A combination treatment based on drug repurposing demonstrates mutation-agnostic efficacy in pre-clinical retinopathy models.

Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6ßrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.

Exploring Pediatric Vision Care: Insights from Five Years of Referral Cases in the UCI Eye Mobile and Implications of COVID-19.

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. 2024;61(5):309-316.].

Cost analysis comparison between anterior and posterior cervical spine approaches.

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.

Utility of adding electrodes in patients undergoing invasive seizure localization: A case series.

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.

In vivo base editing rescues cone photoreceptors in a mouse model of early-onset inherited retinal degeneration.

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.

Bony fixation in the era of spinal robotics: A systematic review and meta-analysis.

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.

Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins.

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.

Use of Tranexamic Acid for Elective Resection of Intracranial Neoplasms: A Systematic Review.

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.

Association of tranexamic acid with decreased blood loss in patients undergoing laminectomy and fusion with posterior instrumentation: a systematic review and meta-analysis.

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.

Elective versus nonelective brain tumor resections: a 5-year propensity score matching cost comparison analysis.

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.

Second opinion in spine surgery: A scoping review.

BACKGROUND: As a growing number of patients seek consultations for increasingly complex and costly spinal surgery, it is of both clinical and economic value to investigate the role for second opinions (SOs). Here, we summarized and focused on the shortcomings of 14 studies regarding the role and value of SOs before proceeding with spine surgery. METHODS: Utilizing PubMed, Google Scholar, and Scopus, we identified 14 studies that met the inclusion criteria that included: English, primary articles, and studies published in the past 20 years. RESULTS: We identified the following findings regarding SO for spine surgery: (1) about 40.6% of spine consultations are SO cases; (2) 61.3% of those received a discordant SO; (3) 75% of discordant SOs recommended conservative management; and (4) SO discordance applied to a variety of procedures. CONCLUSION: The 14 studies reviewed regarding SOs in spine surgery showed that half of the SOs differed from those given in the initial consultation and that SOs in spine surgery can have a substantial impact on patient care. Absent are prospective studies investigating the impact of following a first versus second opinion. These studies are needed to inform the potential benefit of universal implementation of SOs before major spine operations to potentially reduce the frequency and type/extent of surgery.

Ethical considerations and patient safety concerns for cancelling non-urgent surgeries during the COVID-19 pandemic: a review.

At the time of writing of this article, there have been over 110 million cases and 2.4 million deaths worldwide since the start of the Coronavirus Disease 2019 (COVID-19) pandemic, postponing millions of non-urgent surgeries. Existing literature explores the complexities of rationing medical care. However, implications of non-urgent surgery postponement during the COVID-19 pandemic have not yet been analyzed within the context of the four pillars of medical ethics. The objective of this review is to discuss the ethics of elective surgery cancellation during the COVID-19 pandemic in relation to beneficence, non-maleficence, justice, and autonomy. This review hypothesizes that a more equitable decision-making algorithm can be formulated by analyzing the ethical dilemmas of elective surgical care during the pandemic through the lens of these four pillars. This paper's analysis shows that non-urgent surgeries treat conditions that can become urgent if left untreated. Postponement of these surgeries can cause cumulative harm downstream. An improved algorithm can address these issues of beneficence by weighing local pandemic stressors within predictive algorithms to appropriately increase surgeries. Additionally, the potential harms of performing non-urgent surgeries extend beyond the patient. Non-maleficence is maintained through using enhanced screening protocols and modifying surgical techniques to reduce risks to patients and clinicians. This model proposes a system to transfer patients from areas of high to low burden, addressing the challenge of justice by considering facility burden rather than value judgments concerning the nature of a particular surgery, such as cosmetic surgeries. Autonomy can be respected by giving patients the option to cancel or postpone non-urgent surgeries. However, in the context of limited resources in a global pandemic, autonomy is not absolute. Non-urgent surgeries can ethically be postponed in opposition to the patient's preference. The proposed algorithm attempts to uphold the four principles of medical ethics in rationing non-urgent surgical care by building upon existing decision models, using additional measures of resource burden and surgical safety to increase health care access and decrease long-term harm as much as possible. The next global health crisis will undoubtedly present its own unique challenges. This model may serve as a comprehensive starting point in determining future guidelines for non-urgent surgical care.

Comparison of Minimally Invasive Total versus Subtotal Resection of Spinal Tumors: A Systematic Review and Meta-Analysis.

OBJECTIVE: With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical outcomes of MISS for total versus subtotal tumor resection from current evidence. METHODS: A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included. RESULTS: Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval [CI], -47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, -84.72 mL; 95% CI, -342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, -0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34-263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection. CONCLUSIONS: Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit.

An inducible Cre mouse for studying roles of the RPE in retinal physiology and disease.

