Preference Sensitive Care and Shared Decision-Making in Lumbar Spinal Stenosis: A Scoping Review.

STUDY DESIGN: Scoping review. OBJECTIVE: The objective of this study was to conduct a scoping review exploring the extent to which preference sensitivity has been studied in treatment decisions for lumbar spinal stenosis (LSS), utilizing shared decision-making (SDM) as a proxy. BACKGROUND: Preference-sensitive care involves situations where multiple treatment options exist with significant tradeoffs in cost, outcome, recovery time, and quality of life. LSS has gained research focus as a preference-sensitive care scenario. MATERIALS AND METHODS: A scoping review protocol in accordance with "Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews" regulations was registered with the Open Science Framework (ID: 9ewup) and conducted across multiple databases from January 2000 to October 2022. Study selection and characterization were performed by 3 independent reviewers and an unbiased moderator. RESULTS: The search resulted in the inclusion of 16 studies varying in design and sample size, with most published between 2016 and 2021. The studies examined variables related to SDM, patient preferences, surgeon preferences, and decision aids (DAs). The outcomes assessed included treatment choice, patient satisfaction, and patient understanding. Several studies reported that SDM influenced treatment choice and patient satisfaction, while the impact on patient understanding was less clear. DAs were used in some studies to facilitate SDM. CONCLUSION: The scoping review identified a gap in comprehensive studies analyzing the preference sensitivity of treatment for LSS and the role of DAs. Further research is needed to better understand the impact of patient preferences on treatment decisions and the effectiveness of DAs in LSS care. This review provides a foundation for future research in preference-sensitive care and SDM in the context of lumbar stenosis treatment.

Underrepresentation of Non-White Participants in the American Academy of Orthopaedic Surgeons Guidelines for Surgical Management of Knee Osteoarthritis.

BACKGROUND: The aim of this study was to examine the racial and ethnic representation in studies included in the 2015 American Academy of Orthopaedic Surgeons Surgical Management of the Knee Evidence-Based Clinical Practice Guideline relative to their representation of the United States (US). METHODS: The demographic characteristics reported in articles included in the 2015 American Academy of Orthopaedic Surgeons Surgical Management of the Knee Evidence-Based Clinical Practice Guideline were analyzed. The primary outcome of interest was the representation quotient, which is the ratio of the proportion of a racial/ethnic group in the guideline studies relative to their proportion in the US. There were 211 studies included, of which 15 (7%) reported race. There were 35 studies based in the US and 7 of the US-based studies reported race. RESULTS: No US-based studies reported race and ethnicity separately, no studies reported American Indian/Alaska Native participants and no US-based studies reported Asian participants. The representation quotient of US-based studies was 0.66 for Black participants, 0.33 for Hispanic participants, and 1.30 for White participants, which indicates a relative over-representation of White participants compared to national proportions. CONCLUSION: This study illustrated that the evidence base for the surgical management of knee osteoarthritis has been constructed from studies which fail to consider race and ethnicity. Of those US-based studies which do report race or ethnicity, study cohorts do not reflect the US population. These results illustrate a disparity in clinical orthopedic surgical evidence and highlight the need for improved research recruitment strategies.

Assessing the Accuracy of Otomatch.com Data for Individuals Applying to Otolaryngology Residency.

