Citations

ABSTRACTRubinstein‐Taybi syndrome (RTS) is a rare genetic disorder featuring craniofacial abnormalities, intellectual disability, and multi‐organ involvement, including increased risk of keloid formation, pilomatricomas, and hypertrichosis. Hidradenitis suppurativa (HS), a chronic inflammatory skin condition characterized by recurrent abscess formation and draining tunnels, has never been described in a patient affected by RTS. In this report, we detail the history of a 32‐year‐old male with RTS and refractory Hurley stage III HS and discuss the important considerations and risks of managing this unique patient population.

Background: Various medial patellofemoral ligament (MPFL) reconstruction techniques have been developed to minimize risks to the physis in skeletally immature patients. Purpose: To examine outcomes of MPFL reconstruction (MPFLR) based on fixation technique in skeletally immature patients. Study Design: Systematic review; Level of evidence, 4. Methods: PubMed, Scopus, Ovid, Cochrane Library, and CINAHL databases were searched for the literature on outcomes of MPFLR in the pediatric population, utilizing various anatomic and nonanatomic techniques. Primary outcomes were postoperative redislocation rates, return-to-sports (RTS) rates, and patient-reported outcomes (PROs). Moreover, outcomes involving sequela of growth plate disturbance were collected. Results: The final analysis included 17 studies—2 using sling-based techniques, 3 using surface-based techniques, 5 using soft tissue realignments, and 7 utilizing transosseous femoral fixations. Higher rates of postoperative redislocation were found in the sling-based (14.8%) and distal soft tissue realignment using semitendinosus tenodesis (38%) techniques, while lower rates were noted with surface-based (1.3%) and transosseous (3.4%) techniques. For PROs, there were large amounts of heterogeneity among studies, but all reported postoperative improvements, with more positive PROs generally seen in anatomic reconstructions. The RTS rate was 100% for surface-based techniques, 79.4% for distal soft tissue realignments, 79.5% for soft tissue realignment techniques, and 83.2% for transosseous techniques. No negative outcomes as a sequela of growth plate disturbance were reported. Conclusion: Nonanatomic techniques—such as sling-based and distal soft tissue realignment techniques—have higher rates of redislocation and lower RTS rates in skeletally immature patients undergoing MPFLR. Surface-based and transosseous tunnel-based techniques were shown to have lower redislocation and higher RTS rates. Clinical Relevance: This review provides insight into the most appropriate surgical management of patellar instability in patients with open growth plates.

Abstract Background Most oncology therapeutics have limited distribution into the brain, and developing strategies to overcome this limitation would be clinically impactful. While therapeutic radiation is often cited as a strategy to accomplish this, there are no published studies demonstrating the effect of radiation on drug distribution into the brain or brain tumors. Methods Mice were treated with brain radiation (6 Gy × 5, 4 Gy × 10; 40 Gy × 1) and dosed with drugs (levetiracetam, cefazolin, nedisertib, brigimadlin, apitolisib, or GNE-317) at times ranging from just prior to months after radiation. Plasma and tissue drug concentrations were measured by LC-MS/MS. Results Radiation did not significantly enhance drug delivery into brain tissue for levetiracetam, cefazolin, GNE-317, apitolisib, or nedisertib at any time post-radiation. Even a single, supra-therapeutic dose of radiation (40 Gy) did not significantly affect brain distribution of GNE-317 or apitolisib (P ≥ .07) from 16 to 160 hours post-radiation. For brigimadlin, radiation (6 Gy × 5) was associated with a modest but significant increase in drug accumulation only at 72 hours post-radiation (brain-to-plasma ratio 0.014 ± 0.006 vs. 0.025 ± 0.010, respectively; P = .04), but not at any other timepoint (24 hours, 15, 28, 94, 133, 183 days; P > .05). Similarly, radiation (6 Gy × 5) of orthotopic tumors did not increase levels of brigimadlin in GBM10 or GBM108 or nedisertib in GBM108 (P > .05). Conclusions Radiation had no meaningful impact on drug delivery into brain or brain tumors for the drugs tested.

Objectives/Goals: Community-based practices have limited research opportunities for providers. As a rural community-based health system, Mayo Clinic Health System (MCHS) sought to create intramural funding mechanisms to help early-stage researchers conduct pilot research so they are more competitive to compete for more robust extramural funding opportunities. Methods/Study Population: We created a Research Seed Grant Program infrastructure across our four MCHS regions (Southwest and Southeast Minnesota, Northwest and Southwest Wisconsin). This model program featured an initial research funding announcement call based on 6 prioritized programs (AI Validation & Stewardship, Cancer, Health Equity, Population Health, Rural Health, Learning Healthcare System [LHS]), with submissions uploaded to a central electronic repository. Proposal review and ranking was organized on a regional basis, with ranking of all proposals by at least 2 clinical scientist reviewers according to the NIH domain-specific framework (i.e., 1.0 best > 9.0 worst). Awards were competitively selected by conformity to prioritized research areas and through ranking of most competitive overall application scores. Results/Anticipated Results: For our inaugural RFA, we received 55 grant application submissions across the MCHS regions. Fifteen of the most highly ranked applications were selected for awards on a per region basis, providing direct funding as well as protected investigator research time of 10% for up to six months. The selected projects address several research priorities including improving access, reducing health disparities, improving behavioral health in our communities, increasing cancer screening and prevention, and community-based pragmatic trials and interventions. Outcomes from these now completed pilot projects remain pending at this time. Funding for this seed grant program was supported by philanthropy, Mayo Clinic Research Administration, Mayo Clinic Comprehensive Cancer Center, and the Mayo Clinic CCaTS Rural Core. Discussion/Significance of Impact: We present this framework for a LHS-focused Seed Grant program model for consideration of adoption by other national/international LHS. Future plans include tracking of outcome metrics (e.g., published peer review articles, extramural grant applications) of this initial cycle and future expansion of this program to support the goals of our LHS.

