A rare Bosworth Variant Isolated Distal Fibula Dislocation with a Successful Closed Reduction: A Case Report and Technique.

Introduction: The Bosworth fracture-dislocation is a rare injury originally described as an irreducible dislocation of a distal fibula fracture where the proximal fibular fragment becomes incarcerated behind the distal tibia. There have since been a few cases described of an intact distal fibula with dislocation and similar difficulties in closed reduction attempts, typically seen with associated injuries to the ankle or proximal fibula. Regardless of the specific fracture or dislocation pattern, closed reduction attempts have consistently failed in the significant majority of these cases, which can lead to complications including soft-tissue compromise, severe post-traumatic arthritis, compartment syndrome, avascular necrosis of the talus, and neurovascular compromise. There is only one case in recent literature that describes an isolated distal fibula dislocation without associated fractures or dislocations of the lower extremity; however, it required an open reduction. Cases where a closed reduction was successful to achieve an anatomic reduction of a Bosworth-type injury are exceedingly rare. Case Report: We present a rare case of a purely ligamentous, isolated distal fibula dislocation in a 21-year-old male who underwent a successful closed reduction upon initial presentation and later underwent surgical fixation with a syndesmosis repair system. We describe the technique used for a successful closed reduction for this injury and present a 1-year follow-up with excellent outcomes. Conclusion: This is the only known case report of a successful closed reduction in an isolated distal fibula dislocation, as well as demonstrating a minimally invasive technique for definitive treatment with a syndesmosis repair system. Accurate diagnosis, early treatment, and anatomic reduction are imperative for good clinical outcomes and reducing complications for Bosworth injuries. This technique may improve the rates of successful closed reductions of Bosworth injuries upon initial presentation, leading to decreased complications and improved patient outcomes.

Factors influencing geographic gender disparity in neurosurgery: a nationwide geospatial clustering analysis.

OBJECTIVE: Women neurosurgeons (WNs) continue to remain a minority in the specialty despite significant initiatives to increase their representation. One domain less explored is the regional distribution of WNs, facilitated by the hiring practices of neurosurgical departments across the US. In this analysis, the authors coupled the stated practice location of WNs with regional geospatial data to identify hot spots and cold spots of prevalence and examined regional predictors of increases and decreases in WNs over time. METHODS: The authors examined the National Provider Identifier (NPI) numbers of all neurosurgeons obtained via the National Plan and Provider Enumeration System (NPPES), identifying the percentage of WNs in each county for which data were appended with data from the US Census Bureau. Change in WN rates was identified by calculating a regression slope for all years included (2015-2022). Hot spots and cold spots of WNs were identified through Moran's clustering analysis. Population and surgeon features were compared for hot spots and cold spots. RESULTS: WNs constituted 10.73% of all currently active neurosurgical NPIs, which has increased from 2015 (8.81%). Three hot spots were found-including the Middle Atlantic and Pacific divisions-that contrasted with scattered cold spots throughout the East Central regions that included Memphis as a major city. Although relatively rapidly growing, hot spots had significant gender inequality, with a median WN percentage of 11.38% and a median of 0.61 WNs added to each respective county per year. CONCLUSIONS: The authors analyzed the prevalence of WNs by using aggregated data from the NPPES and US Census Bureau. The authors also show regional hot spots of WNs and that the establishment of WNs in a region is a predictor of additional WNs entering the region. These data suggest that female neurosurgical mentorship and representation may be a major driver of acceptance and further gender diversity in a given region.

Trends in medical device company payments in neurosurgery: a nationwide, multidatabase, geospatial analysis.

