bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary artery wedge pressure and left ventricular end-diastolic pressure during exercise in patients with dyspnoea
Authors: Baratto Claudia , Faini Andrea , Gallone Gianluca P. , Dewachter Céline , Perego Giovanni B. , Bondue Antoine , Muraru Denisa , Senni Michele , Badano Luigi P. , Parati Gianfranco , Vachiéry Jean-Luc , Caravita Sergio
Published: March 2023

Background

Pulmonary artery wedge pressure (PAWP) during exercise, as a surrogate for left ventricular (LV) end-diastolic pressure (EDP), is used to diagnose heart failure with preserved ejection fraction (HFpEF). However, LVEDP is the gold standard to assess LV filling, end-diastolic PAWP (PAWPED) is supposed to coincide with LVEDP and mean PAWP throughout the cardiac cycle (PAWPM) better reflects the haemodynamic load imposed on the pulmonary circulation. The objective of the present study was to determine precision and accuracy of PAWP estimates for LVEDP during exercise, as well as the rate of agreement between these measures.

Methods

46 individuals underwent simultaneous right and left heart catheterisation, at rest and during exercise, to confirm/exclude HFpEF. We evaluated: linear regression between LVEDP and PAWP, Bland–Altman graphs, and the rate of concordance of dichotomised LVEDP and PAWP ≥ or < diagnostic thresholds for HFpEF.

Results

At peak exercise, PAWPMand LVEDP, as well as PAWPEDand LVEDP, were fairly correlated (R2>0.69, p<0.01), with minimal bias (+2 and 0 mmHg respectively) but large limits of agreement (±11 mmHg). 89% of individuals had concordant PAWP and LVEDP ≥ or <25 mmHg (Cohen's κ=0.64). Individuals with either LVEDP or PAWPM≥25 mmHg showed a PAWPMincrease relative to cardiac output (CO) changes (PAWPM/CO slope) >2 mmHg·L−1·min−1.

Conclusions

During exercise, PAWP is accurate but not precise for the estimation of LVEDP. Despite a good rate of concordance, these two measures might occasionally disagree.
Factors associated with the choice of supplementary hospital insurance in Switzerland – an analysis of the Swiss Health Survey
Authors: Altwicker-Hámori Szilvia , Stucki Michael
Published: March 2023

Background

Switzerland has universal coverage via mandatory health insurance that covers a generous basket of health services. In addition to the basic coverage, the insured can buy supplementary insurance for the inpatient sector. Supplementary hospital insurance in Switzerland provides additional services during inpatient stays. Little is known about which factors are associated with the choice of semi-private and private hospital insurances. However, this is of importance to policy makers and the insured population, who might be concerned about a “two-class” inpatient care system. Therefore, the aim of the paper was to explore the factors associated with supplementary hospital insurance enrolment in Switzerland.

Methods

We used the five most recent waves of the representative Swiss Health Survey (1997, 2002, 2007, 2012, 2017) to explore which factors are associated with supplementary hospital insurance enrolment in adults aged 25 or older. We estimated the same probit model for all five surveys waves and computed average marginal effects.

Results

Our study shows that in all cross-sections the likelihood of enrolling in supplementary hospital insurance increased with higher age, education, household income and was higher for people with a strong preference for unrestricted choice of a specialist and with a higher-than-default deductible choice. The likelihood of supplementary hospital insurance enrolment was lower for the unemployed relative to their inactive counterparts and those living in rural areas relative to comparable urban residents. Ever-smoker status was not statistically significantly associated with supplementary hospital insurance choice. However, our findings indicated differences in estimates over the years regarding demographic as well as insurance-related variables. For example, women were more likely to choose supplementary hospital insurance than comparable men in earlier years.

Conclusion

Most importantly, our results indicate that factors related to socioeconomic status – such as education, labour market status, and income – consistently show significant associations with the probability of having supplementary hospital insurance for the entire study period, as opposed to demographic variables – such as nationality and sex.
A survival analysis approach to determine factors associated with non-retention of newly hired health workers in Iran
Authors: Ghavami Vahid , Tabatabaee Seyed Saeed
Published: March 2023

Background and aim

One of the main tasks of the healthcare human resource management is to maintain and retain professional staff. The high level turnover of professional staff may reduce the quality of healthcare service delivery. Therefore, this study investigated the factors associated with the turnover of the newly recruited healthcare professionals using survival analysis method in Iran.

Materials and methods

This historical cohort analysis comprised 6811 employees who began working at Mashhad University of Medical Sciences between 2005 and 2020. Employees recruited at any of the university’s units between the years 2005 to 2019 were included. We used appropriate descriptive indices and Log-rank test and the Cox proportional-hazards model to assess the staff turnover. A significance level of 0.05 was used for all tests.

Results

The findings of the survival analysis showed that the probability of turnover in one year, two years, and five years of employment were 0.12, 0.16, and 0.27. Based on the findings of the Log-rank test, the probability of turnover in entire of the study period was not statistically different between male and female (p = 0.573), and likewise between employees with healthcare occupations and non-healthcare occupations (p = 0.351). Employees whose current workplace and birthplace were not similar had a significantly higher probability of turnover (p < 0.001). Accordingly, the Cox regression result showed, the risk of turnover for the singles was 1.22 times higher than the married. For the Ph.D degree was 3.23 times higher compared to those with a diploma or an associate degree, and for a bachelor’s or master’s degree was 2.06 times more likely to change their workplace than those with a diploma or an associate degree.

