Carbon Dots in Treatment of Pediatric Brain Tumors: Past, Present, and Future Directions.

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.

Dropped head syndrome in a patient with Parkinson's disease and inflammatory myopathy, treated with sternocleidomastoid release and circumferential cervical fusion.

BACKGROUND: Dropped head syndrome (DHS) is a recently recognised cause of cervical spinal deformity and disability. The combination of Parkinson's disease (PD) and inflammatory myopathy in the genesis of DHS has not been previously reported. Furthermore, the optimal surgical treatment of progressive DHS remains undefined. CASE DESCRIPTION: We report the case of a 64-year-old patient with severe DHS and coronal plane deformity secondary to underlying PD, precipitated by a focal paraspinal myositis, successfully corrected using asymmetric sternocleidomastoid (SCM) release and circumferential cervical fusion. The nuances of decision-making in this challenging patient population are highlighted, including the benefits of intraoperative traction, anterior column reconstruction and bicortical screw fixation. Postoperatively, significant reductions in pain and disability were achieved, along with restoration of cervical lordosis (CL), C2-7 sagittal vertical axis (CSVA) and chin-brow vertical angle (CBVA). CONCLUSIONS: Circumferential cervical fusion with concomitant SCM release is a useful option in the treatment of recalcitrant DHS with biplanar deformity, addressing the unique biomechanical and endocrinological challenges posed by patients with underlying PD.

The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma.

PURPOSE: Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs). METHODS: Gene expression data was obtained from the online patient-histology database, GlioVis. GSC mitochondria morphology was examined by TEM. Cell viability and effect on GSC self-renewal was determined via MTS assay and neurosphere assay, respectively. Proteins were evaluated by Western Blot. RESULTS: Enzymes necessary for ketone catabolism (BDH1, OXCT1 and ACAT1) are significantly downregulated in adult and pediatric GBM. GSC mitochondrial ultrastructure suggested defects in oxidative phosphorylation. Treatment of both GBM and GSC cell lines resulted in dose-dependent decreases in viability in response to glycolytic inhibitor 2-deoxy-D-glucose (2-DG), and ketone body Acetoacetate (AA), but not ß-hydroxybutyrate (ßHB). AA induced apoptosis was confirmed by western blot analysis, indicating robust caspase activation and PARP cleavage. AA reduced neurosphere formation at concentrations as low as 1 mM. Combined treatment of low dose 2-DG (50 µM) with AA resulted in more cell death than either treatment alone. The effect was greater than additive at low concentrations of AA, reducing viability approximately 50% at 1 mM AA. AA was found to directly upregulate mitochondrial uncoupling protein 2 (UCP2), which may explain this potential drug synergism via multi-faceted inhibition of the glycolytic pathway. CONCLUSION: Targeting the metabolic pathway of GBM via glycolytic inhibition in conjunction with ketogenic diet or exogenous ketone body supplementation warrants further investigation as a promising adjunctive treatment to conventional therapy.

Carbon Nitride Dots: A Selective Bioimaging Nanomaterial.

In contrast to the recent immense attention in carbon nitride quantum dots (CNQDs) as a heteroatom-doped carbon quantum dot (CQD), their biomedical applications have not been thoroughly investigated. Targeted cancer therapy is a prominently researched area in the biomedical field. Here, the ability of CNQDs as a selective bioimaging nanomaterial was investigated to assist targeted cancer therapy. CNQDs were first synthesized using four different precursor sets involving urea derivatives, and the characteristics were compared to select the best candidate material for bioapplications. Characterization techniques such as UV-vis, luminescence, X-ray photoelectron spectroscopy, nuclear magnetic resonance spectroscopy, and transmission electron microscopy were used. These CNQDs were analyzed in in vitro studies of bioimaging and labeling using pediatric glioma cells (SJGBM2) for possible selective biolabeling and nanodistribution inside the cell membrane. The in vitro cellular studies were conducted under long-wavelength emission without the interference of blue autofluorescence. Thus, excitation-dependent emission of CNQDs was proved to be advantageous. Importantly, CNQDs selectively entered SJGBM2 tumor cells, while it did not disperse into normal human embryonic kidney cells (HEK293). The distribution studies in the cell cytoplasm indicated that CNQDs dispersed into lysosomes within approximately 6 h after the incubation. The CNQDs exhibited great potential as a possible nanomaterial in selective bioimaging and drug delivery for targeted cancer therapy.

