Precision oncology in neurofibromatosis type 1: quantification of differential sensitivity to selumetinib in plexiform neurofibromas using single-cell RNA sequencing.

PURPOSE: Selumetinib is an FDA-approved targeted therapy for plexiform neurofibromas in neurofibromatosis type 1(NF1) with durable response rates seen in most, but not all patients. In this proof-of-concept study, we demonstrate single-cell RNA sequencing(scRNAseq) as a technique for quantifying drug response to selumetinib at the single cell level. METHODS: scRNAseq data from neurofibroma biopsies was obtained from a public genomics repository. Schwann cell populations were identified through standard clustering techniques and single-cell selumetinib sensitivity was quantified on a scale of 0(resistant) to 1(sensitive) based on the expression pattern of a 500 gene selumetinib sensitivity signature from the BeyondCell sensitivity library. RESULTS: A total of seven plexiform neurofibromas were included in our final analysis. The median absolute number of Schwann cells across samples was 658 cells (IQR: 1,029 cells, Q1-Q3: 135 cells to 1,163 cells). There was a statistically significant difference in selumetinib sensitivity profiles across samples (p < 0.001). The tumor with the highest median selumetinib sensitivity score had a median selumetinib sensitivity score of 0.64(IQR: 0.14, Q1-Q3: 0.59-0.70, n = 112 cells) and the tumor with the lowest median selumetinib sensitivity score had a median score of 0.37 (IQR: 0.21, Q1-Q3: 0.27-0.48, n = 1,034 cells). CONCLUSIONS: scRNAseq of plexiform neurofibroma biopsies reveals differential susceptibilities to selumetinib on a single cell level. These findings may explain the partial responses seen in clinical trials of selumetinib for NF1 and demonstrate the value of collecting scRNAseq data for future NF1 trials.

Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs. METHODS: MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse. RESULTS: 73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status. CONCLUSIONS: Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy.

That which is unseen: 3D printing for pediatric cerebrovascular education.

INTRODUCTION: Pediatric cerebrovascular lesions are very rare and include aneurysms, arteriovenous malformations (AVM), and vein of Galen malformations (VOGM). OBJECTIVE: To describe and disseminate a validated, reproducible set of 3D models for optimization of neurosurgical training with respect to pediatric cerebrovascular diseases METHODS: All pediatric cerebrovascular lesions treated at our institution with adequate imaging studies during the study period 2015-2020 were reviewed by the study team. Three major diagnostic groups were identified: aneurysm, AVM, and VOGM. For each group, a case deemed highly illustrative of the core diagnostic and therapeutic principles was selected by the lead and senior investigators for printing (CSG/JM). Files for model reproduction and free distribution were prepared for inclusion as Supplemental Materials. RESULTS: Representative cases included a 7-month-old female with a giant left MCA aneurysm; a 3-day-old male with a large, complex, high-flow, choroidal-type VOGM, supplied from bilateral thalamic, choroidal, and pericallosal perforators, with drainage into a large prosencephalic vein; and a 7-year-old male with a left frontal AVM with one feeding arterial vessel from the anterior cerebral artery and one single draining vein into the superior sagittal sinus CONCLUSION: Pediatric cerebrovascular lesions are representative of rare but important neurosurgical diseases that require creative approaches for training optimization. As these lesions are quite rare, 3D-printed models and open source educational materials may provide a meaningful avenue for impactful clinical teaching with respect to a wide swath of uncommon or unusual neurosurgical diseases.

Emerging innovations for lumbar spondylolisthesis management: a systematic review of active and prospective clinical trials.

