Exosomes derived from tumor adjacent fibroblasts efficiently target pancreatic tumors.

The application of extracellular vesicles, particularly exosomes (EXs), is rapidly expanding in the field of medicine, owing to their remarkable properties as natural carriers of biological cargo. This study investigates utilization of exosomes derived from stromal cells of tumor adjacent normal tissues (NAF-EXs) for personalized medicine, which can be derived at the time of diagnosis by endoscopic ultrasound. Herein, we show that exosomes (EXs) derived from NAFs demonstrate differential bio-physical characteristics, efficient cellular internalization, drug loading efficiency, pancreatic tumor targeting and delivery of payloads. NAF-derived EXs (NAF-EXs) were used for loading ormeloxifene (ORM), a potent anti-cancer and desmoplasia inhibitor as a model drug. We found that ORM maintains normal fibroblast cell phenotype and renders them incompatible to be triggered for a CAF-like phenotype, which may be due to regulation of Ca2+ influx in fibroblast cells. NAF-EXs-ORM effectively blocked oncogenic signaling pathways involved in desmoplasia and epithelial mesenchymal transition (EMT) and repressed tumor growth in xenograft mouse model. In conclusion, our data suggests preferential tropism of NAF-EXs for PDAC tumors, thus imply feasibility of developing a novel personalized medicine for PDAC patients using autologous NAF-EXs for improved therapeutic outcome of anti-cancer drugs. Additionally, it provides the opportunity of utilizing this biological scaffold for effective therapeutics in combination with standard therapeutic regimen.

Do Patients Accurately Recall Pain Levels Following Sacroiliac Joint Steroid Injection? A Cohort Study of Recall Bias in Patient-reported Outcomes.

BACKGROUND: Sacroiliac joint (SIJ) injections are crucial in the diagnostic toolkit for evaluating SIJ pathology. Recall bias is an important component in patient-reported outcomes that has not been well studied in SIJ injection. OBJECTIVE: The purpose of this study was to characterize the accuracy, direction, and magnitude of pain level recall bias following SIJ steroid injection and study the factors that affect patient recollection. STUDY DESIGN: Prospective cohort study. SETTING: Level 1 academic medical center. METHODS: Using standardized questionnaires, baseline Numeric Rating Scale (NRS-11) scores were recorded for patients undergoing SIJ steroid injections at preinjection, at 4 hours postinjection, and at 24 hours postinjection. At a minimum of 2 weeks postinjection, patients were asked to recall their preinjection, 4-hour, and 24-hour postinjection NRS-11 scores. Actual and recalled NRS-11 scores were compared using paired t tests for each time interval. Multivariable linear regression was used to identify factors that correlated with consistent recall. RESULTS: Sixty patients with a mean age of 66 years (65% women) were included. Compared to their preinjection pain score, patients showed considerable improvement at both 4 hours (mean difference [MD] = 3.28; 95% CI, 2.68 - 3.89), and 24 hours (MD = 3.23; 95% CI, 2.44 - 4.03) postinjection. Patient recollection of preinjection symptoms was more severe than actual (MD = 0.65; 95% CI, 0.31 - 0.99). Patient recollection of symptoms was also more severe than actual at 4 hours (MD = 0.50; 95% CI .04 - 1.04) as well as at 24 hours postinjection (MD = 0.80; 95% CI, 0.16 - 1.44). The magnitude of recall bias was mild and did not exceed the minimal clinically important difference. There was a moderate correlation between actual and recalled pain levels when comparing preinjection with the 4-hour postinjection NRS-11 score (correlation coefficient [r] =0.64; P < 0.001) and moderate correlation when comparing preinjection with the 24-hour postinjection NRS-11 score (r = 0.62; P < 0.001). Linear regression models showed that at preinjection, patients with a lower body mass index and the presence of coexisting psychiatric diagnoses were better at recalling their pain (P < 0.05). Patients with a higher body mass index also experienced less pain relief when comparing preinjection with the 4-hour postinjection NRS-11 score (P < 0.05). LIMITATIONS: Recall pain scores were obtained via telephone surveys, which can lead to interview bias. One patient died, and 3 were lost to follow-up. We did not control for patient use of adjunctive pain relief modalities, which may modulate the overall response to injection. SIJ injections can also be diagnostic, so some patients may not have shared the same indication for injection or pain-generating diagnosis. CONCLUSIONS: Patients had favorable pain level responses to their SIJ steroid injection for both actual and recall surveys. Although patients demonstrated poor recall of absolute pain scores at preinjection, 4-hour postinjection, and 24-hour postinjection, they demonstrated robust recall of their net pain score improvement at both 4- and 24-hours postinjection. These findings suggest that there is utility in using patient recollection to describe the magnitude of pain relief following treatment for sacroiliac joint dysfunction.

