Modified Clavien-Dindo-Sink Classification System for operative complications in adult spine surgery.

OBJECTIVE: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for applications in spine surgery. METHODS: The Clavien-Dindo-Sink complication classification system was evaluated and modified for spine surgery by four fellowship-trained spine surgeons using a consensus process. A distinct group of three fellowship-trained spine surgeons completed a randomized electronic survey grading 71 real-life clinical case scenarios. The survey was repeated 2 weeks after its initial completion. Fleiss' and Cohen's kappa (κ) statistics were used to evaluate interrater and intrarater reliabilities, respectively. RESULTS: Overall, interobserver reliability during the first and second rounds of grading was excellent with a κ of 0.847 (95% CI 0.785-0.908) and 0.852 (95% CI 0.791-0.913), respectively. In the first round, interrater reliability ranged from good to excellent with a κ of 0.778 for grade I (95% CI 0.644-0.912), 0.698 for grade II (95% CI 0.564-0.832), 0.861 for grade III (95% CI 0.727-0.996), 0.845 for grade IV-A (95% CI 0.711-0.979), 0.962 for grade IV-B (95% CI 0.828-1.097), and 0.960 for grade V (95% CI 0.826-1.094). Intraobserver reliability testing for all three independent observers was excellent with a κ of 0.971 (95% CI 0.944-0.999) for rater 1, 0.963 (95% CI 0.926-1.001) for rater 2, and 0.926 (95% CI 0.869-0.982) for rater 3. CONCLUSIONS: The Modified Clavien-Dindo-Sink Classification System demonstrates excellent interrater and intrarater reliability in adult spine surgery cases. This system provides a useful framework to better communicate the severity of spine-related complications.

Characterizing Negative Online Reviews of Spine Surgeons.

DESIGN: Retrospective review. OBJECTIVE: Characterize negative reviews of spine surgeons in the United States. SUMMARY: Physician rating websites significantly influence the selection of doctors by other patients. Negative experiences are impacted by various factors, both clinical and nonclinical, geography, and practice structure. The purpose of this study was to evaluate and categorize negative reviews of spine surgeons in the United States, with a focus on surgical versus nonsurgical reviewers. METHODS: Spine surgeons were selected from available online professional society membership directories. A search for reviews was performed on Healthgrades.com, Vitals.com, and RateMDs.com for the past 10 years. Free response reviews were coded by complaint, and qualitative analysis was performed. χ 2 and Fisher exact tests were used to compare categorical variables, and multiple comparisons were adjusted with Benjamini-Hochberg correction. A binary logistic regression model was performed for the top three most mentioned nonclinical and clinical complaint labels. A P -value <0.05 was considered statistically significant. RESULTS: A total of 16,695 online reviews were evaluated, including 1690 one-star reviews (10.1%). Among one-star reviews, 64.7% were written by nonsurgical patients and 35.3% by surgical patients. Nonclinical and clinical comments constituted 54.9% and 45.1% of reviews, respectively. Surgeons in the South had more "bedside manner" comments (43.3%, P <0.0001), while Northeast surgeons had more "poor surgical outcome" remarks compared with all other geographic regions (14.4%, P <0.001). Practicing in the South and Northeast were independent predictors of having complaints about "bedside manner" and "poor surgical outcome," respectively. CONCLUSION: Most one-star reviews of spine surgeons were attributed to nonsurgical patients, who tended to be unsatisfied with nonclinical factors, especially "bedside manner." However, there was substantial geographic variation. These results suggest that spine surgeons could benefit from focusing on nonclinical factors (bedside manner), especially among nonoperative patients, and that regional nuances should be considered in delivering spine care. LEVEL OF EVIDENCE: Level- 5.

