Mycobacterium xenopi vertebral osteomyelitis in a patient with systemic lupus erythematosus: illustrative case.

BACKGROUND: Mycobacterium xenopi is a common nontuberculous Mycobacterium (NTM) that is slow growing and an infrequent cause of infection. When infections do occur, it is by exposure to contaminated soil or water or to infectious aerosols. Nontuberculous mycobacterial infections in the spine are exceedingly rare. Risk factors can include immunosuppression, particularly human immunodeficiency virus; however, other systemic diseases such as systemic lupus erythematosus (SLE) have been reported. OBSERVATIONS: The authors report a case of cord compression due to M. xenopi vertebral osteomyelitis with an epidural abscess in a patient with SLE on hydroxychloroquine and recent steroid use. The authors explore the presentation of a patient who developed acute neurological deficits concerning for spinal pathology secondary to NTM. Although considered a rare occurrence, patients with autoimmune pathologies are susceptible to infection by unusual organisms. Standard treatment of autoimmune diseases can predispose patients to infection and warrant surgical correction to prevent long-term neurological deficits. LESSONS: There is still much work and research to be done in the exploration and understanding of nontuberculous mycobacterial infection, pathophysiology, and treatment in the immunocompetent population and in patients with autoimmune disorders.

Determinants of Postoperative Compliance of Patient-Reported Outcome Assessments following Lumbar Spine Surgery.

Introduction: This study aimed to identify demographic, clinical, and operative factors associated with increased postoperative compliance of patient-reported outcome (PRO) assessments following lumbar spine surgery. Methods: A retrospective study of prospectively collected data of 1,680 consecutive adult patients who underwent elective lumbar surgery at a single institution from 2017-2020. Digital assessment questionnaires were used to assess PROs (i.e., VAS-back, VAS-leg, Oswestry Disability Index, Short Form (SF-12) mental & physical health, VR-12 mental and physical, and VR6D scores) and patient compliance, defined as the percentage of questionnaires completed preoperatively, at 3 months and 1 year after surgery. Multivariate logistic regression was used to assess the association between PRO compliance and patient characteristics. Results: A total of 1,680 patients (53.1% male, mean age: 57.7 years) had a mean PRO compliance of 64.7%. Compliance decreased continuously from initial preoperative rates (84.5%) to lower rates at 3 months (54.4%) and 12 months (45.6%), respectively, with 33.2% of patients completing zero assessment questionnaires at 12 months, postoperatively. Factors associated with significantly increased PRO compliance included being employed (preop: odds ratio [OR]=2.58, p=0.002; 3-month postop: OR=1.25, p=0.095; 12-month postop: OR=1.34, p=0.028). Factors associated with decreased compliance included preoperative smoking status (3-month postop: OR=0.63, p=0.029; 12-month postop: OR=0.60, p=0.016). Conclusions: Patients who completed greater than 50% of their PROs demonstrated significantly different rates of being employed compared with those who completed less than 50% throughout 1 year of follow-up. Preoperative smoking status was associated with decreased compliance, whereas a history of employment was associated with increased compliance throughout follow-up. To validate our findings and explore additional parameters that affect postoperative compliance of PROs, further investigation is required.

The Scope and Impact of the COVID-19 Pandemic on Neuroemergent Patient Transfers, Clinical Care and Patient Outcomes.

Introduction: The SARS-CoV-2 (COVID-19) pandemic continues to substantially alter previously established clinical practice patterns and has transformed patient care in American healthcare. However, studies to evaluate the impact of COVID-19 on neuroemergent patient care and associated clinical outcomes are limited. Herein, we describe the impact of COVID-19 on the Neuroemergency Transfer Program (NTP) - a novel, urban, high volume interhospital patient transfer program. Objective: To evaluate and describe the clinical impact of the COVID-19 pandemic on the NTP. Study Design: A single-center retrospective study of prospectively collected consecutive neuroemergent patient transfer data between 2018-2021 was analyzed. Adult patients were divided based upon transfer date into a Pre-COVID (PCOV) or COVID cohort. Patient demographics, transfer characteristics and clinical data and outcomes were analyzed. Results: 3,096 patients were included for analysis. Mean age at transfer in the PCOV and COVID cohorts were 62.4 ± 0.36 and 61.1 ± 0.6 years. A significant decrease in mean transfers per month was observed between cohorts (PCOV = 97.8 vs. COV = 68.2 transfers/month, p < 0.01). Total transfer time in the PCOV cohort was 155.1 ± 3.4 min which increased to 169.3 ± 12.8 min in the COVID cohort (p = 0.13). Overall mean transfer distance was significantly longer in the PCOV cohort at 22.0 ± 0.4 miles vs. 20.3 ± 0.67 miles in the COV cohort (p = 0.03). The relative frequency of transfer diagnoses was unchanged between cohorts. A significant increase in mean inpatient length of stay was noted, 7.9 ± 0.15 days to 9.6 ± 0.33 days in the PCOV vs. COVID cohorts (p < 0.01). Ultimately, no difference in the frequency of good vs. poor clinical outcome were noted between the PCOV (79.8% and 19.4%) vs. COV (78.8% and 20.4%) cohorts. Conclusion: The impact of COVID-19 on current healthcare dynamics are far reaching. Here, we show a significant decrease in interhospital patient transfers and increased length of stay between a Pre-COVID and COVID cohort. Further work to better elucidate the specific interplay of clinical contributors to account for these changes is indicated.