Intraoperative and Postoperative Management of Incidental Durotomies During Open Degenerative Lumbar Spine Surgery: A Systematic Review.

SUMMARY OF BACKGROUND DATA: Incidental durotomy is a common intraoperative complication of lumbar spine surgery. Intra and postoperative protocols in the management of this common complication vary considerably, with no consensus in the literature. OBJECTIVE: To systematically review (1) lumbar dural repair techniques for open degenerative procedures; (2) review described postoperative protocols after lumbar dural repairs. STUDY DESIGN: Systematic review. MATERIALS AND METHODS: A systematic review of the literature was performed for all articles published from inception until September 2022 using Pubmed, EMBASE, Medline, and Cochrane databases to identify articles assessing the management of durotomy in open surgery for degenerative diseases of the lumbar spine. Two independent reviewers assessed the articles for inclusion criteria, and disagreements were resolved by consensus. Outcomes included persistent leaks, return to the operating room, recurrent symptoms, medical complications, or patient satisfaction. RESULTS: A total of 10,227 articles were initially screened. After inclusion criteria were applied, 9 studies were included (n=1270 patients) for final review. Repair techniques included; no primary repair, suture repair in running or interrupted manner with or without adjunctive sealants, sealants alone, or patch repair with muscle, fat, epidural blood patch, or synthetic graft. Postoperative protocols included the placement of a subfascial drain with varying durations of bed rest. Notable findings included no benefit of prolonged bedrest compared with early ambulation ( P =0.4), reduced cerebrospinal fluid leakage with fat graft compared with muscle grafts ( P <0.001), and decreased rates of revision surgery in studies that used subfascial drains (1.7%-2.2% vs 4.34%-6.66%). CONCLUSIONS: Significant variability in intraoperative durotomy repair techniques and postoperative protocols exists. Primary repair with fat graft augmentation seems to have the highest success rate. Postoperatively, the use of a subfascial drain with early ambulation reduces the risk of pseudomenignocele formation, medical complications, and return to the operating room. Further research should focus on prospective studies with the goal to standardize repair techniques and postoperative protocols.

MUC13 drives cancer aggressiveness and metastasis through the YAP1-dependent pathway.

Anchorage-independent survival after intravasation of cancer cells from the primary tumor site represents a critical step in metastasis. Here, we reveal new insights into how MUC13-mediated anoikis resistance, coupled with survival of colorectal tumor cells, leads to distant metastasis. We found that MUC13 targets a potent transcriptional coactivator, YAP1, and drives its nuclear translocation via forming a novel survival complex, which in turn augments the levels of pro-survival and metastasis-associated genes. High expression of MUC13 is correlated well with extensive macrometastasis of colon cancer cells with elevated nuclear YAP1 in physiologically relevant whole animal model systems. Interestingly, a positive correlation of MUC13 and YAP1 expression was observed in human colorectal cancer tissues. In brief, the results presented here broaden the significance of MCU13 in cancer metastasis via targeting YAP1 for the first time and provide new avenues for developing novel strategies for targeting cancer metastasis.

Patient satisfaction with follow-up after spinal fusion.