OBJECTIVES: Otomatch.com is an online forum for residency applicants to discuss the otolaryngology match process including academic metrics. The purpose of this study is to assess the accuracy of self-reported match data on Otomatch relative to official data reported by the National Residency Match Program (NRMP) and the Association of American Medical Colleges (AAMC). METHODS: Data was collected from publicly editable Otomatch forums (2017-2018, 2018-2019, 2019-2020) and curated Otomatch survey responses (2018-2019, 2019-2020) whose results are released after Match Day. Aggregated data was collected from the NRMP 2018 and 2020 Charting Outcomes in the Match and AAMC Report on Residents (2017-2018, 2018-2019). Measures of interest included Step 1 scores, Step 2 CK scores, publications, number of interview invitations, number of interviews attended, and AOA status. ANOVA and 2 tailed T tests were performed to compare variables within each match year. RESULTS: Average Step 2 CK score was significantly higher on publicly editable Otomatch forums than AAMC in 2017-2018 (257vs 253, P < .05) and 2018-2019 (258vs 252, P < .05). Interviews attended were significantly higher on Otomatch survey responses than the publicly editable forum in 2019-2020 (13vs 9, P-value < .05). Step 1 scores, interview invitations, and AOA status were not statistically significantly different when data was available. CONCLUSION: Applicant statistics from online forums, online surveys, NRMP, and AAMC are consistent, except for Step 2 CK scores. Self-reported data on the Otomatch forum is an accurate estimate of academic metrics of otolaryngology residency applicants.

Using Machine Learning and Deep Learning Algorithms to Predict Postoperative Outcomes Following Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: A retrospective cohort study from a multisite academic medical center. OBJECTIVE: To construct, evaluate, and interpret a series of machine learning models to predict outcomes related to inpatient health care resource utilization for patients undergoing anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Reducing postoperative health care utilization is an important goal for improving the delivery of surgical care and serves as a metric for quality assessment. Recent data has shown marked hospital resource utilization after ACDF surgery, including readmissions, and ED visits. The burden of postoperative health care use presents a potential application of machine learning techniques, which may be capable of accurately identifying at-risk patients using patient-specific predictors. METHODS: Patients 18-88 years old who underwent ACDF from 2011 to 2021 at a multisite academic center and had preoperative lab values within 3 months of surgery were included. Outcomes analyzed included 90-day readmissions, postoperative length of stay, and nonhome discharge. Four machine learning models-Extreme Gradient Boosted Trees, Balanced Random Forest, Elastic-Net Penalized Logistic Regression, and a Neural Network-were trained and evaluated through the Area Under the Curve estimates. Feature importance scores were computed for the highest-performing model per outcome through model-specific metrics. RESULTS: A total of 1026 cases were included in the analysis cohort. All machine learning models were predictive for outcomes of interest, with the Random Forest algorithm consistently demonstrating the strongest average area under the curve performance, with a peak performance of 0.84 for nonhome discharge. Important features varied per outcome, though age, body mass index, American Society of Anesthesiologists classification >2, and medical comorbidities were highly weighted in the studied outcomes. CONCLUSIONS: Machine learning models were successfully applied and predictive of postoperative health utilization after ACDF. Deployment of these tools can assist clinicians in determining high-risk patients. LEVEL OF EVIDENCE: III.

Impact of Social Determinants of Health in Spine Surgery.

PURPOSE OF REVIEW: Social determinants of health (SDH) are factors that affect patient health outcomes outside the hospital. SDH are "conditions in the environments where people are born, live, learn, work, play, worship, and age that affect a wide range of health, functioning, and quality-of-life outcomes and risks." Current literature has shown SDH affecting patient reported outcomes in various specialties; however, there is a dearth in research relating spine surgery with SDH. The aim of this review article is to identify connections between SDH and post-operative outcomes in spine surgery. These are important, yet understudied predictors that can impact health outcomes and affect health equity. RECENT FINDINGS: Few studies have shown associations between SDH pillars (environment, race, healthcare, economic, and education) and spine surgery outcomes. The most notable relationships demonstrate increased disability, return to work time, and pain with lower income, education, environmental locations, healthcare status and/or provider. Despite these findings, there remains a significant lack of understanding between SDH and spine surgery. Our manuscript reviews the available literature comparing SDH with various spine conditions and surgeries. We organized our findings into the following narrative themes: 1) education, 2) geography, 3) race, 4) healthcare access, and 5) economics.

Human Astrocytes Exhibit Tumor Microenvironment-, Age-, and Sex-Related Transcriptomic Signatures.

Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurologic diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peritumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurologic disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. These data provide powerful new insights into human astrocyte biology in several biologically relevant states that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENT Astrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurologic diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.

Safety of focused ultrasound neuromodulation in humans with temporal lobe epilepsy.

OBJECTIVE: Transcranial Focused Ultrasound (tFUS) is a promising new potential neuromodulation tool. However, the safety of tFUS neuromodulation has not yet been assessed adequately. Patients with refractory temporal lobe epilepsy electing to undergo an anterior temporal lobe resection present a unique opportunity to evaluate the safety and efficacy of tFUS neuromodulation. Histological changes in tissue after tFUS can be examined after surgical resection, while further potential safety concerns can be assessed using neuropsychological testing. METHODS: Neuropsychological functions were assessed in eight patients before and after focused ultrasound sonication of the temporal lobe at intensities up to 5760 mW/cm2. Using the BrainSonix Pulsar 1002, tFUS was delivered under MR guidance, using the Siemens Magnetom 3T Prisma scanner. Neuropsychological changes were assessed using various batteries. Histological changes were assessed using hematoxylin and eosin staining, among others. RESULTS: With respect to safety, the histological analysis did not reveal any detectable damage to the tissue, except for one subject for whom the histology findings were inconclusive. In addition, neuropsychological testing did not show any statistically significant changes in any test, except for a slight decrease in performance on one of the tests after tFUS. SIGNIFICANCE: This study supports the hypothesis that low-intensity Transcranial Focused Ultrasound (tFUS) used for neuromodulation of brain circuits at intensities up to 5760 mW/cm2 may be safe for use in human research. However, due to methodological limitations in this study and inconclusive findings, more work is warranted to establish the safety. Future directions include greater number of sonications as well as longer exposure at higher intensity levels to further assess the safety of tFUS for modulation of neuronal circuits.

Clonally Focused Public and Private T Cells in Resected Brain Tissue From Surgeries to Treat Children With Intractable Seizures.

Using a targeted transcriptomics approach, we have analyzed resected brain tissue from a cohort of 53 pediatric epilepsy surgery cases, and have found that there is a spectrum of involvement of both the innate and adaptive immune systems as evidenced by the differential expression of immune-specific genes in the affected brain tissue. The specimens with the highest expression of immune-specific genes were from two Rasmussen encephalitis cases, which is known to be a neuro-immunological disease, but also from tuberous sclerosis complex (TSC), focal cortical dysplasia, and hemimegalencephaly surgery cases. We obtained T cell receptor (TCR) Vß chain sequence data from brain tissue and blood from patients with the highest levels of T cell transcripts. The clonality indices and the frequency of the top 50 Vß clonotypes indicated that T cells in the brain were clonally restricted. The top 50 Vß clonotypes comprised both public and private (patient specific) clonotypes, and the TCR Vß chain third complementarity region (CDR3) of the most abundant public Vß clonotype in each brain sample was strikingly similar to a CDR3 that recognizes an immunodominant epitope in either human cytomegalovirus or Epstein Barr virus, or influenza virus A. We found that the frequency of 14 of the top 50 brain Vß clonotypes from a TSC surgery case had significantly increased in brain tissue removed to control recurrent seizures 11 months after the first surgery. Conversely, we found that the frequency in the blood of 18 of the top 50 brain clonotypes from a second TSC patient, who was seizure free, had significantly decreased 5 months after surgery indicating that T cell clones found in the brain had contracted in the periphery after removal of the brain area associated with seizure activity and inflammation. However, the frequency of a public and a private clonotype significantly increased in the brain after seizures recurred and the patient underwent a second surgery. Combined single cell gene expression and TCR sequencing of brain-infiltrating leukocytes from the second surgery showed that the two clones were CD8 effector T cells, indicating that they are likely to be pathologically relevant.

Novel tonometer device distinguishes brain stiffness in epilepsy surgery.