Formal Radiologist Interpretations of Intraoperative Spine Radiographs Have Low Clinical Value.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To evaluate the clinical relevance, usefulness, and financial implications of intraoperative radiograph interpretation by radiologists in spine surgery. SUMMARY OF BACKGROUND DATA: Due to rising healthcare costs, spine surgery is under scrutiny to maximize value-based care. Formal radiographic analysis remains a potential source of unnecessary healthcare costs, especially for intra-operative radiographs. METHODS: A retrospective cohort analysis was performed on all adult elective spine surgeries at a single institution between July 2020 and July 2021. Demographic and radiographic data was collected, including intraoperative localization and post-instrumentation radiographs. Financial data was obtained through the institution's price estimator. Radiographic characteristics included time from radiographic imaging to completion of radiologist interpretation report, completion of radiologist interpretation report prior to the conclusion of surgical procedure, clinical relevance, and clinical usefulness. Reports were considered clinically relevant if spinal level of the procedure was described and clinically useful if completed prior to conclusion of the procedure and deemed clinically relevant. RESULTS: 481 intraoperative localization and post-instrumentation radiographs from 360 patients revealed a median delay of 128 minutes between imaging and completion of interpretive report. Only 38.9% of reports were completed before conclusion of surgery. There were 79.4% deemed clinically relevant and only 33.5% were clinically useful. Localization reports were completed more frequently before conclusion of surgery (67.2% vs. 34.4%), but with lower clinical relevance (90.1% vs. 98.5%) and clinical usefulness (60.3% vs. 33.6%) than post-instrumentation reports. Each patient was charged $32-$34 for interpretation fee, cumulating a minimum total cost of $15,392. CONCLUSION: Formal radiographic interpretation of intraoperative spine radiographs was of low clinical utility for spine surgeons. Institutions should consider optimizing radiology workflows to improve timeliness and clinical relevance or evaluate the necessity of reflexive consultation to radiology for intraoperative imaging interpretation to ensure that value-based care is maximized during spine surgeries. LEVEL OF EVIDENCE: 3.

Addressing the Impact of Race and Ethnicity on Musculoskeletal Spine Care in the United States.

➤ Despite being a social construct, race has an impact on outcomes in musculoskeletal spine care.➤ Race is associated with other social determinants of health that may predispose patients to worse outcomes.➤ The musculoskeletal spine literature is limited in its understanding of the causes of race-related outcome trends.➤ Efforts to mitigate race-related disparities in spine care require individual, institutional, and national initiatives.

MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis.

PURPOSE: Lumbar spinal stenosis (LSS) is the most common reason for spinal surgery in patients over the age of 65, and there are few effective non-surgical treatments. Therefore, the development of novel treatment or preventative modalities to decrease overall cost and morbidity associated with LSS is an urgent matter. The cause of LSS is multifactorial; however, a significant contributor is ligamentum flavum hypertrophy (LFH) which causes mechanical compression of the cauda equina or nerve roots. We assessed the role of a novel target, microRNA-29a (miR-29a), in LFH and investigated the potential for using miR-29a as a therapeutic means to combat LSS. METHODS: Ligamentum flavum (LF) tissue was collected from patients undergoing decompressive surgery for LSS and assessed for levels of miR-29a and pro-fibrotic protein expression. LF cell cultures were then transfected with either miR-29a over-expressor (agonist) or inhibitor (antagonist). The effects of over-expression and under-expression of miR-29a on expression of pro-fibrotic proteins was assessed. RESULTS: We demonstrated that LF at stenotic levels had a loss of miR-29a expression. This was associated with greater LF tissue thickness and higher mRNA levels of collagen I and III. We also demonstrated that miR29-a plays a direct role in the regulation of collagen gene expression in ligamentum flavum. Specifically, agents that increase miR-29a may attenuate LFH, while those that decrease miR-29a promote fibrosis and LFH. CONCLUSION: This study demonstrates that miR-29a may potentially be used to treat LFH and provides groundwork to initiate the development of a therapeutic product for LSS.

The Effects of Cervical Orthoses on Head and Intervertebral Range of Motion.