Conclusion

Policies promoting the recruitment of native-born professionals, given priority to the married candidates than single ones, and/or recurring candidates to pledge to stay in the locality of recruitment site can increase the staff retention and reduce the costs of staff turnover including re-hiring, initial and on-the-job training, accommodation, and other extra living consumptions away from home and family.
Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway
Authors: Ning Yu , Huang Peisen , Chen Guihao , Xiong Yuyan , Gong Zhaoting , Wu Chunxiao , Xu Junyan , Jiang Wenyang , Li Xiaosong , Tang Ruijie , Zhang Lili , Hu Mengjin , Xu Jing , Xu Jun , Qian Haiyan , Jin Chen , Yang Yuejin
Published: March 2023

Background

Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV.

Methods

MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo.

Results

MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P < 0.01–0.0001). On day 28, MSCATV-EV much more significantly improved the cardiac function than MSC-EV with the infarct size markedly reduced (P < 0.05–0.0001). In vitro, MSCATV-EV also significantly reduced the protein and mRNA expressions of M1 markers but increased those of M2 markers in lipopolysaccharide-treated macrophages (P < 0.05–0.0001). EV miR-139-3p was identified as a potential cardiac repair factor mediating macrophage polarization. Knockdown of miR-139-3p in MSCATV-EV significantly attenuated while overexpression of it in MSC-EV enhanced the effect on promoting M2 polarization by suppressing downstream signal transducer and activator of transcription 1 (Stat1). Furthermore, MSCATV-EV loaded with miR-139-3p inhibitors decreased while MSC-EV loaded with miR-139-3p mimics increased the expressions of M2 markers and cardioprotective efficacy.

Conclusions

We uncovered a novel mechanism that MSCATV-EV remarkably facilitate cardiac repair in AMI by promoting macrophage polarization via miR-139-3p/Stat1 pathway, which has the great potential for clinical translation.
The role of the desmosomal protein desmocollin 2 in tumour progression in triple negative breast cancer patients
Authors: Reimer Francesca , Bryan Sarah , Legler Karen , Karn Thomas , Eppenberger-Castori Serenella , Matschke Jakob , Pereira-Veiga Thais , Wikman Harriet , Witzel Isabell , Müller Volkmar , Schmalfeldt Barbara , Milde-Langosch Karin , Schumacher Udo , Stürken Christine , Oliveira-Ferrer Leticia
Published: March 2023

Background

The disruption of epithelial features represents a critical step during breast cancer spread. In this context, the dysregulation of desmosomal proteins has been associated with malignant progression and metastasis formation. Curiously, both tumour suppressive and pro-metastatic roles have been attributed to desmosomal structures in different cancer entities. In the present study, we describe the pro-metastatic role of the desmosomal protein desmocollin 2 (DSC2) in breast cancer.

Methods

We analysed the prognostic role of DSC2 at mRNA and protein level using microarray data, western blot analysis and immunohistochemistry. Functional consequences of DSC2 overexpression and DSC2 knock down were investigated in the triple negative breast cancer (TNBC) cell line MDA-MB-231 and its brain-seeking subline MDA-MB-231-BR, respectively in vitro and in vivo.

Results

We found a significantly higher DSC2 expression in the more aggressive molecular subtypes HER2-positive and TNBC than in luminal breast cancers, as well as a significant correlation between increased DSC2 expression and a shorter disease-free—also in multivariate analysis—and overall survival. Additionally, a significant association between DSC2 expression in the primary tumour and an increased frequency of cerebral and lung metastasis could be observed. In vitro, ectopic DSC2 expression or DSC2 down-regulation in MDA-MB-231 and MDA-MB-231-BR led to a significant tumour cell aggregation increase and decrease, respectively. Furthermore, tumour cells displaying higher DSC2 levels showed increased chemoresistance in 3D structures, but not 2D monolayer structures, suggesting the importance of cell aggregation as a means for reduced drug diffusion. In an in vivo brain dissemination xenograft mouse model, reduced expression of DSC2 in the brain-seeking TNBC cells led to a decreased amount of circulating tumour cells/clusters and, in turn, to fewer and smaller brain metastatic lesions.

Conclusion

We conclude that high DSC2 expression in primary TNBC is associated with a poorer prognosis, firstly by increasing tumour cell aggregation, secondly by reducing the diffusion and effectiveness of chemotherapeutic agents, and, lastly, by promoting the circulation and survival of tumour cell clusters, each of which facilitates distant organ colonisation.
Efficient tumor synergistic chemoimmunotherapy by self-augmented ROS-responsive immunomodulatory polymeric nanodrug
Authors: Song Jinxiao , Cheng Mingyang , Xie Yi , Li Kangkang , Zang Xinlong
Published: March 2023

Immunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-d, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.
Colorectal liver metastases patients prognostic assessment: prospects and limits of radiomics and radiogenomics
Authors: Granata Vincenza , Fusco Roberta , Setola Sergio Venanzio , Galdiero Roberta , Maggialetti Nicola , Patrone Renato , Ottaiano Alessandro , Nasti Guglielmo , Silvestro Lucrezia , Cassata Antonio , Grassi Francesca , Avallone Antonio , Izzo Francesco , Petrillo Antonella
Published: March 2023

