Does surgery for metastatic spinal tumors improve functional outcomes in patients without spinal cord compression but with potentially unstable spines (SINS 7-12)?

OBJECTIVE: In the absence of spinal cord compression, it is unclear if surgery is more effective than radiation treatment for improving functional outcomes in metastatic spinal tumor patients with potentially unstable spines. The authors compared functional status outcomes assessed with Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group (ECOG) scores after surgery or radiation in patients without spinal cord compression with Spine Instability Neoplastic Score (SINS) values of 7-12 indicating possible instability (SINS 7-12). METHODS: A retrospective review was performed of patients with metastatic spinal tumor SINS values of 7-12 at a single institution between 2004 and 2014. Patients were divided into two different groups: 1) those treated with surgery and 2) those treated with radiation. Baseline clinical characteristics were measured, and KPS and ECOG scores were obtained pre- and postradiation or postsurgery. The paired, nonparametric Wilcoxon signed-rank test and ordinal logistic regression analysis were used for statistical analysis. RESULTS: A total of 162 patients met inclusion criteria; 63 patients were treated operatively and 99 patients were treated with radiation. The mean follow-up was 1.9 years, with a median of 1.1 years for the surgical cohort (ranging from 2.5 months to 13.8 years) and a mean of 2 years with a median of 0.8 years for the radiation cohort (ranging from 2 months to 9.3 years). After covariates were accounted for, the average posttreatment changes in KPS scores in the surgical cohort were 7.46 ± 17.3 and in the radiation cohort were -2 ± 13.6 (p = 0.045). No significant difference was observed in ECOG scores. KPS scores improved postoperatively in 60.3% of patients in the surgical group and postradiation in 32.3% of patients in the radiation cohort (p < 0.001). Subanalysis within the radiation cohort revealed no differences in fracture rates or local control between patients treated with external-beam radiation therapy versus stereotactic body radiation therapy. In patients initially treated with radiation, 21.2% eventually developed compression fractures at a treated level. Five of the 99 patients in the radiation cohort-all of whom had a fracture-eventually underwent either methyl methacrylate augmentation or instrumented fusion. CONCLUSIONS: Patients with SINS values of 7-12 who underwent surgery had greater improvement in KPS scores-but not in ECOG scores-than patients undergoing radiation alone. In patients treated with radiation, treatment was converted to a procedural intervention such as surgery only in patients who sustained fractures. Of the patients with fractures after radiation (21 of 99), 5 patients underwent an invasive procedure and 16 did not.

Wound complications in metastatic spine tumor patients with and without preoperative radiation.

OBJECTIVE: Wound complications are a common adverse event following metastatic spine tumor surgery. Some patients with spinal metastases may first undergo radiation but eventually require spinal surgery because of either cord compression or instability. The authors compared wound complication rates in patients who had undergone surgery for metastatic disease and received preoperative radiation treatments, postoperative radiation, or no radiation. METHODS: Records from patients treated at the University of California, San Francisco, for metastatic spine disease between 2005 and 2017 were retrospectively reviewed. Baseline characteristics were collected, including preoperative Karnofsky Performance Status (KPS), Spine Instability Neoplastic Score, total radiation dose, indication for surgery, diabetes status, time between radiation and surgery, use of perioperative chemotherapy or steroids, estimated blood loss, extent of fusion, and preoperative albumin level. Wound complication was defined as poor healing, dehiscence, or infection per the Centers for Disease Control and Prevention guidelines, within 6 months of surgery. One-way ANOVA was used to compare means across groups. Cumulative incidence analysis with competing risk methodology was used to adjust for risk of death during follow-up. Statistical analysis was performed using R software. RESULTS: Two hundred five patients with adequate medical records were identified. Seventy patients had received preoperative radiation, 74 had received postoperative radiation within 6 months after surgery, and 61 had received no radiation at the surgical site. Wound complication rates were similar across the 3 cohorts: 14.3% (n = 10) in the group with preoperative radiation, 10.8% (n = 8) in the group that received postoperative radiation, and 11.5% (n = 7) in the group with no radiation (p = 0.773). Competing risk analysis showed a higher cumulative incidence of wound complications for the preoperative cohort, though this difference was not significant (p = 0.46). Overall, 89 patients were treated with external beam radiation therapy (EBRT), whereas 55 received stereotactic body radiation therapy (SBRT). There was no significant difference in wound complications for patients treated with EBRT (11.2%, n = 10) versus SBRT (14.5%, n = 8; p = 0.825). KPS was the only factor correlated with wound complications on univariate analysis (p = 0.03). CONCLUSIONS: Wound complication rates did not differ across the 3 cohorts: patients treated with preoperative radiation, postoperative radiation within 6 months of surgery, or no radiation. The effect size was small for KPS and likely does not represent a clinically significant predictor of wound complications.

Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models.

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes and therapeutic responses. Accounting for matrix effects earlier in the drug development pipeline is expected to increase the likelihood of clinical success of novel therapeutics. Biomaterial-based strategies recapitulating specific tissue microenvironments in 3D cell culture exist but integrating these with the 2D culture methods primarily used for drug screening has been challenging. Thus, the protocol presented here details the development of methods for 3D culture within miniaturized biomaterial matrices in a multi-well plate format to facilitate integration with existing drug screening pipelines and conventional assays for cell viability. Since the matrix features critical for preserving clinically relevant phenotypes in cultured cells are expected to be highly tissue- and disease-specific, combinatorial screening of matrix parameters will be necessary to identify appropriate conditions for specific applications. The methods described here use a miniaturized culture format to assess cancer cell responses to orthogonal variation of matrix mechanics and ligand presentation. Specifically, this study demonstrates the use of this platform to investigate the effects of matrix parameters on the responses of patient-derived glioblastoma (GBM) cells to chemotherapy.

Intraoperative Monitoring for Spinal Surgery.

The use of intraoperative neuromonitoring (IONM) can improve surgical outcomes. Although inclusion of IONM is considered standard practice in more complicated spine surgeries, there are no national-level guidelines for the usage of IONM in spine surgery. Technical advancement in IONM has increased both its sensitivity and specificity, and with a recently developed algorithmic checklist it can be more easily adopted by the surgical team in their practice.

Management of Thoracic Disc Pathology via the Lateral Approach: Advances Using the Minimally Invasive Approach and Navigation.

Historically, thoracic disc pathology has been treated via open thoracotomy or open posterior costotransversectomy or lateral extracavitary approaches. However, these approaches are associated with approach-related morbidity. With advancement in such minimally invasive approaches as the lateral interbody fusion coupled with navigation, the morbidity of approaching anterior thoracic spinal pathology may be reduced. There are subtleties and nuances in the thoracic approaches that are different from the lateral lumbar interbody approaches. We discuss our technique of the minimally invasive approach to the thoracic spine, management of the rib and pleura, and incorporation of navigation into the procedure.

Orthogonally induced differentiation of stem cells for the programmatic patterning of vascularized organoids and bioprinted tissues.

The generation of organoids and tissues with programmable cellular complexity, architecture and function would benefit from the simultaneous differentiation of human induced pluripotent stem cells (hiPSCs) into divergent cell types. Yet differentiation protocols for the overexpression of specific transcription factors typically produce a single cell type. Here we show that patterned organoids and bioprinted tissues with controlled composition and organization can be generated by simultaneously co-differentiating hiPSCs into distinct cell types via the forced overexpression of transcription factors, independently of culture-media composition. Specifically, we used such orthogonally induced differentiation to generate endothelial cells and neurons from hiPSCs in a one-pot system containing either neural or endothelial stem-cell-specifying media, and to produce vascularized and patterned cortical organoids within days by aggregating inducible-transcription-factor and wild-type hiPSCs into randomly pooled or multicore-shell embryoid bodies. Moreover, by leveraging multimaterial bioprinting of hiPSC inks without extracellular matrix, we generated patterned neural tissues with layered regions composed of neural stem cells, endothelium and neurons. Orthogonally induced differentiation of stem cells may facilitate the fabrication of engineered tissues for biomedical applications.

