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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.
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Pontos Quânticos , Água , Humanos , Animais , Carbono , Peixe-Zebra , Linhagem CelularRESUMO
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.
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Glioblastoma , Pontos Quânticos , Animais , Carbono , Glioblastoma/diagnóstico por imagem , Peixe-Zebra , Corantes FluorescentesRESUMO
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.
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Neoplasias Encefálicas , Nanopartículas , Pontos Quânticos , Humanos , Criança , Sistemas de Liberação de Medicamentos , Carbono/uso terapêutico , Carbono/química , Neoplasias Encefálicas/tratamento farmacológico , Lipossomos , Nanopartículas/uso terapêutico , Nanopartículas/química , Nanomedicina TeranósticaRESUMO
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.
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Neuroblastoma , Pontos Quânticos , Ratos , Animais , Carbono/química , Pontos Quânticos/química , Micro-Ondas , Nitrogênio/química , Peixe-Zebra , Linhagem Celular , Neuroblastoma/tratamento farmacológico , GlucoseRESUMO
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.
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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.
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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.
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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.
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Antineoplásicos , Neuroblastoma , Antineoplásicos/farmacologia , Carbono/farmacologia , Criança , Eflornitina/farmacologia , Humanos , Neuroblastoma/diagnóstico por imagem , Inibidores da Ornitina Descarboxilase/uso terapêuticoRESUMO
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.
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Carbono , Neoplasias , Carbono/química , Humanos , Neoplasias/tratamento farmacológico , Nitrilas/químicaRESUMO
Loss of hand function after cervical spinal cord injury severely impairs functional independence. We describe a method for restoring volitional control of hand grasp in one 21-year-old male subject with complete cervical quadriplegia (C5 American Spinal Injury Association Impairment Scale A) using a portable fully implanted brain-computer interface within the home environment. The brain-computer interface consists of subdural surface electrodes placed over the dominant-hand motor cortex and connects to a transmitter implanted subcutaneously below the clavicle, which allows continuous reading of the electrocorticographic activity. Movement-intent was used to trigger functional electrical stimulation of the dominant hand during an initial 29-weeks laboratory study and subsequently via a mechanical hand orthosis during in-home use. Movement-intent information could be decoded consistently throughout the 29-weeks in-laboratory study with a mean accuracy of 89.0% (range 78-93.3%). Improvements were observed in both the speed and accuracy of various upper extremity tasks, including lifting small objects and transferring objects to specific targets. At-home decoding accuracy during open-loop trials reached an accuracy of 91.3% (range 80-98.95%) and an accuracy of 88.3% (range 77.6-95.5%) during closed-loop trials. Importantly, the temporal stability of both the functional outcomes and decoder metrics were not explored in this study. A fully implanted brain-computer interface can be safely used to reliably decode movement-intent from motor cortex, allowing for accurate volitional control of hand grasp.
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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.
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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.
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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.
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Antibióticos Antineoplásicos , Carbono , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Concentração de Íons de Hidrogênio , OxirreduçãoRESUMO
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.
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Carbon dots (CDs) have been intensively studied since their discovery in 2004 because of their unique properties such as low toxicity, excellent biocompatibility, high photoluminescence (PL) and good water dispersibility. In this study metformin derived carbon dots (Met-CDs) were synthesized using a microwave assisted method. Met-CDs were meticulously characterized using ultra-violet spectroscopy (UV-vis), photoluminescence (PL), Fourier Transform Infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), atomic force (AFM) and transmission electron (TEM) microscopies. According to results of cytotoxicity studies, Met-CDs possess low-toxicity and excellent biocompatibility towards both non-tumor and tumor cell lines indicating that Met-CDs are outstanding candidates for living cell bioimaging studies. Furthermore, bioimaging studies have displayed that Met-CDs can penetrate the cell membrane and disperse throughout the cell structure including the nucleus and mitochondria. More specifically, Met-CDs tend to start localizing selectively inside the mitochondria of cancer cells, but not of non-tumor cells after 1 h of incubation. Finally, a zebrafish study confirmed that Met-CDs cross the blood-brain barrier (BBB) without the need of any other ligands. In summary, this study presents synthesis of Met-CDs which feature abilities such as mitochondrial and nucleus localizations along with BBB penetration.