Objective Early‐onset Alzheimer's disease (EOAD) and late‐onset Alzheimer's disease (LOAD) differ in many respects. Here, we address the issue of possible differences in fibrillar amyloid pathology as measured by positron emission tomography (PET), which remains unresolved due to the lack of large‐scale comparative studies. Methods Three hundred ninety‐nine cognitively impaired participants younger than 65 years of age from the multicenter Longitudinal Early‐onset Alzheimer's Disease Study (LEADS) and 450 cognitively impaired participants older than 65 years from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent clinical assessment, brain magnetic resonance imaging (MRI), and amyloid PET and were included in this study. We compared amyloid PET outcomes (positivity rate based on visual read and quantified tracer uptake expressed as Centiloids [CLs]) between the 2 cohorts and studied their association with age, sex, APOE genotype, and cognition. Results The amyloid positivity rate was higher in LEADS (78%, 95% confidence interval [CI] = 74–82) than in ADNI (71%, 95% CI = 67–75, p = 0.02). Lower Mini‐Mental State Examination (MMSE) and APOE4 genotype increased the odds of amyloid positivity in both cohorts. Visually positive scans had higher CLs in LEADS (EOAD, mean = 95.3 ± 26.1) than in ADNI (LOAD, mean = 80.9 ± 36.8, p < 0.0001), predominantly in parietal cortex/precuneus, superior temporal, and frontal cortices. In amyloid‐positive patients, (1) CLs were higher in female patients in both cohorts; (2) APOE4 carriership was associated with lower CLs in EOAD, which was not observed in LOAD; and (3) correlations between CLs and MMSE scores were significantly stronger in EOAD than in LOAD. Interpretation Differences in the burden of amyloid pathology may contribute to differences in clinical and anatomic patterns in sporadic EOAD and LOAD, and have implications for optimizing therapeutic strategies in each group. ANN NEUROL 2025;98:236–248

Background: Medial patellofemoral ligament reconstruction is frequently indicated for recurrent lateral patellar instability. The preoperative presence and severity of a J-sign have been associated with poorer postoperative outcomes. Purpose: To determine the underlying anatomic factors that contribute to the presence, severity, and jumping quality of the J-sign. Study Design: Cross-sectional study; Level of evidence, 3. Methods: All patients undergoing evaluation for patellar instability at a single institution between 2013 and 2023 and healthy controls without patellar instability were included. Patients with a history of knee osteotomies were excluded. The presence of a jumping J-sign and its relationship to patellofemoral measures including the Caton-Deschamps Index (CDI), trochlear dysplasia (Dejour grade), tibial tubercle–trochlear groove (TT-TG) distance, tibial tubercle lateralization, trochlear bump height, mechanical alignment, femoral anteversion, tibial torsion, trochlear medialization, patellar width, axial patellar/trochlear overlap, patellar height, trochlear height, and knee rotation angle (KRA) were measured using standardized 1.5-T magnetic resonance imaging (MRI). Univariate pairwise and multivariable analyses were performed to determine the factors associated with J-sign presence, severity, and quality. Results: Of the 130 knees with patellar instability, 89 (68.5%) demonstrated a J-sign on physical examination. In total, 44 (33.8%) patients demonstrated a 1-quadrant J-sign, 32 (24.6%) demonstrated a 2-quadrant smooth J-sign, and 13 (10.0%) demonstrated a jumping J-sign. A total of 22 control, noninstability cases were included. On multivariable analysis, increasing TT-TG distance (OR, 1.1 increase per millimeter; P = .04), external KRA (OR, 1.1 increase per degree; P = .02), and increasing CDI (OR, 1.3 increase per 0.1 increase in CDI; P = .02) were associated with J-sign presence. Increasing bump height (OR, 1.72 increase per millimeter; P = .007) and decreasing patellar width (OR, 0.89 decrease per millimeter; P = .076) were associated with a larger J-sign, when present. Increasing bump height (OR, 1.80 increase per millimeter; P = .018), increasing patellar width (OR, 1.33 increase per millimeter; P = .047), and decreasing CDI (OR, 0.009 decrease per 0.01 increase in ratio; P = .008) were associated with a jumping J-sign in comparison with a smooth 2-quadrant J-sign. A KRA of 10° (AUC, 0.70) and a cartilaginous bump height of 6.6 mm (AUC, 0.73) were thresholds associated with jumping J-sign presence. Conclusion: The presence of a J-sign is associated with MRI findings of relatively greater external tibiofemoral rotation, increased TT-TG distance, and increased patellar height, while J-sign severity and jumping quality are associated with the presence of additional underlying trochlear factors such as increased bump height. The anatomic drivers identified in this study should be further evaluated as possible factors associated with suboptimal outcomes after surgical management.

Abstract Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.