In this narrative review, we reported un up-to-date on the role of radiomics to assess prognostic features, which can impact on the liver metastases patient treatment choice. In the liver metastases patients, the possibility to assess mutational status (RAS or MSI), the tumor growth pattern and the histological subtype (NOS or mucinous) allows a better treatment selection to avoid unnecessary therapies. However, today, the detection of these features require an invasive approach. Recently, radiomics analysis application has improved rapidly, with a consequent growing interest in the oncological field. Radiomics analysis allows the textural characteristics assessment, which are correlated to biological data. This approach is captivating since it should allow to extract biological data from the radiological images, without invasive approach, so that to reduce costs and time, avoiding any risk for the patients. Several studies showed the ability of Radiomics to identify mutational status, tumor growth pattern and histological type in colorectal liver metastases. Although, radiomics analysis in a non-invasive and repeatable way, however features as the poor standardization and generalization of clinical studies results limit the translation of this analysis into clinical practice. Clear limits are data-quality control, reproducibility, repeatability, generalizability of results, and issues related to model overfitting.
Sex differences in myocardial injury after non-cardiac surgery and postoperative mortality
Authors: Kwon Ji-Hye , Park Jungchan , Lee Seung-Hwa , Hyun Cheol Won , Kim Jihoon , Yang Kwangmo , Min Jeong Jin , Lee Jong Hwan , Lee Sangmin Maria , Choi Jin-ho , Lee Sang-Chol , Gwon Hyeon-Cheol , Her Sukyoung , Kim Kyunga , Ahn Joonghyun
Published: March 2023

Background

Myocardial injury after non-cardiac surgery (MINS) has recently been accepted as a predictor of mortality. However, sex differences in the incidence of MINS and survival thereafter are not fully understood. This study aimed to compare the incidence of MINS and mortality among male and female patients.

Methods

This single-center study was conducted using the database of a large tertiary referral hospital. Consecutive patients with cardiac troponin (cTn) detected within 30 days after non-cardiac surgery performed between January 2010 and June 2019 were grouped according to sex. The incidence of MINS and mortality of patients with MINS were compared between men and women.

Results

Of the 33,311 patients, 18,546 (55.7%) were men and 14,765 (44.3%) were women. In a multivariable analysis, women showed a significantly lower incidence of MINS than did men (17.9% vs. 14.2%; odds ratio, 0.76; 95% confidence interval [CI], 0.71–0.81; P < 0.001). In patients with MINS, the propensity-score-matched analysis showed that 30-day mortality did not differ according to sex, but mortality in females was significantly lower than that in males during the overall follow-up (33.0% vs. 25.7%; hazard ratio, 0.75; 95% CI, 0.66–0.84; P < 0.001).

Conclusion

The incidence of MINS was lower in women than in men. In patients with MINS, female sex may be associated with a survival benefit. Further studies are needed to confirm these findings.
Cadmium-induced Sertoli Cell Injury Through p38-MAPK and Related Signaling Proteins—A Study by RNA Sequencing
Authors: Wang Lingling , Li Xinyao , Bu Tiao , Wu Xiaolong , Li Linxi , Gao Sheng , Yun Damin , Zhang Yan , Chen Hao , Sun Fei , Cheng C Yan
Published: March 2023

Environmental toxicants, such as cadmium, found in foods, water, and consumer products are known to induce male reproductive dysfunction. However, the underlying molecular mechanism(s) by which cadmium-induced Sertoli cell injury as manifested by a disruption of the blood-testis barrier (BTB) remains unknown. Interestingly, one of the primary targets of cadmium toxicity in the testis is the cytoskeletons of the Sertoli cells, which, in turn, impedes cell junctions in the seminiferous epithelium. In order to expand these earlier observations and to provide a roadmap for future studies, we embarked a study using RNA sequencing to identify the pertinent genes involved in cadmium-induced Sertoli cell injury. Using bioinformatics analyses, multiple gene sets that regulated actin and microtubule (MT) cytoskeletons were identified along with components of the mitogen-activated protein kinase (MAPK) signaling protein and several signaling pathways. More important, we have also discovered that while the gene expression of p38-MAPK (also JNK or c-Jun) was considerably up- or downregulated during cadmium-induced Sertoli cell injury, the activated (phosphorylated) form was upregulated. Importantly, doramapimod (also known as BIRB 796), a specific p38-MARK inhibitor, that was shown to selectively block cadmium-induced p-p38 MAPK activation via phosphorylation in Sertoli cells, was indeed capable of blocking cadmium-induced Sertoli cell injury including disruption of the Sertoli cell-permeability barrier function, disruptive distribution of BTB-associated proteins, and disruptive organization of the actin and MT cytoskeletons. These data provide a helpful source of information for investigators to probe the role of signaling proteins and/or their signaling cascades, besides MAPKs, that likely utilized by cadmium to induce reproductive dysfunction.
Neurotrans
Authors: Smilges J. Logan
Published: March 2023