OBJECTIVE: Industry partnerships help advance the field of neurosurgery. Given the nature of the field and its close relationship with innovation, neurosurgeons frequently partner with the medical device industry to advance technology and improve outcomes. However, this can create important ethical concerns for patients. In this paper, the authors sought to comprehensively study how physician payments from medical device companies have changed and what geographic parameters influence the trends observed over the years. METHODS: The authors queried and merged several large databases, including Medicare and Medicaid provider usage data and databases from the Open Payments Program, National Plan and Provider Enumeration System, and US Census Bureau. Geospatial analysis was performed using Moran's I and II clustering. Univariate and multivariable analyses were performed using the Mann-Whitney U-test and geospatially weighted multivariable regression for hot spot and cold spot membership. RESULTS: Data for 952 counties across the continental United States were analyzed. Ninety-seven counties constituted geographic hot spots. These hot spots were primarily concentrated in Florida, the New York-Pennsylvania region, central Colorado, and southwestern United States. Independent predictors of hot spot membership included greater unemployment rates, the percentage of White patients, the presence of mobile homes, and the percentage of county Hispanic and Black populations. Company-based differences were examined. The vast majority of Medtronic's payments were in the form of royalties and licensing (86.6%). Royalties and licensing accounted for the majority of payments for DePuy (69.4%), Globus Medical (62%), and NuVasive (77.1%). In contrast, other companies, such as Boston Scientific, opted to pay physicians in the form of ownership and investment interests (42.1%). The impact of the COVID-19 pandemic was also assessed. During the onset of the pandemic in 2020, physician payments fell or remained the same across all regions with the exception of the South Atlantic region. However, it was observed that nearly all regions rebounded, with stark elevations in physician payments immediately in 2021. CONCLUSIONS: This analysis demonstrates that there are national hot spots and cold spots of physician payments, and offers some social, economic, and company-dependent predictors that may influence the magnitude of payments. Further analysis is needed to better understand this clinical-commercial partnership in healthcare, specifically within neurosurgical practice.

Academic career progression in AANS/CNS Spine Section award recipients.

OBJECTIVE: The American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Spine Section awards highlight outstanding abstracts submitted to the AANS/CNS Section on Disorders of the Spine and Peripheral Nerves by trainees interested in spine surgery, although the academic trajectory of awardees has not been studied. The aim of this study was to assess the academic career progression of prior recipients of the Journalistic and Academic Neurosurgical Excellence (JANE), Mayfield, and Kuntz research awards. METHODS: Prior JANE, Mayfield, and Kuntz award recipients were identified using awardee records accrued between 1984 and February 2022. Awardee sex, country of residence, specialty, subspecialty focus, and current academic appointment status (if applicable) were searched online. Awardee h-indices and number of peer-reviewed publications were assessed via Google Scholar profiles (or Scopus if unavailable) and PubMed, respectively. Receipt of federal research funding as principal investigator (PI) was determined using the websites of the National Institutes of Health, the National Science Foundation, and the Department of Defense Congressionally Directed Medical Research Programs. The abstract-to-publication rate was assessed. RESULTS: A total of 7 JANE awards, 57 Mayfield awards, and 149 Kuntz awards were identified. Of the JANE awardees, all recipients were male. Of the 4 unique JANE awardees who completed training, 2 (50.0%) held academic appointments at the time of the study. All of the JANE abstracts were published in peer-reviewed journals. The mean h-index of all JANE awardees was 28 and the mean number of publications was 126. None of the awardees have received federal research funding. Of the Mayfield awards, 98.2% were awarded to males. Of the 43 unique Mayfield awardees who completed training, 20 (46.5%) held faculty appointments at academic medical centers. All of the Mayfield abstracts since 2011 were published in peer-reviewed journals. The mean h-index of all Mayfield awardees was 26 and the mean number of publications was 82. Five Mayfield awardees received National Institutes of Health funding as PI, and 7 awardees received Department of Defense funding as PI. Of the Kuntz awards, 95.3% were awarded to males. Most awards were given to current residents and fellows (46.3%). Of the 55 unique Kuntz awardees who completed training, 31 (56.4%) held faculty appointments at academic medical centers. The abstract-to-publication rate of the total Kuntz abstracts was 70.5%. The mean h-index of all Kuntz awardees was 15 and the mean number of publications was 58. Five Kuntz awardees (3.4%) received federal research funding as PI. CONCLUSIONS: Many recipients of the JANE, Mayfield, and Kuntz Joint Spine Section awards have successfully translated award abstracts into peer-reviewed publications. Furthermore, approximately one-third of the awardees are active in academic neurosurgery, with some having secured federal research funding.

Diagnostic predictive values for sport-related concussions: a systematic review and diagnostic meta-analysis.