Expandable versus Static Transforaminal Lumbar Interbody Fusion Cages: 1-year Radiographic Parameters and Patient-Reported Outcomes.

OBJECTIVE: Expandable transforaminal lumbar interbody fusion (TLIF) cages capable of multidirectional in situ expansion have gained popularity as they increase axial surface area for fusion and may enhance lordotic correction through a traditional minimally invasive surgery (MIS) surgical corridor. We evaluated and compared the radiographic and clinical outcomes between a novel expandable versus static minimally invasive surgery TLIF cage for the treatment of degenerative disk disease. METHODS: A single-center retrospective review of 120 consecutive adult patients undergoing 1- or 2-level MIS TLIF with an expandable (n = 60) or static cage was performed between 2015 and 2019. Preoperative and 1-year postoperative radiographic and clinical outcomes were assessed by upright flexion/extension radiographs and serial confidential surveys. RESULTS: One-hundred twenty patients (mean age 63.5 years, 60.0% female) undergoing 1- and 2-level MIS TLIF met inclusion criteria. A statistically significant reduction of spondylolisthesis, restoration of foraminal height as well as anterior and posterior disk height was achieved in both cohorts, however was greater in the expandable cage cohort (ECC) (all P < 0.05). Comparable rates of fusion, 93% and 91%, were observed in the ECC and static cage cohort. A significant reduction in Numeric Pain Rating Scale back and Oswestry Disability Index scores were observed in both cohorts but were more pronounced in the ECC (5.9 ± 2.4 to 2.2 ± 1.9 and 37.3 ± 16.2 to 17.1 ± 15.2) versus static cage cohort (6.2 ± 2.8 to 3.2 ± 2.5 and 41.8 ± 16.1 to 24.3 ± 17.5) (P < 0.05). One instance of cage migration requiring reoperation occurred in the ECC. CONCLUSIONS: Taken together, these radiographic and clinical findings suggest an expandable cage placed through an MIS corridor represents a safe, equitable, and efficacious alternative to a static TLIF in adults with degenerative lumbar pathology.

Transforaminal lumbar interbody fusion using a novel minimally invasive expandable interbody cage: patient-reported outcomes and radiographic parameters.

OBJECTIVE: The goal of this study was to evaluate the clinical and radiographic outcomes of a novel multidirectional in situ expandable minimally invasive surgery (MIS) transforaminal lumbar interbody fusion (TLIF) cage. METHODS: A retrospective analysis of 69 consecutive patients undergoing a 1- or 2-level MIS TLIF using an expandable cage was performed over a 2-year period. Standard MIS techniques with pedicle screw fixation were used in all cases. Upright lateral dynamic flexion/extension radiographs were reviewed prior to and at 1 year after surgery. Clinical metrics included numeric rating scale for back and leg pain, Oswestry Disability Index, and the SF-12 and VR-12 physical and mental health surveys. Radiographic parameters included anterior and posterior disc height, neuroforaminal height, spondylolisthesis, segmental lordosis, lumbar lordosis, and fusion rate. RESULTS: A total of 69 patients representing 75 operative levels met study inclusion criteria. The mean patient age at surgery was 63.4 ± 1.2 years, with a female predominance of 51%. The average radiographic and clinical follow-ups were 372 and 368 days, respectively. A total of 63 patients (91%) underwent 1-level surgery and 6 patients (9%) underwent 2-level surgery. Significant reductions of numeric rating scale scores for back and leg pain were observed-from 6.1 ± 0.7 to 2.5 ± 0.3 (p < 0.0001) and 4.9 ± 0.6 to 1.9 ± 0.2 (p < 0.0001), respectively. A similar reduction in Oswestry Disability Index from 38.0 ± 4.6 to 20.0 ± 2.3 (p < 0.0001) was noted. Likewise, SF-12 and VR-12 scores all showed statistically significant improvement from baseline (p < 0.001). The mean anterior and posterior disc heights improved from 8.7 ± 1.0 mm to 13.4 ± 1.5 mm (p = 0.0001) and 6.5 ± 0.8 mm to 9.6 ± 1.1 mm (p = 0.0001), respectively. Neuroforaminal height improved from 17.6 ± 2.0 mm to 21.9 ± 2.5 mm (p = 0.0001). When present, spondylolisthesis was, on average, reduced from 4.3 ± 0.5 mm to 1.9 ± 0.2 mm (p = 0.0001). Lumbar lordosis improved from 47.8° ± 5.5° to 58.5° ± 6.8° (p = 0.2687), and no significant change in segmental lordosis was observed. The overall rate of radiographic fusion was 93.3% at 1 year. No perioperative complications requiring operative revision were encountered. CONCLUSIONS: In this series of MIS TLIFs, use of this novel interbody cage was shown to be safe and effective. Significant improvements in pain and disability were observed. Effective and durable restoration of disc height and neuroforaminal height and reduction of spondylolisthesis were obtained, with concurrent gains in lumbar lordosis. Taken together, this device offers excellent clinical and radiographic outcomes via an MIS approach.

