Citations

Background: Emerging neuromodulation approaches, including epidural electrical stimulation (EES), offer hope for restoration of function following chronic spinal cord injury (SCI). However, integrating neuromodulation therapies into clinical procedures is challenging due to the unique needs of the SCI population. Objectives: The purpose of this study was to understand the experiences of participants during a first-in-human trial of perilesional EES aimed at restoring sensorimotor function. Methods: We report participants’ experiences by describing their clinical care, experiences during experimental neuromodulation sessions, and perspectives on the utility of a perilesional EES system. Three participants with chronic thoracic SCI participated in semistructured interviews after completing a 14-day inpatient experimental protocol, which included stimulation mapping, lower extremity motor control experiments, and treadmill stepping. Interview data were analyzed using an applied thematic analysis approach. Nine key themes addressed 4 major topic areas: clinical experiences, experiences during laboratory experiments, experiences as a research participant, and perceived value of perilesional EES. Results: All participants noted the potential for EES to enhance functional recovery, though their postoperative experiences related to clinical care, postoperative pain, and disruptions to routine care differed. Insights gained from qualitative analyses highlighted challenges and opportunities for improving postsurgical care and refining application of EES technology. Further, these results inform recommendations for neuromodulation trials in the SCI community to help mitigate postoperative complications and improve study participant experiences. Conclusion: Key recommendations include being proactive regarding potential postsurgical complications, educating clinical staff regarding common SCI comorbidities, and customizing experimental protocols to align with the priorities and clinical needs of each participant.

ABSTRACT Background Adolescents with youth‐onset type 2 diabetes (YO‐T2D) have an increased risk for cardiometabolic complications. The impact of vertical sleeve gastrectomy (VSG) on fat distribution and cardiac morphology/function in YO‐T2D is unknown. Objectives To evaluate changes in body composition, abdominal and cardiac fat depots, and cardiometabolic health in adolescents with YO‐T2D undergoing VSG. Methods Anthropometrics, labs and imaging were used to assess participants pre‐surgery and 3–12 months post‐surgery. MRI quantified pericardial (PAT), epicardial (EAT), subcutaneous (SAT) and visceral adipose tissue (VAT), hepatic fat fraction (HFF) and cardiac morphology/function. Mixed‐effects models assessed longitudinal changes. Results By 12 months, weight decreased from 134.3 ± 5.1 to 103.3 ± 5.2 kg, VAT 1943 ± 148 to 1248 ± 150 cm 3 , HFF 23.2% ± 2.3% to 5.3% ± 2.3% and PAT and EAT by 27% and 33% (all p < 0.01). Homeostatic model assessment of insulin resistance (HOMA‐IR) improved (7.8 ± 1.2 to 1.7 ± 1.2 [ p < 0.01]). BMI, SAT, resting heart rate (RHR), left ventricular (LV) mass and cardiac output (CO) also decreased (all p < 0.05). VAT decreases correlated with decreases in HFF ( r = 0.70, p = 0.01), HOMA‐IR ( r = 0.60, p = 0.04) and CO ( r = 0.70, p = 0.03). HFF decreases correlated with decreases in BMI ( r = 0.70, p = 0.03), HOMA‐IR ( r = 0.90, p < 0.001), RHR ( r = 0.90, p = 0.002), CO ( r = 0.80, p = 0.007) and LV mass ( r = 0.70, p = 0.02). Conclusions VSG reduces ectopic and regional fat and improves associated insulin sensitivity and cardiac health in adolescents with YO‐T2D.

OBJECTIVE Hundreds of thousands of Americans undergo decompression for lumbar spinal stenosis annually. The mild (minimally invasive lumbar decompression) procedure was developed as a potentially less invasive alternative to open decompression; however, much of the evidence has been gathered from industry-sponsored studies. The present study sought to compare real-world clinical outcomes between the mild procedure and open decompression for lumbar spinal stenosis. METHODS All patients who underwent the mild procedure at a single-institution, multisite, tertiary care center from 2005 to October 2024 were included. One-to-one propensity score matching was used to identify patients who underwent open decompression at the same institution, with age, sex, smoking, and comorbidities as covariates. Primary outcomes were change in pain on the numeric rating scale (NRS), surgical reoperation, and perioperative complications. For pain, the minimal clinically important difference (MCID) was defined as a 30% improvement in NRS score. RESULTS A total of 175 patients who underwent the mild procedure (mean age 76.3 ± 8.7 years; 44.6% female) were matched to 175 patients treated with open decompression (mean age 75.4 ± 8.7 years; 44.0% female). Among patients with at least 60 days of follow-up, those treated with open decompression were more likely to achieve the MCID for pain (43.1% vs 22.2%, p < 0.001). Patients treated with mild were more likely to require reoperation (46.2% vs 29.3%, p = 0.008). Those who underwent the mild procedure experienced lower rates of durotomies (0% vs 2.9%, p = 0.024) but had higher rates of neurological deficits (6.3% vs 0.6%, p = 0.003). CONCLUSIONS For patients with symptomatic lumbar stenosis, those who underwent open decompression were more likely to achieve pain improvement and less likely to require reoperation compared with those who underwent the mild procedure.