OBJECTIVE: Sport-related concussions (SRCs) can cause significant neurological symptoms, and approximately 10%-15% of athletes with SRC experience a prolonged recovery. Given the lack of visible injury on brain imaging and their varied presentations, concussions can be difficult to diagnose. A variety of tests and examination methods have been used to elicit a concussion diagnosis; however, the sensitivity and specificity of these tests are variable. The authors performed a systematic review and meta-analysis to evaluate the sensitivity and specificity of standardized tests and visible signs like balance and vision changes in the diagnosis of SRC. METHODS: A PRISMA-adherent systematic review of concussion diagnostic examinations was performed using the PubMed, MEDLINE, Scopus, Cochrane, Web of Science, and Google Scholar databases on December 1, 2022. Search terms included "concussion," "traumatic brain injury," "diagnosis," "sensitivity," and "specificity." Each method of examination was categorized into larger group-based symptomatologic presentations or standardized tools. The primary outcome was the diagnosis of concussion. Pooled specificity and sensitivity for each method were calculated using a meta-analysis of proportion and were hierarchically ranked using P-scores calculated from a diagnostic frequentist network meta-analysis. RESULTS: Thirty full-length articles were identified for inclusion, 13 of which evaluated grouped symptomology examinations (balance and overall clinical presentation) and 17 of which evaluated established formalized tools (ImPACT, King-Devick [K-D] Test, Sport Concussion Assessment Tool [SCAT]). The pooled specificity of the examination methods differed minimally (0.8-0.85), whereas the sensitivity varied to a larger degree (0.5-0.88). In a random effects model, the SCAT had the greatest diagnostic yield (diagnostic OR 31.65, 95% CI 11.06-90.57). Additionally, P-score hierarchical ranking revealed SCAT as having the greatest diagnostic utility (p = 0.9733), followed sequentially by ImPACT, clinical presentation, K-D, and balance. CONCLUSIONS: In deciphering which concussion symptom-focused examinations and standardized tools are most accurate in making a concussion diagnosis, the authors found that the SCAT examination has the greatest diagnostic yield, followed by ImPACT, clinical presentation, and K-D, which have comparable value for diagnosis. Given the indirect nature of this analysis, however, further comparative studies are needed to validate the findings.

Spinal Subdural Hematoma in Ankylosing Spondylitis Patients Without Anticoagulation Therapy.

Patients with ankylosing spondylitis are at high risk of significant spinal trauma after relatively low-impact events, such as ground-level falls. Because of the osteopenic nature of the disease process, complex spinal fractures are common in these patients. Additionally, patients may sustain rare traumatic complications from these fractures, such as a spinal subdural hematoma (SSDH) or epidural hematoma. Traumatic SSDH is extremely rare, with few cases described in the literature, and cases are typically associated with antiplatelet or anticoagulant use. This study reviews the literature related to traumatic SSDH in patients with ankylosing spondylitis and describes two cases of traumatic SSDH in patients with ankylosing spondylitis without anticoagulation or antiplatelet therapy, which has not previously been reported in the literature.

Radiographic and Clinical Outcomes After Stand-Alone Anterior Lumbar Interbody Fusion for Symptomatic L5-S1 Retrolisthesis.

BACKGROUND AND OBJECTIVES: Degenerative lumbar spondylolisthesis is associated with significant pain and disability. The literature on the treatment options and clinical outcomes for lumbar anterolisthesis is robust, but very few reports specifically evaluate lumbar retrolisthesis. This study investigated surgical outcomes for symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 anterior lumbar interbody fusion (ALIF). METHODS: All patients with symptomatic L5-S1 retrolisthesis treated with stand-alone L5-S1 ALIF at a single institution over a 7-year period were identified. Exhaustive nonoperative management had failed for all patients. Patients with previous lumbar fusion were excluded. Preoperative and postoperative radiographic images and patient-reported outcome measures for 20 patients (14 males and 6 females; mean [SD] age, 50.3 [13.7] years) were analyzed. RESULTS: The mean (SD) follow-up was 43.0 (23.7) months (range, 12.1-102.5 months). Patients experienced postoperative improvements in L5-S1 retrolisthesis (P = .048), L5-S1 disk height and angle (P < .001), L5 foraminal height (P < .001), L5-S1 lordosis (P < .001), and lumbar lordosis (P = .01). There were no significant changes in spinopelvic parameters. At the most recent follow-up, minimal clinically important differences in Oswestry Disability Index score, 36-Item Short-Form Survey (SF-36), and numerical rating scale score for leg pain were achieved in 11 of 20 (55%), 7 of 14 (50%), and 7 of 13 (54%) patients, respectively. All patients demonstrated fusion with no graft subsidence at up to 32 months. No patient experienced intraoperative complications, was readmitted, or required a subsequent posterior decompression or fusion because of refractory symptoms. CONCLUSION: In our cohort, stand-alone L5-S1 ALIF was associated with radiographic and clinical improvement in patients with symptomatic L5-S1 retrolisthesis.