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Metformina , Pontos Quânticos , Animais , Biomarcadores , Barreira Hematoencefálica , Carbono , Sobrevivência Celular , Metformina/farmacologia , Mitocôndrias , Peixe-ZebraRESUMO
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.
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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.
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Lesões Encefálicas Traumáticas/epidemiologia , COVID-19/epidemiologia , Admissão do Paciente/tendências , Quarentena/tendências , Traumatismos da Medula Espinal/epidemiologia , Centros de Traumatologia/tendências , Acidentes por Quedas , Lesões Encefálicas Traumáticas/diagnóstico , COVID-19/prevenção & controle , Humanos , Pandemias/prevenção & controle , Estudos Retrospectivos , Traumatismos da Medula Espinal/diagnósticoRESUMO
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.
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BACKGROUND: Cervical teardrop fractures are hyperflexion and axial loading injuries associated with significant ligamentous disruption. Patients sustaining these types of injury are classically treated with a cervical corpectomy and anterior fusion. However, there are notable disadvantages of this approach, namely, disruption of the patient's true anatomic alignment and a reduction in the number of fixation points available for cervical fusion. Here we present a novel method of open reduction and internal fixation in a neurologically intact patient with cervical teardrop fracture. CASE DESCRIPTION: A 34-year-old man presented to Ryder Trauma Center after a helmeted motorcycle accident. The patient was found to be neurologically intact on arrival, and imaging demonstrated a C5 teardrop fracture without bony retropulsion. The patient was taken to the operating room for an open reduction and internal fixation of the fracture using a novel technique. This technique used traditional diskectomies at the C4-5 and C5-6 levels, along with a temporary, unicortical screw into the C5 body to capture the anteriorly displaced fragment. A bicortical screw was then placed into the contralateral side, and now, having fully reduced the fracture, the first (temporary) screw was replaced with a bicortical screw. The patient was neurologically intact postoperatively, with 2-month follow-up computed tomography scan demonstrating stable reduction of the fracture. CONCLUSIONS: Here we present a novel technique for open reduction and internal fixation of a cervical teardrop fracture that does not require cervical corpectomy. This technique is particularly useful in patients with an anteriorly displaced fragment and without neurologic deficit or compromise.
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Parafusos Ósseos , Vértebras Cervicais/cirurgia , Fixação Interna de Fraturas/métodos , Redução Aberta/métodos , Fraturas da Coluna Vertebral/cirurgia , Acidentes de Trânsito , Adulto , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/lesões , Discotomia/métodos , Humanos , Masculino , Motocicletas , Fraturas da Coluna Vertebral/diagnóstico por imagemRESUMO
Pediatric glioblastomas are known to be one of the most dangerous and life-threatening cancers among many others regardless of the low number of cases reported. The major obstacles in the treatment of these tumors can be identified as the lack of prognosis data and the therapeutic requirement to be able to cross the blood-brain barrier (BBB). Due to this lack of data and techniques, pediatric patients could face drastic side effects over a long-time span even after survival. Therefore, in this study, the capability of non-toxic carbon nitride dots (CNDs) to selectively target pediatric glioblastoma cells was studied in vitro. Furthermore, the nanocarrier capability and efficiency of CNDs were also investigated through conjugation of a chemotherapeutic agent and transferrin (Tf) protein. Gemcitabine (GM) was introduced into the system as a chemotherapeutic agent, which has never been successfully used for the treatment of any central nervous system (CNS) cancer. More than 95% of selective damage of SJGBM2 glioma cells was observed at 1 µM of CN-GM conjugate with almost 100% viability of non-cancerous HEK293 cells, although this ability was diminished at lower concentrations. However, further conjugation of Tf to obtain CN-GM-Tf allowed the achievement of selective targeting and prominent anti-cancer activity at a 100-fold lower concentration of 10 nM. Furthermore, both conjugates were capable of effectively damaging several other brain tumor cells, which were not well responsive towards the single treatment of GM. The capability of BBB penetration of the conjugates was observed using a zebrafish model, which confirms the CNDs' competence as an excellent nanocarrier to the CNS.