The literature has had some conflicting evidence regarding the effective management of lumbar spondylolisthesis (LS). Herein, we review active and prospective clinical trials to identify the emerging trends for the management of LS. A systematic search was conducted utilizing the NIH Clinical Trials database using the search term "lumbar spondylolisthesis" on February 2, 2022. Currently active and prospective clinical trials for LS were included and analyzed. All statistical analyses were performed on R 4.1.2. We identified 37 clinical trials. Nearly half the trials (n = 18, 48.6%) include novel technologies; 6 (16.2%) are comparing surgical approaches, of which 4 (67%) include decompression alone versus decompression with instrumented fusion; 6 (16.2%) are evaluating perioperative pain management protocols, of which 3 (50%) include bupivacaine or ropivacaine; 3 (8.1%) are evaluating alternative medicines in LS; 2 (5.4%) are observational studies about the natural history of LS; 1 (2.7%) involves surgical infection prophylaxis; and 1 (2.7%) is evaluating AK1320 microspheres. The 18 trials involving novel technologies include 3D-printed titanium cages (n = 3, 16.7%), interbody implants (n = 4, 22.2%), bone graft materials (n = 4, 22.2%), and miscellaneous intraoperative devices (n = 7, 38.9%). The top 3 outcomes measured were Oswestry Disability Index (n = 28, 75.7%), visual analog scale (n = 21, 56.7%), and postoperative radiographs (n = 16, 43.2%). Patient-reported outcome measures (PROMs) were included in 34 (91.9%) trials, while 23 (62.2%) trials included lumbar spine imaging. LS can often require a multifaceted approach. Novel technologies and utilization of PROMs appear to be a significant emerging trend in LS management.

Management strategies for pediatric patients with tectal gliomas: a systematic review.

Pediatric tectal gliomas generally have a benign clinical course with the majority of these observed radiologically. However, patients often need treatment for obstructive hydrocephalus and occasionally require cytotoxic therapy. Given the lack of level I data, there is a need to further characterize management strategies for these rare tumors. We have therefore performed the first systematic review comparing various management strategies. The literature was systematically searched from January 1, 2000, to July 30, 2020, to identify studies reporting treatment strategies for pediatric tectal gliomas. The systematic review included 355 patients from 14 studies. Abnormal ocular findings-including gaze palsies, papilledema, diplopia, and visual field changes-were a common presentation with between 13.6 and 88.9% of patients experiencing such findings. CSF diversion was the most performed procedure, occurring in 317 patients (89.3%). In individual studies, use of CSF diversion ranged from 73.1 to 100.0%. For management options, 232 patients were radiologically monitored (65.4%), 69 received resection (19.4%), 30 received radiotherapy (8.4%), and 19 received chemotherapy (5.4%). When examining frequencies within individual studies, chemotherapy ranged from 2.5 to 29.6% and radiotherapy ranged from 2.5 to 28.6%. Resection was the most variable treatment option between individual studies, ranging from 2.3 to 100.0%. Most tectal gliomas in the pediatric population can be observed through radiographic surveillance and CSF diversion. Other forms of management (i.e., chemotherapy and radiotherapy) are warranted for more aggressive tumors demonstrating radiological progression. Surgical resection should be reserved for large tumors and/or those that are refractory to other treatment modalities.

Systems neuroimmunology: a review of multiomics methodologies to characterize neuroimmunological interactions in spinal and cranial diseases.

Neuroimmunology plays a critical role in our understanding of the pathophysiological processes that underlie a variety of diseases treated by neurosurgeons, including degenerative disc disease (DDD), glioblastoma (GBM), aneurysmal subarachnoid hemorrhage (aSAH), and others. Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level. In this review, the authors summarize key concepts for gathering and analyzing multiomics data so that neurosurgeons can contribute to the emerging field of systems neuroimmunology. Additionally, they describe 3 use cases, based on original research published by their group and others, that utilize transcriptomic, metabolomic, and proteomic analyses to study immune-signaling pathways in DDD, aSAH, and GBM. Through these use cases, techniques for performing machine learning and network-based analyses to generate new clinical insights from multiomics data are shared. The authors hope that neurosurgeons might use this review as a summary of common tools and principles in systems immunology to better engage in creating the immunotherapies of tomorrow.

The role of bevacizumab for treatment-refractory intracranial meningiomas: a single institution's experience and a systematic review of the literature.