Pooled data analysis on anterior versus posterior approach for rheumatoid arthritis at the craniovertebral junction.

OBJECT: Rheumatoid arthritis (RA) is one of the most debilitating autoimmune diseases affecting the craniovertebral junction (CVJ). Patients predominantly present with myelopathic symptoms and intractable neck pain. The surgical approach traditionally has been either a combined anterior and posterior approach or a posterior-only approach. In this article, the authors review pooled data from the literature and discuss the benefits of the two types of approaches. METHODS: A search of the PubMed database was conducted using key words that describe spine deformities in RA and specific spinal interventions. The authors evaluated the neurological outcomes based on the Ranawat scale in both the groups through chi-square analysis. Multiple logistic regression was carried out to further examine for potential confounders. Any adverse sequalae resulting from either approach were also documented. Because all the procedures performed via a transoral approach in the analyzed articles also involved posterior fixation, for convenience of comparison, the combined procedures are referred to as "anterior approach" or "anterior-posterior" in the present study. RESULTS: The search yielded 233 articles, of which 11 described anterior approaches and 14 evaluated posterior approaches. The statistical analysis showed that patients treated with a posterior approach fared better than those treated with an anterior (combined) approach. It was noted that those patients in whom the cervical subluxations were reducible on traction predominantly underwent posterior approaches. CONCLUSIONS: CVJ instability is a serious complication of RA that requires surgical intervention. Although the anterior-posterior combined approach can provide direct decompression, it is associated with morbidity, and the analysis showed no statistically significant benefit to patients. In contrast, the posterior approach has been shown to provide statistically significant superiority with respect to stabilization and subsequent pannus reduction. Surgical approaches are undertaken based on the reducibility of subluxations with traction and the vector of compressive force. However, the choice of surgical approach should be based on the individual patient's pathology.

Direct lateral retroperitoneal approach for the surgical treatment of lumbar discitis and osteomyelitis.

OBJECT: The medical management of discitis and osteomyelitis with long-term antibiotic therapy and bracing usually results in eradicated infection. Surgical management is appropriate when medical management fails and in some cases with pyogenic deformity or neurological deficit. The success of surgery depends on adequate debridement of the necrotic infected disc and vertebral body, along with anterior column reconstruction and vertebral stabilization. Debridement is typically performed via an anterior retroperitoneal approach, which can necessitate mobilization of the great vessels for proper exposure. Mobilization can be technically difficult and lead to vascular injury. The purpose of this study was to evaluate an alternative technique for the surgical treatment of lumbar discitis and osteomyelitis using a direct lateral retroperitoneal approach, which allows for thorough debridement and anterior column reconstruction while avoiding the need to mobilize the great vessels. METHODS: A retrospective chart analysis was performed for all patients who had presented with lumbar discitis and osteomyelitis and had undergone surgical management via the direct lateral retroperitoneal approach in the period from 2006 to 2013. Collected data included surgical blood loss, perioperative complications (wound infection, vascular injury, approach-related complications, and neurological injury), need for secondary procedures, microbiological and laboratory results, and efficacy of infection eradication. Imaging studies were reviewed as well. RESULTS: Ten patients, 7 male and 3 female, underwent this procedure at the authors' institution in the defined period. Average blood loss was 272 ml (range 150-800 ml, with 800 ml in the only 2-level case). There were no vascular injuries. Average follow-up was 680 days, although 4 patients did not complete the follow-up beyond 6 months. Eight patients underwent immediate posterior pedicle screw instrumentation. Two patients did not undergo posterior instrumentation, and one of these developed a kyphotic deformity that required a secondary posterior procedure. Infection was eradicated in all patients according to a history, physical examination, imaging studies, and laboratory parameters (complete blood count, erythrocyte sedimentation rate, and C-reactive protein). One patient developed a painful neuroma at the iliac crest harvest site, and one patient had a retroperitoneal hematoma. Otherwise, there were no approach-related neurological injuries or complications. Neither was there any postoperative surgical site infection. CONCLUSIONS: The direct lateral approach for the surgical treatment of lumbar discitis and osteomyelitis allows for thorough debridement and spinal reconstruction without the need to mobilize the great vessels. This technique effectively eradicated infection in all cases, with reasonable blood loss and no vascular injuries. This approach should be considered as an alternative to the open anterior approach. The authors recommend posterior instrumentation to prevent the development of kyphosis.

