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1.
Clin Ophthalmol ; 18: 1667-1678, 2024.
Article En | MEDLINE | ID: mdl-38860118

Purpose: Uncorrected refractive errors (REs) and amblyopia can lead to visual impairment with deleterious effects on quality of life and academic performance. Early detection and treatment by community vision care programs, such as the UCI EyeMobile for Children, can aid in addressing preventable vision loss. Methods: A total of 5074 children between the ages of 3 and 10 years were screened at 153 locations, including preschools, head start programs, and elementary schools within Orange County (OC), California (CA). Subsequently, 1024 children presented for comprehensive eye examinations. A retrospective analysis of all examined children was conducted, determining the frequency and severity of REs and amblyopia and the spectacle prescription rate by age. Propensity score matching analysis evaluated the effect of median household income on RE and amblyopia frequency. Results: Among those who failed initial screening and were subsequently examined, significant rates of REs and amblyopia were detected: myopia (24.4%), hyperopia (35.4%), astigmatism (71.8%), anisometropia (8.9%), amblyopia (7.0%), and amblyopia risk (14.4%). A majority (65.0%) of those examined received prescription spectacles from UCI EyeMobile, with around a third requiring a new or updated prescription. The frequency of REs and amblyopia and the spectacle prescription rate were uniform across OC congressional districts. Myopia and amblyopia risk was positively and negatively associated with household income, respectively. Conclusion: The UCI EyeMobile for Children serves as a vital vision care program, providing free vision screening, comprehensive eye examinations, and spectacles. A significant number of children required examination, and a high frequency of REs and amblyopia were detected in examined children, with subsequent provision of prescription spectacles to most children.

2.
J Biol Chem ; 300(6): 107344, 2024 May 04.
Article En | MEDLINE | ID: mdl-38705389

MicroRNAs (miRs) are short, evolutionarily conserved noncoding RNAs that canonically downregulate expression of target genes. The miR family composed of miR-204 and miR-211 is among the most highly expressed miRs in the retinal pigment epithelium (RPE) in both mouse and human and also retains high sequence identity. To assess the role of this miR family in the developed mouse eye, we generated two floxed conditional KO mouse lines crossed to the RPE65-ERT2-Cre driver mouse line to perform an RPE-specific conditional KO of this miR family in adult mice. After Cre-mediated deletion, we observed retinal structural changes by optical coherence tomography; dysfunction and loss of photoreceptors by retinal imaging; and retinal inflammation marked by subretinal infiltration of immune cells by imaging and immunostaining. Single-cell RNA sequencing of diseased RPE and retinas showed potential miR-regulated target genes, as well as changes in noncoding RNAs in the RPE, rod photoreceptors, and Müller glia. This work thus highlights the role of miR-204 and miR-211 in maintaining RPE function and how the loss of miRs in the RPE exerts effects on the neural retina, leading to inflammation and retinal degeneration.

3.
J Pediatr Ophthalmol Strabismus ; : 1-8, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38661310

PURPOSE: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses. RESULTS: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age (P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender (P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years (P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76). CONCLUSIONS: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XXX-XXX.].

4.
Cell Rep ; 43(5): 114143, 2024 May 28.
Article En | MEDLINE | ID: mdl-38676924

Cellular retinaldehyde-binding protein (CRALBP) supports production of 11-cis-retinaldehyde and its delivery to photoreceptors. It is found in the retinal pigment epithelium (RPE) and Müller glia (MG), but the relative functional importance of these two cellular pools is debated. Here, we report RPE- and MG-specific CRALBP knockout (KO) mice and examine their photoreceptor and visual cycle function. Bulk visual chromophore regeneration in RPE-KO mice is 15-fold slower than in controls, accounting for their delayed rod dark adaptation and protection against retinal phototoxicity, whereas MG-KO mice have normal bulk visual chromophore regeneration and retinal light damage susceptibility. Cone pigment regeneration is significantly impaired in RPE-KO mice but mildly affected in MG-KO mice, disclosing an unexpectedly strong reliance of cone photoreceptors on the RPE-based visual cycle. These data reveal a dominant role for RPE-CRALBP in supporting rod and cone function and highlight the importance of RPE cell targeting for CRALBP gene therapies.