Pediatric Brainstem Gliomas: A Retrospective Study of 180 Patients from the SEER Database.

BACKGROUND/AIMS: Large population-based studies are needed to assess the epidemiology and survival risk factors associated with pediatric brainstem gliomas. This retrospective study explores factors that may influence survival in this population. METHODS: Utilizing the SEER database, the authors retrospectively assessed survival in histologically confirmed brainstem gliomas in patients aged 17 and younger. Survival was described with Kaplan-Meyer curves and multivariate regression analysis. RESULTS: This analysis of 180 cases showed that age (hazard ratio [HR] 1.04, 95% CI 0.96-1.14, p = 0.34), non-white race (HR 1.00, 95% CI 0.35-2.85 p > 0.99), distant or invasive extension of the tumor (HR 0.4, 95% CI 0.08-2.53, p = 0.37), and radiation therapy (HR 1.27, 95% CI 0.52-3.11, p = 0.61) were not associated with decreased survival. High-grade tumor status (HR 8.64, 95% CI 3.49-21.41, p < 0.001) was associated with decreased survival. Partial resection (HR 0.11, 95% CI 0.04-0.30, p < 0.001) and gross-total resection (HR 0.03, 95% CI 0.01-0.14, p < 0.001) were associated with improved survival. CONCLUSIONS: High-grade brainstem gliomas have a worse prognosis. Early diagnosis and surgery appear to be associated with improved survival, while the role of radiation is unclear.

Retraction: Limited post-operative dexamethasone use does not affect lumbar fusion: a single institutional experience.

[This retracts the article DOI: 10.21037/jss.2018.05.20.].

Limited post-operative dexamethasone use does not affect lumbar fusion: a single institutional experience.

BACKGROUND: The use of exogenous dexamethasone during and after lumbar spine surgery remains controversial. The preponderance of studies on this topic is primarily from animal models and little is known about the effects of exogenous dexamethasone use on fusion outcomes in human subjects undergoing lumbar arthrodesis. The aim of this study is to investigate the effect of limited exogenous dexamethasone use on bone fusion after instrumented lumbar arthrodesis. METHODS: Consecutive adult patients (18 years and older) undergoing one and two level lumbar decompression and fusion between January 2013 and December 2014 were reviewed. Patients were dichotomized into one of two groups (A & B) based on whether they received dexamethasone-Group (A) dexamethasone; and Group (B) no dexamethasone. Baseline characteristics, operative details, length of hospital stay, rates of wound infection, and fusion rates at 1 year were gathered by direct medical record review. All patients enrolled in this study were followed for a minimum of 12 months after surgery. RESULTS: One hundred sixty-five consecutive patients undergoing 1- and 2-level fusions were included in the study. Fifty eight patients received dexamethasone and 107 patients did not. The mean ± SD age was similar between both cohorts ("dexamethasone": 58.12±16.25 years vs. "no dexamethasone": 61.00±12.95, P=0.24). The was no difference in the prevalence of smoking (P=0.72) between both cohorts. Length of in-hospital stay was similar between cohorts ("dexamethasone": 4.08±3.44 days vs. "no dexamethasone": 4.50±2.85 days, P=0.43). The incidence of post-operative infections was similar between cohorts. At 12 months after surgery, 70% of patients in the dexamethasone cohort had radiographic evidence of bony fusion compared to 73% of patients in the no-dexamethasone cohort (P=0.68). CONCLUSIONS: Our study suggests that a limited exposure to exogenous dexamethasone after lumbar spine fusion may not be associated with a lower fusion rate. Prospective randomized control trials are needed to corroborate our findings.