Background: Postoperative follow-up visits (PFUs) allow providers to track patient recovery but can be costly to patients. With the advent of the novel coronavirus pandemic, virtual/phone visits have been utilized as an alternative to in-person PFUs. Patients were surveyed to elucidate patient satisfaction with postoperative care in the setting of increased virtual follow-up visits. A prospective survey with retrospective cohort analysis of chart data was conducted to better understand the factors influencing patient satisfaction related to their PFUs after spine fusion with the goal of improving the value of postoperative care. Methods: Adult patients at least 1 year postoperative from cervical or lumbar fusion surgery completed a telephone survey related to their postoperative clinic experience. Medical record data including complications, number of visits and length of follow-up, and presence of phone/virtual visits were abstracted and analyzed. Results: Fifty patients (54% female) were included. Univariate analysis demonstrated no association between satisfaction and patient demographics, rates of complication, mean length or number of PFUs, or incidence of phone/virtual visits. Patients "very satisfied" with their clinic experience were more likely to be "very satisfied" with their outcome (P<0.01), and to feel their concerns were "very well addressed" (P<0.01). Multivariate analysis additionally demonstrated that satisfaction was positively associated with how well patient concerns were addressed (P<0.01) and the incidence of virtual/phone visits (P=0.01), and negatively associated with age (P=0.01) and level of education (P=0.01). Conclusions: After spinal fusion, patient satisfaction is positively related to virtual/phone visits and to how well their concerns are addressed. As long as patient concerns remain adequately addressed, surgeons can eliminate excess PFUs which are not clinically beneficial without adversely impacting patients' postoperative experience.

Short- and Long-Term Effects of Chlorpyrifos on Thyroid Hormone Axis and Brain Development in Xenopus laevis.

INTRODUCTION: The extensive use of the insecticide chlorpyrifos (CPF) throughout the world has brought increased scrutiny on its environmental and health impact. CPF is a cholinergic neurotoxicant; however, exposure to low noncholinergic doses is associated with numerous neurodevelopmental effects in animal models. In this study, we aimed to assess CPF for its potential to disrupt thyroid hormone signalling and investigate the short- and long-term effects on neurodevelopment by using Xenopus laevis. METHODS: The thyroid hormone (TH) disrupting potential of CPF was assessed using TH-sensitive transgenic Tg(thibz:eGFP) tadpoles. The consequences of early embryonic exposure were examined by exposing fertilized eggs for 72 h to environmentally relevant CPF concentrations (10-10 M and 10-8 M). Three endpoints were evaluated: (1) gene expression in whole embryonic brains immediately after exposure, (2) mobility and brain morphology 1 week after exposure, and (3) brain morphology and axon diameters at the end of metamorphosis (2 months after the exposure). RESULTS: CPF disrupted TH signalling in Tg(thibz:eGFP) tadpoles. The expression of genes klf9, cntn4, oatp1c1, and tubb2b was downregulated in response to CPF. Tadpoles exposed to CPF exhibited increased mobility and altered brain morphology compared to control tadpoles. Early embryonic exposure of CPF affected myelinated axon diameter, with exposed animals exhibiting shifted frequency distributions of myelinated axons diameters towards smaller diameters in the hindbrain of froglets. DISCUSSION/CONCLUSION: This study provides more evidence of the endocrine and neurodevelopment disrupting activity of CPF. Further experimental and epidemiological studies are warranted to determine the long-term consequences of early CPF exposure on brain development.

Reprogramming of pancreatic adenocarcinoma immunosurveillance by a microbial probiotic siderophore.

There is increasing evidence suggesting the role of microbiome alterations in relation to pancreatic adenocarcinoma and tumor immune functionality. However, molecular mechanisms of the interplay between microbiome signatures and/or their metabolites in pancreatic tumor immunosurveillance are not well understood. We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms tumor-associated macrophages (TAMs) and increases CD8 + T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages. This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve immune checkpoint inhibitors therapy response in pancreatic cancer.

Do Patients Accurately Recall Their Pain Levels Following Epidural Steroid Injection? A Cohort Study of Recall Bias in Patient-Reported Outcomes.