Complete surgical resection of abnormal brain tissue is the most important predictor of seizure freedom following surgery for cortical dysplasia. While lesional tissue is often visually indiscernible from normal brain, anecdotally, it is subjectively stiffer. We report the first experience of the use of a digital tonometer to understand the biomechanical properties of epilepsy tissue and to guide the conduct of epilepsy surgery. Consecutive epilepsy surgery patients (n = 24) from UCLA Mattel Children's Hospital were recruited to undergo intraoperative brain tonometry at the time of open craniotomy for epilepsy surgery. Brain stiffness measurements were corrected with abnormalities on neuroimaging and histopathology using mixed-effects multivariable linear regression. We collected 249 measurements across 30 operations involving 24 patients through the pediatric epilepsy surgery program at UCLA Mattel Children's Hospital. On multivariable mixed-effects regression, brain stiffness was significantly associated with the presence of MRI lesion (ß = 32.3, 95%CI 16.3-48.2; p < 0.001), severity of cortical disorganization (ß = 19.8, 95%CI 9.4-30.2; p = 0.001), and recent subdural grid implantation (ß = 42.8, 95%CI 11.8-73.8; p = 0.009). Brain tonometry offers the potential of real-time intraoperative feedback to identify abnormal brain tissue with millimeter spatial resolution. We present the first experience with this novel intraoperative tool for the conduct of epilepsy surgery. A carefully designed prospective study is required to elucidate whether the clinical application of brain tonometry during resective procedures could guide the area of resection and improve seizure outcomes.

Evidence for Innate and Adaptive Immune Responses in a Cohort of Intractable Pediatric Epilepsy Surgery Patients.

Brain-infiltrating lymphocytes (BILs) were isolated from resected brain tissue from 10 pediatric epilepsy patients who had undergone surgery for Hemimegalencephaly (HME) (n = 1), Tuberous sclerosis complex (TSC) (n = 2), Focal cortical dysplasia (FCD) (n = 4), and Rasmussen encephalitis (RE) (n = 3). Peripheral blood mononuclear cells (PBMCs) were also isolated from blood collected at the time of the surgery. Cells were immunostained with a panel of 20 antibody markers, and analyzed by mass cytometry. To identify and quantify the immune cell types in the samples, an unbiased clustering method was applied to the entire data set. More than 85 percent of the CD45+ cells isolated from resected RE brain tissue comprised T cells; by contrast NK cells and myeloid cells constituted 80-95 percent of the CD45+ cells isolated from the TSC and the FCD brain specimens. Three populations of myeloid cells made up >50 percent of all of the myeloid cells in all of the samples of which a population of HLA-DR+ CD11b+ CD4- cells comprised the vast majority of myeloid cells in the BIL fractions from the FCD and TSC cases. CD45RA+ HLA-DR- CD11b+ CD16+ NK cells constituted the major population of NK cells in the blood from all of the cases. This subset also comprised the majority of NK cells in BILs from the resected RE and HME brain tissue, whereas NK cells defined as CD45RA- HLA-DR+ CD11b- CD16- cells comprised 86-96 percent of the NK cells isolated from the FCD and TSC brain tissue. Thirteen different subsets of CD4 and CD8 αß T cells and γδ T cells accounted for over 80% of the CD3+ T cells in all of the BIL and PBMC samples. At least 90 percent of the T cells in the RE BILs, 80 percent of the T cells in the HME BILs and 40-66 percent in the TSC and FCD BILs comprised activated antigen-experienced (CD45RO+ HLA-DR+ CD69+) T cells. We conclude that even in cases where there is no evidence for an infection or an immune disorder, activated peripheral immune cells may be present in epileptogenic areas of the brain, possibly in response to seizure-driven brain inflammation.

Multifactorial Optimizations for Directing Endothelial Fate from Stem Cells.