STUDY DESIGN: Prospective Cohort. OBJECTIVE: Quantify and compare the effectiveness of cervical orthoses in restricting intervertebral kinematics during multiplanar motions. SUMMARY OF BACKGROUND DATA: Previous studies evaluating the efficacy of cervical orthoses measured global head motion and did not evaluate individual cervical motion segment mobility. Prior studies focused only on the flexion/extension motion. METHODS: Twenty adults without neck pain participated. Vertebral motion from the occiput through T1 was imaged using dynamic biplane radiography. Intervertebral motion was measured using an automated registration process with validated accuracy better than 1 degree. Participants performed independent trials of maximal flexion/extension, axial rotation, and lateral bending in a randomized order of unbraced, soft collar (foam), hard collar (Aspen), and cervical thoracic orthosis (CTO) (Aspen) conditions. Repeated-measures ANOVA was used to identify differences in the range of motion (ROM) among brace conditions for each motion. RESULTS: Compared with no collar, the soft collar reduced flexion/extension ROM from occiput/C1 through C4/C5, and reduced axial rotation ROM at C1/C2 and from C3/C4 through C5/C6. The soft collar did not reduce motion at any motion segment during lateral bending. Compared with the soft collar, the hard collar reduced intervertebral motion at every motion segment during all motions, except for occiput/C1 during axial rotation and C1/C2 during lateral bending. The CTO reduced motion compared with the hard collar only at C6/C7 during flexion/extension and lateral bending. CONCLUSIONS: The soft collar was ineffective as a restraint to intervertebral motion during lateral bending, but it did reduce intervertebral motion during flexion/extension and axial rotation. The hard collar reduced intervertebral motion compared with the soft collar across all motion directions. The CTO provided a minimal reduction in intervertebral motion compared with the hard collar. The utility in using a CTO rather than a hard collar is questionable, given the cost and little or no additional motion restriction.

Increasing Quality and Frequency of Goals-of-Care Documentation in the Highest-Risk Surgical Candidates: One-Year Results of the Surgical Pause Program.

Patient values may be obscured when decisions are made under the circumstances of constrained time and limited counseling. The objective of this study was to determine if a multidisciplinary review aimed at ensuring goal-concordant treatment and perioperative risk assessment in high-risk orthopaedic trauma patients would increase the quality and frequency of goals-of-care documentation without increasing the rate of adverse events. Methods: We prospectively analyzed a longitudinal cohort of adult patients treated for traumatic orthopaedic injuries that were neither life- nor limb-threatening between January 1, 2020, and July 1, 2021. A rapid multidisciplinary review termed a "surgical pause" (SP) was available to those who were ≥80 years old, were nonambulatory or had minimal ambulation at baseline, and/or resided in a skilled nursing facility, as well as upon clinician request. Metrics analyzed include the proportion and quality of goals-of-care documentation, rate of return to the hospital, complications, length of stay, and mortality. Statistical analysis utilized the Kruskal-Wallis rank and Wilcoxon rank-sum tests for continuous variables and the likelihood-ratio chi-square test for categorical variables. Results: A total of 133 patients were either eligible for the SP or referred by a clinician. Compared with SP-eligible patients who did not undergo an SP, patients who underwent an SP more frequently had goals-of-care notes identified (92.4% versus 75.0%, p = 0.014) and recorded in the appropriate location (71.2% versus 27.5%, p < 0.001), and the notes were more often of high quality (77.3% versus 45.0%, p < 0.001). Mortality rates were nominally higher among SP patients, but these differences were not significant (10.6% versus 5.0%, 5.1% versus 0.0%, and 14.3% versus 7.9% for in-hospital, 30-day, and 90-day mortality, respectively; p > 0.08 for all). Conclusions: The pilot program indicated that an SP is a feasible and effective means of increasing the quality and frequency of goals-of-care documentation in high-risk operative candidates whose traumatic orthopaedic injuries are neither life- nor limb-threatening. This multidisciplinary program aims for goal-concordant treatment plans that minimize modifiable perioperative risks. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Spine Fractures of Patients with Ankylosing Spondylitis and Diffuse Idiopathic Skeletal Hyperostosis: Fracture Severity and Injury-Related Mortality at a Level I Trauma Center.