BACKGROUND: Although patient-reported outcomes (PROs) have become important in the evaluation of spine surgery patients, the accuracy of patient recall of pre- or post-intervention  symptoms following epidural steroid injection remains unknown. OBJECTIVES: The purpose of this study was to: 1) characterize the accuracy of patient recollection of back/leg pain following epidural steroid injection; 2) characterize the direction and magnitude of recall bias; and 3) characterize factors that impact patient recollection. STUDY DESIGN: A prospective cohort study. SETTING: Level 1 Academic Medical Center. METHODS: Using standardized questionnaires, we recorded numeric pain scores for patients undergoing lumbar epidural steroid injections at our institution. Baseline pain scores were obtained prior to injection, 4-hours and 24-hours postinjection. At a minimum of 2 weeks following the injection, patients were asked to recall their symptoms preinjection and at 4 hours and 24-hours postinjection. Actual and recalled scores, at each time point, were compared using paired t tests. Multivariable linear regression was used to identify factors that impacted recollection. RESULTS: Sixty-one patients with a mean age of 61.4 years (56% women) were included. Compared to their preinjection pain score, patients showed considerable improvement at both 4 hours (Mean Difference [MD] = 2.18, 95% Confidence Interval [CI] 1.42 to 2.94) and 24 hours (MD = 2.64, 95% CI 1.91 to 3.34) postinjection. Patient recollection of preinjection symptoms was significantly more severe than actual at the 2-week time point (MD = 1.39, 95% CI 4.82 to 6.08). The magnitude of recall bias was mild and exceeded the minimal clinically important difference (MCID). No significant recall bias was noted on patient recollection of postinjection symptoms at 4 hours (MD = 0.41, 95% CI -1.05 to 0.23). Patient recollection of symptoms was also significantly more severe than actual at 24 hours (MD = 0.63, 95% CI -1.17 to -0.07), mild magnitude of bias that did not exceed MCID. Linear regression models for differences between actual and recalled pain scores reveal that for recall at 4 hours postinjection, older patients were better at recalling pain. LIMITATIONS: Baseline pain scores were completed in person, in front of a provider. The short-term pain scores were completed while at home, and then recalled scores were obtained by phone call encounter. Telephone surveys can lead to interview bias. All patients received incentive for completion of study. It is unclear if patient incentives have any impact on patient recall. Patients were contacted 2 weeks postinjection; this time point is standard at our institution, but could vary depending on practice location. Lastly, the enrolled patients did not all share the same indication for injection, and pain was not stratified between back and leg pain. CONCLUSIONS: Relying on patient recollection does not provide an accurate measure of preinjection status after lumbar epidural steroid injection, although patients did recall their 4-hour postinjection status. These findings support previous studies indicating that relying on patient recollection does not provide an accurate measure of preintervention symptoms. Patient recollection of postintervention symptoms, however, may have some clinical utility and requires further study.

Steviol Represses Glucose Metabolism and Translation Initiation in Pancreatic Cancer Cells.

Pancreatic cancer has the worst prognosis and lowest survival rate among all cancers. Pancreatic cancer cells are highly metabolically active and typically reprogrammed for aberrant glucose metabolism; thus they respond poorly to therapeutic modalities. It is highly imperative to understand mechanisms that are responsible for high glucose metabolism and identify natural/synthetic agents that can repress glucose metabolic machinery in pancreatic cancer cells, to improve the therapeutic outcomes/management of pancreatic cancer patients. We have identified a glycoside, steviol that effectively represses glucose consumption in pancreatic cancer cells via the inhibition of the translation initiation machinery of the molecular components. Herein, we report that steviol effectively inhibits the glucose uptake and lactate production in pancreatic cancer cells (AsPC1 and HPAF-II). The growth, colonization, and invasion characteristics of pancreatic cancer cells were also determined by in vitro functional assay. Steviol treatment also inhibited the tumorigenic and metastatic potential of human pancreatic cancer cells by inducing apoptosis and cell cycle arrest in the G1/M phase. The metabolic shift by steviol was mediated through the repression of the phosphorylation of mTOR and translation initiation proteins (4E-BP1, eIF4e, eIF4B, and eIF4G). Overall, the results of this study suggest that steviol can effectively suppress the glucose metabolism and translation initiation in pancreatic cancer cells to mitigate their aggressiveness. This study might help in the design of newer combination therapeutic strategies for pancreatic cancer treatment.

Lateral mass screw placement in the atlas: description of a novel surgical technique, radiographic parameters, and review of the literature.

