A structure-based mechanism for vesicle capture by the multisubunit tethering complex Dsl1.

Vesicle trafficking requires membrane fusion, mediated by SNARE proteins, and upstream events that probably include "tethering," an initial long-range attachment between a vesicle and its target organelle. Among the factors proposed to mediate tethering are a set of multisubunit tethering complexes (MTCs). The Dsl1 complex, with only three subunits, is the simplest known MTC and is essential for the retrograde traffic of COPI-coated vesicles from the Golgi to the ER. To elucidate structural principles underlying MTC function, we have determined the structure of the Dsl1 complex, revealing a tower containing at its base the binding sites for two ER SNAREs and at its tip a flexible lasso for capturing vesicles. The Dsl1 complex binds to individual SNAREs via their N-terminal regulatory domains and also to assembled SNARE complexes; moreover, it is capable of accelerating SNARE complex assembly. Our results suggest that even the simplest MTC may be capable of orchestrating vesicle capture, uncoating, and fusion.

Evolution of Cervical Endoscopic Spine Surgery: Current Progress and Future Directions-A Narrative Review.

Cervical endoscopic spine surgery is rapidly evolving and gaining popularity for the treatment of cervical radiculopathy and myelopathy. This approach significantly reduces muscular damage and blood loss by minimizing soft tissue stripping, leading to less postoperative pain and a faster postoperative recovery. As scientific evidence accumulates, the efficacy and safety of cervical endoscopic spine surgery are continually affirmed. Both anterior and posterior endoscopic approaches have surfaced as viable alternative treatments for various cervical spine pathologies. Newer techniques, such as endoscopic-assisted fusion, the anterior transcorporeal approach, and unilateral laminotomy for bilateral decompression, have been developed to enhance clinical outcomes and broaden surgical indications. Despite its advantages, this approach faces challenges, including a steep learning curve, increased radiation exposure for both surgeons and patients, and a relative limitation in addressing multi-level pathologies. However, the future of cervical endoscopic spine surgery is promising, with potential enhancements in clinical outcomes and safety on the horizon. This progress is fueled by integrating advanced imaging and navigation technologies, applying regional anesthesia for improved and facilitated postoperative recovery, and incorporating cutting-edge technologies, such as augmented reality. With these advancements, cervical endoscopic spine surgery is poised to broaden its scope in treating cervical spine pathologies while maintaining the benefits of minimized tissue damage and rapid recovery.

Pushing the Limits of Minimally Invasive Spine Surgery-From Preoperative to Intraoperative to Postoperative Management.

The introduction of minimally invasive surgery ushered in a new era of spine surgery by minimizing the undue iatrogenic injury, recovery time, and blood loss, among other complications, of traditional open procedures. Over time, technological advancements have further refined the care of the operative minimally invasive spine patient. Moreover, pre-, and postoperative care have also undergone significant change by way of artificial intelligence risk stratification, advanced imaging for surgical planning and patient selection, postoperative recovery pathways, and digital health solutions. Despite these advancements, challenges persist necessitating ongoing research and collaboration to further optimize patient care in minimally invasive spine surgery.

Erratum to "E.C. Lerner, E.S. Srinivasan, G. Broadwater, et al. Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases. Adv Radiat Oncol. 2022;7:101054."

[This corrects the article DOI: 10.1016/j.adro.2022.101054.].

Preoperative validation of edema-corrected tractography in neurosurgical practice: translating surgeon insights into novel software implementation.

Background: Peritumoral edema alters diffusion anisotropy, resulting in false negatives in tractography reconstructions negatively impacting surgical decision-making. With supratotal resections tied to survival benefit in glioma patients, advanced diffusion modeling is critical to visualize fibers within the peritumoral zone to prevent eloquent fiber transection thereafter. A preoperative assessment paradigm is therefore warranted to systematically evaluate multi-subject tractograms along clinically meaningful parameters. We propose a novel noninvasive surgically-focused survey to evaluate the benefits of a tractography algorithm for preoperative planning, subsequently applied to Synaptive Medical's free-water correction algorithm developed for clinically feasible single-shell DTI data. Methods: Ten neurosurgeons participated in the study and were presented with patient datasets containing histological lesions of varying degrees of edema. They were asked to compare standard (uncorrected) tractography reconstructions overlaid onto anatomical images with enhanced (corrected) reconstructions. The raters assessed the datasets in terms of overall data quality, tract alteration patterns, and the impact of the correction on lesion definition, brain-tumor interface, and optimal surgical pathway. Inter-rater reliability coefficients were calculated, and statistical comparisons were made. Results: Standard tractography was perceived as problematic in areas proximal to the lesion, presenting with significant tract reduction that challenged assessment of the brain-tumor interface and of tract infiltration. With correction applied, significant reduction in false negatives were reported along with additional insight into tract infiltration. Significant positive correlations were shown between favorable responses to the correction algorithm and the lesion-to-edema ratio, such that the correction offered further clarification in increasingly edematous and malignant lesions. Lastly, the correction was perceived to introduce false tracts in CSF spaces and - to a lesser degree - the grey-white matter interface, highlighting the need for noise mitigation. As a result, the algorithm was modified by free-water-parameterizing the tractography dataset and introducing a novel adaptive thresholding tool for customizable correction guided by the surgeon's discretion. Conclusion: Here we translate surgeon insights into a clinically deployable software implementation capable of recovering peritumoral tracts in edematous zones while mitigating artifacts through the introduction of a novel and adaptive case-specific correction tool. Together, these advances maximize tractography's clinical potential to personalize surgical decisions when faced with complex pathologies.

Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases.

Purpose: Stereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and Materials: Patients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. Results: The cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. Conclusions: Our data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

Older Patients Have Better Pain Outcomes Following Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) increases in prevalence with age. Although microvascular decompression (MVD) is the most effective long-term operative treatment for TN, its use in older patient populations has been debated due to its invasive nature. Recent studies have demonstrated safety of MVD in older patients; however, efficacy data are more limited. OBJECTIVE: To determine the relationship between age and pain outcomes following MVD for TN. METHODS: Subjects underwent MVD for TN at our institution between 1/1/2004 and 12/31/2013, had typical TN, and demonstrated neurovascular compression on preoperative imaging. We performed a retrospective case series study by reviewing the electronic medical records and performing phone interviews to determine long-term outcomes. We divided patients into 2 groups for analysis, under 60 and 60 yr of age and older. RESULTS: One hundred twenty-four subjects were included in the study, 82 under 60, and 42 60 yr of age and older. The average length of follow-up was 42.4 mo. Patients in the older age group had average pain score of 1.57 at most recent follow-up, while for the younger age group it was 2.18 (P = .0084). Multiple regression analysis found that older age, male gender, and preoperative medication responsiveness were significantly correlated with lower long-term pain scores, while V2 dermatome involvement was correlated with higher long-term pain scores. CONCLUSION: Patients 60 yr of age and older have significantly better long-term pain outcomes following MVD than younger patients.