INTRODUCTION: Meningiomas account for over 30% of all primary brain tumors. While surgery can be curative for these tumors, several factors may lead to a higher likelihood of recurrence. For recurrent meningiomas, bevacizumab may be considered as a therapeutic agent, but literature regarding its efficacy is sparse. Thus, we present a systematic review of the literature and case series of patients from our institution with treatment-refractory meningiomas who received bevacizumab. METHODS: Patients at our institution who were diagnosed with recurrent meningioma between January 2000 and September 2020 and received bevacizumab monotherapy were included in this study. Bevacizumab duration and dosages were noted, as well as progression-free survival (PFS) after the first bevacizumab injection. A systematic review of the literature was also performed. RESULTS: Twenty-three patients at our institution with a median age of 55 years at initial diagnosis qualified for this study. When bevacizumab was administered, 2 patients had WHO grade I meningiomas, 10 patients had WHO grade II meningiomas, and 11 patients had WHO grade III meningiomas. Median PFS after the first bevacizumab injection was 7 months. Progression-free survival rate at 6 months was 57%. Two patients stopped bevacizumab due to hypertension and aphasia. Systematic review of the literature showed limited ability for bevacizumab to control tumor growth. CONCLUSION: Bevacizumab is administered to patients with treatment-refractory meningiomas and, though its effectiveness is limited, outperforms other systemic therapies reported in the literature. Further studies are required to identify a successful patient profile for utilization of bevacizumab.

Transcatheter aortic valve replacement outcomes in solid organ transplant recipients.

BACKGROUND AND AIMS: Transcatheter aortic valve replacement (TAVR) has become the primary treatment for severe symptomatic aortic stenosis in patients >65 years with volumes exceeding surgical aortic valve replacements (SAVR) since 2019. As a less invasive procedure with lower complication rates, TAVR is preferable in most patient populations, particularly those with increased surgical risk. One such population is patients who have undergone solid organ transplant (SOT). We aimed to evaluate periprocedural outcomes and complication rates following TAVR in SOT recipients as compared to the general TAVR population. METHODS: The 2016-2018 National Inpatient Sample (NIS) was queried by ICD-10 PCS codes to identify TAVR cases; hospitalizations were subsequently stratified by SOT history. Multivariate analyses were completed to evaluate complication rates, length of stay (LOS), and cost of stay (COS). RESULTS: No significant difference was observed in mortality rates or post-procedural complications between SOT recipients (n = 223) and those without transplant history undergoing TAVR (n = 29,448) except for increased thromboembolic events captured in transplant patients (p < .001). There was no significant variation in LOS or COS between the two populations; female sex and Black or Hispanic race were predictors of increased inpatient time. CONCLUSIONS: SOT recipients have no increased risk of mortality or periprocedural complications when undergoing TAVR. Though the rate of thromboembolic events was higher in SOT recipients, observation size was small (n = 27 TAVR, n = 4 TAVR + SOT) thus external validity is limited. Based on these data, transplant recipients experience no difference in outcomes following TAVR as compared to patients without a history of organ transplant.

Single-level awake transforaminal lumbar interbody fusion: a Mayo Clinic institutional experience and national analysis.

OBJECTIVE: Awake transforaminal lumbar interbody fusion (TLIF) is a novel technique for performing spinal fusions in patients under conscious sedation. Whether awake TLIF can reduce operative times and decrease the hospital length of stay (LOS) remains to be shown. In this study, the authors sought to assess the differences in clinical outcomes between patients who underwent awake TLIF and those who underwent TLIF under general anesthesia by using institutional experience at the Mayo Clinic and the National Surgical Quality Improvement Program (NSQIP) database. METHODS: Chart review was performed for a consecutive series of patients who underwent single-level minimally invasive surgery (MIS)-TLIF performed by a single surgeon (K.A.I.) at a single institution. Additionally, the NSQIP database was queried from 2016 to 2019 for patients who underwent awake TLIF as well as propensity score-matched patients who underwent TLIF under general anesthesia. RESULTS: A total of 20 patients at Mayo Clinic underwent awake single-level MIS-TLIF. The mean operative time was 122 ± 16.68 minutes, and the mean estimated blood loss was 39 ± 30.24 ml. No intraoperative complications were reported. A total of 96 patients who underwent TLIF (24 awake and 72 under general anesthesia) were analyzed from the NSQIP database. The mean LOS was less in the awake cohort (1.4 ± 1.381 days) than the general anesthesia cohort (3 ± 2.274 days) (p = 0.002). CONCLUSIONS: Evidence from the authors' institutional experience and national analysis has demonstrated that awake MIS-TLIF is efficient and can reduce hospital LOS.