Carrier Proteins , Mice, Knockout , Retinal Cone Photoreceptor Cells , Retinal Pigment Epithelium , Animals , Retinal Pigment Epithelium/metabolism , Mice , Carrier Proteins/metabolism , Carrier Proteins/genetics , Retinal Cone Photoreceptor Cells/metabolism , Ependymoglial Cells/metabolism , Retinal Rod Photoreceptor Cells/metabolism , Mice, Inbred C57BL , Retinal Pigments/metabolism
5.
J Biol Chem ; 300(3): 105678, 2024 Mar.
Article En | MEDLINE | ID: mdl-38272218

Rhodopsin (Rho) and cone opsins are essential for detection of light. They respond via photoisomerization, converting their Schiff-base-adducted 11-cis-retinylidene chromophores to the all-trans configuration, eliciting conformational changes to activate opsin signaling. Subsequent Schiff-base hydrolysis releases all-trans-retinal, initiating two important cycles that maintain continuous vision-the Rho photocycle and visual cycle pathway. Schiff-base hydrolysis has been thoroughly studied with photoactivated Rho but not with cone opsins. Using established methodology, we directly measured the formation of Schiff-base between retinal chromophores with mammalian visual and nonvisual opsins of the eye. Next, we determined the rate of light-induced chromophore hydrolysis. We found that retinal hydrolysis from photoactivated cone opsins was markedly faster than from photoactivated Rho. Bovine retinal G protein-coupled receptor (bRGR) displayed rapid hydrolysis of its 11-cis-retinylidene photoproduct to quickly supply 11-cis-retinal and re-bind all-trans-retinal. Hydrolysis within bRGR in native retinal pigment epithelium microsomal membranes was >6-times faster than that of bRGR purified in detergent micelles. N-terminal-targeted antibodies significantly slowed bRGR hydrolysis, while C-terminal antibodies had no effect. Our study highlights the much faster photocycle of cone opsins relative to Rho and the crucial role of RGR in chromophore recycling in daylight. By contrast, in our experimental conditions, bovine peropsin did not form pigment in the presence of all-trans-retinal nor with any mono-cis retinal isomers, leaving uncertain the role of this opsin as a light sensor.


Cone Opsins , Opsins , Retinoids , Animals , Cattle , Hydrolysis , Opsins/chemistry , Retinaldehyde/chemistry , Rhodopsin
6.
Cell Rep ; 42(8): 112982, 2023 08 29.
Article En | MEDLINE | ID: mdl-37585292

In daylight, demand for visual chromophore (11-cis-retinal) exceeds supply by the classical visual cycle. This shortfall is compensated, in part, by the retinal G-protein-coupled receptor (RGR) photoisomerase, which is expressed in both the retinal pigment epithelium (RPE) and in Müller cells. The relative contributions of these two cellular pools of RGR to the maintenance of photoreceptor light responses are not known. Here, we use a cell-specific gene reactivation approach to elucidate the kinetics of RGR-mediated recovery of photoreceptor responses following light exposure. Electroretinographic measurements in mice with RGR expression limited to either cell type reveal that the RPE and a specialized subset of Müller glia contribute both to scotopic and photopic function. We demonstrate that 11-cis-retinal formed through photoisomerization is rapidly hydrolyzed, consistent with its role in a rapid visual pigment regeneration process. Our study shows that RGR provides a pan-retinal sink for all-trans-retinal released under sustained light conditions and supports rapid chromophore regeneration through the photic visual cycle.


Retinal Pigment Epithelium , Retinaldehyde , Animals , Mice , Retinal Pigment Epithelium/metabolism , Retinaldehyde/metabolism , Retinal Pigments/metabolism , Receptors, G-Protein-Coupled/metabolism , Neuroglia/metabolism , Retinal Cone Photoreceptor Cells/metabolism
7.
Exp Mol Med ; 55(8): 1678-1690, 2023 08.
Article En | MEDLINE | ID: mdl-37524870

