Patient Frailty Influences Outcome After Open, But Not Minimally Invasive, Transforaminal Interbody Fusion: A Case Series of 115 Patients With Lumbar Degenerative Disease.

BACKGROUND: For transforaminal lumbar interbody fusion (TLIF), there are equally good open and minimally invasive surgery (MIS) options. OBJECTIVE: To determine if frailty has a differential effect on outcome for open vs MIS TLIF. METHODS: We performed a retrospective review of 115 TLIF surgeries (1-3 levels) for lumbar degenerative disease performed at a single center; 44 MIS transforaminal interbody fusions and 71 open TLIFs were included. All patients had at least a 2-year follow up, and any revision surgery during that time was recorded. The Adult Spinal Deformity Frailty Index (ASD-FI) was used to separate patients into nonfrail (ASD-FI < 0.3) and frail (ASD-FI > 0.3) cohorts. The primary outcome variables were revision surgery and discharge disposition. Univariate analyses were performed to reveal associations in demographic, radiographic, and surgical data with the outcome variables. Multivariate logistic regression was used to assess independent predictors of outcome. RESULTS: Frailty uniquely predicted both reoperation (odds ratio 8.1, 95% CI 2.5-26.1, P = .0005) and discharge to a location other than home (odds ratio 3.9, 95% CI 1.2-12.7, P = .0239). Post hoc analysis indicated that frail patients undergoing open TLIF had a higher revision surgery rate (51.72%) compared with frail patients undergoing MIS-TLIF (16.7%). Nonfrail patients undergoing open and MIS TLIF had a revision surgery rate of 7.5% and 7.7%, respectively. CONCLUSION: Frailty was associated with increased revision rate and increased probability to discharge to a location other than home after open transforaminal interbody fusions, but not MIS transforaminal interbody fusions. These data suggest that patients with high frailty scores may benefit from MIS-TLIF procedures.

Multiomic screening of invasive GBM cells reveals targetable transsulfuration pathway alterations.

While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multiomics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Among oncologic ROS, H2O2 specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine γ-lyase (CTH), which converts cystathionine to the nonessential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.

The neurosurgery applicant's "arms race": analysis of medical student publication in the Neurosurgery Residency Match.

OBJECTIVE: Neurosurgery is consistently one of the most competitive specialties for resident applicants. The emphasis on research in neurosurgery has led to an increasing number of publications by applicants seeking a successful residency match. The authors sought to produce a comprehensive analysis of research produced by neurosurgical applicants and to establish baseline data of neurosurgery applicant research productivity given the increased emphasis on research output for successful residency match. METHODS: A retrospective review of publication volume for all neurosurgery interns in 2009, 2011, 2014, 2016, and 2018 was performed using PubMed and Google Scholar. Missing data rates were 11% (2009), 9% (2011), and < 5% (all others). The National Resident Matching Program report "Charting Outcomes in the Match" (ChOM) was interrogated for total research products (i.e., abstracts, presentations, and publications). The publication rates of interns at top 40 programs, students from top 20 medical schools, MD/PhD applicants, and applicants based on location of residency program and medical school were compared statistically against all others. RESULTS: Total publications per neurosurgery intern (mean ± SD) based on PubMed and Google Scholar were 5.5 ± 0.6 in 2018 (1.7 ± 0.3, 2009; 2.1 ± 0.3, 2011; 2.6 ± 0.4, 2014; 3.8 ± 0.4, 2016), compared to 18.3 research products based on ChOM. In 2018, the mean numbers of publications were as follows: neurosurgery-specific publications per intern, 4.3 ± 0.6; first/last author publications, 2.1 ± 0.3; neurosurgical first/last author publications, 1.6 ± 0.2; basic science publications, 1.5 ± 0.2; and clinical research publications, 4.0 ± 0.5. Mean publication numbers among interns at top 40 programs were significantly higher than those of all other programs in every category (p < 0.001). Except for mean number of basic science publications (p = 0.1), the mean number of publications was higher for interns who attended a top 20 medical school than for those who did not (p < 0.05). Applicants with PhD degrees produced statistically more research in all categories (p < 0.05) except neurosurgery-specific (p = 0.07) and clinical research (p = 0.3). While there was no statistical difference in publication volume based on the geographical location of the residency program, students from medical schools in the Western US produced more research than all other regions (p < 0.01). Finally, research productivity did not correlate with likelihood of medical students staying at their home institution for residency. CONCLUSIONS: The authors found that the temporal trend toward increased total research products over time in neurosurgery applicants was driven mostly by increased nonindexed research (abstracts, presentations, chapters) rather than by increased peer-reviewed publications. While we also identified applicant-specific factors (MD/PhDs and applicants from the Western US) and an outcome (matching at research-focused institutions) associated with increased applicant publications, further work will be needed to determine the emphasis that programs and applicants will need to place on these publications.