Synthetic and systems biology principles in the design of programmable oncolytic virus immunotherapies for glioblastoma.

Oncolytic viruses (OVs) are a class of immunotherapeutic agents with promising preclinical results for the treatment of glioblastoma (GBM) but have shown limited success in recent clinical trials. Advanced bioengineering principles from disciplines such as synthetic and systems biology are needed to overcome the current challenges faced in developing effective OV-based immunotherapies for GBMs, including off-target effects and poor clinical responses. Synthetic biology is an emerging field that focuses on the development of synthetic DNA constructs that encode networks of genes and proteins (synthetic genetic circuits) to perform novel functions, whereas systems biology is an analytical framework that enables the study of complex interactions between host pathways and these synthetic genetic circuits. In this review, the authors summarize synthetic and systems biology concepts for developing programmable, logic-based OVs to treat GBMs. Programmable OVs can increase selectivity for tumor cells and enhance the local immunological response using synthetic genetic circuits. The authors discuss key principles for developing programmable OV-based immunotherapies, including how to 1) select an appropriate chassis, a vector that carries a synthetic genetic circuit, and 2) design a synthetic genetic circuit that can be programmed to sense key signals in the GBM microenvironment and trigger release of a therapeutic payload. To illustrate these principles, some original laboratory data are included, highlighting the need for systems biology studies, as well as some preliminary network analyses in preparation for synthetic biology applications. Examples from the literature of state-of-the-art synthetic genetic circuits that can be packaged into leading candidate OV chassis are also surveyed and discussed.

International trends in grant and fellowship funding awarded to women in neurosurgery.

OBJECTIVE: Metric tracking of grant funding over time for academic neurosurgeons sorted by gender informs the current climate of career development internationally for women in neurosurgery. METHODS: Multivariate linear trend analysis of grant funding awarded to neurosurgeons in the NIH and World Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) was performed. Traveling fellowships for international neurosurgery residents sponsored by the AANS and Congress of Neurological Surgeons (CNS) were also analyzed. RESULTS: Within the US, funding awarded to female neurosurgeons has remained static from 2009 to 2019 after adjusting for inflation and overall trends in NIH funding (ß = -$0.3 million per year, p = 0.16). Internationally, female neurosurgeons represented 21.7% (n = 5) of project leads for World RePORTER grants. Traveling fellowships are also an important building block for young international female neurosurgeons, of which 7.4% (n = 2) of AANS international traveling fellowships and 19.4% (n = 7) of AANS/CNS pediatrics international traveling fellowships are women. CONCLUSIONS: Over the past decade, funding has increased in neurosurgery without a concordant increase in funding awarded to women. Recognition of this trend is essential to focus efforts on research and career development opportunities for women in neurosurgery. Worldwide, female neurosurgeons head one-fifth of the funded project leads and constitute a minority of international traveling fellowships awarded by organized neurosurgery.

An Integrated Voice Recognition and Natural Language Processing Platform to Automatically Extract Thoracolumbar Injury Classification Score Features From Radiology Reports.