The art of simplicity: Water-soluble porphyrin-like carbon dots self-assemble into mesmerizing red glow.

In this new study, we present an intriguing development in the field of theranostics: the simplistic self-assembly of red-emissive amphiphilic porphyrin-like carbon dots (P-CDs). By harnessing their exceptional photophysical properties, we have revealed a strong candidate as the ideal photosensitizer (PS) for applications, particularly in the realm of imaging. Spanning a remarkable size average between 1-4 nm, these particles exhibit both highly stable and unparalleled emission characteristics between 650 and 715 nm in water in comparison to current carbon dots (CDs) available. Lastly, these CDs were fairly non-toxic when tested against normal human cell lines as well as were found to have favorable imaging capabilities in zebrafish embryo.

Advancing glioblastoma imaging: Exploring the potential of organic fluorophore-based red emissive carbon dots.

Over time, the interest in developing stable photosensitizers (PS) which both absorb and emit light in the red region (650 and 950 nm) has gained noticeable interest. Recently, carbon dots (CDs) have become the material of focus to act as a PS due to their high extinction coefficient, low cytotoxicity, and both high photo and thermal stability. In this work, a Federal and Drug Association (FDA) approved Near Infra-Red (NIR) organic fluorophore used for photo-imaging, indocyanine green (ICG), has been explored as a precursor to develop water-soluble red emissive CDs which possess red emission at 697 nm. Furthermore, our material was found to yield favorable red-imaging capabilities of glioblastoma stem-like cells (GSCs) meanwhile boasting low toxicity. Additionally with post modifications, our CDs have been found to have selectivity towards tumors over healthy tissue as well as crossing the blood-brain barrier (BBB) in zebrafish models.

Hydrothermal vs microwave nanoarchitechtonics of carbon dots significantly affects the structure, physicochemical properties, and anti-cancer activity against a specific neuroblastoma cell line.

Carbon dots (CDs) from glucose were synthesized using two of the most common bottom-up methods, namely, microwave assisted (MW) and hydrothermal carbonization (HT). Synthetic parameters such as reaction time, temperature, and precursor concentration were changed to study the effects of each parameter on CD size, structure, surface functionalities, charge, photoluminescence behavior, quantum yield, cytotoxicity, blood-brain barrier (BBB) crossing ability and bioimaging. A detailed analysis is performed to compare the structure and properties of the CDs synthesized in ten different conditions. We show that the synthesis route drastically changes the structure, properties, and related functions of glucose-derived CDs yielding two different subtypes of CDs. Surprisingly, CDs that was synthesized via HT method showed specific anticancer activity against a neuroblastoma cell line while being non-toxic towards healthy cell lines, indicating significant potential for therapeutic applications. CDs synthesized via MW crosses the BBB in zebrafish and rat models, and accumulates in neurons. CDs synthesized via MW method showed high biocompatibility and a great potential to be used for bioimaging applications in vitro and in vivo targeting neurons. Finally, a formation mechanism of CDs is proposed for both HT and MW synthesis routes.