The retinal pigment epithelium (RPE) provides vital metabolic support for retinal photoreceptor cells and is an important player in numerous retinal diseases. Gene manipulation in mice using the Cre-LoxP system is an invaluable tool for studying the genetic basis of these retinal diseases. However, existing RPE-targeted Cre mouse lines have critical limitations that restrict their reliability for studies of disease pathogenesis and treatment, including mosaic Cre expression, inducer-independent activity, off-target Cre expression, and intrinsic toxicity. Here, we report the generation and characterization of a knockin mouse line in which a P2A-CreERT2 coding sequence is fused with the native RPE-specific 65 kDa protein (Rpe65) gene for cotranslational expression of CreERT2. Cre+/- mice were able to recombine a stringent Cre reporter allele with more than 99% efficiency and absolute RPE specificity upon tamoxifen induction at both postnatal days (PD) 21 and 50. Tamoxifen-independent Cre activity was negligible at PD64. Moreover, tamoxifen-treated Cre+/- mice displayed no signs of structural or functional retinal pathology up to 4 months of age. Despite weak RPE65 expression from the knockin allele, visual cycle function was normal in Cre+/- mice. These data indicate that Rpe65CreERT2 mice are well suited for studies of gene function and pathophysiology in the RPE.

Effectiveness of Repair Techniques for Spinal Dural Tears: A Systematic Review.

BACKGROUND: Incidental or intentional durotomy in spine surgery is associated with a risk of cerebrospinal fluid (CSF) leakage and reoperation. Several strategies have been introduced, but the incomplete closure is still relatively frequent and troublesome. In this study, we review current evidence on spinal dural repair strategies and evaluate their efficacy. METHODS: PubMed, Web of Science, and Scopus were used to search primary studies about the repair of the spinal dura with different techniques. Of 265 articles found, 11 studies, which specified repair techniques and postoperative outcomes, were included for qualitative and quantitative analysis. The primary outcomes were CSF leakage and postoperative infection. RESULTS: The outcomes of different dural repair techniques were available in 776 cases. Pooled analysis of 11 studies demonstrated that the most commonly used technique was a combination of primary closure, patch or graft, and sealant (22.7%, 176/776). A combination of primary closure and patch or graft resulted in the lowest rate of CSF leakage (5.5%, 7/128). In this study, sealants as an adjunct to primary closure (13.7%, 18/131) did not significantly reduce the rate of CSF leakage compared with primary closure alone (17.6%, 18/102). The rates of infection and postoperative neurologic deficit were similar regardless of the repair techniques. CONCLUSIONS: Although the use of sealants has become prevalent, available sealants as an adjunct to primary closure did not reduce the rate of CSF leakage compared with primary closure. The combination of primary closure and patches or grafts could be effective in decreasing postoperative CSF leakage.

The 100 Most Influential Publications on Medulloblastoma: Areas of Past, Current, and Future Focus.

BACKGROUND: This article is the first to identify the most influential articles on medulloblastoma using the citation analysis methodology. OBJECTIVE: To perform a bibliometric analysis of the 100 most-cited articles on medulloblastoma. METHODS: Using the Web of Science database, search criteria included the title-specific keyword "medulloblastoma" OR "cerebellar primitive neuroectodermal tumor (PNET)" OR "cerebellar PNET." Publications from 1900 to 2020 labeled "article," "review," "data set," or "clinical trial" were chosen and ranked based on total number of citations in descending order. Each article was evaluated based on the following variables: total citations, average citations per year, first author, institution of first author, title, publication year, country of origin, SCImago Journal Rank, and Scopus SNIP (Source Normalized Impact per Paper). RESULTS: Our search yielded 4928 articles on medulloblastoma. The 100 most-cited articles ranged from 192 to 2017 across 42 unique journals; Journal of Clinical Oncology accounted for the most publications (16%). Paul A. Northcott was first author of the most articles on the list (n = 7.7%), and the most widely cited article was "Altered neural cell fates and medulloblastoma in mouse patched mutants" by Goodrich et al., published in Science (1997). CONCLUSIONS: Because medulloblastoma represents the most common form of pediatric cancerous brain tumor, it is important to identify works that have significantly contributed to the body of knowledge regarding this disease. The 100 most-cited medulloblastoma articles comprise a significant collection of data regarding the histopathologic and molecular classification of medulloblastoma as well as clinical outcomes of therapeutics used to treat this disease.

The market landscape of online second opinion services for spine surgery.

BACKGROUND: The aim of this study was to identify patient interest in second opinion services online and identify the options patients have in obtaining second opinions from spine surgeons in the United States. METHODS: We utilized Google Trends (i.e., search data since 2010) to ascertain the level of interest in receiving second opinions for spinal surgery. In addition, we contacted the top 30 hospitals for neurology and neurosurgery in the U.S. News rankings by phone to obtain information regarding when/how and at what cost they provide second opinions for spine surgery. RESULTS: The cost of the second surgical opinions averaged $493 (±$343) USD (range $90-$1,300); the time to receive a second opinion averaged 20 (±19) days (range 1 day-5 months). Remote or "online second opinion" programs charged an average of $643 (±$259) USD (range $100-$850), and the time to receive an "online second opinion" averaged 14 (±7) days (range 1-4 weeks). CONCLUSION: Although second opinions have been shown to be beneficial to patients, ambiguous or high costs and long wait times may serve as barriers for certain groups (i.e., uninsured or underinsured) and potentially diminish the quality of care.

