The mammalian brain contains diverse neuronal types, yet we lack single-cell epigenomic assays that are able to identify and characterize them. DNA methylation is a stable epigenetic mark that ...distinguishes cell types and marks regulatory elements. We generated >6000 methylomes from single neuronal nuclei and used them to identify 16 mouse and 21 human neuronal subpopulations in the frontal cortex. CG and non-CG methylation exhibited cell type–specific distributions, and we identified regulatory elements with differential methylation across neuron types. Methylation signatures identified a layer 6 excitatory neuron subtype and a unique human parvalbumin-expressing inhibitory neuron subtype. We observed stronger cross-species conservation of regulatory elements in inhibitory neurons than in excitatory neurons. Single-nucleus methylomes expand the atlas of brain cell types and identify regulatory elements that drive conserved brain cell diversity.
Highlights • Virtual reality (VR) and augmented reality (AR) have great potential in neurosurgery. • Immersive VR has the potential to be used an educational tool. • AR has the added potential of use ...in the live operative field. • Further improvement of VR and AR is crucial to its integration into neurosurgery.
Highlights • Glioblastoma multiforme (GBM) is the most common and deadly primary brain tumor. • CD44 is a transmembrane molecule overexpressed in GBM. • Processes involving CD44 promote GBM invasion, ...proliferation and therapy resistance. • Targeting CD44 is a promising GBM therapy.
Highlights • There is a paucity of literature on patients undergoing cranioplasty with PEEK. • To our knowledge, this is the first systematic review and meta-analysis for cranioplasty. • There is a ...trend toward lower complication rates following PEEK versus autologous grafts. • There is a trend toward lower implant failure rates with PEEK versus titanium mesh.
IMPORTANCE: Vismodegib is a targeted agent recently approved for treating patients who develop recurrent or locally advanced basal cell carcinoma (BCC), and will inevitably be integrated into ...existing therapy for advanced BCC as it becomes increasingly used. Improved understanding of how vismodegib interacts with other treatment modalities, including radiotherapy, would help optimize multidisciplinary therapy and clinical outcomes. OBSERVATIONS: We report 2 cases of recurrent, advanced BCC treated from April 1, 2012, through October 31, 2014, with concurrent radiotherapy and vismodegib. Concurrent treatment appeared to be well tolerated and efficacious, with both patients having no evidence of progressive disease at last follow-up. CONCLUSIONS AND RELEVANCE: We found that the combination of vismodegib and radiotherapy is feasible for patients with recurrent or locally advanced BCC and that combined use of currently available therapies for advanced BCC warrants further prospective study.
Highlights • Differences between systems are probe design, delivery, cooling, and wavelength. • Epilepsy is the most common indication for Visualase therapy. • Brain mass is the most common ...indication for NeuroBlate therapy. • NeuroBlate group is nearly twice as old as the Visualase group.
Oral cavity squamous cell carcinoma (OCSCC) commonly occurs in elderly patients. This study explores the clinical outcomes in elderly patients with OCSCC based on their functional status and clinical ...comorbidities.
We retrospectively reviewed 180 patients aged ≥70 who were treated with definitive intent with surgery followed by adjuvant therapy if indicated for newly diagnosed OCSCC from 1998 to 2013. Pathology review was conducted, and Eastern Cooperative Oncology Group (ECOG) performance status and the Head and Neck Charlson Comorbidity Index (HN-CCI) were assessed. We performed Kaplan-Meier analyses and cumulative incidence estimates to assess overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LRR). Univariate and multivariate analyses were used to test age, adjuvant therapy, adverse pathologic features, ECOG status, and HN-CCI status as predictors.
