the sensitivity analyses based on the per‐protocol set. Conclusion Twice‐daily administration of 0.01% atropine was more effective than once daily in slowing AL elongation and SER progression in children 8 to 10 years of age. Further investigation with extended follow‐up is warranted to substantiate this finding.

Abstract Aging increases the vulnerability of kidneys to injury and impairs their regenerative capacity. SIRT3 expression declines with aging and is associated with multiple age‐related pathologies. The expression profile and functional role of SIRT3 in renal aging remain unclear. Here, SIRT3 expression in aging kidneys is assessed and analyzed for its promoter methylation patterns using methylation‐specific PCR (MSP). It is found that aging exacerbates UUO‐induced renal fibrosis, associated with downregulated SIRT3 expression. Mechanistically, age‐related SIRT3 downregulation is mediated by hypermethylation of its promoter region. SIRT3 knockout exacerbated renal fibrosis in young mice subjected to UUO, whereas SIRT3 overexpression attenuated fibrosis in aged UUO mice. Integration of RNA‐seq and immunoprecipitation‐mass spectrometry (IP‐MS) analyses revealed that SIRT3 deficiency leads to hyperacetylation of GSK3β at lysine 15 (K15). This K15 hyperacetylation inhibited GSK3β activity, consequently stabilizing its substrate β‐catenin. Furthermore, self‐assembled PEG‐PCL‐PEG micelles are designed and synthesized to encapsulate hydrophobic honokiol (HKL). These micelles significantly enhanced the aqueous solubility and oral bioavailability of free HKL, maintained stable blood concentrations, and ultimately improved its anti‐fibrotic efficacy. These findings propose novel therapeutic strategies for managing renal fibrosis in the aging population and provide a foundation for developing new drugs and combination therapies.

Introduction Alzheimer’s disease and related dementias (ADRD) are conditions with progressive cognitive decline. Still, people living with late-stage ADRD (PLWD) have been reported to exhibit transient recovery of communication or behavioural abilities that had seemingly been lost. These lucid episodes (LEs) are underinvestigated and poorly understood. This study aims to advance scientific understanding of the incidence, prevalence and predictors of LEs and assess from family caregivers if LEs are associated with changes they make in care planning or experiences with burden, distress or grief. Methods This study recruited 545 caregivers from five ADRD-related registries in the USA. Eligibility included caregivers over 18 years who currently provide care to someone with moderate to very severe ADRD and can complete online questionnaires. Using a longitudinal observational study design, consented caregivers will be assessed monthly for 1 year using online questionnaires that inquire about witnessing LEs. If witnessed, the context and content of the LE is reported. Changes in caregiver decision-making about care for the PLWD, and caregiver burden, distress and grief are assessed at baseline, 6 and 12 months. Analysis Analysis of baseline data will assess descriptive aspects of LEs that are currently unknown (eg, prevalence, content, antecedents, duration). Longitudinal analysis will examine the incidence of LEs, characteristics of PLWD and caregivers that are predictors of episodes, and the associations between LEs and caregiver outcomes (eg, burden, distress, grief). Ethics and dissemination This study is being conducted in accordance with all Federal Policies for the Protection of Human Subjects. The protocol has been approved by the Mayo Clinic Institutional Review Board (ID 22-006861). Findings will be presented at scientific conferences and disseminated through journal publications and outreach efforts with collaborating partners invested in brain health and caregiver support.

Introduction: Despite ongoing diversity initiatives, Otolaryngology – Head and Neck surgery continues to face a widening representation gap as the Latinx population in the United States grows. To address this disparity, novel strategies for recruiting Latinx medical students into the specialty must be explored. Methods: A descriptive, cross-sectional survey was distributed to Latinx medical students in the United States via social media platforms (Facebook, Twitter, Instagram) and Latino Medical Student Association (LMSA) chapters. Results: Most respondents were unfamiliar with Otolaryngology-specific health disparities affecting Latinx communities and indicated an interest in learning more about these disparities. Most respondents indicated that early exposure to Otolaryngology disparities affecting Latinx communities could increase interest in exploring the specialty. Additionally, most participants deemed a department's commitment to diversity, equity and inclusion and opportunities to serve Latinx patients to be necessary residency program attributes when deciding between programs (69.2% and 66.7%, respectively). Conclusion: Integrating community outreach and education on Otolaryngology-related health disparities into undergraduate medical education may serve as a promising strategy to enhance Latinx recruitment and representation in the specialty.