BACKGROUND: Numerous techniques of C1 lateral mass screw placement have been described. We sought to delineate the radiographic angle of safety medially and laterally and describe a novel surgical technique of C1 lateral mass screw placement. We sought to (I) determine the angle of safety medially and laterally of the C1 lateral mass; (II) assess the size available of the lateral mass in the AP and coronal planes; (III) describe novel technique of insertion of a C1 lateral mass screw utilizing navigation and a novel start point. METHODS: We retrospectively reviewed cervical computed tomography (CT) images of normal adults. Radiographic measurements were then obtained using these images including the angle (degrees) of safety medially and lateral of the C1 lateral mass bilaterally, as well as the length and width (mm) of the C1 lateral masses. A novel surgical technique was used by identifying the confluence of the medial aspect of the posterior arch and the lateral mass. This confluence is then marked out as the C1 screw start point. Under navigation guidance, lateral mass screws were placed with 0 degrees of medial-lateral angulation from posterior to anterior. RESULTS: Forty-five patients with a mean age of 52.6±25.6 years (33% female) were included. The mean medial and lateral angle of safety of the C1 lateral mass bilaterally was 23±3.8 degrees and 32±5 degrees, respectively. Average length and width of the lateral mass was 17.7 and 13.3 mm respectively. CONCLUSIONS: This study describes the radiographic window of safety medially and laterally for safe and reproducible placement of C1 lateral mass screws. Further, a novel technique using a medial start point and navigation guidance with 0 degrees of angulation in the coronal plane is described. Further research is required to assess outcomes of patients utilizing this method as well as biomechanical studies to assess this construct strength compared to others that are frequently used.

A Multicenter Evaluation of the Feasibility, Patient/Provider Satisfaction, and Value of Virtual Spine Consultation During the COVID-19 Pandemic.

OBJECTIVE: To assess the feasibility, patient/provider satisfaction, and perceived value of telehealth spine consultation after rapid conversion from traditional in-office visits during the COVID-19 pandemic. METHODS: Data were obtained for patients undergoing telehealth visits with spine surgeons in the first 3 weeks after government restriction of elective surgical care at 4 sites (March 23, 2020, to April 17, 2020). Demographic factors, technique-specific elements of the telehealth experience, provider confidence in diagnostic and therapeutic assessment, patient/surgeon satisfaction, and perceived value were collected. RESULTS: A total of 128 unique visits were analyzed. New (74 [58%]), preoperative (26 [20%]), and postoperative (28 [22%]) patients were assessed. A total of 116 (91%) visits had successful connection on the first attempt. Surgeons felt very confident 101 times (79%) when assessing diagnosis and 107 times (84%) when assessing treatment plan. The mean and median patient satisfaction was 89% and 94%, respectively. Patient satisfaction was significantly higher for video over audio-only visits (P < 0.05). Patient satisfaction was not significantly different with patient age, location of chief complaint (cervical or thoracolumbar), or visit type (new, preoperative, or postoperative). Providers reported that 76% of the time they would choose to perform the visit again in telehealth format. Sixty percent of patients valued the visit cost as the same or slightly less than an in-office consultation. CONCLUSIONS: This is the first study to demonstrate the feasibility and high patient/provider satisfaction of virtual spine surgical consultation, and appropriate reimbursement and balanced regulation for spine telehealth care is essential to continue this existing work.

The pyriproxyfen metabolite, 4'-OH-PPF, disrupts thyroid hormone signaling in neural stem cells, modifying neurodevelopmental genes affected by ZIKA virus infection.