The median age was 80 years (range, 70-95 years), with a median follow-up time of 23 months. The median OS was 18 months and 46 months for patients aged 70 to 84 and ≥85, respectively (P=.0017). The LRR was 24% at 1 year and 30% at 2 years for all patients. On univariate analysis, ECOG score ≥2 (hazard ratio HR = 1.96; confidence interval CI 1.19-3.21; P=.008) and HN-CCI score ≥2 (HR=1.97; CI 1.17-3.34; P=.011) were predictors of worse OS. On multivariate analysis, HN-CCI score was a better predictor of OS, PFS, and LRR than was ECOG score. Predictors of worse OS were age ≥85 (HR=1.78; CI 1.07-2.96; P=.026), HN-CCI score of ≥2 (HR=2.21; CI 1.20-4.08; P=.011), and adverse features (HR=2.35; CI 1.34-4.13; P=.003). Adjuvant therapy did not have a significant impact on OS or LRR for patients with adverse features even though 48% of them did not receive it.
Elderly patients with good health and performance status may live long enough to experience disease progression from OCSCC. ECOG and HN-CCI scores may be useful to evaluate the candidacy of elderly patients for adjuvant therapy. However, the benefit of adjuvant therapy in this population remains elusive and should be investigated prospectively.
Abstract Objective To review the literature on isolated transverse process fractures (ITPFs) and provide evidence for and validate the current practice of conservative management. Methods The PubMed ...database was searched for published literature related to ITPFs. Baseline patient (age, sex, presentation, mechanism of injury) and fracture (number of fractures, level, single or multi-segmental) characteristics were extracted. Management, and outcomes were also recorded. Statistical comparisons were ascertained through N-1 Pearson Chi-squared tests. Results A total of 4 studies comprised of 398 patients with 819 ITPFs were evaluated. Mean age was 33.5 years (69% male and 31% female). No patients presented with neurological deficits. The most common mechanism of injury was motor vehicle accident (MVA), followed by falls. MVAs were more commonly the cause of ITPFs in pediatric versus adult patients (88% vs. 65%, p = 0.0001 ) . Falls were more commonly the cause of ITPFs in adults than in children (18% vs. 9%, p = 0.05). Management strategies involved unrestricted movement, bracing and orthotics. Radiologic evidence of spinal instability or deformity was not reported in any of the cases. Mean follow-up was 20.5 months. Conclusions Our data suggests that non-surgical management of ITPFs leads to complete resolution of the fracture without evidence of permanent neurological deficit or spinal instability. However, interpretation of our results is limited by the paucity of meaningful literature reporting on long-term outcomes. Nevertheless, the results provide support for conservative management and highlights the need to markers or scenarios where the diagnosis of ITPF is actually likely to be erroneous.
Highlights • Modality-specific outcomes of SRS and FSRT for benign meningiomas are unclear. • Significant differences in tumor regression rates between SRS and FSRT were found. • No difference in ...survival, local control and complication rate between SRS and FSRT. • SRS and FSRT are likely comparable treatments for benign intracranial meningioma.
Abstract Objectives Atypical meningioma (AM) is an aggressive subtype of meningioma that is associated with high recurrence rates following surgical resection. Recent studies have compared outcomes ...of various treatment strategies, but advantages of adjuvant radiosurgery (ARS) over serial surveillance (SS) following subtotal resection (STR) remain unclear. To further elucidate this issue, the authors systematically analyze the current literature on AM and compare outcomes of ARS versus SS after STR. Methods Embase, PubMed, and Cochrane databases were queried using relevant search terms. Retrospective case series that described patients with AM treated with ARS and SS after STR were included. Tests of proportions were performed to detect significant variations in recurrence rate, 5-year progression-free (PFS), and 5-year overall survival (OS) between the treatment strategies (ARS versus SS) and among individual studies. Results A total of 619 patients (263 ARS and 356 SS) were identified. Mean recurrence rates, 5-year PFS, and 5-year OS were 53.5%, 50.3%, and 74.9% for ARS versus 89.8%, 19.1%, and 89.8% for SS, respectively. Recurrence rates between treatment strategies and ARS studies differed (p < .001). 5-year PFS between treatment strategies, ARS, and SS studies differed (p < .001, p = .007 and p < .001, respectively). Conclusion The evidence demonstrates significant differences in recurrence rates and 5-year PFS between ARS and SS, suggesting a potential benefit of ARS. As we further our understanding of the clinical outcomes of various treatment strategies for AM, we also move closer to integrating modalities, such as radiosurgery, into management guidelines.
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