This essay makes the case for neurotrans, which names the nexus of neurodivergence and trans as an epistemic source, a place from which neurotrans people think neurotrans thoughts to pursue a neurotrans world. Bringing the interwoven histories of mental disability and trans experience to bear on HIV/AIDS, the author argues that HIV has long served as a racialized weapon of the state to subjugate neurodivergent and gender variant people, especially those of color. The AIDS crisis, following the rise of antipsychotics in psychiatry, offered the medical industrial complex and the criminal punishment system a new opportunity to surveil and control disabled and trans populations. In addition to racializing gender variance and neurodivergence as threats to white supremacy, the state could now use HIV to justify incarcerating neurotrans people, although carceral spaces, such as hospitals, mental institutions, and prisons, are largely responsible for facilitating HIV transmission. Drawing on the life and activism of Black mad and trans activist Marsha P. Johnson, this essay illuminates the entanglement of mental disability and gender nonconformance and the necessity to center mental disability in trans studies, prioritize neurodivergent people in HIV prevention efforts, and advocate for the participation and leadership of neurotrans people in AIDS activism.
102 AI-Based Molecular Classification of Diffuse Gliomas using Rapid, Label-Free Optical Imaging
Authors: Hollon Todd Charles , Golfinos John G. , Orringer Daniel A. , Berger Mitchel , Hervey-Jumper Shawn L. , Muraszko Karin M. , Freudiger Christian , Heth Jason , Sagher Oren , Jiang Cheng , Chowdury Asadur , Moin Mustafa Nasir , Kondepudi Akhil , Aabedi Alexander Arash , Adapa Arjun R. , Al-Holou Wajd , Wadiura Lisa , Widhalm Georg , Neuschmelting Volker , Reinecke David , Camelo-Piragua Sandra
Published: March 2023

INTRODUCTION:

Molecular classification has transformed the management of brain tumors by enabling more accurate prognostication and personalized treatment. Access to timely molecular diagnostic testing for brain tumor patients is limited, complicating surgical and adjuvant treatment and obstructing clinical trial enrollment.

METHODS:

By combining stimulated Raman histology (SRH), a rapid, label-free, non-consumptive, optical imaging method, and deep learning-based image classification, we are able to predict the molecular genetic features used by the World Health Organization (WHO) to define the adult-type diffuse glioma taxonomy, including IDH-1/2, 1p19q-codeletion, and ATRX loss. We developed a multimodal deep neural network training strategy that uses both SRH images and large-scale, public diffuse glioma genomic data (i.e. TCGA, CGGA, etc.) in order to achieve optimal molecular classification performance.

RESULTS:

One institution was used for model training (University of Michigan) and four institutions (NYU, UCSF, Medical University of Vienna, and University Hospital Cologne) were included for patient enrollment in the prospective testing cohort. Using our system, called DeepGlioma, we achieved an average molecular genetic classification accuracy of 93.2% and identified the correct diffuse glioma molecular subgroup with 91.5% accuracy within 2 minutes in the operating room. DeepGlioma outperformed conventional IDH1-R132H immunohistochemistry (94.2% versus 91.4% accuracy) as a first-line molecular diagnostic screening method for diffuse gliomas and can detect canonical and non-canonical IDH mutations.

CONCLUSIONS:

Our results demonstrate how artificial intelligence and optical histology can be used to provide a rapid and scalable alternative to wet lab methods for the molecular diagnosis of brain tumor patients during surgery.
104 A Safety and Efficacy Study of NicaPlant® in Aneurysmal Subarachnoid Haemorrhage Patients Undergoing Aneurysm Clipping
Authors: Vajkoczy Peter , Thomé Claudius , Kerschbaumer Johannes , Meyer Bernhard , Wostrack Maria , Adage Tiziana , Breitenbach Jörg , Bavinzski Gerhard , Hirschmann Dorian , Bendszus Martin , Rohde Veit , Mielke Dorothee , Wessels Lars
Published: March 2023

INTRODUCTION:

Aneurysmal subarachnoid hemorrhage (SAH) has high morbidity and mortality. Secondary mechanisms of injury can aggravate the high negative impact. Cerebral vasospasm (CV) is one of the most relevant causes of this secondary injury. To improve the current treatment options, NicaPlant® was developed.

METHODS:

The trial was performed as an international randomized, controlled, single-blinded multicenter study. 40 Patients with WFNS grade 3 and 4 SAH undergoing surgical repair of their ruptured aneurysm were randomized to receive ten pellets of NicaPlant® (40 mg) plus standard of care or standard of care alone. The implants were administered immediately following clip ligation of the ruptured aneurysm in proximity to all the exposed cerebral blood vessels. The primary endpoint was the incidence of moderate to severe CV (day 8 ± 1). A blinded independent outcome accessor analyzed all imaging data.

RESULTS:

In the implant group, 20% (4/20) of patients reached the primary endpoint, compared to 58% (11/19) of patients in the control group (p = 0.024). Including mild CV, 75% of all patients in the control group developed CV compared to 30% in the implant group (p = 0.0129). 32% (6/19) of the patients in the control group developed new cerebral infarction, compared to 10% (2/20) in the implant group (p = 0.1273). Endovascular rescue therapy was performed in 10% of the patients in the implant group compared to 58% in the control group (p = 0.002). 4 subjects (20%) in the control group experienced Treatment-emergent adverse events (TEAE), compared with none in the active group.

CONCLUSIONS:

In this prospective randomized multicenter Phase 2b trial, we could demonstrate the safety and efficacy of NicaPlant® implants in preventing CV in patients with SAH.
106 Reimbursement Trends in Neuroendovascular Interventions 2013-2022
Authors: Steiger Kyle , Singh Rohin , Koester Stefan Wolfgang , Nguyen Brandon , Brown Nolan James , Shahrestani Shane , Catapano Joshua , Srinivasan Visish M. , Gendreau Julian Lassiter , Patel Naresh P. , Erben Young
Published: March 2023

INTRODUCTION:

Neuroendovascular surgeries are increasingly important, particularly with the advent of thrombectomy as the gold standard in the management of large vessel stroke.