North-Eastern Brazil saw intensive application of the insecticide pyriproxyfen (PPF) during the microcephaly outbreak caused by the Zika virus (ZIKV). ZIKV requires the neural RNA-binding protein Musashi-1 to replicate. Thyroid hormone (TH) represses MSI1. PPF is a suspected TH disruptor. We hypothesized that co-exposure to the main metabolite of PPF, 4'-OH-PPF, could exacerbate ZIKV effects through increased MSI1 expression. Exposing an in vivo reporter model, Xenopus laevis, to 4'-OH-PPF decreased TH signaling and increased msi1 mRNA and protein, confirming TH-antagonistic properties. Next, we investigated the metabolite's effects on mouse subventricular zone-derived neural stem cells (NSCs). Exposure to 4'-OH-PPF dose-dependently reduced neuroprogenitor proliferation and dysregulated genes implicated in neurogliogenesis. The highest dose induced Msi1 mRNA and protein, increasing cell apoptosis and the ratio of neurons to glial cells. Given these effects of the metabolite alone, we considered if combined infection with ZIKV worsened neurogenic events. Only at the fourth and last day of incubation did co-exposure of 4'-OH-PPF and ZIKV decrease viral replication, but viral RNA copies stayed within the same order of magnitude. Intracellular RNA content of NSCs was decreased in the combined presence of 4'-OH-PPF and ZIKV, suggesting a synergistic block of transcriptional machinery. Seven out of 12 tested key genes in TH signaling and neuroglial commitment were dysregulated by co-exposure, of which four were unaltered when exposed to 4'-OH-PPF alone. We conclude that 4'-OH-PPF is an active TH-antagonist, altering NSC processes known to underlie correct cortical development. A combination of the TH-disrupting metabolite and ZIKV could aggravate the microcephaly phenotype.

Congenital defect of the posterior arch of C1: a case report.

Odontoid fractures are one of the most common injuries to the cervical spine in geriatric patients. Congenital C1 arch absence, however, is a very rare anomaly found in the population. We describe the first reported case of a congenital C1 posterior arch absence and C1 anterior cleft presenting with odontoid fracture. We present the case of a 58-year-old male who was found to have a comminuted type III odontoid fracture with significant angulation and displacement. CT scan demonstrated this fracture and also demonstrated congenital cleft of his left anterior arch and absence of left C1 posterior arch. Given his anatomic anomaly, we elected to perform occipitocervical fusion. The patient underwent occipito-cervical fusion to avoid iatrogenic vertebral artery injury. He was also immobilized in a halo vest given patient-specific social factors and compromised bone quality. The patient had no intra- or post-operative complications, but a prolonged hospital stay due to alcohol withdrawal. At 3-month postoperatively the patient had no neck pain and return to baseline function. This case highlights the importance of obtaining a CT scan preoperatively to not only to further characterize the fracture but also for surgical planning and recognition of anatomic anomalies as this may significantly impact the operative strategy.

Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment.

Exosomes are nanoscale vesicles generated by cells for intercellular communication. Due to their composition, significant research has been conducted to transform these particles into specific delivery systems for various disease states. In this review, we discuss the common isolation and loading methods of exosomes, some of the major roles of exosomes in the tumor microenvironment, as well as discuss recent applications of exosomes as drug delivery vessels and the resulting clinical implications.

Perioperative Corticosteroids Reduce Dysphagia Severity Following Anterior Cervical Spinal Fusion: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The anterior approach to the cervical spine is commonly used to treat cervical pathology. It is, however, associated with high rates of dysphagia, which may be associated with substantial patient morbidity. Perioperative corticosteroid administration has been advocated to decrease dysphagia rates; its efficacy, however, remains uncertain. We conducted a meta-analysis of randomized trials to determine the efficacy of perioperative corticosteroid administration in reducing postoperative dysphagia as well as any adverse effects, such as pseudarthrosis and infection. METHODS: We conducted a systematic search of electronic databases (MEDLINE, Embase, CENTRAL [Cochrane Central Register of Controlled Trials], ClinicalTrials.gov) to identify randomized controlled trials (RCTs) that evaluated corticosteroids versus any comparator for prevention of postoperative dysphagia after anterior cervical spine procedures. Two independent reviewers used the GRADE (Grades of Recommendation Assessment, Development and Evaluation) criteria to assess eligibility and risk of bias, perform data extraction, and rate the quality of evidence. The primary outcome was severity of postoperative dysphagia. We conducted meta-analyses of dysphagia (both overall and by delivery method), pseudarthrosis, and postoperative infection. RESULTS: After screening of 927 articles, a total of 7 studies were eligible for final inclusion. These included 431 patients, of whom 247 received corticosteroids and 184 received placebo or a control treatment. Moderate-quality evidence demonstrated a significant improvement in postoperative dysphagia rates (odds ratio, 0.35; 95% confidence interval, 0.20 to 0.63; p < 0.001), and this finding was robust to both permutation analyses and sensitivity analyses removing the studies with a high risk of bias. There was no significant difference between intravenous and local steroid administration (p = 0.16). There were no documented infections. There was no significantly increased risk of pseudarthrosis in those receiving steroids compared with placebo or a control treatment (p = 0.13). CONCLUSIONS: This meta-analysis found moderate-quality evidence supporting the use of perioperative corticosteroid administration as an adjunct to anterior cervical spinal procedures. Patients treated with corticosteroids intravenously or locally had significantly decreased severity of dysphagia. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Physical Examination of the Spine Using Telemedicine: A Systematic Review.