STUDY DESIGN: Retrospective review of prospectively collected cohort. PURPOSE: To identify differences in treatment and mortality of spine fractures in patients with ankylosing conditions of the spine. OVERVIEW OF LITERATURE: Ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH) are the two most common etiologies of ankylosing spinal disorder (ASD). However, studies on the treatment and outcomes of spine fractures in AS and DISH patients remain few. METHODS: Patients presenting with a spine fracture were diagnosed with AS or DISH at a single tertiary care center between 2010 and 2019. We excluded those who lacked cross-sectional imaging or fractures occurring at spinal segments affected by ankylosis, as well as polytraumatized patients. Patient demographics, injury mechanism, fracture level, neurologic status, treatment, and 1-year mortality were recorded. Computed tomography imaging was reviewed by two independent readers and graded according to the indicated AO Spine Injury Classification System. Differences in fracture severity, treatment method, and mortality were examined using Student t -tests, chi-square tests, and two-proportion Z-tests with significance set to p <0.05. RESULTS: We identified 167 patients with spine fracture diagnosed with AS or DISH. Patients with AS had more severe fractures and more commonly had surgery than patients with DISH (p <0.001). Despite these differences, 1-year mortality did not significantly differ between AS and DISH patients (p =0.14). CONCLUSIONS: Although patients with AS suffered more severe fractures compared to DISH and more frequently underwent surgery for these injuries, outcomes and 1-year mortality did not differ significantly between the two groups. For patients with ASDs and fractures, outcomes appear similar regardless of treatment modality. Consequently, there may be an opportunity for critical reappraisal of operative indications in ASD and a larger role for nonoperative management in these challenging patients.

Neck Symptoms and Associated Clinical Outcomes in Patients Following Concussion.

OBJECTIVE: To examine the frequency and association of neck pain symptoms in patients with a concussion. STUDY SETTING AND PARTICIPANTS: Three-hundred and thirty-one consecutively enrolled patients aged 9 to 68 years with a diagnosed concussion 1 to 384 days post-injury were enrolled at a concussion clinic from a single integrated healthcare system in Western Pennsylvania between 2019 and 2021. DESIGN: Retrospective cohort analysis of prospectively collected concussion screening tool intake survey responses and clinical outcomes data. The primary outcome was self-reported neck pain or difficulty with neck movement on the Concussion Clinical Profiles Screening (CP Screen) tool, recovery time, and incidence of treatment referral. Immediate Post-concussion Assessment and Cognitive Testing (ImPACT) composite scores, Vestibular/Ocular Motor Screening (VOMS) item scores, type and severity of neck symptoms, mechanism of injury, time from injury to clinic presentation, medical history, and concussion symptom profile were secondary outcomes. RESULTS: Of the 306 consecutively enrolled eligible patients in the registry, 145 (47%) reported neck pain, 68 (22.2%) reported difficulty moving their neck, and 146 (47.7%) reported either symptom. A total of 47 (15.4%) participants reported more severe neck symptoms, and this group took longer to recover (40 ± 27 days) than those not reporting neck symptoms (30 ± 28 days; U = 8316, P < .001). Stepwise logistic regression predicting more severe neck symptoms was significant (Nagelkerke R2 = 0.174, χ 2 = 9.315, P = .316) with older age ( P = .019) and mechanism of injury including motor vehicle collisions (MVCs) ( P = .047) and falls ( P = .044) as risk factors. MVCs and falls were associated with over 4 times and 2 times greater risk, respectively, for reporting more severe neck symptoms. CONCLUSION: Neck pain and stiffness symptoms are common in patients with a concussion following high-energy mechanisms of injury including MVCs or falls from height. These symptoms are associated with prolonged recovery. Providers should evaluate neck symptoms and consider targeted treatment strategies to limit their effects in patients with a concussion.

Multilevel tandem spondylolisthesis associated with a reduced "safe zone" for a transpsoas lateral lumbar interbody fusion at L4-5.