BACKGROUND: Many predictive models for estimating clinical outcomes after spine surgery have been reported in the literature. However, implementation of predictive scores in practice is limited by the time-intensive nature of manually abstracting relevant predictors. In this study, we designed natural language processing (NLP) algorithms to automate data abstraction for the thoracolumbar injury classification score (TLICS). METHODS: We retrieved the radiology reports of all Mayo Clinic patients with an International Classification of Diseases, 9th or 10th revision, code corresponding to a fracture of the thoracolumbar spine between January 2005 and October 2020. Annotated data were used to train an N-gram NLP model using machine learning methods, including random forest, stepwise linear discriminant analysis, k-nearest neighbors, and penalized logistic regression models. RESULTS: A total of 1085 spine radiology reports were included in our analysis. Our dataset included 483 compression, 401 burst, 103 translational/rotational, and 98 distraction fractures. A total of 103 reports had documented an injury of the posterior ligamentous complex. The overall accuracy of the random forest model for fracture morphology feature detection was 76.96% versus 65.90% in the stepwise linear discriminant analysis, 50.69% in the k-nearest neighbors, and 62.67% in the penalized logistic regression. The overall accuracy to detect posterior ligamentous complex integrity was highest in the random forest model at 83.41%. Our random forest model was implemented in the backend of a web application in which users can dictate reports and have TLICS features automatically extracted. CONCLUSIONS: We have developed a machine learning NLP model for extracting TLICS features from radiology reports, which we deployed in a web application that can be integrated into clinical practice.

High-Value Epilepsy Care in the United States: Predictors of Increased Costs and Complications from the National Inpatient Sample Database 2016-2019.

BACKGROUND: For patients with medically refractory epilepsy, newer minimally invasive techniques such as laser interstitial thermal therapy (LITT) have been developed in recent years. This study aims to characterize trends in the utilization of surgical resection versus LITT to treat medically refractory epilepsy, characterize complications, and understand the cost of this innovative technique to the public. METHODS: The National Inpatient Sample database was queried from 2016 to 2019 for all patients admitted with a diagnosis of medically refractory epilepsy. Patient demographics, hospital length of stay, complications, and costs were tabulated for all patients who underwent LITT or surgical resection within these cohorts. RESULTS: A total of 6019 patients were included, 223 underwent LITT procedures, while 5796 underwent resection. Significant predictors of increased patient charges for both cohorts included diabetes (odds ratio: 1.7, confidence interval [CI]: 1.44-2.19), infection (odds ratio: 5.12, CI 2.73-9.58), and hemorrhage (odds ratio: 2.95, CI 2.04-4.12). Procedures performed at nonteaching hospitals had 1.54 greater odds (CI 1.02-2.33) of resulting in a complication compared to teaching hospitals. Insurance status did significantly differ (P = 0.001) between those receiving LITT (23.3% Medicare; 25.6% Medicaid; 44.4% private insurance; 6.7 Other) and those undergoing resection (35.3% Medicare; 22.5% Medicaid; 34.7% private Insurance; 7.5% other). When adjusting for patient demographics, LITT patients had shorter length of stay (2.3 vs. 8.9 days, P < 0.001), lower complication rate (1.9% vs. 3.1%, P = 0.385), and lower mean hospital ($139,412.79 vs. $233,120.99, P < 0.001) and patient ($55,394.34 vs. $37,756.66, P < 0.001) costs. CONCLUSIONS: The present study highlights LITT's advantages through its association with lower costs and shorter length of stay. The present study also highlights the associated predictors of LITT versus resection, such as that most LITT cases happen at academic centers for patients with private insurance. As the adoption of LITT continues, more data will become available to further understand these issues.

Socioeconomic predictors of cost and length of stay for erythroderma: a cross-sectional analysis of the national inpatient sample.