Surface modification of carbon nitride dots by nanoarchitectonics for better drug loading and higher cancer selectivity.

Carbon Dots (CDs) have recently attracted a considerable amount of attention thanks to their well-documented biocompatibility, tunable photoluminescence, and excellent water solubility. However, CDs need further analysis before their potential use in clinical trials. Previously, we reported a new type of carbon nitride dot (CND) that displayed selective cancer uptake traits attributed to structural resemblances between CNDs and glutamine. Here, the effects of surface structural differences on the cellular uptake of CNDs are further investigated to understand their selective cancer cell uptake trend. Beyond enhanced drug loading on modified CNDs, our cytotoxicity, western blotting and bioimaging studies proposed that modified CNDs' cellular uptake mechanism is thoroughly linked with ASCT2 and LAT1 transporters. Therefore, CNDs have a promising trait of selective cancer cell targeting by utilizing highly expressed transporters on cancer cells. Additionally, drug loaded CNDs exhibited improved anti-cancer efficacies towards cancer cells along with good non-tumor biocompatibilities.

NAMPT Inhibition Induces Neuroblastoma Cell Death and Blocks Tumor Growth.

High-risk neuroblastoma (NB) portends very poor prognoses in children. Targeting tumor metabolism has emerged as a novel therapeutic strategy. High levels of nicotinamide-adenine-dinucleotide (NAD+) are required for rapid cell proliferation. Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme for NAD+ salvage and is overexpressed in several cancers. Here, we determine the potential of NAMPT as a therapeutic target for NB treatment. NAMPT inhibition cytotoxicity was determined by trypan blue exclusion and LDH assays. Neuroblastoma stem cell self-renewal was evaluated by neurosphere assay. Protein expression was evaluated via Western blot. The effect of targeting NAMPT in vivo was determined using an NB1691-xenografted mouse model. Robust NAMPT expression was demonstrated in multiple N-MYC amplified, high-risk neuroblastoma cell lines. NAMPT inhibition with STF-118804 (STF) decreased ATP, induced apoptosis, and reduced NB stem cell neurosphere formation. STF treatment down-regulated N-MYC levels and abrogated AKT activation. AKT and glycolytic pathway inhibitors in combination with NAMPT inhibition induced robust, greater-than-additive neuroblastoma cell death. Lastly, STF treatment blocked neuroblastoma tumor growth in mouse xenograft models. NAMPT is a valid therapeutic target as inhibition promoted neuroblastoma cell death in vitro and prevented tumor growth in vivo. Further investigation is warranted to establish this therapy's role as an adjunctive modality.

DFMO Carbon Dots for Treatment of Neuroblastoma and Bioimaging.

Neuroblastoma (NB) is a pediatric malignancy affecting the peripheral nervous system. Despite recent advancements in treatment, many children affected with NB continue to submit to this illness, and new therapeutic strategies are desperately needed. In recent years, studies of carbon dots (CDs) as nanocarriers have mostly focused on the delivery of anticancer agents because of their biocompatibility, good aqueous dissolution, and photostability. Their fluorescence properties, surface functionalities, and surface charges differ on the basis of the type of precursors used and the synthetic approach implemented. At present, most CDs are used as nanocarriers by directly linking them either covalently or electrostatically to drug molecules. Though most modern CDs are synthesized from large carbon macromolecules and conjugated to anticancerous drugs, constructing CDs from the anticancerous drugs and precursors themselves to increase antitumoral activity requires further investigation. Herein, CDs were synthesized using difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor commonly used in high-risk neuroblastoma treatment regiments. In this study, NB cell lines, SMS-KCNR and SK-N-AS, were treated with DFMO, the newly synthesized DFMO CDs, and conventional DFMO conjugated to black carbon dots. Bioimaging was done to determine the cellular localization of a fluorescent drug over time. The mobility of DNA mixed with DFMO CDs was evaluated by gel electrophoresis. DFMO CDs were effectively synthesized from DFMO precursor and characterized using spectroscopic methods. The DFMO CDs effectively reduced cell viability with increasing dose. The effects were dramatic in the N-MYC-amplified line SMS-KCNR at 500 µM, which is comparable to high doses of conventional DFMO at a 60-fold lower concentration. In vitro bioimaging as well as DNA electrophoresis showed that synthesized DFMO CDs were able to enter the nucleus of neuroblastoma cells and neuronal cells and interact with DNA. Our new DFMO CDs exhibit a robust advantage over conventional DFMO because they induce comparable reductions in viability at a dramatically lower concentration.