Embryonic stem cells (ESC) and induced pluripotent stem (iPS) cells are attractive in vitro models of vascular development, therapeutic angiogenesis, and tissue engineering. However, distinct ESC and iPS cell lines respond differentially to the same microenvironmental factors. Developing improved/optimized differentiation methodologies tailored/applicable in a number of distinct iPS and ESC lines remains a challenge in the field. Currently published methods for deriving endothelial cells (EC) robustly generate high numbers of endothlelial progenitor cells (EPC) within a week, but their maturation to definitive EC is much more difficult, taking up to 2 months and requiring additional purification. Therefore, we set out to examine combinations/levels of putative EC induction factors-utilizing our stage-specific chemically-defined derivation methodology in 4 ESC lines including: kinetics, cell seeding density, matrix signaling, as well as medium treatment with vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). The results indicate that temporal development in both early and late stages is the most significant factor generating the desired cells. The generation of early Flk-1+/KDR+ vascular progenitor cells (VPC) from pluripotent ESC is directed predominantly by high cell seeding density and matrix signaling from fibronectin, while VEGF supplementation was NOT statistically significant in more than one cell line, especially with fibronectin matrix which sequesters autocrine VEGF production by the differentiating stem cells. Although some groups have shown that the GSK3-kinase inhibitor (CHIR) can facilitate EPC fate, it hindered the generation of KDR+ cells in our preoptimized medium formulations. The methods summarized here significantly increased the production of mature vascular endothelial (VE)-cadherin+ EC, with up to 93% and 57% purity from mouse and human ESC, respectively, before VE-cadherin+ EC purification.

Primary Aspergillosis of the Larynx.

Laryngeal aspergillosis is most commonly seen as a result of secondary invasion from the lungs and tracheobronchial tree in immunocompromised hosts. Primary aspergillosis of the larynx is, however, rare with few cases documented over the past fifty years. We report a case of a 73-year-old woman who presented with persistent hoarseness. She is a nonsmoker with a history of asthma and chronic bronchiectasis treated with bronchodilators, inhaled and oral corticosteroids, and nebulized tobramycin. Direct laryngoscopy with vocal cord stripping confirmed the diagnosis of invasive aspergillosis with no manifestations elsewhere. The patient was successfully treated with oral voriconazole with no signs of recurrence. Although several major risk factors contributing to the development of primary aspergillosis of the larynx have been discussed in the literature, there has been no mention of inhaled antibiotics causing this rare presentation to the best of our knowledge. We, therefore, highlight the use of inhaled tobramycin as a unique catalyst leading to the rapid onset of this rare presentation.

Creation of a 3D printed temporal bone model from clinical CT data.

PURPOSE: Generate and describe the process of creating a 3D printed, rapid prototype temporal bone model from clinical quality CT images. MATERIALS AND METHODS: We describe a technique to create an accurate, alterable, and reproducible rapid prototype temporal bone model using freely available software to segment clinical CT data and generate three different 3D models composed of ABS plastic. Each model was evaluated based on the appearance and size of anatomical structures and response to surgical drilling. RESULTS: Mastoid air cells had retained scaffolding material in the initial versions. This required modifying the model to allow drainage of the scaffolding material. External auditory canal dimensions were similar to those measured from the clinical data. Malleus, incus, oval window, round window, promontory, horizontal semicircular canal, and mastoid segment of the facial nerve canal were identified in all models. The stapes was only partially formed in two models and absent in the third. Qualitative feel of the ABS plastic was softer than bone. The pate produced by drilling was similar to bone dust when appropriate irrigation was used. CONCLUSION: We present a rapid prototype temporal bone model made based on clinical CT data using 3D printing technology. The model can be made quickly and inexpensively enough to have potential applications for educational training.

Analysis of an online match discussion board: improving the otolaryngology-head and neck surgery match.