Abstract This review explores smart catheters as an emerging class of medical devices that combine embedded sensors, robotics, and communication systems with increasing functionality and complexity to enable real‐time health monitoring, diagnostics, and treatment. Evolving from traditional catheters used as drains or entry ports, smart systems are now able to track blood pressure, temperature, biochemical signals, and mechanical forces within the body with a high degree of accuracy. Advances in materials, wireless communication, and robotic navigation have helped reduce common risks like infection and catheter blockage while also improving precision catheter placement for minimally invasive procedures. This review highlights recent developments across a variety of different types of smart catheters, ranging from sensing and imaging tools to therapeutic and multimodal systems. Additionally, it discusses the challenges that remain, including biocompatibility, long‐term performance, and clinical translation. The incorporation of new capabilities is changing how catheters are used, and these new uses promise to enable more personalized and responsive healthcare.

Background: Meniscal preservation has been demonstrated to contribute to long-term knee health and has been a successful intervention in isolation and in patients with anterior cruciate ligament reconstruction (ACLR). The long-term results of meniscal repair in the setting of revision ACLR have yet to be documented. Purpose: To report the incidence of meniscal repair failures at the 6-year follow-up in a cohort of patients who underwent concurrent revision ACLR and primary meniscal repair. Study Design: Prospective cohort study; Level of evidence, 2. Methods: All revision ACLRs with concomitant primary meniscal repair cases from a multicenter group between 2006 and 2011 were selected. Six-year follow-up was obtained to determine whether any subsequent surgery had occurred since their initial revision ACLR. If so, operative reports were obtained, whenever possible, to verify pathological condition and treatment. Results: In total, 221 patients from 1234 revision ACLRs underwent concurrent primary meniscal repairs (18% of the cohort). There were 238 repairs performed: 173 medial and 65 lateral. The majority of these repairs (n = 181; 76%) were performed with an all-inside technique. Six-year surgical follow-up was obtained in 77% (171/221) of the cohort, or 189 of 238 (79%) of the repairs (136 medial, 53 lateral). The meniscal repair failure rate, defined as reoperation, was 16% (31/189) at 6 years. Of the 31 failures, 28 were medial (24 all-inside, 4 inside-out; 28/136 = 20.6% failure rate) and 3 were lateral (2 all-inside, 1 inside-out; 3/53 = 5.7% failure rate). Three medial failures were treated in conjunction with a subsequent repeat revision ACLR. Medial tears underwent reoperation for failure at a significantly higher rate than lateral tears (20.6% vs 5.7%; P = .01) and had a significantly shorter survival time compared with lateral tears ( P = .02). No difference was found between the failure and nonfailure groups when it came to tear type, tear length, repair technique utilized, suture/implant type, or number of sutures used between the 2 groups. Conclusion: Meniscal repair in the revision ACLR setting has a 16% failure rate at 6 years. Failure rates for medial tears (20.6%) were found to be higher than that for lateral tears (5.7%), which aligns with previous studies in both the revision and primary ACLR setting.

Malignant glioma is considered invariably recalcitrant, thus necessitating development of new therapeutic approaches. Spontaneously arising canine glioma exhibits important molecular and pathological similarities to malignant pediatric glioma, making it an invaluable model for testing novel therapies. We evaluated safety and activity of RNA lipid particle aggregates (LPAs) designed to provoke cancer immunogenicity in 10 dogs with histologically confirmed glioma. Vaccine manufacturing was feasible in all subjects and generally well tolerated. Median survival time was 123 and 155 days in dogs receiving three (Group A) or four (Group B) vaccines, respectively; this was increased from historical reporting of subjects receiving palliative care. Responding animals had a robust cytokine response following infusions. In animals receiving non-specific RNA-LPAs, there was localization of messenger RNA (mRNA) payloads to the brain tumor microenvironment and a rapid shift in immunologic gene signatures consistent with a viral response. These data demonstrate the ability to induce rapid viremic response in the tumor microenvironment following a single peripherally administered mRNA vaccine. Since RNA-LPAs are amenable to repeat boosts, these formulations may overcome challenges of tumor immunosuppression and therapeutic access and are currently under evaluation in first-in-human trials ( NCT04573140 , NCT06389591 ).

