Citations

AbstractBackgroundTraditional management of olfactory neuroblastoma (ONB) includes margin‐negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be overtreating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes.MethodsThis retrospective, multi‐institutional cohort study examined clinical covariates associated with occult intracranial involvement. Patient demographics, staging, Hyam's grade, and pathologic involvement of dura, olfactory bulb/tract, and brain were collected. Diagnostic imaging was reviewed. Positive and negative predictive value (NPV) were estimated along with effect size estimates. Cox hazard regression examined associations with overall survival (OS) and disease‐free survival (DFS).ResultsA total of 224 subjects with new diagnoses of ONB (2005–2021) were identified. Skull base bone involvement on computed tomography (CT) had the highest NPV for pathologic dura (88.0%), olfactory bulb (88%), and brain involvement (97.3%). Hyam's grade category was significantly associated with dural involvement (φC = 0.26; 95% confidence interval [CI]: 0.16, 0.42). Subjects without radiologic skull base involvement (n = 66) had pathologic positivity of 12.1%. Within this subgroup, Hyam's grade was clinically significant for dural positivity (φ = 0.34; 95% CI: −0.12, 0.71) with 28.6% involvement in high grade tumors. Neither clinical nor pathologic positivity of intracranial structures were associated with significantly different OS or DFS.ConclusionsBoth CT and magnetic resonance imaging (MRI) had reasonably good NPV for involvement of dura and olfactory bulb. Higher Hyam's grade was associated with dural involvement. Patients with low‐grade tumors not involving the skull base may be suitable for avoiding skull base resection; however, further investigation is warranted.

BACKGROUND: Anterior approaches to the cervical spine are among the most common exposures by which neurosurgeons and orthopedic surgeons access the prevertebral space and ultimately the cervical disk and vertebral bodies. There is a paucity of literature describing the microanatomic fascial planes of the neck with respect to anterior cervical approaches. OBJECTIVE: To delineate the microanatomic connections of the cervical fascial planes pertinent to anterior cervical exposure. METHODS: Using a cadaveric model, original illustrations, the Visible Human Project, and an original surgical video, we demonstrate a stepwise method for identifying the correct planes for anterior cervical exposure. RESULTS: A step-by-step method for identifying the anterior cervical fascial planes intraoperatively is demonstrated. CONCLUSION: A comprehensive understanding of anterior cervical microsurgical anatomy is vital for performing a methodical yet efficient approach to the prevertebral space while minimizing retraction and iatrogenic injury to the surrounding neurovascular structures.

Abstract Aims To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). Methods and results This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0–70.0) years, 53.3% male]. The median LASr was 13.9% (10.5–20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879–0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337–8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). Conclusion LASr was an independent predictor of NOAF in patients with ALCA.

BACKGROUND: Graduate surgical education is highly variable across regions and institutions regarding case volume and degree of trainee participation in each case. Dedicated educational curriculum using cadaveric tissue has been shown to enhance graduate surgical training, however with associated financial and utility burden to the institution. OBJECTIVE: To investigate the utility of educational and cost applications of a novel method of combining mixed organic hydrogel polymers and 3-dimensional printed anatomic structures to create a complete “start-to-finish” simulation for resident education in spinal anatomy, instrumentation, and surgical techniques. METHODS: This qualitative pilot study investigated 14 international participants on achievement of objective and personal learning goals in a standardized curriculum using biomimetic simulation compared with cadaveric tissue. A questionnaire was developed to examine trainee evaluation of individual anatomic components of the biomimetic simulators compared with previous experience with cadaveric tissue. RESULTS: A total of 210 responses were acquired from 14 participants. Six participants originated from US residency education programs and 8 from transcontinental residency programs. Survey results for the simulation session revealed high user satisfaction. Score averages for each portion of the simulation session indicated learner validation of anatomic features for the simulation compared with previous cadaveric experience. Cost analysis resulted in an estimated savings of $10 833.00 for this single simulation session compared with previous cadaveric tissue sessions. CONCLUSION: The results of this study indicate a strong potential of establishing biomimetic simulation as a cost-effective and high-quality alternative to cadaveric tissue for the instruction of fundamental spine surgical techniques.