Genome-editing technologies have ushered in a new era in gene therapy, providing novel therapeutic strategies for a wide range of diseases, including both genetic and nongenetic ocular diseases. These technologies offer new hope for patients suffering from previously untreatable conditions. The unique anatomical and physiological features of the eye, including its immune-privileged status, size, and compartmentalized structure, provide an optimal environment for the application of these cutting-edge technologies. Moreover, the development of various delivery methods has facilitated the efficient and targeted administration of genome engineering tools designed to correct specific ocular tissues. Additionally, advancements in noninvasive ocular imaging techniques and electroretinography have enabled real-time monitoring of therapeutic efficacy and safety. Herein, we discuss the discovery and development of genome-editing technologies, their application to ocular diseases from the anterior segment to the posterior segment, current limitations encountered in translating these technologies into clinical practice, and ongoing research endeavors aimed at overcoming these challenges.


Gene Editing , Genetic Therapy , Humans , Gene Editing/methods , Genetic Therapy/methods
8.
Proc Natl Acad Sci U S A ; 120(19): e2221045120, 2023 05 09.
Article En | MEDLINE | ID: mdl-37126699

Chronic, progressive retinal diseases, such as age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa, arise from genetic and environmental perturbations of cellular and tissue homeostasis. These disruptions accumulate with repeated exposures to stress over time, leading to progressive visual impairment and, in many cases, legal blindness. Despite decades of research, therapeutic options for the millions of patients suffering from these disorders remain severely limited, especially for treating earlier stages of pathogenesis when the opportunity to preserve the retinal structure and visual function is greatest. To address this urgent, unmet medical need, we employed a systems pharmacology platform for therapeutic development. Through integrative single-cell transcriptomics, proteomics, and phosphoproteomics, we identified universal molecular mechanisms across distinct models of age-related and inherited retinal degenerations, characterized by impaired physiological resilience to stress. Here, we report that selective, targeted pharmacological inhibition of cyclic nucleotide phosphodiesterases (PDEs), which serve as critical regulatory nodes that modulate intracellular second messenger signaling pathways, stabilized the transcriptome, proteome, and phosphoproteome through downstream activation of protective mechanisms coupled with synergistic inhibition of degenerative processes. This therapeutic intervention enhanced resilience to acute and chronic forms of stress in the degenerating retina, thus preserving tissue structure and function across various models of age-related and inherited retinal disease. Taken together, these findings exemplify a systems pharmacology approach to drug discovery and development, revealing a new class of therapeutics with potential clinical utility in the treatment or prevention of the most common causes of blindness.


Diabetic Retinopathy , Macular Degeneration , Retinal Degeneration , Retinitis Pigmentosa , Humans , Retina/metabolism , Retinal Degeneration/metabolism , Retinitis Pigmentosa/metabolism , Macular Degeneration/pathology , Diabetic Retinopathy/metabolism
9.
Neuromodulation ; 26(2): 292-301, 2023 Feb.
Article En | MEDLINE | ID: mdl-35840520

OBJECTIVES: The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS: The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS: The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.


Depressive Disorder, Major , Obsessive-Compulsive Disorder , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/psychology , Obsessive-Compulsive Disorder/therapy , Brain
10.
Proc Natl Acad Sci U S A ; 119(39): e2210104119, 2022 09 27.
Article En | MEDLINE | ID: mdl-36122230

CRISPR-Cas-based genome editing technologies could, in principle, be used to treat a wide variety of inherited diseases, including genetic disorders of vision. Programmable CRISPR-Cas nucleases are effective tools for gene disruption, but they are poorly suited for precisely correcting pathogenic mutations in most therapeutic settings. Recently developed precision genome editing agents, including base editors and prime editors, have enabled precise gene correction and disease rescue in multiple preclinical models of genetic disorders. Additionally, new delivery technologies that transiently deliver precision genome editing agents in vivo offer minimized off-target editing and improved safety profiles. These improvements to precision genome editing and delivery technologies are expected to revolutionize the treatment of genetic disorders of vision and other diseases. In this Perspective, we describe current preclinical and clinical genome editing approaches for treating inherited retinal degenerative diseases, and we discuss important considerations that should be addressed as these approaches are translated into clinical practice.