Methanol decomposition on Ni(111) and O/Ni(111).

Methanol decomposition on Ni(111) surfaces has been studied in the presence and absence of oxygen using temperature-programmed desorption and temperature-dependent sum frequency generation spectroscopy. Under both conditions the C-H and O-H bonds break, forming carbon monoxide and atomic hydrogen on the surface. No C-O bond scission was observed, limiting the number of reaction pathways. The O-H bonds break first (>150 K), forming surface methoxy, followed by C-H bond breakage (>250 K). All atomic hydrogen desorbs from the surface as H2 through H+H recombinative desorption. H2 desorbs at a higher temperature in the presence of oxygen (>300 K) than the absence of oxygen (>250 K) as the oxygen on the surface stabilizes the H atoms, forming surface hydroxide (OH). The surface oxygen also appears to stabilize the O-H and C-H bonds, leading to slightly higher dissociation temperatures. The CO molecules occupy both the bridge sites and the top sites of the Ni atoms as surface H appears to force the CO molecules to the top sites. There is a slight blueshift in the C-O bond vibration for both the O covered and O free surfaces due to CO being more mobile. On the O free surface, the C-O peak width broadens as low-frequency modes are activated. Finally, CO desorbs between 350 and 400 K.

A comprehensive library of human transcription factors for cell fate engineering.

Human pluripotent stem cells (hPSCs) offer an unprecedented opportunity to model diverse cell types and tissues. To enable systematic exploration of the programming landscape mediated by transcription factors (TFs), we present the Human TFome, a comprehensive library containing 1,564 TF genes and 1,732 TF splice isoforms. By screening the library in three hPSC lines, we discovered 290 TFs, including 241 that were previously unreported, that induce differentiation in 4 days without alteration of external soluble or biomechanical cues. We used four of the hits to program hPSCs into neurons, fibroblasts, oligodendrocytes and vascular endothelial-like cells that have molecular and functional similarity to primary cells. Our cell-autonomous approach enabled parallel programming of hPSCs into multiple cell types simultaneously. We also demonstrated orthogonal programming by including oligodendrocyte-inducible hPSCs with unmodified hPSCs to generate cerebral organoids, which expedited in situ myelination. Large-scale combinatorial screening of the Human TFome will complement other strategies for cell engineering based on developmental biology and computational systems biology.

Parallel phylogeography of Prochlorococcus and Synechococcus.

The globally abundant marine Cyanobacteria Prochlorococcus and Synechococcus share many physiological traits but presumably have different evolutionary histories and associated phylogeography. In Prochlorococcus, there is a clear phylogenetic hierarchy of ecotypes, whereas multiple Synechococcus clades have overlapping physiologies and environmental distributions. However, microbial traits are associated with different phylogenetic depths. Using this principle, we reclassified diversity at different phylogenetic levels and compared the phylogeography. We sequenced the genetic diversity of Prochlorococcus and Synechococcus from 339 samples across the tropical Pacific Ocean and North Atlantic Ocean using a highly variable phylogenetic marker gene (rpoC1). We observed clear parallel niche distributions of ecotypes leading to high Pianka's Index values driven by distinct shifts at two transition points. The first transition point at 6°N distinguished ecotypes adapted to warm waters but separated by macronutrient content. At 39°N, ecotypes adapted to warm, low macronutrient vs. colder, high macronutrient waters shifted. Finally, we detected parallel vertical and regional single-nucleotide polymorphism microdiversity within clades from both Prochlorococcus and Synechococcus, suggesting uniquely adapted populations at very specific depths, as well as between the Atlantic and Pacific Oceans. Overall, this study demonstrates that Prochlorococcus and Synechococcus have shared phylogenetic organization of traits and associated phylogeography.