METHODS:

The Physician Fee Schedule Look-Up Tool was queried from 2013 to 2019 for all primary Current Procedural Terminology (CPT) codes identified by the American Medical Association as pertaining to endovascular procedures of the nervous system (61623, 61624, 61630, 61635, 61626, 61645, and 61650). The facility prices were averaged for each procedure and subsequently adjusted for inflation using the United States Bureau of Labor Statistics’ Consumer Price Index Inflation Calculator as adjusted to January of 2022. Statistical analyses, including data aggregation, exploratory analysis, and propensity adjustment, were performed using R, version 4.0.1 (The R Foundation, Vienna, Austria). The two-sided Mann-Kendall trend test, a non-parametric statistical test that assesses for monotonic trends in either an upward or downward trend, was utilized to assess for trends over time. Within each year analyzed, a Chi-squared test for trend in proportions was used. A significance level of 0.05 was used.

RESULTS:

Decreases in reimbursement were noted for all neuroendovascular procedures. This trend was statistically significant for temporary balloon occlusion, CPT61623 (2013:$677.04; 2022:586.96; p: 0.01), central nervous system transcatheter permanent occlusion or embolization, CPT61624 (2013:$1349.61; 2022:$1175.02; p: 0.02), non-central nervous system transcatheter permanent occlusion or embolization, CPT61626 (2013:$1040.86; 2019:$912.29; p: 0.002), stent placement, CPT61635 (2013:$1697.18; 2022:$1490.68; p: 0.05), and when viewed as aggregate procedures (2013:$1265.01; 2022:$1000.45; p < 0.01).

CONCLUSIONS:

Inflation-adjusted reimbursement is decreasing for certain neuroendovascular procedures over time and for all neuroendovascular procedures when viewed as an aggregate group. This suggests a need for reevaluation of the market value and advocacy for neuroendovascular providers and procedures in the era of value/quality-based care.
107 Nerve Transfers in Spinal Cord Injury: Analysis of Factors Influencing Motor Recovery
Authors: Javeed Saad , Dibble Christopher , Greenberg Jacob K. , Zhang Justin , Khalifeh Jawad M. , Ray Zack
Published: March 2023

INTRODUCTION:

Nerve transfers have the potential to reanimate lost upper limb function following cervical spinal cord injury (SCI). However, the factors influencing motor recovery following nerve transfers in cervical SCI remains unknown.

METHODS:

A prospective cohort of cervical SCI patients 18 years of age with American Spinal Injury Association [ASIA] grade A-C underwent nerve transfers and followed-up until 48-months. Preoperative variables included age, time-delay post-SCI, neurological level-of-injury, ASIA grades, international classification of surgery of hand in tetraplegia (ICSHT) indicating preserved upper limb function, and recipient-nerve-electrodiagnosis. Univariate analyses were performed followed by multivariable proportional-odds logistic-regression of significant predictors. The primary outcome was motor recovery in medical research council (MRC) grades categorized as: poor-recovery (MRC grades 0-2); good-recovery (grade 3); and excellent-recovery (grades 4-5). The ICSHT was categorized into very-high-level (ICSHT-0; absent-function); high-level (ICSHT 1-2; intact biceps/brachioradialis); and low-level-injury (ICSHT 3-4; intact wrist-extension/pronation).

RESULTS:

21 cervical SCI patients underwent 57 nerve transfers (33 upper limbs) at median of 21 (range: 6-142) months post-SCI. At final follow-up, median-gain in triceps MRC was: 3 ([IQR] 2.5-4, p = 0.011), finger-extensors: 4 (2-4, p < 0.001), and finger-flexors: 2 (1-3, p < 0.001). On univariate analysis, age, time-delay post-SCI, and ICSHT were significantly associated with motor recovery. On multivariable analysis, the low-level-injury (ICSHT 3-4) was significantly associated with superior motor outcomes as compared to higher-level injuries (Odds ratio [OR] 12.2, 95% CI, 2.34-91.4; p = 0.005). Each month delay increased 5% odds of superior motor function (OR 1.05, 95% CI, 1.01-1.11; p = 0.03).

CONCLUSIONS:

The preserved motor function in upper limb (ICSHT-grouping) significantly predicts motor outcomes following nerve transfers in cervical SCI. Nerve transfers in chronic SCI (12 months) results in comparable motor outcomes to earlier reinnervation.
109 A Small RNA Signature from Extracellular Vesicles in Patient Plasma Correlates With Recurrence or Progression of High-Grade Gliomas
Authors: Han Jae Ho , Attwood Kathleen , Roy Jeremy , Weeks Adrienne
Published: March 2023

INTRODUCTION:

Glial cell-derived tumors of the central nervous system make up the largest group of brain tumors. Most are high-grade gliomas (HGG) and are universally fatal despite multimodal therapy. In managing patients with HGG, predicting recurrence, or differentiating between pseudoprogression (radiation necrosis) and true tumor progression would be invaluable in improving overall prognosis. Characterizing small RNA (sRNA) expression profiles from plasma-derived extracellular vesicles (EVs) over the course of a patient’s treatments, may allow for patient-specific treatment modifications and improve outcomes.