Chalcones as Anti-Glioblastoma Stem Cell Agent Alone or as Nanoparticle Formulation Using Carbon Dots as Nanocarrier.

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.

Short lever arm, bipedicular handlebar construct for correction of acute angular kyphosis in spondylodiscitis-induced kyphotic deformity: illustrative case.

BACKGROUND: Pyogenic spondylodiscitis diminishes spinal structural integrity via disruption of the anterior and middle column, sometimes further compounded by iatrogenic violation of the posterior tension band during initial posterior decompressive surgeries. Although medical management is typically sufficient, refractory infection or progressive deformity may require aggressive debridement and reconstructive arthrodesis. Although anterior debridement plus reconstruction with posterior stabilization is an effective treatment option, existing techniques have limited efficacy for correcting focal deformity, leaving patients at risk for long-term sagittal imbalance, pain, and disability. OBSERVATIONS: The authors present a case of chronic lumbar pyogenic spondylodiscitis in a patient in whom initial surgical debridement failed and pronounced angular kyphosis and intractable low back pain developed. A novel bipedicular handlebar construct was used to achieve angular correction of the kyphosis through simultaneous anterior interbody grafting and posterior instrumentation with the patient in the lateral position. LESSONS: Leveraging both pedicle screws at the same level to transmit controlled corrective distraction forces through the segment allows for kyphosis correction without relying on long posterior constructs for cantilever reduction. Simultaneous anterior reconstruction with a posterior short lever arm, bipedicular handlebar construct is an effective technique for achieving high angular correction during circumferential reconstructive approaches to postinfectious focal kyphotic deformities.

UCP2 as a Potential Biomarker for Adjunctive Metabolic Therapies in Tumor Management.

Glioblastoma (GBM) remains one of the most lethal primary brain tumors in both adult and pediatric patients. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs). Neoplastic cells, especially those with high proliferative potential such as GSCs, have been shown to upregulate UCP2 as a cytoprotective mechanism in response to chronic increased reactive oxygen species (ROS) exposure. This upregulation plays a central role in the induction of the highly glycolytic phenotype associated with many tumors. In addition to shifting metabolism away from oxidative phosphorylation, UCP2 has also been implicated in increased mitochondrial Ca2+ sequestration, apoptotic evasion, dampened immune response, and chemotherapeutic resistance. A query of the CGGA RNA-seq and the TCGA GBMLGG database demonstrated that UCP2 expression increases with increased WHO tumor-grade and is associated with much poorer prognosis across a cohort of brain tumors. UCP2 expression could potentially serve as a biomarker to stratify patients for adjunctive anti-tumor metabolic therapies, such as glycolytic inhibition alongside current standard of care, particularly in adult and pediatric gliomas. Additionally, because UCP2 correlates with tumor grade, monitoring serum protein levels in the future may allow clinicians a relatively minimally invasive marker to correlate with disease progression. Further investigation of UCP2's role in metabolic reprogramming is warranted to fully appreciate its clinical translatability and utility.

Incidence and Clinical Outcomes of Hypothyroidism in Patients Undergoing Spinal Fusion.