Erythroderma is an uncommon but serious dermatologic disorder that often requires hospitalization for diagnosis and treatment. However, little is known about predictors influencing cost and patient outcomes. The present study sought to characterize the sociodemographic factors that predict patient outcomes and hospital cost. Data were obtained from the 2016-2018 National Inpatient Sample (NIS) provided by the Healthcare Cost and Utilization Project from the Agency for Healthcare Research and Quality for patients of any age with a primary or secondary diagnosis of exfoliative dermatitis. Regression analyses were performed to find predictors for hospital costs and patient outcomes, represented by the length of stay (LOS). Univariate analysis of LOS revealed urban teaching hospitals were associated with prolonged LOS (p = 0.023). Univariate analysis of hospital cost yielded the following factors associated with increased hospital cost: Black and Asian patients (p = .045), urban teaching hospitals (p = .035), and northeast or south geographic location (p = .004). Multivariable regression analysis revealed prolonged LOS was associated with female sex (p = .043) and large bed capacity (p = .044) while shorter LOS was associated with increased age (p = .025); lower hospital costs were associated with private-owned hospitals -  (p = .025). In patients diagnosed with erythroderma, there appear to be racial, economic, and geographic disparities for patients that lead to greater hospital costs and longer LOS.

Prediction Model for Neurogenic Bladder Recovery One Year After Traumatic Spinal Cord Injury.

INTRODUCTION: Neurogenic bladder is a common complication after spinal cord injury (SCI) that carries substantial burdens on the inflicted individual. The objective of this study is to build a prediction model for neurogenic bladder recovery 1 year after traumatic SCI. METHODS: We queried the National Spinal Cord Injury Model Systems database for patients with traumatic SCI who had neurogenic bladder at the time of injury. The primary outcome of interest was the complete recovery of bladder function at 1 year. Multiple imputations were performed to generate replacement values for missing data, and the final imputed data were used for our analysis. A multivariable odds logistic regression model was developed for complete bladder recovery at 1 year. RESULTS: We identified a total of 2515 patients with abnormal bladder function at baseline who had an annual follow-up. A total of 417 patients (16.6%) recovered bladder function in 1 year. Predictors of complete bladder recovery included the following baseline parameters: sacral sensation, American Spinal Injury Association (ASIA) impairment score, bowel function at baseline, voluntary sphincter contraction, anal sensation, S1 motor scores, and the number of days in the rehabilitation facility. The model performed with a discriminative capacity of 90.5%. CONCLUSIONS: We developed a prediction model for the probability of complete bladder recovery 1 year after SCI. The model performed with a high discriminative capacity. This prediction model demonstrates potential utility in the counseling, research allocation, and management of individuals with SCI.

Peritumoral edema in meningiomas: pathophysiology, predictors, and principles for treatment.

Meningiomas is a tumor of the meninges and is among the most common intracranial neoplasms in adults, accounting for over a third of all primary brain tumors in the United States. Meningiomas can be associated with peritumoral brain edema (PTBE) which if not managed appropriately can lead to poor clinical outcomes. In this review, we summarize the relevant pathophysiology, predictors, and principles for treatment of PTBE. The results of various case-reports and case-series have found that meningioma-associated PTBE have patterns in age, tumor size, and hormone receptor positivity. Our study describes how increased age, increased tumor size, tumor location in the middle fossa, and positive expression of hormone receptors, VEGF, and MMP-9 can all be predictors for worse clinical outcomes. We also characterize treatment options for PTBE such as glucocorticoids and VEGF inhibitors along with the ongoing clinical trials attempting to alleviate PTBE in meningioma cases. The trends summarized in this review can be used to better predict the behavior of meningioma-associated PTBE and establish prognosis models to identify at risk patients.