METHODS:

Plasma EVs were isolated using Vn96 capture from HGG patients perioperatively and with routine, follow-up surveillance imaging. Small RNA sequencing was conducted and unsupervised hierarchal clustering of sRNA signatures were completed. Expression profiles were grouped longitudinally with the clinical status of patients.

RESULTS:

Cluster analysis of nine HGG patients, has revealed a sRNA signature that is able to distinguish between tumors showing evidence of progression and those remaining stable over time. Those samples obtained from patients where a clinical diagnosis of tumor progression or pseudoprogression were uncertain, were found to cluster into progression vs. stable signatures. Annotation of differentially expressed small RNAs identified from stable vs. clinically progressed patient include small nuclear RNA, ribosomal RNA, and micro RNA among others. MiRNA species we have identified correspond to previously identified miRNA, which have been ascribed functional significance to HGG aggressiveness and progression.

CONCLUSIONS:

These preliminary findings demonstrate the potential utility of sRNA profiling of plasma-derived EVs obtained from patients with high-grade gliomas as non-invasive biomarkers for recurrent/progressive disease or stability/pseudoprogression.
110 Macrophage Cross Talk following Subarachnoid Hemorrhage: Contribution of Peripheral Immune Activation in the Development of Cerebral Vasospasm
Authors: Lucke-Wold Brandon , Hoh Brian Lim
Published: March 2023

INTRODUCTION:

Microglia respond to the initial insult of aneurysm rupture, but become overwhelmed by ferritin toxicity. These microglia release inflammatory cytokines that cause vasospasm to facilitate peripheral macrophage diapedesis. This process is dependent on the p-STAT3 pathway.

METHODS:

The autologous SAH pre-clinical model was utilized and compared to blood and CSF from human patients. Mouse blood was injected along the skull base to c57/bl6 and CCR2/Cx3CR1 mice. Microglia depletion was done with pexidartinib. Ferritin within microglia, TLR4, and NFKb were measured via immunohistochemistry. Vasospasm was measured via India Ink gelatin assay. The Modified Garcia Scale and right turn test was utilized. Clarity assay was utilized to determine association between macrophages and brain microglia. Cerebral doppler was used to measure spreading cortical depressions. p-STAT3 was measured via western blot. For all experiments, saline sham, subarachnoid hemorrhage, and subarachnoid hemorrhage with p-STAT3 inhibitor were utilized.

RESULTS:

Microglia recruitment occured within parenchyma along the skull base adjacent to subarachnoid blood. Ferritin toxicity was noted by day 5 (r-0.95, p < 0.05) and persisted to day 9 (r-0.98, p < 0.01). A shift in microglia occured following SAH with Cox-2 and INOS predominance (k1 0.76, k2 1.21). Blockade of p-STAT3 resulted in decreased vasospasm (p<0.01), improved modified Garcia scores (p < 0.05), and improved right turn test (p < 0.05) following SAH. Peripheral macrophage diapedesis occured in regions of microglia activation. P-STAT3 blockade improved cerebral blood flow and prevented spreading cortical depressions (p < 0.01). NFKb and TLR4 activation was markedly reduced by p-Stat3 inhibition (p < 0.05). Results correlated closely to human aneurysmal blood and CSF data.

CONCLUSIONS:

Microglia ferritin toxicity contributes to vasospasm to facilitate peripheral macrophage diapedesis. Targeting the p-STAT3 pathway leads to reduced vasospasm and improved behavioral outcomes.
111 Improved Functional Outcomes of Stroke Patients Undergoing Mechanical Thrombectomy After Arriving via Mobile Stroke Unit
Authors: Al Saiegh Fadi , Velagapudi Lohit , Khanna Omaditya , Tjoumakaris Stavropoula I. , Gooch M. Reid , Rosenwasser Robert H. , Jabbour Pascal
Published: March 2023

INTRODUCTION:

Mobile stroke units (MSUs) have been implemented worldwide for stroke care, but outcome data is lacking to show their efficacy specifically in patients undergoing mechanical thrombectomy (MT).

METHODS:

A retrospective review of a stroke database was performed to identify patients who underwent MT after arrival via MSU from August 2019 to December 2020. Demographic factors, past medical history, stroke characteristics, treatment variables, complications, and functional outcomes were recorded. These were compared to date-matched patients who underwent MT after arrival via conventional means.

RESULTS:

Seven patients were treated with MT after arriving by MSU. These were compared to 50 date- matched patients who underwent thrombectomy after arrival through conventional means. No statistically significant difference between cohorts was observed in terms of demographic variables, co-morbidities, stroke characteristics, or tPA administration. Patients from the MSU cohort had significantly shorter time from symptom onset to groin puncture time (191.33 mins ± 77.53 vs 483.51 mins ± 322.66, p = 0.034). Importantly, MSU-transferred patients had significantly better discharge functional status measured by modified Rankin Scale (mRS) (1.86 ± 1.35 vs 3.57 ± 1.88, p = 0.024). No significant difference in final TICI score, complications, length of stay, or mortality was observed.

