Frederic Anthony Vallejo

Pediatric brain tumors remain a significant source of morbidity and mortality. Though developments have been made in treating these malignancies, the blood–brain barrier, intra- and inter-tumoral heterogeneity, and therapeutic toxicity pose challenges to improving outcomes. Varying types of nanoparticles, including metallic, organic, and micellar molecules of varying structures and compositions, have been investigated as a potential therapy to circumvent some of these inherent challenges. Carbon dots (CDs) have recently gained popularity as a novel nanoparticle with theranostic properties. This carbon-based modality is highly modifiable, allowing for conjugation to drugs, as well as tumor-specific ligands in an effort to more effectively target cancerous cells and reduce peripheral toxicity. CDs are being studied pre-clinically. The ClinicalTrials.gov site was queried using the search terms: brain tumor and nanoparticle, liposome, micelle, dendrimer, quantum dot, or carbon dot. At the time of this review, 36 studies were found, 6 of which included pediatric patients. Two of the six studies investigated nanoparticle drug formulations, whereas the other four studies were on varying liposomal nanoparticle formulations for the treatment of pediatric brain tumors. Here, we reviewed the context of CDs within the broader realm of nanoparticles, their development, promising pre-clinical potential, and proposed future translational utility.

The carbon nitride dot (CND) is an emerging carbon-based nanomaterial. It possesses rich surface functional moieties and a carbon nitride core. Spectroscopic data have demonstrated the analogy between CNDs and cytosine/uracil. Recently, it was found that CNDs could interrupt the normal embryogenesis of zebrafish. Modifying CNDs with various nucleobases, especially cytosine, further decreased embryo viability and increased deformities. Physicochemical property characterization demonstrated that adenine- and cytosine-incorporated CNDs are similar but different from guanine-, thymine- and uracil-incorporated CNDs in many properties, morphology, and structure. To investigate the embryogenesis interruption at the cellular level, bare and different nucleobase-incorporated CNDs were applied to normal and cancerous cell lines. A dose-dependent decline was observed in the viability of normal and cancerous cells incubated with cytosine-incorporated CNDs, which matched results from the zebrafish embryogenesis experiment. In addition, nucleobase-incorporated CNDs were observed to enter cell nuclei, demonstrating a possibility of CND–DNA interactions. CNDs modified by complementary nucleobases could bind each other via hydrogen bonds, which suggests nucleobase-incorporated CNDs can potentially bind the complementary nucleobases in a DNA double helix. Nonetheless, neither bare nor nucleobase-incorporated CNDs were observed to intervene in the amplification of the zebrafish polymerase-alpha 1 gene in quantitative polymerase chain reactions. Thus, in conclusion, the embryogenesis interruption by bare and nucleobase-incorporated CNDs might not be a consequence of CND–DNA interactions during DNA replication. Instead, CND–Ca²⁺ interactions offer a plausible mechanism that hindered cell proliferation and zebrafish embryogenesis originating from disturbed Ca²⁺ homeostasis by CNDs. Eventually, the hypothesis that raw or nucleobase-incorporated CNDs can be nucleobase analogs proved to be invalid.

Cranial neurosurgery confers psychological stress, as well as the stress of being in the hospital rather than in one’s preferred surroundings. Compared with inpatient admissions, same-day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. Also, it reduces costs to the health care system. To report the results of a pilot study that prospectively evaluated for the first time in a United States hospital, the outcomes of patients that underwent brain tumor surgery and are discharged home the same day as surgery. A quality intervention study including patients who underwent outpatient craniotomy for brain tumors by a single neurosurgeon (R.J.K) at the University of Miami from August 2020 to August 2021 was performed. Patients included were between 16 to 85 years old, with a Karnofsky Performance Status score of ≥ 70, and with supratentorial tumors with a maximum diameter of 4 cm. Complete demographic and clinical data were collected prospectively for each patient. In all patients, the minimum observation period was 6 h after surgery. 37 of 334 patients met the inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after overnight observation. No postoperative complications were noted at two-week follow-up. With appropriate selection and postoperative monitoring, same-day discharge can be considered a safe and feasible option for certain craniotomy cases. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history