OBJECTIVE: The aim of this study was to investigate the effect of degenerative spondylolisthesis (DS) on psoas anatomy and the L4-5 safe zone during lateral lumbar interbody fusion (LLIF). METHODS: In this retrospective, single-institution analysis, patients managed for low-back pain between 2016 and 2021 were identified. Inclusion criteria were adequate lumbar MR images and radiographs. Exclusion criteria were spine trauma, infection, metastases, transitional anatomy, or prior surgery. There were three age and sex propensity-matched cohorts: 1) controls without DS; 2) patients with single-level DS (SLDS); and 3) patients with multilevel, tandem DS (TDS). Axial T2-weighted MRI was used to measure the apical (ventral) and central positions of the psoas relative to the posterior tangent line at the L4-5 disc. Lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI-LL mismatch were measured on lumbar radiographs. The primary outcomes were apical and central psoas positions at L4-5, which were calculated using stepwise multivariate linear regression including demographics, spinopelvic parameters, and degree of DS. Secondary outcomes were associations between single- and multilevel DS and spinopelvic parameters, which were calculated using one-way ANOVA with Bonferroni correction for between-group comparisons. RESULTS: A total of 230 patients (92 without DS, 92 with SLDS, and 46 with TDS) were included. The mean age was 68.0 ± 8.9 years, and 185 patients (80.4%) were female. The mean BMI was 31.0 ± 7.1, and the mean age-adjusted Charlson Comorbidity Index (aCCI) was 4.2 ± 1.8. Age, BMI, sex, and aCCI were similar between the groups. Each increased grade of DS (no DS to SLDS to TDS) was associated with significantly increased PI (p < 0.05 for all relationships). PT, PI-LL mismatch, center psoas, and apical position were all significantly greater in the TDS group than in the no-DS and SLDS groups (p < 0.05). DS severity was independently associated with 2.4-mm (95% CI 1.1-3.8 mm) center and 2.6-mm (95% CI 1.2-3.9 mm) apical psoas anterior displacement per increased grade (increasing from no DS to SLDS to TDS). CONCLUSIONS: TDS represents more severe sagittal malalignment (PI-LL mismatch), pelvic compensation (PT), and changes in the psoas major muscle compared with no DS, and SLDS and is a risk factor for lumbar plexus injury during L4-5 LLIF due to a smaller safe zone.

Changes in intervertebral sagittal alignment of the cervical spine from supine to upright.

Cervical sagittal alignment is a critical component of successful surgical outcomes. Unrecognized differences in intervertebral alignment between supine and upright positions may affect clinical outcomes; however, these differences have not been quantified. Sixty-four patients scheduled to undergo one or two-level cervical arthrodesis for symptomatic pathology from C4-C5 to C6-C7, and forty-seven controls were recruited. Upright sagittal alignment was obtained through biplane radiographic imaging and measured using a validated process with accuracy better than 1° in rotation. Supine alignment was obtained from computed tomography scans. Coordinate systems used to measure supine and upright alignment were identical. Distances between adjacent bony endplates were measured to calculate disc height in each position. For both patients and controls, the C1-C2, C2-C3, and C3-C4 motion segments were in more lordosis when upright as compared with supine (all p < 0.001). However, the C4-C5, C5-C6, and C6-C7 motion segments were in less lordosis when upright as compared with supine (all p ≤ 0.004). There was an interaction between group and position at the C1-C2 (p = 0.002) and C2-C3 (p = 0.001) motion segments, with the controls demonstrating a greater increase in lordosis at both motion segments when moving from supine to upright. The results indicate that cervical motion segment alignment changes between supine and upright positioning, those changes differ among motion segments, and cervical pathology affects the magnitude of these changes. Clinical Significance: Surgeons should be mindful of the differences in alignment between supine and upright imaging and the implications they may have on clinical outcomes.

To Cross the Cervicothoracic Junction? Terminating Posterior Cervical Fusion Constructs Proximal to the Cervicothoracic Junction Does Not Impart Increased Risk of Reoperation in Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To evaluate the effect of caudal instrumentation level on revision rates following posterior cervical laminectomy and fusion. METHODS: A retrospective review of a prospectively collected database was performed. Minimum follow-up was one year. Patients were divided into two groups based on the caudal level of their index fusion construct (Group 1-cervical and Group 2- thoracic). Reoperation rates were compared between the two groups, and preoperative demographics and radiographic parameters were compared between patients who required revision and those who did not. Multivariate binomial regression analysis was performed to determine independent risk factors for revision surgery. RESULTS: One hundred thirty-seven (137/204) patients received fusion constructs that terminated at C7 (Group 1), while 67 (67/204) received fusion constructs that terminated at T1 or T2 (Group 2). The revision rate was 8.33% in the combined cohort, 7.3% in Group 1, and 10.4% in Group 2. There was no significant difference in revision rates between the 2 groups (P = .43). Multivariate regression analysis did not identify any independent risk factors for revision surgery. CONCLUSION: This study shows no evidence of increased risk of revision in patients with fusion constructs terminating in the cervical spine when compared to patients with constructs crossing the cervicothoracic junction. These findings support terminating the fusion construct proximal to the cervicothoracic junction when indicated. LEVEL OF EVIDENCE: III.