STUDY DESIGN: This is a systematic review. OBJECTIVE: To systematically review (1) the reliability of the physical examination of the spine using telehealth as it pertains to spinal pathology and (2) patient satisfaction with the virtual spine physical examination. METHODS: We searched EMBASE, PubMed, Medline Ovid, and SCOPUS databases from inception until April 2020. Eligible studies included those that reported on performing a virtual spine physical examination. Two reviewers independently assessed all potential studies for eligibility and extracted data. The primary outcome of interest was the reliability of the virtual spine physical exam. Secondary outcomes of interest were patient satisfaction with the virtual encounter. RESULTS: A total of 2321 studies were initially screened. After inclusion criteria were applied, 3 studies (88 patients) were included that compared virtual with in-person spine physical examinations. These studies showed acceptable reliability for portions of the low back virtual exam. Patient satisfaction surveys were conducted in 2 of the studies and showed general satisfaction (>80% would recommend). CONCLUSIONS: These results suggest that the virtual spine examination may be comparable to the in-person physical examination for low back pain, though there is a significant void in the literature regarding the reliability of the physical examination as it pertains to specific surgical pathology of the spine. Because patients are overall satisfied with virtual spine assessments, validating a virtual physical examination of the spine is an important area that requires further research.

Stereotactic navigation in anterior cervical spine surgery: surgical setup and technique.

Intraoperative stereotactic navigation in spine surgery is quickly becoming popularized for accurate placement of spinal instrumentation as well as assisting in the verification of anatomic landmarks. Navigation is less commonly utilized in anterior cervical spine surgery due to instrumentation being able to be placed under direct visualization. The utility of navigation in anterior cervical spine surgery is its ability to aid in the verification of anatomic location, particularly when anatomy is distorted or pathology comes close to critical neurovascular structures. We present a technique guide for anterior cervical spine navigation that we have applied at our institution and have found to be very beneficial in select patients, particularly those with complex anatomy, large body mass index, undergoing revision surgery, sustained spinal trauma and those patients with severe anterior ossification where depth or medial-lateral landmarks are difficult to visualize. We describe utilization of the technique using a case examples and specifically in a patient with significant ossification of the posterior longitudinal ligament and severe spinal cord compression that underwent multilevel cervical corpectomy. The described technique was found to be reproducible and effective, allowing cervical spine surgeons to perform more complex or minimally invasive procedures with safety and accuracy. We emphasize that navigation does not replace knowledge of anatomy or technical aspects of the procedure.

Surgical correction of rigid cervicothoracic deformity in a transgender patient: case report.

A number of spinal pathologies result in fusion of the spine, including ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis (DISH), as well as severe degenerative arthropathies. This fusion of spinal elements may result in spinal deformity affecting any region of the spine. Cervicothoracic deformity resulting in chin on chest deformity is poorly tolerated due to inability to maintain a horizontal gaze. Surgical treatment options for this condition are complex and require extensive discussion between the patient and surgical team. Here we present a case report of a 26-year-old transgender female (male to female) patient with severe chin on chest deformity and a unique pattern of spinal fusion involving only the posterior elements. She underwent C2-T8 posterior spinal fusion with thoracic pedicle subtraction osteotomy and multiple cervical facet osteotomies with good functional result. She did have severe dysphagia and required feeding tube for several weeks but did very well by 1 year postoperatively. While posterior elements of the spine are normally affected first in spondyloarthropathies such as ankylosing spondylitis, the lack of anterior spinal involvement is unique and could be attributed to hormonal therapy in this patient. This case describes a unique pattern of spondyloarthropathy and highlights the importance of a having a multi-disciplinary team for the treatment of patients with complex spinal pathologies.