Abstract We describe a 46-year-old male with Neurofibromatosis type 1 (NF1) and a previously known parenchymal medullary mass identified in 2022, initially managed with surveillance. In late 2023, he developed a progressive brainstem syndrome prompting presentation to our center. MRI showed a T2/FLAIR hyperintense, heterogeneously enhancing ventral medullary mass with leptomeningeal involvement, a non-enhancing right pontine lesion, right optic nerve glioma, and nodular leptomeningeal foci at T4 and L4–L5. He received IMRT to the brainstem prior to tissue diagnosis with good local response. Due to progression at T4, biopsy revealed a hypercellular, mitotically active glioma without necrosis or microvascular proliferation. Molecular profiling demonstrated IDH1/2-wildtype, H3K27M-negative, retained ATRX, intact 1p/19q, and CDKN2A/B homozygous deletion. DNA methylation profiling classified the tumor as high-grade astrocytoma with piloid features (HGAP). Spinal lesions responded to proton therapy, but new metastatic foci emerged in the subependymal lateral ventricles, leptomeninges, and cervical spinal cord. He underwent whole-brain radiation, oral temozolomide, and intrathecal cytarabine/etoposide. In June 2024, cell-free DNA analysis showed a similar molecular profile with newly identified 1p/19q codeletion, diverging from tissue findings. The patient remains alive &gt;3 years from initial presentation. HGAP is a novel molecular class of IDH-wildtype gliomas defined by DNA methylation profiling and MAPK pathway alterations (commonly NF1, BRAF, FGFR1), CDKN2A/B codeletion, and ATRX alterations. These tumors often resemble glioblastoma or diffuse midline gliomas on imaging and are typically infratentorial or spinal, complicating biopsy. Prognostic data are limited, with &lt;50% 5-year overall survival and no clear prognostic value of MGMT promoter methylation. This case illustrates multifocal HGAP in a patient with NF1 with favorable survival. The acquired 1p/19q codeletion raises questions about tumor mosaicism, subclonal evolution, and prognostic implications.

Abstract BACKGROUND Tovorafenib is a type II rapidly accelerated fibrosarcoma (RAF) kinase inhibitor approved by the FDA in 2024 for relapsing or chemotherapy-refractory pediatric low-grade gliomas with mutations or alterations in the gene BRAF. There is potential for the use of this drug outside the pediatric population. We present a single institution case series of adults with CNS tumors with mutations or alterations in BRAF treated (off-label) with tovorafenib. METHODS Chart review. RESULTS 8 adult (age &gt;18) patients were treated with tovorafenib at our institution between March 2024 and June 2025. Age range was 21-66 years old (median age 42). The population included 5 males and 3 females. Indications for treatment were pilocytic astrocytoma (n = 2), high grade astrocytoma with piloid features (HGAP) (n = 2), Erdheim-Chester disease (n = 2), pleomorphic xanthoastrocytoma (n = 1), and otherwise unclassified low-grade glioma (n = 1). All patients had mutations or alterations in BRAF including KIAA1549 fusion (n = 4), V600E mutation (n = 3), or GAB2 fusion (n = 1). Radiographic response to therapy was seen in 5/8 patients with 3 cases of radiographic stability (though one patient later progressed) and 2 cases of decrease in tumor size (in a pilocytic astrocytoma and in an HGAP). Both cases of decreased tumor size after treatment were in tumors with KIAA1549 fusions. Adverse effects of tovorafenib included fatigue (n=2), headache, myalgias, diplopia, cytopenias, and transaminitis (n=1). 3/8 patients had to pause or stop treatment due to adverse effects (intolerable headache, cytopenias, and transaminitis respectively). CONCLUSION Tovorafenib is a promising new treatment for CNS tumors with BRAF mutations or alterations. Our single institution case series suggests the efficacy of this drug for multiple tumor types in adults. Certain tumor subtypes such as KIAA1549 fusions may be more likely to benefit from this treatment.

Abstract BACKGROUND Understanding long-term sequelae of cancer care is critical. Cognitive impairment is a common and disabling survivorship issue. Because sex influences tumor biology, therapy exposure, and dementia risk, we examined whether cancer care for a prior malignancy alters late-life cognitive outcomes differently in males and females. METHODS We assessed adults ≥50 years, cognitively normal at study entry, from a longitudinal, population-based cohort (Mayo Clinic Study of Aging). Participants were linked to our institutional cancer registry (excluding non-melanoma skin cancers). Mild cognitive impairment (MCI) and dementia were adjudicated by consensus. We fitted multivariable Cox proportional-hazards models to estimate how prevalent cancer diagnosis influenced the risk of developing MCI/dementia. Sex-specific effects were determined by incorporating a cancer×sex interaction term and by generating separate hazard ratios. Analyses were controlled for age, APOE4 status, education, and presence of vascular/metabolic conditions. RESULTS 5793 MCSA participants (female: 49.4%, APOE4 positive: 27.5%) were included in the study, with a mean age of 73 years at study entry. Incident MCI was recorded in 866 participants, and 737 were diagnosed with incident dementia. About 20% (n=1176) of the cohort had a cancer diagnosis, most commonly prostate (n=423) and breast (n=277). There was no independent relationship between history of cancer and risk for MCI or dementia. We found that males with cancer had an increased risk for MCI (HR 1.28, 95% CI 1.04-1.57, p=0.003) and dementia (HR 1.29, 95% CI 1.04-1.6, p=0.053). Conversely, females with cancer had a lower risk for MCI (HR 0.79, 95% CI 0.61-1.01, p=0.063), although this was not statistically significant. CONCLUSIONS Our data suggests male cancer survivors may be more susceptible to cognitive impairment, independent of age, APOE4 status, education, and vascular/metabolic burden. Elucidating the hormonal, treatment-related, and systemic pathways driving this should be a priority for future mechanistic studies.