Chiari I malformation with acute neurological deficit after craniocervical trauma: Case report, imaging, and anatomic considerations.

BACKGROUND: In patients with Chiari I malformation (CMI), the occurrence of acute neurologic deficit after craniocervical trauma is rare. However, the pathologic potential of exacerbating anatomic overcrowding of the posterior fossa has immense clinical consequences and prompt recognition is essential. CASE DESCRIPTION: This case study describes a 41-year-old male who sustained a single blow to the face, fell, and struck the occiput. On admission, neurological examination revealed a profound paraparesis, upper extremity diplegia, a C4 sensory level and apnea that required intubation. On arrival, computerized axial tomography of the head showed a small amount of contrecoup left frontal traumatic subarachnoid hemorrhage. Magnetic resonance imaging (MRI) performed 19 h after admission was negative except for the presence of a CMI. He acutely declined on post injury day 2, prompting emergent decompression of the posterior fossa where anatomic overcrowding was observed. At 19 weeks post injury, his motor function had significantly improved. CONCLUSION: The constellation of severe neurologic deficit in patients with CMI after relatively minor craniocervical trauma has been previously described. In our patient, neurologic deficit disproportionate to the mechanism of injury was observed and likely in part attributed to the presence of a Chiari malformation. Unfortunately, MRI has not yet been able to clearly define the underlying pathoanatomy, help understand the mechanism of injury, and delineate when operative intervention is indicated in these patients. Here, we review similar cases from the literature, examine findings on MRI, and evaluate mechanisms of injury following craniocervical trauma in patients with CMI to help clarify these questions.

Pediatric Spinal Ependymomas: An Epidemiologic Study.

OBJECTIVE: Pediatric intramedullary spinal cord ependymomas represent a rare central nervous system neoplasm with few available data regarding incidence and outcomes. To this end, large population-based studies are needed to assess the epidemiology and survival risk factors associated with these tumors in the hope of better understanding these tumors as well as improving outcomes. This retrospective study was undertaken to explore factors that may influence survival in pediatric patients with intramedullary spinal cord ependymomas. METHODS: Using the SEER (Surveillance Epidemiology and End Results) database, a prospective cancer registry, we retrospectively assessed survival in histologically confirmed spinal ependymomas in patients 17 years of age and younger. Survival was described with Kaplan-Meier curves, and a multivariate regression analysis was used to assess the association of several variables with survival, controlling for confounding variables. RESULTS: Invasive tumor extension (P < 0.001) was associated with decreased survival, whereas gross total resection (P = 0.028) correlated with better rates of survival. Age, gender, tumor size, tumor extension, the use and sequence of radiation therapy, or use of chemotherapy were not found to have a statistically significant association with survival outcomes. CONCLUSIONS: Invasive ependymomas occurring in the spine have a worse prognosis, whereas higher tumor grades do not clearly show worse rates of survival. Early diagnosis and surgery seem to be associated with improved survival and outcomes, whereas radiation therapy and chemotherapy have an unclear role.

Integrative molecular network analysis identifies emergent enzalutamide resistance mechanisms in prostate cancer.

Recent work demonstrates that castration-resistant prostate cancer (CRPC) tumors harbor countless genomic aberrations that control many hallmarks of cancer. While some specific mutations in CRPC may be actionable, many others are not. We hypothesized that genomic aberrations in cancer may operate in concert to promote drug resistance and tumor progression, and that organization of these genomic aberrations into therapeutically targetable pathways may improve our ability to treat CRPC. To identify the molecular underpinnings of enzalutamide-resistant CRPC, we performed transcriptional and copy number profiling studies using paired enzalutamide-sensitive and resistant LNCaP prostate cancer cell lines. Gene networks associated with enzalutamide resistance were revealed by performing an integrative genomic analysis with the PAthway Representation and Analysis by Direct Reference on Graphical Models (PARADIGM) tool. Amongst the pathways enriched in the enzalutamide-resistant cells were those associated with MEK, EGFR, RAS, and NFKB. Functional validation studies of 64 genes identified 10 candidate genes whose suppression led to greater effects on cell viability in enzalutamide-resistant cells as compared to sensitive parental cells. Examination of a patient cohort demonstrated that several of our functionally-validated gene hits are deregulated in metastatic CRPC tumor samples, suggesting that they may be clinically relevant therapeutic targets for patients with enzalutamide-resistant CRPC. Altogether, our approach demonstrates the potential of integrative genomic analyses to clarify determinants of drug resistance and rational co-targeting strategies to overcome resistance.