CONCLUSIONS:

Our pilot study demonstrates the efficacy of the MSU in decreasing door-to-puncture time and a concordant improvement in discharge mRS. Further prospective studies are needed to assess cost-efficacy and optimal protocol for MSUs in stroke care.
117 Social Determinants of Health and Spine Tumor Surgery Outcomes: A Nationwide Analysis of Disparities from 2002-2019
Authors: Tang Oliver Young , Ayala Cameron , Feler Joshua , Rivera Perla Krissia M. , Bajaj Ankush , Ganga Arjun , Fridley Jared , Toms Steven A. , Gokaslan Ziya L. , Sullivan Patricia Zadnik
Published: March 2023

INTRODUCTION:

Earlier research has demonstrated that social determinants of health (SDoH) impact neurosurgical access and outcomes, influencing patient disparities.

METHODS:

We identified all admissions with a spine tumor diagnosis in the National Inpatient Sample from 2002-2019. Four SDoH were analyzed: race and ethnicity, insurance, household income, and safety-net hospital (SNH) treatment. Hospitals in the top quartile of safety-net burden (percentage of patients receiving Medicaid or uninsured) were categorized as SNHs. Multivariable regression queried the association between 22 variables and six perioperative outcomes: mortality, discharge disposition, complications, length of stay (LOS), and hospitalization costs. Relative importance of predictors for disposition were assessed using random forest models.

RESULTS:

Of 6,593,391 total admissions with spine tumors, 219,380 (3.3%) underwent surgery. Non-white race (odds ratio [OR] = 0.80–0.91, P = 0.001) and non-private insurance (OR = 0.76–0.83, p = 0.001) were associated with lower odds of surgery. Among surgical admissions, presenting severity, including myelopathy and plegia, was elevated among nonwhite, non-private insurance, and low-income admissions (all P = 0.001). Black race (OR = 0.70, P = 0.001), Medicare (OR = 0.70, P = 0.001), Medicaid (OR = 0.90, P = 0.001), and lower income (OR = 0.88–0.93, all P = 0.001) were associated with decreased odds of favorable discharge disposition. Elevated LOS and costs were observed among non-white (LOS: +6-10%, costs: +5-9%, both P = 0.001) and Medicaid (LOS: +16%, costs: +6%, both P = 0.001) admissions. SNH treatment was also associated with higher mortality (OR = 1.49, P = 0.001) and complications (OR = 1.20, P = 0.001). From 2002-2019, disposition improved annually for Medicaid patients (OR = 1.03 per year, P = 0.022) but worsened for Black patients (OR = 0.98 per year, P = 0.046). Random forest models identified household income as the most important disposition predictor.

CONCLUSIONS:

For spine tumor admissions, SDoH predicted surgical intervention, presenting severity, and perioperative outcomes. Over two decades, disparities improved for Medicaid patients but worsened for Black patients.
119 An Institutional Analysis of Venous Sinus Stenting and Cerebrospinal Fluid Shunting for Idiopathic Intracranial Hypertension
Authors: Yamamoto Erin A. , Mazur-Hart David , Lee Daniel , Schoettler Woll S. Cody , Ramos Christian Lopez , Munger Daniel , Richie Emma , Bozorgchami Hormodz , Dogan Aclan , Nesbit Gary , Priest Ryan , Falardeau Julie , Jia-Xin Liu Jesse
Published: March 2023

INTRODUCTION:

Idiopathic intracranial hypertension (IIH) is a debilitating disease that can present with severe vision loss. Although medical management is the first-line treatment, these cases commonly require intervention by either ventriculoperitoneal/pleural shunting (VPS) or, more recently, by venous sinus stenting (VSS). Unfortunately, this chronic disease can lead to multiple clinical encounters which increases financial burden. Therefore, identifying ways to effectively treat IIH definitively while limiting healthcare costs are of great interest.

METHODS:

This is a retrospective study of IIH patients diagnosed via modified Dandy criteria who received VPS (n=27) or VSS (n=27) from May 2008–May 2019. Visual outcomes were reported by a neuro-ophthalmologist at approximately 1-month post-procedure. Costs of emergency department as well as and outpatient/inpatient encounters for neurosurgery and ophthalmology were obtained from the index procedure to 3 years post-procedure.

RESULTS:

VSS patients had higher pre-intervention ophthalmology evaluation rates (stents: n = 22, 88.9%; shunts: n = 7, 23.1%; p < 0.0001). Papilledema was present in most patients (VSS 82.6% vs VPS 66.7%, p = 0.60) and all patients had stable/improved papilledema at follow-up. Two VSS patients (4.9%) required a second stent. Four VSS patients (9.8%) had a VPS placed. No VPS patients received a VSS. Encounter cost for VSS placement were more expensive than primary VPS placement ($10,749 vs $13,648; p = 0.002). However, at 1.5 years after index procedure, cumulative VPS cost surpassed VSS and persisted at 3 years ($22,674 vs $17,441, p = 0.039).

CONCLUSIONS:

VPS and VSS have similar visual outcomes with all cases having stable or improved papilledema. The upfront cost of VSS is greater than VPS; however, VPS quickly surpasses VSS in cost by 1.5 years after index procedure and continues to study endpoint at 3 years. These results may help guide multi-disciplinary care for patients with IIH.
122 Prospective, Randomized, Blinded Clinical Trial Comparing PEEK and Allograft Spacers in Patients Undergoing ACDF Surgeries
Authors: Villavicencio Alan T. , Nelson Ewell Lee , Rajpal Sharad , Beasley Kara D. , Burneikiene Sigita
Published: March 2023

INTRODUCTION:

The biomechanical qualities as well as osteoconductive, osteogenic, and osteoinductive properties of various graft materials have been previously evaluated. There remain questions, however as to whether there are any clinical and/or radiographic outcome differences in the selection of interbody graft types for ACDF.

