Objective. Brain functions such as perception, motor control, learning, and memory arise from the coordinated activity of neuronal assemblies distributed across multiple brain regions. While major progress has been made in understanding the function of individual neurons, circuit interactions remain poorly understood. A fundamental obstacle to deciphering circuit interactions is the limited availability of research tools to observe and manipulate the activity of large, distributed neuronal populations in humans. Here we describe the development, validation, and dissemination of flexible, high-resolution, thin-film (TF) electrodes for recording neural activity in animals and humans. Approach. We leveraged standard flexible printed-circuit manufacturing processes to build high-resolution TF electrode arrays. We used biocompatible materials to form the substrate (liquid crystal polymer; LCP), metals (Au, PtIr, and Pd), molding (medical-grade silicone), and 3D-printed housing (nylon). We designed a custom, miniaturized, digitizing headstage to reduce the number of cables required to connect to the acquisition system and reduce the distance between the electrodes and the amplifiers. A custom mechanical system enabled the electrodes and headstages to be pre-assembled prior to sterilization, minimizing the setup time required in the operating room. PtIr electrode coatings lowered impedance and enabled stimulation. High-volume, commercial manufacturing enables cost-effective production of LCP-TF electrodes in large quantities. Main Results. Our LCP-TF arrays achieve 25× higher electrode density, 20× higher channel count, and 11× reduced stiffness than conventional clinical electrodes. We validated our LCP-TF electrodes in multiple human intraoperative recording sessions and have disseminated this technology to >10 research groups. Using these arrays, we have observed high-frequency neural activity with sub-millimeter resolution. Significance. Our LCP-TF electrodes will advance human neuroscience research and improve clinical care by enabling broad access to transformative, high-resolution electrode arrays.

Cobalt is known to produce a variety of symptoms in patients who accumulate a toxic amount in their blood. Cobalt poisoning can arise from metal implants due to wear and tear on the metal implant surfaces, but implant deterioration has not yet been reported to cause muscle spasticity. A 45-year-old male patient with a medical history of multiple sclerosis (MS) and bilateral hip arthroplasty presented with spasticity that persisted despite administration of anti-spasmodic medication and intrathecal baclofen. Concerns of high cobalt levels, confirmed via blood testing, led to revisions of both of his hip prosthesis, which alleviated his muscle spasms. To our knowledge, this is the first reported case of muscle spasticity associated with increased blood cobalt levels. Reduction in the patient's spasticity was associated with prosthesis revision and subsequent reduction in blood cobalt, suggesting that cobalt was involved in the pathogenesis or at minimum worsening of his spasticity given his concurrent MS. Review of the literature suggests that increased levels of cobalt can interfere with metabolism in neurons and damage muscle fibers, providing possible pathological mechanisms for the patient's spasticity.

Glucocorticosteroid injections into the shoulder are commonly used in the treatment of rotator cuff tendinitis. These injections rarely result in any serious complications and are generally considered a safe therapeutic intervention. Despite the extensive application of this treatment, there have been no reports of dysphonia occurring after corticosteroid injection into the subacromial space. We report the case of a 66-yr-old man with dysphonia after undergoing subacromial glucocorticosteroid injection for treatment of rotator cuff tendinitis.

1033 Background: In metastatic and locally recurrent breast cancer the antibody drug conjugate, sacituzumab govitecan-hziy (SG), is approved as a second-line therapy in triple negative disease and a third-line therapy and beyond for ER+, endocrine resistant disease. UGT1A1 metabolizes the SN-38 payload of SG, and polymorphisms of the gene can lead to decreased enzyme activity and increased toxicity. We sought to determine if patients who were homozygous for the UGT1A1*28 allele polymorphism (*28/*28) experienced increased toxicity and a lower rate of disease progression when treated with SG. Methods: To evaluate the association of the *28/*28 genotype with the competing endpoints of Discontinuations for Disease Progression, Toxicity, and Futility, this pilot study undertook a single-center, retrospective chart review of breast cancer patients who received SG at City of Hope. Eligible subjects included breast cancer patients who received at least one dose of SG, had a known UGT1A1 status, and were followed for toxicity and disease progression. Data collection and analysis included reasons for discontinuing SG, onset of adverse effects, UGT1A1 status, age, gender, race and ethnicity, prior lines of therapy, and tumor receptor status. Results: Between July 2020 and September 2022, 67 women and 1 man underwent UGT1A1 testing prior to initiation of SG; the median age was 57.8 years, 75.0% had triple negative disease, and SG was given as a median third line of therapy. Seventeen (25%) patients were homozygous for *28 and 24 (35.3%) were heterozygous. Notably relating race and genotype, all 7 self-reported Black subjects were either carriers or homozygous for *28; there were no Black wildtype subjects. Most subjects were followed until Discontinuation for Disease Progression (55.9%), Toxicity (8.8%), or Futility (5.9%). Alternatively, 4.4% of subjects were lost to follow-up and 1 subject halted treatment due to cancer remission. The remaining 23.5% of subjects still took SG by the close of study in November 2022. On competing risk analysis comparing the wildtype group, *28/*28’s association with increased Discontinuation for Toxicity, was confirmed with a Hazards Ratio of 5.52 (95% confidence interval [CI] 1.15-26.49, p = 0.03). In contrast, Discontinuation for Disease Progression was unassociated to *28/*28 status in comparison to the wildtype group with a Hazards Ratio of 0.80 (95% CI 0.39-1.65, p = 0.54). Conclusions: Despite the relatively small sample size, 25% of patients had the *28/*28 genotype. We confirmed that *28/*28 is associated with a higher risk for discontinuation of SG for toxicity without an association to disease progression based on mutation status. Early UGT1A1 testing as standard practice may identify patients at risk for excess toxicity, who may undergo early dose reductions to prevent discontinuation of this important advanced breast cancer treatment.

No abstract