Alginate hydrogels: A potential tissue engineering intervention for intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a major cause of low back pain and disability, affecting millions of people worldwide. Current treatments for IVD degeneration are limited to invasive surgery or pain management. Recently, there has been increasing interest in the use of biomaterials, such as alginate hydrogels, for the treatment of IVD degeneration. Alginate hydrogels are an example of such a biomaterial that is biocompatible and can be tailored to mimic the native extracellular matrix of the IVD. Derived from alginate, a naturally derived polysaccharide from brown seaweed that can be transformed into a gelatinous solution, alginate hydrogels are emerging in the field of tissue engineering. They can be used to deliver therapeutic agents, such as growth factors or cells, to the site of injury, providing a localized and sustained release that may enhance treatment outcomes. This paper provides an overview on the use of alginate hydrogels for the treatment of IVD degeneration. We discuss the properties of alginate hydrogels and their potential applications for IVD regeneration, including the mechanism against IVD degeneration. We also highlight the research outcomes to date along with the challenges and limitations of using alginate hydrogels for IVD regeneration, including their mechanical properties, biocompatibility, and surgical compatibility. Overall, this review paper aims to provide a comprehensive overview of the current research on alginate hydrogels for IVD degeneration and to identify future directions for research in this area.

The association between bone mineral density and proximal junctional kyphosis in adult spinal deformity: a systematic review and meta-analysis.

OBJECTIVE: Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity (ASD) with a multifactorial etiology. Many risk factors are controversial, and their relative importance is not fully understood. The authors aimed to elucidate the association between bone mineral density (BMD) and PJK. METHODS: A systematic literature search was performed using PubMed and Web of Science keywords of "Proximal Junctional Kyphosis [MeSH] OR Proximal Junctional Failure [MeSH]" AND "Bone Mineral Density [MeSH] OR Hounsfield Units [MeSH] OR DEXA [MeSH]" set to the date range of January 2002 to July 2022. Studies required a minimum of 10 patients and 12 months of follow-up. Articles were included if they were in the English language and presented a primary retrospective cohort that included a comparison of patients with and without PJK, as well as a radiographic biomarker for BMD, such as Hounsfield units (HU) or T-score. RESULTS: A total of 18 unique studies with 2185 patients who underwent ASD surgery were identified. Of these, 537 patients (24.6%) developed PJK. Eight studies provided T-scores that were amenable to comparison, which found that patients who developed PJK were found to have lower BMD T-scores by a mean of -0.69 (95% CI -0.88 to -0.50; I2 = 63.9%, p < 0.001). The HU at the UIV among patients with the PJK group (n = 101) compared with the non-PJK group (n = 156) was found to be significantly lower (mean difference -32.35, 95% CI -46.05 to -18.65; I2 = 28.7%, p < 0.001). CONCLUSIONS: This meta-analysis suggests that low preoperative BMD as measured by T-score and a diagnosis of osteoporosis were associated with higher postoperative PJK. Additionally, lower HU on CT at the UIV were found to be significant risk factors for postoperative PJK as well. These findings suggest that more attention to preoperative BMD is a risk factor for PJK among ASD patients is warranted.

Bariatric surgery reduces odds of perioperative complications after inpatient hysterectomy: Analysis from a national database, 2016 to 2018.

BACKGROUND: Increased body mass index is a known risk factor for increased adverse events post-hysterectomy. The effects of previous bariatric surgery on outcomes after inpatient hysterectomy are not well elucidated. METHODS: The 2016 to 2018 National Inpatient Sample was queried for patients who underwent hysterectomy using International Classification of Disease 10 Procedure Codes before a matched analysis was performed to neutralize the potential confounding effects of comorbidities, body mass index, and age. Patients were divided into the following 2 groups: a case group (those with a history of bariatric surgery) and a control group (those without a history of bariatric surgery). Patients in the respective groups were matched 1:2 by age, Elixhauser comorbidity score, and body mass index at the time of surgery to analyze the risk of complications and mean length of stay. RESULTS: When 1:2 case-control matching was performed, women with a history of bariatric surgery (N = 595) had significantly fewer complications and decreased mean length of stay than the non-bariatric group (N = 1,190), even after controlling for body mass index at the time of hysterectomy. CONCLUSIONS: When matched for age, body mass index, and comorbidity score, patients with previous bariatric surgery had fewer complications and shorter lengths of stay than patients without a history of bariatric surgery. Women with a body mass index ≥40 kg/m2 requiring non-urgent hysterectomy may benefit from undergoing bariatric surgery first.