CRISPR-Cas Systems , Gene Editing , Vision Disorders , CRISPR-Cas Systems/genetics , Endonucleases/genetics , Mutation , Vision Disorders/genetics , Vision Disorders/therapy
11.
Surg Neurol Int ; 13: 300, 2022.
Article En | MEDLINE | ID: mdl-35928309

Background: The costs of cervical spine surgery have steadily increased. We performed a 5-year propensity scoring-matched analysis of 276 patients undergoing anterior versus posterior cervical surgery at one institution. Methods: We performed propensity score matching on financial data from 276 patients undergoing 1-3 level anterior versus posterior cervical fusions for degenerative disease (2015-2019). Results: We found no significant difference between anterior versus posterior approaches for hospital costs ($42,529.63 vs. $45,110.52), net revenue ($40,877.25 vs. $34,036.01), or contribution margins ($14,230.19 vs. $6,312.54). Multivariate regression analysis showed variables significantly associated with the lower contribution margins included age (ß = -392.3) and length of stay (LOS; ß = -1151). Removing age/LOS from the analysis, contribution margins were significantly higher for the anterior versus posterior approach ($17,824.16 vs. $6,312.54, P = 0.01). Conclusion: Anterior cervical surgery produced higher contribution margins compared to posterior approaches, most likely because posterior surgery was typically performed in older patients requiring longer LOS.

12.
Ann Med Surg (Lond) ; 80: 104139, 2022 Aug.
Article En | MEDLINE | ID: mdl-35846863

Introduction: Surgery can be an effective treatment for epilepsy if the seizure onset is adequately localized. Invasive monitoring is used if noninvasive methods are inconclusive. Initial invasive monitoring may fail if the pre-surgical hypothesis regarding location of epileptic foci is wrong. At this point, a decision must be made whether to remove all electrodes without a clearly defined location of onset or to implant additional electrodes with the aim of achieving localization by expanding coverage. Methods: Electrodes were placed according to a hypothesis derived from noninvasive monitoring techniques in adult patients with long term epilepsy. Seizure onset was not clearly localized at the end of the invasive monitoring period in ten patients, and additional electrodes were placed based on a new hypothesis that incorporated data from the invasive monitoring period. Results: Successful localization was achieved in nine patients. There were no complications with adding additional electrodes. At final follow up, four patients were seizure free while four others had at least a 50% reduction in seizures after undergoing surgical intervention. Conclusion: Seizure foci were localized safely in 90% of adult patients with long term epilepsy after implanting additional electrodes and expanding coverage. Patients undergoing invasive monitoring without clear localization should have additional electrodes placed to expand monitoring coverage as it is safe and effective.

13.
Nat Commun ; 13(1): 1830, 2022 04 05.
Article En | MEDLINE | ID: mdl-35383196

Leber congenital amaurosis (LCA) is the most common cause of inherited retinal degeneration in children. LCA patients with RPE65 mutations show accelerated cone photoreceptor dysfunction and death, resulting in early visual impairment. It is therefore crucial to develop a robust therapy that not only compensates for lost RPE65 function but also protects photoreceptors from further degeneration. Here, we show that in vivo correction of an Rpe65 mutation by adenine base editor (ABE) prolongs the survival of cones in an LCA mouse model. In vitro screening of ABEs and sgRNAs enables the identification of a variant that enhances in vivo correction efficiency. Subretinal delivery of ABE and sgRNA corrects up to 40% of Rpe65 transcripts, restores cone-mediated visual function, and preserves cones in LCA mice. Single-cell RNA-seq reveals upregulation of genes associated with cone phototransduction and survival. Our findings demonstrate base editing as a potential gene therapy that confers long-lasting retinal protection.