Stable Regional and Global Alignment in Patients Treated With Minimally Invasive Lateral Retropleural Thoracic Diskectomy Without Fixation.

BACKGROUND AND OBJECTIVES: Thoracic disk herniations are challenging to treat, and open transthoracic or minimally invasive thoracoscopic approaches are associated with significant morbidity, substantial costs, and steep learning curves. The minimally invasive lateral retropleural thoracic diskectomy (MIS-LRP-TD) approach is straightforward and is associated with lower perioperative morbidity. With MIS-LRP-TD, the overlying rib, ipsilateral pedicle, ligamentum flavum, posterior longitudinal ligament, and posterior third of the adjacent vertebral bodies are resected. Adjunct fixation is typically not performed, eliminating hardware-related complications and costs. This radiographic study investigates long-term global and thoracic spine alignment after MIS-LRP-TD without fixation. METHODS: This study was a single-institution, retrospective evaluation of all patients who underwent MIS-LRP-TD without fixation between November 7, 2017 and July 19, 2022. Preoperative and the most recent postoperative radiographs were used to determine the C7 plumb line to central sacral vertical line, thoracic Cobb angle (TCA), segmental Cobb angle, C7 to sagittal vertical axis, thoracic kyphosis, and segmental kyphosis. RESULTS: In total, 22 patients with 24 disk herniations underwent MIS-LRP-TD without fixation. The mean (SD) radiographic follow-up was 12.9 (11.2) months. Overall, no significant differences were seen in C7 plumb line to central sacral vertical line (P = .65), C7 to sagittal vertical axis (P = .99), thoracic kyphosis (P = .30), TCA (P = .28), segmental kyphosis (P = .27), or segmental Cobb angle (P = .56) at follow-up. One patient demonstrated a >5° change in TCA but remained asymptomatic. CONCLUSION: Despite requiring extensive resection of the middle column and ipsilateral costovertebral joint at the index level, MIS-LRP-TD without adjunct fixation does not lead to significant global, regional, or segmental deformity. Thus, MIS-LRP-TD appears to be a safe, effective treatment approach for challenging thoracic disk herniations.

Conserved 5-methyluridine tRNA modification modulates ribosome translocation.

While the centrality of post-transcriptional modifications to RNA biology has long been acknowledged, the function of the vast majority of modified sites remains to be discovered. Illustrative of this, there is not yet a discrete biological role assigned for one the most highly conserved modifications, 5-methyluridine at position 54 in tRNAs (m 5 U54). Here, we uncover contributions of m 5 U54 to both tRNA maturation and protein synthesis. Our mass spectrometry analyses demonstrate that cells lacking the enzyme that installs m 5 U in the T-loop (TrmA in E. coli , Trm2 in S. cerevisiae ) exhibit altered tRNA modifications patterns. Furthermore, m 5 U54 deficient tRNAs are desensitized to small molecules that prevent translocation in vitro. This finding is consistent with our observations that, relative to wild-type cells, trm2 Δ cell growth and transcriptome-wide gene expression are less perturbed by translocation inhibitors. Together our data suggest a model in which m 5 U54 acts as an important modulator of tRNA maturation and translocation of the ribosome during protein synthesis.

Pentobarbital coma for management of intracranial hypertension following traumatic brain injury: Lack of early response to treatment portends poor outcomes.