Cellular androgen content influences enzalutamide agonism of F877L mutant androgen receptor.

Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) - the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. This insight led to the development of the AR antagonist enzalutamide. However, resistance to enzalutamide invariably develops, and disease progression is nearly universal. One mechanism of resistance to enzalutamide is an F877L mutation in the AR ligand-binding domain that can convert enzalutamide to an agonist of AR activity. However, mechanisms that contribute to the agonist switch had not been fully clarified, and there were no therapies to block AR F877L. Using cell line models of castration-resistant prostate cancer (CRPC), we determined that cellular androgen content influences enzalutamide agonism of mutant F877L AR. Further, enzalutamide treatment of AR F877L-expressing cell lines recapitulated the effects of androgen activation of F877L AR or wild-type AR. Because the BET bromodomain inhibitor JQ-1 was previously shown to block androgen activation of wild-type AR, we tested JQ-1 in AR F877L-expressing CRPC models. We determined that JQ-1 suppressed androgen or enzalutamide activation of mutant F877L AR and suppressed growth of mutant F877L AR CRPC tumors in vivo, demonstrating a new strategy to treat tumors harboring this mutation.

The Ribosome-Sec61 Translocon Complex Forms a Cytosolically Restricted Environment for Early Polytopic Membrane Protein Folding.

Transmembrane topology of polytopic membrane proteins (PMPs) is established in the endoplasmic reticulum (ER) by the ribosome Sec61-translocon complex (RTC) through iterative cycles of translocation initiation and termination. It remains unknown, however, whether tertiary folding of transmembrane domains begins after the nascent polypeptide integrates into the lipid bilayer or within a proteinaceous environment proximal to translocon components. To address this question, we used cysteine scanning mutagenesis to monitor aqueous accessibility of stalled translation intermediates to determine when, during biogenesis, hydrophilic peptide loops of the aquaporin-4 (AQP4) water channel are delivered to cytosolic and lumenal compartments. Results showed that following ribosome docking on the ER membrane, the nascent polypeptide was shielded from the cytosol as it emerged from the ribosome exit tunnel. Extracellular loops followed a well defined path through the ribosome, the ribosome translocon junction, the Sec61-translocon pore, and into the ER lumen coincident with chain elongation. In contrast, intracellular loops (ICLs) and C-terminalresidues exited the ribosome into a cytosolically shielded environment and remained inaccessible to both cytosolic and lumenal compartments until translation was terminated. Shielding of ICL1 and ICL2, but not the C terminus, became resistant to maneuvers that disrupt electrostatic ribosome interactions. Thus, the early folding landscape of polytopic proteins is shaped by a spatially restricted environment localized within the assembled ribosome translocon complex.

Entry kinetics and cell-cell transmission of surface-bound retroviral vector particles.

BACKGROUND: Transduction with recombinant HIV-1 derived lentivirus vectors is a multi-step process initiated by surface attachment and subsequent receptor-directed uptake into the target cell. We previously reported the retention of vesicular stomatitis virus G protein pseudotyped particles on murine progenitor cells and their delayed cell-cell transfer. METHODS: To examine the underlying mechanism in more detail, we used a combination of approaches focused on investigating the role of receptor-independent factors in modulating attachment. RESULTS: The investigation of synchronized transduction reveals cell-type specific rates of vector particle clearance with substantial delays during particle entry into murine hematopoietic progenitor cells. The observed uptake kinetics from the surface of the 1 degrees cell correlate inversely with the magnitude of transfer to 2 degrees targets, corresponding with our initial observation of preferential cell-cell transfer in the context of brief vector exposures. We further demonstrate that vector particle entry into cells is associated with the cell-type specific abundance of extracellular matrix fibronectin. Residual particle-extracellular fibronectin matrix binding and 2 degrees transfer can be competitively disrupted by heparin exposure without affecting murine progenitor homing and repopulation. CONCLUSIONS: Although cellular attachment factors, including fibronectin, aid gene transfer by colocalizing particles to cells and disfavoring early dissociation from targets, they also appear to stabilize particles on the cell surface. The present study highlights the inadvertent consequences for cell entry and cell-cell transfer.