Background Hypothyroidism has been independently associated with the development of several comorbidities and is known to increase complication rates in non-spinal surgeries. However, there are limited data regarding the effects of hypothyroidism in major spine surgery. Therefore, we present the largest retrospective analysis evaluating outcomes in hypothyroid patients undergoing spinal fusion. Methods A retrospective review of the National Inpatient Sample (NIS) from 2004-2014 was performed. Patients with an International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) procedure code indicating spinal fusion (81.04-81.08, 81.34-81.38, 81.0x, 81.3x) were included. Patients with an ICD-9-CM diagnosis code indicating hypothyroidism (244.x) were compared to those without. Cervical and lumbar fusions were evaluated independently. Significant covariates in univariable logistic regression were utilized to construct multivariable models to analyze the effect of hypothyroidism on perioperative morbidity and mortality. Results A total of 4,149,125 patients were identified, of which 9.4% were hypothyroid. Although, hypothyroid patients had a higher risk of hematologic complications (lumbar - odds ratio [OR] 1.176, p < 0.0001; cervical - OR 1.162, p < 0.0001), they exhibited decreased in-hospital mortality (lumbar - OR .643, p < 0.0001; cervical - OR .606, p < 0.0001). Hypothyroid lumbar fusion patients also demonstrated decreased rates of perioperative myocardial infarction (MI) (OR .851, p < 0.0001). All these results were independent of patient gender. Conclusions Hypothyroid patients undergoing spinal fusion demonstrated lower rates of inpatient mortality and, in lumbar fusions, also had lower rates of acute MI when compared to their euthyroid counterparts. This suggests that hypothyroidism may offer protection against all-cause mortality and may be cardioprotective in the postoperative period for lumbar spinal fusions independent of patient gender.

The Effects of Lockdown During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pandemic on Neurotrauma-Related Hospital Admissions.

BACKGROUND: The response to the global severe acute respiratory syndrome coronavirus 2 pandemic culminated in mandatory isolation throughout the world, with nationwide confinement orders issued to decrease viral spread. These drastic measures were successful in "flattening the curve" and maintaining the previous rate of coronavirus disease 2019 infections and deaths. To date, the effects of the coronavirus disease 2019 pandemic on neurotrauma has not been reported. METHODS: We retrospectively analyzed hospital admissions from Ryder Trauma Center at Jackson Memorial Hospital, during the months of March and April from 2016 to 2020. Specifically, we identified all patients who had cranial neurotrauma consisting of traumatic brain injury and/or skull fractures, as well as spinal neurotrauma consisting of vertebral fractures and/or spinal cord injury. We then performed chart review to determine mechanism of injury and if emergent surgical intervention was required. RESULTS: Compared with previous years, we saw a significant decline in the number of neurotraumas during the pandemic, with a 62% decline after the lockdown began. The number of emergent neurotrauma surgical cases also significantly decreased by 84% in the month of April. Interestingly, although the number of vehicular traumas decreased by 77%, there was a significant 100% increase in the number of gunshot wounds. CONCLUSIONS: Population seclusion had a direct effect on the frequency of neurotrauma, whereas the change in relative proportion of certain mechanisms may be associated with the psychosocial effects of social distancing and quarantine.

National Trends and Correlates of Dysphagia After Anterior Cervical Discectomy and Fusion Surgery.

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the most common performed surgery in the cervical spine. Dysphagia is one of the most frequent complications following ACDF. Several studies have identified certain demographic and perioperative risk factors associated with increased dysphagia rates, but few have reported recent trends. Our study aims to report current trends and factors associated with the development of inpatient postoperative dysphagia after ACDF. METHODS: The National Inpatient Sample was evaluated from 2004 to 2014 and discharges with International Classification of Diseases procedure codes indicating ACDF were selected. Time trend series plots were created for the yearly treatment trends for each fusion level by dysphagia outcome. Separate univariable followed by multivariable logistic regression analyses were performed to evaluate predictors of dysphagia. RESULTS: A total of 1,212,475 ACDFs were identified in which 3.3% experienced postoperative dysphagia. A significant increase in annual dysphagia rates was observed from 2004-2014. Frailty, intraoperative neuromonitoring, 4 or more level fusions, African American race, fluid/electrolyte disorders, blood loss, and coagulopathy were all identified as significant independent risk factors for the development of postoperative dysphagia following ACDF. CONCLUSION: Postoperative dysphagia is a well-known postsurgical complication associated with ACDF. Our cohort showed a significant increase in the annual dysphagia rates independent of levels fused. We identified several risk factors associated with the development of postoperative dysphagia after ACDF.

pH and redox triggered doxorubicin release from covalently linked carbon dots conjugates.