Percutaneous lumbar annular puncture: A rat model to study intervertebral disc degeneration and pain-related behavior.

Background: Previous animal models of intervertebral disc degeneration (IDD) rely on open surgical approaches, which confound the degenerative response and pain behaviors due to injury to surrounding tissues during the surgical approach. To overcome these challenges, we developed a minimally invasive percutaneous puncture procedure to induce IDD in a rat model. Methods: Ten Fischer 344 male rats underwent percutaneous annular puncture of lumbar intervertebral discs (IVDs) at L2-3, L3-4, and L4-5. Ten unpunctured rats were used as controls. Magnetic resonance imagings (MRIs), serum biomarkers, and behavioral tests were performed at baseline and 6, 12, and 18 weeks post puncture. Rats were sacrificed at 18 weeks and disc histology, immunohistochemistry, and glycosaminoglycan (GAG) assays were performed. Results: Punctured IVDs exhibited significant reductions in MRI signal intensity and disc volume. Disc histology, immunohistochemistry, and GAG assay results were consistent with features of IDD. IVD-punctured rats demonstrated significant changes in pain-related behaviors, including total distance moved, twitching frequency, and rearing duration. Conclusions: This is the first reported study of the successful establishment of a reproducible rodent model of a percutaneous lumbar annular puncture resulting in discogenic pain. This model will be useful to test therapeutics and elucidate the basic mechanisms of IDD and discogenic pain.

Ionizing Radiation Induces Disc Annulus Fibrosus Senescence and Matrix Catabolism via MMP-Mediated Pathways.

Previous research has identified an association between external radiation and disc degeneration, but the mechanism was poorly understood. This study explores the effects of ionizing radiation (IR) on inducing cellular senescence of annulus fibrosus (AF) in cell culture and in an in vivo mouse model. Exposure of AF cell culture to 10-15 Gy IR for 5 min followed by 5 days of culture incubation resulted in almost complete senescence induction as evidenced by SA-ßgal positive staining of cells and elevated mRNA expression of the p16 and p21 senescent markers. IR-induced senescent AF cells exhibited increased matrix catabolism, including elevated matrix metalloproteinase (MMP)-1 and -3 protein expression and aggrecanolysis. Analogous results were seen with whole body IR-exposed mice, demonstrating that genotoxic stress also drives disc cellular senescence and matrix catabolism in vivo. These results have important clinical implications in the potential adverse effects of ionizing radiation on spinal health.

Obstructive sleep apnea in patients with Down syndrome: current perspectives.

For individuals with Down syndrome (DS), obstructive sleep apnea (OSA) is a complex disorder with significant clinical consequences. OSA is seen frequently in DS, and when present, it tends to be more severe. This increased prevalence is likely related to common anatomic abnormalities and a greater risk of additional comorbidities such as hypotonia and obesity. Because signs and symptoms do not often correlate with disease, all children and adults with DS should receive routine screening for OSA. Similar to the general population, polysomnography remains the gold standard for diagnosis. Because individuals with DS may be more susceptible to cardiovascular and neurocognitive sequelae, early diagnosis and treatment of OSA is becoming increasingly important. Treatment options generally involve upper airway surgery (primarily adenotonsillectomy) and continuous positive airway pressure (CPAP); however, various adjunctive therapies including intranasal steroids, palatal expansion, and oropharyngeal exercises are also available. Residual disease status post adenotonsillectomy is common, and further evaluation (eg, drug-induced sleep endoscopy [DISE]) is often needed. More advanced and directed airway surgery can be performed if additional sites of obstruction are observed. Novel therapies including hypoglossal nerve stimulation are emerging as effective treatments for refractory OSA. Due to the diversity among individuals with DS, personalized treatment plans should be developed. Within this arena, opportunities for research remain abundant and should include areas involving patient risk factors, alternative diagnostic methods, and outcome analysis.