OBJECTIVE: "The Match" has become the accepted selection process for graduate medical education. Otomatch.com has provided an online forum for Otolaryngology-Head and Neck Surgery (OHNS) Match-related questions for over a decade. Herein, we aim to delineate the type of posts on Otomatch to better understand the perspective of medical students applying for OHNS residency. STUDY DESIGN: Retrospective review of an OHNS Match-related online forum. SUBJECTS AND METHODS: Subjects were contributors to an OHNS Match-related online forum. Posts on Otomatch between December 2001 and April 2014 were reviewed. The title of each thread and number of views were recorded for quantitative analysis. Each thread was organized into 1 of 6 major categories and 1 of 18 subcategories. National Resident Matching Program (NRMP) data were utilized for comparison. RESULTS: We identified 1921 threads corresponding to over 2 million page views. Over 40% of threads were related to questions about specific programs, and 27% were discussions about interviews. Views, a surrogate measure for popularity, reflected different trends. The majority of individuals viewed posts on interviews (42%), program-specific questions (20%), and how to rank programs (11%). There was an increase in viewership tracked with a rise in applicant numbers based on NRMP data. CONCLUSION: Our study provides an in-depth analysis of a popular discussion forum for medical students interested in the OHNS Match process. The most viewed posts are about interview dates and questions regarding specific programs. We provide suggestions to address unmet needs for medical students and potentially improve the Match process.

High-resolution computed tomography analysis of the medial infratemporal fossa: a pilot study.

BACKGROUND: The medial aspect of the infratemporal fossa (ITF) can be accessed endoscopically. Two important landmarks to help guide dissection in this area have previously been identified: the anterior border of the foramen ovale (AFO) and the "bony bridge" (BB), a consistent bridge of bone between the foramen ovale and spinosum. We conducted a pilot study using high-resolution computed tomography (HRCT) to measure the distances to these structures. METHODS: Thirty measurements were acquired from 15 adult patients undergoing HRCT scans of the sinuses. The position of the anterior nasal spine (ANS), AFO, and BB on the 3 orthogonal planes were identified by 3 observers. Euclidian distances between each of these structures were calculated. A cadaveric dissection was performed and images were acquired to provide an endoscopic view. RESULTS: Fifteen HRCT scans of the sinuses (8 females) were analyzed. The mean distances from the ANS to the AFO and BB were 78.5 ± 5.9 mm and 83.2 ± 6.0 mm, respectively. For males alone, these distances were 80.3 ± 4.3 mm and 85.3 ± 4.8 mm, respectively, and in females 77.0 ± 6.5 mm and 81.4 ± 6.7 mm, respectively. CONCLUSION: Average distance from the ANS to the AFO and BB was 78.5 mm and 83.2 mm, respectively. These measurements can be used by endoscopic skull base surgeons to guide dissection in the ITF.

Synthesis and biological activity of 2-aminoimidazole triazoles accessed by Suzuki-Miyaura cross-coupling.

A pilot library of 2-aminoimidazole triazoles (2-AITs) was synthesized and assayed against Acinetobacter baumannii and methicillin-resistant Staphylococus aureus (MRSA). Results from these studies show that these new derivatives have improved biofilm dispersal activities as well as antibacterial properties against A. baumannii. With MRSA biofilms they are found to possess biofilm inhibition capabilities at low micromolar concentrations.

Reprogramming bacteria to seek and destroy an herbicide.

A major goal of synthetic biology is to reprogram cells to perform complex tasks. Here we show how a combination of in vitro and in vivo selection rapidly identifies a synthetic riboswitch that activates protein translation in response to the herbicide atrazine. We further demonstrate that this riboswitch can reprogram bacteria to migrate in the presence of atrazine. Finally, we show that incorporating a gene from an atrazine catabolic pathway allows these cells to seek and destroy atrazine.

The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumannii.

Multidrug-resistant bacterial infections continue to be a rising global health concern. Herein is described the development of a class of novel 2-aminobenzimidazoles with antibiotic activity. These active 2-aminobenzimidazoles retain their antibiotic activity against several strains of multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii when compared to susceptible strains.