INTRODUCTION: Traumatic brain injury (TBI) results in the death of over 50,000 and the permanent disability of 80,000 individuals annually in the United States. Much of the permanent disability is the result of secondary brain injury from intracranial hypertension (ICH). Pentobarbital coma is often instituted following the failure of osmotic interventions and sedation to control intracranial pressure (ICP). The goal of this study was to evaluate the efficacy of pentobarbital coma with respect to ICP management and long-term functional outcome. METHODS: Traumatic brain injury patients who underwent pentobarbital coma at a level 1 trauma center between 2014 and 2021 were identified. Patient demographics, injury characteristics, Glasgow Coma Scale (GCS) scores, intracranial pressures (ICPs), and outcomes were obtained from the trauma registry as well as inpatient and outpatient medical records. The proportion of ICPs below 20 for each hospitalized patient-day was calculated. The primary outcome measured was GCS score at the last follow-up visit. RESULTS: 25 patients were identified, and the majority were male (n â€‹= â€‹23, 92%) with an average age of 30.0 years â€‹± â€‹12.9 and median injury severity score of 30 (21.5-33.5). ICPs were monitored for all patients with a median of 464 (326-1034) measurements. The average hospital stay was 16.9 days â€‹± â€‹11.5 and intensive care stay was 16.9 â€‹± â€‹10.8 days. 9 (36.0%) patients survived to hospital discharge. Mean follow-up time in months was 36.9 â€‹± â€‹28.0 (min-max 3-80). 7 of the 9 surviving patients presented as GCS 15 on follow-up and the remaining were both GCS 9. Patients presenting at last follow-up with GCS 15 had a significantly higher proportion of controlled ICPs throughout their hospitalization compared to patients who expired or with follow-up GCS <15 (GCS 15: 88% â€‹± â€‹10% vs. GCS <15 or dead: 68% â€‹± â€‹22%, P â€‹= â€‹0.006). A comparison of the daily proportion of controlled ICPs by group revealed negligible differences prior to pentobarbital initiation. Groups diverged nearly immediately upon pentobarbital coma initiation with a higher proportion of controlled ICPs for patients with follow-up GCS of 15. CONCLUSION: Patients that do not have an immediate response to pentobarbital coma therapy for ICH universally had poor outcomes. Alternative therapy or earlier palliation should be considered for such patients. In contrast, patients whose ICPs responded quickly to pentobarbital had excellent long-term outcomes.

Complications associated with single-position prone lateral lumbar interbody fusion: a systematic review and pooled analysis.

OBJECTIVE: Lateral lumbar interbody fusion (LLIF) is a workhorse surgical approach for lumbar arthrodesis. There is growing interest in techniques for performing single-position surgery in which LLIF and pedicle screw fixation are performed with the patient in the prone position. Most studies of prone LLIF are of poor quality and without long-term follow-up; therefore, the complication profile related to this novel approach is not well known. The objective of this study was to perform a systematic review and pooled analysis to understand the safety profile of prone LLIF. METHODS: A systematic review of the literature and a pooled analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All studies reporting prone LLIF were assessed for inclusion. Studies not reporting complication rates were excluded. RESULTS: Ten studies meeting the inclusion criteria were analyzed. Overall, 286 patients were treated with prone LLIF across these studies, and a mean (SD) of 1.3 (0.2) levels per patient were treated. The 18 intraoperative complications reported included cage subsidence (3.8% [3/78]), anterior longitudinal ligament rupture (2.3% [5/215]), cage repositioning (2.1% [2/95]), segmental artery injury (2.0% [5/244]), aborted prone interbody placement (0.8% [2/244]), and durotomy (0.6% [1/156]). No major vascular or peritoneal injuries were reported. Sixty-eight postoperative complications occurred, including hip flexor weakness (17.8% [21/118]), thigh and groin sensory symptoms (13.3% [31/233]), revision surgery (3.8% [3/78]), wound infection (1.9% [3/156]), psoas hematoma (1.3% [2/156]), and motor neural injury (1.2% [2/166]). CONCLUSIONS: Single-position LLIF in the prone position appears to be a safe surgical approach with a low complication profile. Longer-term follow-up and prospective studies are needed to better characterize the long-term complication rates related to this approach.

Methylated guanosine and uridine modifications in S. cerevisiae mRNAs modulate translation elongation.