AbstractPurposeWhile standard MR elastography (MRE) uses harmonic mechanical waves, there are some applications in which imaging and analysis of transient mechanical motion are of interest. Wavelet MRE has been developed for detecting broadband motion from transient excitation. The goal of this study was to evaluate the accuracy and efficiency of wavelet MRE for transient displacement detection in brain MRE applications.MethodsTransient motion was induced in a gel phantom, while MRE images were acquired using bipolar motion‐encoding gradient (MEG) at multiple frequencies (20–200 Hz). Displacements were estimated using (1) combinations of multiple MEGs forming the wavelet MRE and (2) deconvolution from a single MEG. These estimated displacements were used to calculate the MRE phase for each MEG. Correlation (r2) between the calculated and acquired phases was evaluated.Three healthy volunteers were scanned twice in a clinical scanner using wavelet MRE with an occipital impact. Time‐resolved brain translation, rotation, and maximal principal strain were calculated. Repeatability was assessed both qualitatively and through Pearson correlation.ResultsWavelet MRE outperformed standard MRE in displacement estimation, showing higher correlations between calculated and acquired phase, even with fewer phase offsets. In the volunteer study, consistent temporal motion dynamics and spatial maximal principal strain distributions across repeated scans demonstrated the repeatability of wavelet MRE.ConclusionThis study validated the accuracy and efficiency of wavelet MRE for broadband motion detection and demonstrated its feasibility and repeatability in vivo. This technique shows promise for advancing our understanding of the injury risks and mechanisms associated with sports‐related head trauma.

Background: The role of fine-needle aspiration (FNA) in diagnosing parotid tumors remains debated due to varying accuracy. This study evaluates FNA’s accuracy in diagnosing Warthin’s tumor (WT) and its safety in guiding observational management. Study design: Retrospective cohort study. Setting: Single institution, Tertiary referral center. Methods: Data from 2010 to 2022 including demographics, cytology, pathology, and surgical outcomes were extracted. Accuracy was assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: Among 808 patients with parotid tumors, 234 were WTs. Seventy-eight patients underwent surgery with pathology while 156 underwent observation. FNA sensitivity, specificity, PPV, and NPV for WTs were 98.2%, 98.1%, 91.8%, and 99.6% respectively. No observational patients developed clinical signs of malignancy, and the median change in tumor size was 0 cm (range −3.1 to 2.1). Conclusions: FNA is highly specific for WT but limited by nondiagnostic results. Observation is a safe approach with minimal risk of growth, malignancy, or infection.

ABSTRACT Peritoneal fibrosis is one of the main causes of peritoneal dysfunction and withdrawal of patients from peritoneal dialysis (PD). Our previous study has shown that high‐glucose dialysis solution promotes glycolysis in peritoneal mesothelial cells, leading to mesothelial‐to‐mesenchymal transition (MMT) and peritoneal fibrosis. However, the molecular mechanisms remain unclear. Using single‐cell RNA sequencing (scRNA‐seq) analysis of cells from the effluent of patients undergoing PD from our previous study, we found that pyruvate kinase isozymes M2 (PKM2), a key rate‐limiting enzyme of glucose metabolism, was significantly upregulated in the mesothelial cells of patients with long‐term peritoneal dialysis (LPD). Using co‐immunoprecipitation, chromatin immunoprecipitation assay, and gene silencing techniques, we revealed that PKM2 promotes the expression of transcription factor SNAI2 by acetylating histone H3K9 (H3K9ac), thereby promoting the occurrence of MMT and hence peritoneal fibrosis. l ‐cysteine, a known PKM2 inhibitor, blocked these responses and prevented PD‐induced peritoneal fibrosis. These results could provide a novel therapeutic strategy for treating peritoneal fibrosis.