The current prognosis for glioblastoma is dismal. Treatment-resistant glioblastoma stem cells (GSCs) and the failure of most drugs to reach therapeutic levels within the tumor remain formidable obstacles to successful treatment. Chalcones are aromatic ketones demonstrated to reduce malignant properties in cancers including glioblastoma. Nanomedicines can increase drug accumulation and tumor cell death. Carbon-dots are promising nanocarriers that can be easily functionalized with tumor-targeting ligands and anti-cancer drugs. Therefore, we synthesized a series of 4′-amino chalcones with the rationale that the amino group would serve as a “handle” to facilitate covalent attachment to carbon-dots and tested their cytotoxicity toward GSCs. We generated 31 chalcones (22 4′-amino and 9 4′ derivatives) including 5 novel chalcones, and found that 13 had an IC₅₀ below 10 µM in all GSC lines. After confirming that the 4-amino group was not part of the active pharmacophore, chalcones were attached to transferrin-conjugated carbon-dots. These conjugates were significantly more cytotoxic than the free chalcones, with the C-dot-transferrin-2,5, dimethoxy chalcone conjugate inducing up to 100-fold more GSC death. Several of the tested chalcones represent promising lead compounds for the development of novel anti-GSC drugs. Furthermore, designing amino chalcones for carbon-dot mediated drug delivery is a rational and effective methodology.

Provides a chem/bio basis to understand surface functional group effects on nanocarriers & their cancer cellular uptake, helping to increase the <5% of nanomaterials clinically approved for personalized nanomedicine.

Purpose Outpatient brain surgery has many advantages for the psychological and physical wellbeing of patients, as well as reduced costs to the health care system. Compared with inpatient admissions, same day discharges reduce patient exposure to nosocomial infection, thromboembolic complications, and medical error. We aim to establish a prospectively collected quality outcomes database to examine the outcomes of patients that undergo brain tumor resection and are discharged home the same day as surgery. Methods We have established a prospectively collected quality outcomes database to examine the outcomes of all patients that underwent brain tumor resection by a single neurosurgeon (R.J.K) at our institution from August 2020 to August 2021 and were discharged home the same day as surgery. Results Over the one-year period this study was conducted, 37 of 334 patients met inclusion criteria for the outpatient protocol. Thirty-two patients were discharged on the same day as surgery. Five patients (14%) were considered eligible for outpatient surgery but were ultimately admitted to the hospital postoperatively and were discharged after an overnight observation. No postoperative complications were noted at two-week postoperative follow-up. Conclusion In select patients undergoing brain tumor surgery, same day discharge should be considered. Establishing a multidisciplinary team of physicians, nurses, radiologists, and physical therapists is critical to achieving this aim. Physicians should have a low threshold to admit a patient with concerning exam findings, complications, or complicated past medical history. Once discharged, open communication with the patient and their family is critical to detect complications that should trigger rehospitalization and intervention.

Background: The surgical treatment of normal pressure hydrocephalus (NPH) with shunting remains controversial due to the difficulty in distinguishing such pathology from other neurological conditions that can present similarly. Thus, patients with suspected NPH should be carefully selected for surgical intervention. Historically, clinical improvement has been measured by the use of functional grades, alleviation of symptoms, and/or patient/family-member reported surveys. Such outcome analysis can be subjective, and there is difficulty in quantifying cognition. Thus, a push for a more quantifiable and objective investigation is warranted, especially for patients with idiopathic NPH (INPH), for which the final diagnosis is confirmed with postoperative clinical improvement. We aimed to use Apple Health (Apple Inc., Cupertino, CA) data to approximate physical activity levels before and after shunt placement for NPH as an objective outcome measurement. The patients were contacted and verbally consented to export Apple Health activity data. The patient’s physical activity data were then analyzed. A chart review from the patient’s EMR was performed to understand and better correlate recovery. Case Description: Our first patient had short-term improvements in activity levels when compared to his preoperative activity. The patient’s activity level subsequently decreased at 6 months and onward. This decline was simultaneous to new-onset lumbar pain. Our second patient experienced sustained improvements in activity levels for 12 months after his operation. His mobility data were in congruence with his subjectively reported improvement in clinical symptoms. He subsequently experienced a late-decline that began at 48-months. His late deterioration was likely confounded by exogenous factors such as further neurodegenerative diseases coupled with old age. Conclusion: The use of objective activity data offers a number of key benefits in the analysis of shunted patients with NPH/INPH. In this distinctive patient population, detailed functional outcome analysis is imperative because the long-term prognosis can be affected by comorbid factors or life expectancy. The benefits from using smartphone-based accelerometers for objective outcome metrics are abundant and such an application can serve as a clinical aid to better optimize surgical and recovery care.