Chemical modifications to protein encoding messenger RNAs (mRNAs) influence their localization, translation, and stability within cells. Over 15 different types of mRNA modifications have been observed by sequencing and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) approaches. While LC-MS/MS is arguably the most essential tool available for studying analogous protein post-translational modifications, the high-throughput discovery and quantitative characterization of mRNA modifications by LC-MS/MS has been hampered by the difficulty of obtaining sufficient quantities of pure mRNA and limited sensitivities for modified nucleosides. We have overcome these challenges by improving the mRNA purification and LC-MS/MS pipelines. The methodologies we developed result in no detectable non-coding RNA modifications signals in our purified mRNA samples, quantify 50 ribonucleosides in a single analysis, and provide the lowest limit of detection reported for ribonucleoside modification LC-MS/MS analyses. These advancements enabled the detection and quantification of 13 S. cerevisiae mRNA ribonucleoside modifications and reveal the presence of four new S. cerevisiae mRNA modifications at low to moderate levels (1-methyguanosine, N2-methylguanosine, N2,N2-dimethylguanosine, and 5-methyluridine). We identified four enzymes that incorporate these modifications into S. cerevisiae mRNAs (Trm10, Trm11, Trm1, and Trm2, respectively), though our results suggest that guanosine and uridine nucleobases are also non-enzymatically methylated at low levels. Regardless of whether they are incorporated in a programmed manner or as the result of RNA damage, we reasoned that the ribosome will encounter the modifications that we detect in cells. To evaluate this possibility, we used a reconstituted translation system to investigate the consequences of modifications on translation elongation. Our findings demonstrate that the introduction of 1-methyguanosine, N2-methylguanosine and 5-methyluridine into mRNA codons impedes amino acid addition in a position dependent manner. This work expands the repertoire of nucleoside modifications that the ribosome must decode in S. cerevisiae. Additionally, it highlights the challenge of predicting the effect of discrete modified mRNA sites on translation de novo because individual modifications influence translation differently depending on mRNA sequence context.

Structural basis of a transcription pre-initiation complex on a divergent promoter.

Most eukaryotic promoter regions are divergently transcribed. As the RNA polymerase II pre-initiation complex (PIC) is intrinsically asymmetric and responsible for transcription in a single direction, it is unknown how divergent transcription arises. Here, the Saccharomyces cerevisiae Mediator complexed with a PIC (Med-PIC) was assembled on a divergent promoter and analyzed by cryoelectron microscopy. The structure reveals two distinct Med-PICs forming a dimer through the Mediator tail module, induced by a homodimeric activator protein localized near the dimerization interface. The tail dimer is associated with ∼80-bp upstream DNA, such that two flanking core promoter regions are positioned and oriented in a suitable form for PIC assembly in opposite directions. Also, cryoelectron tomography visualized the progress of the PIC assembly on the two core promoter regions, providing direct evidence for the role of the Med-PIC dimer in divergent transcription.

Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic.

Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) for programmable capture and concentration of specific RNAs from complex mixtures. The target bound TtCsm complex generates two cyclic oligoadenylates (i.e., cA3 and cA4) that allosterically activate ancillary nucleases. We show that both Can1 and Can2 nucleases cleave single-stranded RNA, single-stranded DNA, and double-stranded DNA in the presence of cA4. We integrate the Can2 nuclease with type III-A RNA capture and concentration for direct detection of SARS-CoV-2 RNA in nasopharyngeal swabs with 15 fM sensitivity. Collectively, this work demonstrates how type-III CRISPR-based RNA capture and concentration simultaneously increases sensitivity, limits time to result, lowers cost of the assay, eliminates solvents used for RNA extraction, and reduces sample handling.

Mini-open lateral retropleural thoracic discectomy approach.

The lateral retropleural approach provides an eloquent, mini-open, safe corridor to address various pathologies in the thoracolumbar spine, including herniated thoracic discs. Traditional approaches (e.g., transpedicular, costotransversectomy, or transthoracic) have their own benefits and pitfalls but are generally associated with significant morbidity and often require instrumentation. In this video, the authors highlight the retropleural approach and its nuances, including patient positioning, surgical planning, relevant anatomy, surgical technique, and postoperative care. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2217.

Safe dissection and complication avoidance for L1-2 interbody placement via a lateral access approach.