Leber Congenital Amaurosis , Retinal Degeneration , cis-trans-Isomerases , Animals , Eye Proteins/genetics , Humans , Leber Congenital Amaurosis/genetics , Leber Congenital Amaurosis/therapy , Mice , Mice, Knockout , Retinal Cone Photoreceptor Cells/physiology , Retinal Degeneration/complications , Retinal Degeneration/genetics , Retinal Degeneration/therapy , cis-trans-Isomerases/genetics
14.
J Clin Neurosci ; 97: 62-74, 2022 Mar.
Article En | MEDLINE | ID: mdl-35065405

BACKGROUND: Accurate spinal screw placement in spinal instrumentation is of utmost importance to avoid injury to surrounding neurovascular structures. This study was performed to investigate differences in accuracy, operating room time, length of stay, and operative blood loss across studies involving all types of spinal fixation. METHODS: PubMed, EMBASE, and Scopus were systematically queried to identify articles that fit the inclusion and exclusion criteria. Meta-analysis was performed using R software, and odds ratios and 95% CIs were calculated. RESULTS: Sixty-nine articles were included in qualitative synthesis, and 35 studies in the meta-analysis, for a total of 8,174 robotically placed screws in 1,492 patients compared to 9,791 conventionally placed screws in 1,638 patients. A total of 9 screw trajectories were studied in the literature, although only 4 had enough evidence to be included in the meta-analysis. Robotic screw placement was more accurate than conventional screw placement (OR 2.24; 95% CI, 1.71-2.94). Robotic placement was not associated with significantly different postoperative length of stay (SMD -0.32; 95% CI, -1.20, 0.51), operative blood loss (SMD -0.25; 95% CI, -0.79, 0.19), or operative duration (SMD 0.08; 95% CI -1.00, 1.39). A total of 8 robotic platforms were found in the literature with accuracy rates above 93%. CONCLUSION: Robotic spinal fixation is associated with increased screw placement accuracy and similar operative blood loss, length of stay, and operative duration. These findings support the safety and cost-effectiveness of robotic spinal surgery across the spectrum of robotic systems and screw types.


Pedicle Screws , Robotic Surgical Procedures , Robotics , Spinal Fusion , Humans , Spine/surgery
15.
Cell ; 185(2): 250-265.e16, 2022 01 20.
Article En | MEDLINE | ID: mdl-35021064

Methods to deliver gene editing agents in vivo as ribonucleoproteins could offer safety advantages over nucleic acid delivery approaches. We report the development and application of engineered DNA-free virus-like particles (eVLPs) that efficiently package and deliver base editor or Cas9 ribonucleoproteins. By engineering VLPs to overcome cargo packaging, release, and localization bottlenecks, we developed fourth-generation eVLPs that mediate efficient base editing in several primary mouse and human cell types. Using different glycoproteins in eVLPs alters their cellular tropism. Single injections of eVLPs into mice support therapeutic levels of base editing in multiple tissues, reducing serum Pcsk9 levels 78% following 63% liver editing, and partially restoring visual function in a mouse model of genetic blindness. In vitro and in vivo off-target editing from eVLPs was virtually undetected, an improvement over AAV or plasmid delivery. These results establish eVLPs as promising vehicles for therapeutic macromolecule delivery that combine key advantages of both viral and nonviral delivery.


Drug Delivery Systems , Genetic Engineering , Proteins/therapeutic use , Virion/genetics , Animals , Base Sequence , Blindness/genetics , Blindness/therapy , Brain/metabolism , DNA/metabolism , Disease Models, Animal , Fibroblasts/metabolism , Gene Editing , HEK293 Cells , Humans , Liver/pathology , Mice , Mice, Inbred C57BL , Proprotein Convertase 9/metabolism , Retinal Pigment Epithelium/pathology , Retroviridae , Virion/ultrastructure , Vision, Ocular
16.
JCI Insight ; 7(4)2022 02 22.
Article En | MEDLINE | ID: mdl-35015730

Adiponectin receptor 1 (ADIPOR1) is a lipid and glucose metabolism regulator that possesses intrinsic ceramidase activity. Mutations of the ADIPOR1 gene have been associated with nonsyndromic and syndromic retinitis pigmentosa. Here, we show that the absence of AdipoR1 in mice leads to progressive photoreceptor degeneration, significant reduction of electroretinogram amplitudes, decreased retinoid content in the retina, and reduced cone opsin expression. Single-cell RNA-Seq results indicate that ADIPOR1 encoded the most abundantly expressed ceramidase in mice and one of the 2 most highly expressed ceramidases in the human retina, next to acid ceramidase ASAH1. We discovered an accumulation of ceramides in the AdipoR1-/- retina, likely due to insufficient ceramidase activity for healthy retina function, resulting in photoreceptor death. Combined treatment with desipramine/L-cycloserine (DC) lowered ceramide levels and exerted a protective effect on photoreceptors in AdipoR1-/- mice. Moreover, we observed improvement in cone-mediated retinal function in the DC-treated animals. Lastly, we found that prolonged DC treatment corrected the electrical responses of the primary visual cortex to visual stimuli, approaching near-normal levels for some parameters. These results highlight the importance of ADIPOR1 ceramidase in the retina and show that pharmacological inhibition of ceramide generation can provide a therapeutic strategy for ADIPOR1-related retinopathy.