Abstract B-cell lymphoma is a potential cause of spinal cord compression that presents with nonspecific symptoms and inconsistent imaging findings. Surgical decompression is a mainstay for both diagnosis and management especially in patients with acute neurologic deficits; however, the long-term efficacy of intervention is still unclear. We perform a systematic review of the clinical symptoms, radiographic findings, and outcome after spinal decompression in B-cell lymphoma. The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, histological markers, treatment and survival outcomes were extracted. Bivariate and Multivariate Cox survival regression models and Kaplan-Meier curves were generated using R software survival package. In total, 57 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. Mean age was 56.22 (IQR: 45.00-70.25) with 68% of patients being male and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%) with B symptoms and cauda equina symptoms present in only 6% and 29% respectively. Mean length of symptoms before presentation was 3.81 months (IQR: 0.45-3.25). The most common location was the thoracic spine (53%), with a majority of the lesions being hyperintense (28%) on T2 MRI. Surgical resection was performed in 83% of patients. Symptoms improved in 88% of patients after surgery and 80% of patients treated nonoperatively. OS at one- and five-years was 85% (95% CI: 0.749-0.953; n=72) and 66% (95% CI: 0.512-0.847; n=72), respectively. Age > 70 was associated with poorer OS in bivariate (HR 4.07 [95% CI: 1.328-12.46], p < 0.01; n=72) and multivariate analysis (HR 3.829 [95% CI: 1.158-12.662], p < 0.03; n=72). Primary spinal B-cell lymphoma can have a variety of presentations. Both surgery and nonoperative management may have similar improvement in symptoms. Age > 70 appears to confer poorer OS.

Abstract Posterior Fossa Group A (PFA) ependymomas are pediatric brain tumors with extremely poor survival outcomes. As protein-coding mutations in PFA are exceedingly rare, the underlying etiology of these tumors remains elusive. Elevated CpG island methylation and depletion of H3K27me3 have been described in PFA, leading to the hypothesis that PFA may be driven by a dysregulated epigenetic state. In this study, we sought to determine how three-dimensional (3D) genome features (such as DNA loops, domains, and compartments) differ between pediatric brain tumors. We performed Hi-C sequencing on a collection of 64 patient specimens and patient-derived primary cultures that collectively span multiple subgroups of ependymoma, medulloblastoma, high-grade glioma, and non-neoplastic brain. For certain samples, we further performed RNA-seq, histone modification ChIP-seq, or whole-genome bisulfite sequencing to allow multiomic data integration. Overall, the 3D genome organization of PFA samples appeared distinct from other tumor types. We identified and defined TULIPs: a subset of type B compartments, separated by genomic distances greater than 10 Mbp, that exhibit a striking fivefold increase in reciprocal interaction strength. These TULIPs recurred at the same genomic positions across the vast majority of PFA samples with minimal representation among other tumor or non-tumor samples. TULIPs displayed enrichment for heterochromatic features such as H3K9me3 and late replication timing and were depleted of euchromatic features such as H3K27ac and protein-coding genes. By using immuno-fluorescence for H3K9me3 and oligo-FISH to label TULIP regions, we demonstrated that TULIP regions are more compact in PFA than other tumors. Finally, by applying inhibitors of H3K9 lysine methylation to PFA cultures we showed that TULIPs become more diffuse and cell viability is reduced. Altogether, this work defines TULIPs as highly recurrent epigenetic features of PFA tumors.

PurposeAsymmetric gradient coils introduce zeroth‐ and first‐order concomitant field terms, in addition to higher‐order terms common to both asymmetric and symmetric gradients. Salient to compensation strategies is the accurate calibration of the concomitant field spatial offset parameters for asymmetric coils. A method that allows for one‐time calibration of the offset parameters is described.Theory and MethodsA modified phase contrast pulse sequence with single‐sided bipolar flow encoding is proposed to calibrate the offsets for asymmetric, transverse gradient coils. By fitting the measured phase offsets to different gradient amplitudes, the spatial offsets were calculated by fitting the phase variation. This was used for calibrating real‐time pre‐emphasis compensation of the zeroth‐ and first‐order concomitant fields.ResultsImage quality improvement with the proposed corrections was demonstrated in phantom and healthy volunteers with non‐Cartesian and Cartesian trajectory acquisitions. Concomitant field compensation using the calibrated offsets resulted in a residual phase error <3% at the highest gradient amplitude and demonstrated substantial reduction of image blur and slice position/selection artifacts.ConclusionsThe proposed implementation provides an accurate method for calibrating spatial offsets that can be used for real‐time concomitant field compensation of zeroth and first‐order terms, substantially reducing artifacts without retrospective correction or sequence specific waveform modifications.

Importance Given that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. Results The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT ( P &lt; .001 vs cycle 1 hypericin) and to 49% after 3 cycles ( P &lt; .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. Conclusion and Relevance The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. Trial Registration ClinicalTrials.gov Identifier: NCT02448381