METHODS:

Patients undergoing one- to three-level ACDF with single anterior plate fixation were randomized (1:1 ratio) to receive either cortical allograft or PEEK interbody spacers. Radiographic and clinical outcomes were assessed at 3, 6, 12 and 24 months with an additional postoperative radiographic assessment.

RESULTS:

A total of 120 patients were enrolled and randomized. Comparing clinical outcomes, no differences in arm or neck pain scores were noted, however, there was a statistically significant (<0.041) improvement in SF-36 PCS scores for the allograft group at all follow-up time points and a tendency towards lower disability scores. Overall, evidence of radiographic fusion was achieved in 87 (91.6%) patients: five (10.2%) and three (6.5%) patients had pseudoarthrosis (p=0.72) in the PEEK and allograft groups, respectively. At the 24-month follow-up, any cervical or segmental alignment restoration achieved with surgery was lost and no statistically significant changes were detected when all levels of surgery were included. Likewise, there were no statistically significant differences between the groups for anterior or posterior body height measurements at the 24-month follow-up. Approximately 20% of patients had anterior and posterior subsidence, all grade 0 regardless of the group assignment.

CONCLUSIONS:

Comparable radiographic outcomes were observed for patients undergoing one- to three-level PEEK vs. allograft-assisted ACDF surgeries.
123 Early Postural Stability Changes in Patients Undergoing Correction of Spinal Deformity
Authors: Keister Alex , Grossbach Andrew James , Toop Nathaniel , Mallory Noah , Gibbs David Charles , Xu David S. , Viljoen Stephanus
Published: March 2023

INTRODUCTION:

Adult spinal deformity (ASD) is an increasingly prevalent cause of pain and disability. It is known that ASD correction results in improved alignment, but not whether this alignment results in objective improvements in postural stability.

METHODS:

A retrospective review of a prospectively maintained database identified 16 patients undergoing ASD correction surgery with five or more segments. Balance was assessed via a force plate pre- and three months postoperatively. Participants were instructed to stand still, with their hands at their sides and eyes open. Center of pressure (COP) and center of gravity (COG) parameters were analyzed and used to derive head sway in the Dubousset cone of economy (COE). Spinopelvic parameters (PI, PT, SVA, and LL) on standing scoliosis radiographic films were also measured pre- and three months postoperatively.

RESULTS:

In our 16-patient series, there was a mean age of 61.3 years-old, and a median of 10 segments fused. Postoperative force plate assessment showed a decrease in total COP sway and sway velocity (p < 0.05). Coronal COP sway and sway velocity also decreased (p < 0.05). There was a decrease in total, coronal and sagittal COG sway and sway velocity postoperatively (p < 0.05). In the COE, total head sway decreased (p < 0.05). PT remained unchanged following surgical correction, while LL and SVA improved from 44.9° to 56.7° (p < 0.01) and 82.2 to 22.5 mm (p < 0.01), respectively. PI-LL mismatch also improved from 16.2° to 4.8° (p < 0.01).

CONCLUSIONS:

Following long segment fusion for ASD, postural stability may improve as early as three months, concomitant with improved spinopelvic alignment. We believe force plate assessment warrants further study for postoperative evaluation of postural alignment and clinical outcomes in ASD patients.
124 Multidimensional Approach to Frailty Improves Prediction of Adverse Outcomes in Metastatic Spine Tumor Surgery
Authors: Rigney Grant Harding , Razak Shahaan , Duvall Julia , Kiapour Ali , Williamson Theresa , Massaad Elie , Shin John H.
Published: March 2023

INTRODUCTION:

Surgery for individuals with spinal metastases can have a substantial impact on a patient’s quality of life. Recent research has highlighted the importance of preoperative nutritional status and frailty on outcomes, but little is known about which aspects of malnutrition carry clinical significance.

METHODS:

Cancer patients who underwent surgery for spinal metastases between August 1, 2014, to March 20, 2019, were stratified by New England Spinal Metastasis Score (NESMS). Frailty was assessed using the Metastatic Spinal Tumor Frailty Index. Nutrition was assessed via the prognostic nutritional index. The primary outcome was overall postoperative survival. Secondary outcomes included 6- and 12-month survival rates, postoperative complication rates, and readmission after surgery.

RESULTS:

Our study included 154 patients with a mean (SD) age of 63.23 (13.14) years, of whom 94 (61%) were female. 56 patients (36.3%) were classified as NESMS grade 3, while 46 (29.9%) were NESMS 2, 36 (23.4%) were NESMS 1, and (16) 10% were NESMS 0. NESMS 0 group had the highest proportion of severely frail patients (56.2%). Poor nutritional status (PNI < 40.4; Odds ratio; OR 1.87; 95% CI; 0.398-8.82) and increased inflammation (PLR; OR 1.80; 95% CI, 0.766-4.21) were associated with a meaningful increased rate of complications after surgery. Patients with normal nutritional status (AGR, PNI) had a better prognosis than those with poor nutritional status in the same NESMS group.

CONCLUSIONS:

Malnutrition and severe frailty are associated with high rates of adverse events in high-risk cancer patients with spinal metastases within NESMS prognostic groups. Further work should assess the effectiveness of pre-habilitation programs to improve physiological reserves for patients with spinal metastasis.