Ceramidases/antagonists & inhibitors , DNA/genetics , Mutation , Receptors, Adiponectin/genetics , Retinal Cone Photoreceptor Cells/metabolism , Retinal Diseases/genetics , Animals , DNA Mutational Analysis , Disease Models, Animal , Mice , Mice, Inbred C57BL , Mice, Mutant Strains , Receptors, Adiponectin/metabolism , Retinal Cone Photoreceptor Cells/pathology , Retinal Diseases/metabolism , Retinal Diseases/pathology
17.
World Neurosurg ; 160: e209-e219, 2022 04.
Article En | MEDLINE | ID: mdl-34995825

BACKGROUND: As an established antifibrinolytic agent, tranexamic acid (TXA) has garnered widespread use during surgery to limit intraoperative blood loss. In the field of neurosurgery, TXA is often introduced in cases of traumatic brain injury or elective spine surgeries; however, its role during elective cranial surgeries is not well established. We report a systematic review of the use of TXA in elective surgical resection of intracranial neoplasms. METHODS: We performed this systematic review following PRISMA guidelines to identify studies investigating the use of TXA in elective neurosurgical resection of intracranial neoplasms. Variables extracted included patient demographics, surgical indications, type of surgery performed, TXA dose and route of administration, operative duration, blood loss, transfusion rate, postoperative hemoglobin level, and complications. RESULTS: After careful screening, 4 articles (consisting of 682 patients) met our inclusion/exclusion criteria. The studies included 2 prospective cohort studies, 1 retrospective cohort study, and 1 case series. A χ2 test of pooled data demonstrated that patients administered TXA had a significantly decreased need for blood transfusions during surgery (odds ratio, 0.6273; 95% confidence interval, 0.4254-0.9251; P = 0.018). Mean total blood loss was 821.9 mL in the TXA group and 1099.0 mL in the control group across the studies. There was no significant difference in postoperative hemoglobin levels, with a mean of 11.4 g/dL in both the TXA and control groups. CONCLUSIONS: These results support the use of intraoperative TXA in tumor resection. However, its role in tumor resection has been less well investigated compared with its use in other areas of neurosurgery.


Antifibrinolytic Agents , Brain Neoplasms , Tranexamic Acid , Antifibrinolytic Agents/therapeutic use , Blood Loss, Surgical/prevention & control , Brain Neoplasms/surgery , Humans , Prospective Studies , Retrospective Studies , Tranexamic Acid/therapeutic use
18.
Clin Neurol Neurosurg ; 213: 107126, 2022 02.
Article En | MEDLINE | ID: mdl-35066250

External ventricular drainage is a common and invaluable neurosurgical procedure and is one of the first procedures learned and performed independently by neurosurgical residents. As accuracy and precision are paramount to EVD placement, attention to technique is paid early in a resident's training. With the advancement of virtual technology, it has become increasingly possible to move away from traditional training situations and human error, and towards automated assistance and superior cyber learning environments. Although there is significant room for improvement, there are promising results with computerized placement guides and virtually augmented practice. Here, we provide a review of the updates on EVD placement techniques, technology and training, all of which serve to improve the precision, accuracy and efficiency of EVD placement.