Tumor microenvironment responsive drug delivery systems are potential approaches to reduce the acute toxicity caused by high-dose cancer chemotherapy. Notwithstanding the conventional nano-drug delivery systems, the redox and pH stimuli drug delivery systems are currently gaining attention. Therefore, the current study was designed to compare three different covalent carbon dots (C-dots) systems based on doxorubicin (dox) release profiles and cancer cell viability efficacy under acidic and physiological conditions. The C-dots nanosystems that were examined in this study are directly conjugated (C-dots-dox), pH triggered (C-dots-HBA-dox), and the redox stimuli (C-dots-S-S-dox) conjugates. The drug loading content (DLC%) of the C-dots-S-S-dox, C-dots-HBA-dox, and C-dots-dox was 34.2 ± 0.4, 60.0 ± 0.3, and 70.0 ± 0.2%, respectively, that examined by UV-vis spectral analysis. The dox release paradigms were emphasized that all three conjugates were promisingly released the dox from C-dots faster in acidic pH than in physiological pH. The displayed highest dox released percentage in the acidic medium was 74.6 ± 0.8% obtained by the pH stimuli, C-dots-HBA-dox conjugate. When introducing the redox inducer, dithiothreitol (DTT), preferentially, the redox stimuli C-dot-S-S-dox conjugate demonstrated a faster dox release at acidic pH than in the pH 7.4. The SJGBM2 cell viability experiments revealed that the pH stimuli, C-dots-HBA-dox conjugate, displayed a significant cell viability drop in the artificially acidified pH 6.4 medium. However, in the physiological pH, the redox stimuli, C-dots-S-S-dox conjugate, was promising over the pH stimuli C-dots-HBA-dox, exhibiting cell viability of 60%, though its' efficacy dropped slightly in the artificially acidified pH 6.4 medium. Moreover, the current study illustrates the stimuli conjugates' remarkable efficacy on sustain drug release than direct amide linkage.

Effects of Body Mass Index on Perioperative Outcomes in Patients Undergoing Anterior Cervical Discectomy and Fusion Surgery.

OBJECTIVE: Obesity has become a public health crisis and continues to be on the rise. An elevated body mass index has been linked to higher rates of spinal degenerative disease requiring surgical intervention. Limited studies exist that evaluate the effects of obesity on perioperative complications in patients undergoing anterior cervical discectomy and fusion (ACDF). Our study aims to determine the incidence of obesity in the ACDF population and the effects it may have on postoperative inpatient complications. METHODS: The National Inpatient Sample was evaluated from 2004 to 2014 and discharges with International Classification of Diseases procedure codes indicating ACDF were identified. This cohort was stratified into patients with diagnosis codes indicating obesity. Separate univariable followed by multivariable logistic regression analysis were performed for the likelihood of perioperative inpatient outcomes among the patients with obesity. RESULTS: From 2004 to 2014, estimated 1,212,475 ACDFs were identified in which 9.2% of the patients were obese. The incidence of obesity amongst ACDF patients has risen dramatically during those years from 5.8% to 13.4%. Obese ACDF patients had higher inpatient likelihood of dysphagia, neurological, respiratory, and hematologic complications as well as pulmonary emboli, and intraoperative durotomy. CONCLUSION: Obesity is a well-established modifiable comorbidity that leads to increased perioperative complications in various surgical specialties. We present one of the largest retrospective analyses evaluating the effects of obesity on inpatient complications following ACDF. Our data suggest that the number of obese patients undergoing ACDF is steadily increasing and had a higher inpatient likelihood of developing perioperative complications.