Three-dimensional Printed Drill Guides Versus Fluoroscopic-guided Freehand Technique for Pedicle Screw Placement: A Systematic Review and Meta-analysis of Radiographic, Operative, and Clinical Outcomes.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: The objective of this study was to compare surgical, clinical, and radiographic outcomes of 3-dimensional printed (3DP) drill guides to the fluoroscopic-guided, freehand placement of pedicle screws in the spine. SUMMARY OF BACKGROUND DATA: 3DP is a budding technology in spine surgery and has recently been applied to patient-specific drill guides for pedicle screw placement. Several authors have reported the benefits of these drill guides, but no clear consensus exists on their utility. MATERIALS AND METHODS: A comprehensive search of the literature was conducted and independent reviewers assessed eligibility for included studies. Outcomes analyzed included: total operation time, estimated blood loss, screw accuracy, pain score, Japanese Orthopedic Association score, and postoperative complications. Weighted mean differences (WMD) and weighted risk differences were calculated using a random-effects model. RESULTS: Six studies with a total of 205 patients were included. There were significantly lower operation times [WMD=-32.32 min, 95% confidence interval (CI)=-53.19 to -11.45] and estimated blood loss (WMD=-51.42 mL, 95% CI=-81.12 to -21.72) in procedures performed with 3DP drill guides as compared with freehand technique. The probability of "excellent" screw placement was significantly higher in 3DP guides versus freehand (weighted risk difference=-0.12, 95% CI=-0.17 to 0.07); however, no differences were observed in "poor" or "good" screw placement. There were no significant differences between groups in pain scores or Japanese Orthopedic Association scores. No difference in the rate of surgical complications was noted between the groups. CONCLUSIONS: Pedicle screws placed with 3DP drill guides may result in shorter operative time, less blood loss, and a greater probability of excellent screw placement as compared with those placed with freehand techniques. We conclude that 3DP guides may potentially develop into an efficient and accurate option for pedicle screw placement. However, more prospective, randomized controlled trials are needed to strengthen the confidence of these conclusions. LEVEL OF EVIDENCE: Level III.

Novel Paclitaxel Nanoformulation Impairs De Novo Lipid Synthesis in Pancreatic Cancer Cells and Enhances Gemcitabine Efficacy.

Pancreatic cancer (PanCa) is a highly lethal disease with a poor 5 year survival rate, less than 7%. It has a dismal prognosis, and more than 50% of cases are detected at an advanced and metastatic stage. Gemcitabine (GEM) is a gold standard chemotherapy used for PanCa treatment. However, GEM-acquired resistance in cancer cells is considered as a major setback for its continued clinical implementation. This phenomenon is evidently linked to de novo lipid synthesis. PanCa cells rely on de novo lipid synthesis, which is a prime event in survival and one of the key drivers for tumorigenesis, cancer progression, and drug resistance. Thus, the depletion of lipogenesis or lipid metabolism can not only improve treatment outcomes but also overcome chemoresistance, which is an unmet clinical need. Toward this effort, our study reports a unique paclitaxel-poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PPNPs) formulation which can target lipid metabolism and improve anticancer efficacy of GEM in PanCa cells. PPNPs inhibit excessive lipid formation and alter membrane stability with compromised membrane integrity, which was confirmed by Fourier transform infrared and zeta potential measurements. The effective interference of PPNPs in lipid metabolic signaling was determined by reduction in the expression of FASN, ACC, lipin, and Cox-2 proteins. This molecular action profoundly enhances efficacy of GEM as evident through enhanced inhibitory effects on the tumorigenic and metastasis assays in PanCa cells. These data clearly suggest that the ablation of lipid metabolism might offer an innovative approach for the improved therapeutic outcome in PanCa patients.