Drainage , Ventriculostomy , Drainage/methods , Humans , Neurosurgical Procedures/methods , Technology
19.
J Neurosurg Spine ; 36(4): 686-693, 2022 04 01.
Article En | MEDLINE | ID: mdl-34740174

OBJECTIVE: Tranexamic acid (TXA) is an antifibrinolytic agent associated with reduced blood loss and mortality in a wide range of procedures, including spine surgery, traumatic brain injury, and craniosynostosis. Despite this wide use, the safety and efficacy of TXA in spine surgery has been considered controversial due to a relative scarcity of literature and lack of statistical power in reported studies. However, if TXA can be shown to reduce blood loss in laminectomy with fusion and posterior instrumentation, more surgeons may include it in their armamentarium. The authors aimed to conduct an up-to-date systematic review and meta-analysis of the efficacy of TXA in reducing blood loss in laminectomy and fusion with posterior instrumentation. METHODS: A systematic review and meta-analysis, abiding by PRISMA guidelines, was performed by searching the databases of PubMed, Web of Science, and Cochrane. These platforms were queried for all studies reporting the use of TXA in laminectomy and fusion with posterior instrumentation. Variables retrieved included patient demographics, surgical indications, involved spinal levels, type of laminectomy performed, TXA administration dose, TXA route of administration, operative duration, blood loss, blood transfusion rate, postoperative hemoglobin level, and perioperative complications. Heterogeneity across studies was evaluated using a chi-square test, Cochran's Q test, and I2 test performed with R statistical programming software. RESULTS: A total of 7 articles were included in the qualitative study, while 6 articles featuring 411 patients underwent statistical analysis. The most common route of administration for TXA was intravenous with 15 mg/kg administered preoperatively. After the beginning of surgery, TXA administration patterns were varied among studies. Blood transfusions were increased in non-TXA cohorts compared to TXA cohorts. Patients administered TXA demonstrated a significant reduction in blood loss (mean difference -218.44 mL; 95% CI -379.34 to -57.53; p = 0.018). TXA administration was not associated with statistically significant reductions in operative durations. There were no adverse events reported in either the TXA or non-TXA patient cohorts. CONCLUSIONS: TXA can significantly reduce perioperative blood loss in cervical, thoracic, and lumbar laminectomy and fusion procedures, while demonstrating a minimal complication profile.


Antifibrinolytic Agents , Tranexamic Acid , Antifibrinolytic Agents/therapeutic use , Blood Loss, Surgical/prevention & control , Blood Transfusion/methods , Humans , Laminectomy/adverse effects , Tranexamic Acid/therapeutic use
20.
J Neurosurg ; 136(1): 40-44, 2022 01 01.
Article En | MEDLINE | ID: mdl-34243148

OBJECTIVE: Elective surgical cases generally have lower costs, higher profit margins, and better outcomes than nonelective cases. Investigating the differences in cost and profit between elective and nonelective cases would help hospitals in planning strategies to withstand financial losses due to potential pandemics. The authors sought to evaluate the exact cost and profit margin differences between elective and nonelective supratentorial tumor resections at a single institution. METHODS: The authors collected economic analysis data in all patients who underwent supratentorial tumor resection at their institution between January 2014 and December 2018. The patients were grouped into elective and nonelective cases. Propensity score matching was used to adjust for heterogeneity of baseline characteristics between the two groups. RESULTS: There were 143 elective cases and 232 nonelective cases over the 5 years. Patients in the majority of elective cases had private insurance and in the majority of nonelective cases the patients had Medicare/Medicaid (p < 0.01). The total charges were significantly lower for elective cases ($168,800.12) compared to nonelective cases ($254,839.30, p < 0.01). The profit margins were almost 6 times higher for elective than for nonelective cases ($13,025.28 vs $2,128.01, p = 0.04). After propensity score matching, there was still a significant difference between total charges and total cost. CONCLUSIONS: Elective supratentorial tumor resections were associated with significantly lower costs with shorter lengths of stay while also being roughly 6 times more profitable than nonelective cases. These findings may help future planning for hospital strategies to survive financial losses during future pandemics that require widespread cancellation of elective cases.


Brain Neoplasms/economics , Brain Neoplasms/surgery , Costs and Cost Analysis/trends , Elective Surgical Procedures/economics , Elective Surgical Procedures/trends , Propensity Score , Female , Humans , Insurance Coverage/economics , Insurance Coverage/trends , Length of Stay/economics , Length of Stay/trends , Male , Middle Aged , Postoperative Complications/economics , Postoperative Complications/prevention & control , Retrospective Studies , Risk Factors
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