The lateral access approach for L1-2 interbody placement or other levels at or near the thoracolumbar junction may be difficult without proper knowledge and visualization of anatomy. Specifically, understanding where the fibers of the diaphragm travel and avoiding injury to the diaphragm are paramount. The video can be found here: https://stream.cadmore.media/r10.3171/2022.3.FOCVID2221.

Sequence-specific capture and concentration of viral RNA by type III CRISPR system enhances diagnostic.

Type-III CRISPR-Cas systems have recently been adopted for sequence-specific detection of SARS-CoV-2. Here, we make two major advances that simultaneously limit sample handling and significantly enhance the sensitivity of SARS-CoV-2 RNA detection directly from patient samples. First, we repurpose the type III-A CRISPR complex from Thermus thermophilus (TtCsm) for programmable capture and concentration of specific RNAs from complex mixtures. The target bound TtCsm complex primarily generates two cyclic oligoadenylates (i.e., cA3 and cA4) that allosterically activate ancillary nucleases. To improve sensitivity of the diagnostic, we identify and test several ancillary nucleases (i.e., Can1, Can2, and NucC). We show that Can1 and Can2 are activated by both cA3 and cA4, and that different activators trigger changes in the substrate specificity of these nucleases. Finally, we integrate the type III-A CRISPR RNA-guided capture technique with the Can2 nuclease for 90 fM (5x104 copies/ul) detection of SARS-CoV-2 RNA directly from nasopharyngeal swab samples.

Surgical Technique, Indications, and Outcomes of BIOM-Assisted Transvitreal Biopsy for Uveal Melanoma.

PURPOSE: Controversy exists regarding the best method for biopsy of uveal melanoma. We describe our transvitreal technique and evaluate the safety of this technique as well as the efficacy for obtaining sample for prognostic genetic profiling. METHODS: Description of surgical technique and retrospective case series. Medical records for uveal melanoma patients who underwent transvitreal biopsy using our described technique were analyzed for tumor size, location, primary treatment, method of biopsy, and any complications thereof. Characteristics of tumors that underwent transvitreal biopsy were noted including tumor size, location, or presence of subretinal fluid, to see whether these affected surgeon preference for biopsy modality. A cohort of contemporaneous uveal melanoma patients who underwent biopsy through a transscleral technique served as a comparator group for these patient, tumor, and complication factors. RESULTS: A total of 27 patients aged 27.2 to 88.6 years (mean 64.8) underwent transvitreal biopsy using our described technique between 2013 and 2016. There were 15 small, 10 medium, and 2 large tumors at diagnosis with the majority (n = 17) posterior to the equator. Intraoperative complications included a clot or small trickle of blood at the biopsy site in 20 (74.1%) of patients, small localized subretinal hemorrhage in 8 (29.6%), small vitreous hemorrhage in 4 (14.8%), and small transient choroidal detachments in 1 patient (3.6%). When subretinal hemorrhage occurred, it was almost always into a pre-existing pocket of subretinal fluid ( P = 0.0093). However, the presence of subretinal fluid was not associated with the decision to proceed with any biopsy ( P = 0.36) or transvitreal biopsy specifically ( P = 1.00). By 3 months, subretinal and/or vitreous hemorrhage resolved in essentially all cases. There were no cases of iatrogenic retinal detachment or extraocular tumor spread over a mean follow-up of 41.7 (range: 20-62.1) months. Adequate tissue for gene expression profiling was obtained from each biopsy. The comparator group of patients undergoing transscleral biopsy including 21 uveal melanomas in 20 patients (one eye had two melanomas). Transvitreal biopsies were more common in patients with small (n = 15; P < 0.0001), posterior (n = 17; P < 0.0001) tumors, compared with patients who underwent transscleral biopsy during the same period. CONCLUSION: This technique can be used for small or posterior tumors or for small anterior tumors where a transscleral approach would risk tumor perforation. Complications were minor, transient, and self-limited. Biopsy yields for molecular prognosis were adequate in all cases. The presence of subretinal fluid may be considered a relative contraindication because it may lead to subretinal hemorrhage in the fluid pocket but did not dissuade us from using this transvitreal technique for patients who would benefit from it.