Back pain outcomes after minimally invasive anterior lumbar interbody fusion: a systematic review.

OBJECTIVE: Minimally invasive anterior lumbar interbody fusion surgery (MIS ALIF) is a technique that restores disc height and lumbar lordosis through a smaller exposure and less soft-tissue trauma compared to open approaches. The mini-open and laparoscopic assistance techniques are two main forms of MIS ALIF. The authors conducted a systematic review that sought to critically summarize the literature on back pain following MIS ALIF. METHODS: In March 2020, the authors searched the PubMed, Web of Science, and Cochrane Library databases for studies describing back pain visual analog scale (VAS) outcomes after MIS ALIF. The following exclusion criteria were applied to studies evaluated in full text: 1) the study included fewer than 20 patients, 2) the mean follow-up duration was shorter than 12 months, 3) the study did not report back pain VAS score as an outcome measure, and 4) MIS ALIF was not studied specifically. The methodology for the included studies were evaluated for potential biases and assigned a level of evidence. RESULTS: There were a total of 552 patients included from 13 studies. The most common biases were selection and interviewer bias. The majority of studies were retrospective. The mean sample size was 42.3 patients. The mean follow-up duration was approximately 41.8 months. The mean postoperative VAS reduction was 5.1 points. The mean VAS reduction for standalone grafts was 5.9 points, and 5.0 points for those augmented with posterior fixation. The most common complications included bladder or urinary dysfunction, infection, and hardware-related complications. CONCLUSIONS: This was a systematic review of back pain outcomes following MIS ALIF. Back pain VAS score was reduced postoperatively across all studies. The complication rates were low overall. MIS ALIF is safe and effective at reducing back pain in appropriate patient populations.

A Mixture of U.S. Food and Drug Administration-Approved Monoaminergic Drugs Protects the Retina From Light Damage in Diverse Models of Night Blindness.

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors. Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (ß1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and tamsulosin (α1-receptor antagonist) before bright light exposure. Light damage was primarily assessed with optical coherence tomography and inspection of cone population in retinal whole mounts. Retinal inflammation was assessed in a subset of experiments using autofluorescence imaging by scanning laser ophthalmoscopy and by postmortem inspection of microglia and astrocyte activity. Results: The Gnat1-/- mice showed slightly increased susceptibility to rod light damage, whereas the Gnat2-/- mice were very resistant. The Arr1-/- and Grk1-/- mice were sensitive for both rod and cone light damage and showed robust retinal inflammation 7 days after bright light exposure. Pretreatment with metoprolol + bromocriptine + tamsulosin rescued the retina in all genetic backgrounds, starting at doses of 0.2 mg/kg metoprolol, 0.02 mg/kg bromocriptine, and 0.01 mg/kg tamsulosin in the Gnat1-/- mice. The therapeutic drug doses increased in parallel with light-damage severity. Conclusions: Our results suggest that congenital stationary night blindness and Oguchi disease patients can be at an elevated risk of the toxic effects of bright light. Furthermore, systems pharmacology drug regimens that stimulate Gi signaling and attenuate Gs and Gq signaling present a promising disease-modifying therapy for photoreceptor degenerative diseases.

Activated T cells induce proliferation of oligodendrocyte progenitor cells via release of vascular endothelial cell growth factor-A.

Neuroinflammatory diseases such as multiple sclerosis are characterized by infiltration of lymphocytes into the central nervous system followed by demyelination and axonal degeneration. While evidence suggests that activated T lymphocytes induce neurotoxicity and impair function of neural stem cells, the effect of T cells on oligodendrocyte progenitor cells (OPCs) is still uncertain, partly due to the difficulty in obtaining human OPCs. Here we studied the effect of activated T cells on OPCs using OPCs derived from human hematopoietic stem cells or from human fetal brain. OPCs were exposed to supernatants (sups) from activated T cells. Cell proliferation was determined by EdU incorporation and CellQuanti-Blue assays. Surprisingly, we found that sups from activated T cells induced OPC proliferation by regulating cell cycle progression. Vascular endothelial growth factor A (VEGF-A) transcripts were increased in T cells after activation. Immunodepletion of VEGF-A from activated T cell sups significantly attenuated its effect on OPC proliferation. Furthermore, VEGF receptor 2 (VEGFR2) was expressed on OPCs and its inhibition also attenuated activated T cell-induced OPC proliferation. Thus, activated T cells have a trophic role by promoting OPC proliferation via the VEGFR2 pathway.