Acquired tracheomalacia due to SARS-CoV-2 pneumonia.

INTRODUCTION: Several studies mentioned parenchymal findings after SARS-CoV-2 pneumonia, but few studies have mentioned alterations in the airways. The aim of this study was to estimate the prevalence of tracheomalacia and to analyse the clinical characteristics in a cohort of patients with SARS-CoV-2. METHODS: The study population consisted of all patients with SARS-CoV-2 admitted a hospital serving a population of 500 000 inhabitants. Patients were visited between 2 and 6 months after hospital discharge. In this visit, all patients were subjected to an exhaustive clinical questionnaire and underwent clinical examination, pulmonary function tests and chest CT. RESULTS: From February 2020 to August 2021, 1920 patients were included in the cohort and tracheomalacia was observed in 15 (0.8%) on expiratory HRCT imaging. All patients with tracheomalacia also presented ground glass opacities in the CT scan and 12 patients had airway sequelae. CONCLUSIONS: Tracheomalacia is an exceptional sequela of SARS-CoV-2 survivors.

Study on the rationality of small diameter metallic airway stent in treatment of tracheal stenosis in injured rabbits.

BACKGROUND: To observe the occurrence of related complications after self-expandable metallic (SEM) airway stents implantation with different diameters at different time points, and to provide theoretical basis for the optimal chioce of existing airway stents in clinical practice. METHODS: Healthy New Zealand white rabbits were used to establish benign tracheal stenosis models after chest CT examination. Forty-fivemodel rabbits with more than 50% of airway stenosis were divided into two groups. Small-diameter SEM stents (The ratio of stent diameter to airway diameter is nearly 1.0) were implanted in Group A in 21 rabbits, and large-diameter tracheal stents (The ratio of stent diameter to airway diameter is more than 1.2) were implanted in Group B in 24 rabbits. Stent-related complications were observed after stent implantation in 2nd,4th,8th, and 12th week by bronchoscopygross anatomy, pathological and the expressions of IL-1RA, IL-8 and MMP9 in involved tracheal. RESULTS: The incidence rate of tracheomalacia of stent was significantly higher in group B (24/24 100%) than that in group A (1 /21,4.8%) (P < 0.05). The incidence rate of scar contracture at both ends of stent was significantly higher than in group B (11 / 24,45.8%) that in group A (2 /21, 9.5%) (P < 0.05). The pathological results of both A and B showed that the columnar epithelium of bronchial mucosa began to damage and detach, inflammatory cells infiltrated after 2nd and 4th week of stenting, The epithelium was repaired, the lamina propria glands almost disappeared, collagen fiber proliferation was obvious, and scars were formed after 8th and 12th week of stenting. ELISA results revealed that the expressions of IL-1RA, IL-8, and MMP9 were increased in the stent group than in model rabbit with benign tracheal stenosis. IL-1RA and MMP9 increased at different periods in group B, but the expression of IL-1RA and MMP9 showed a tread of increasing in the early stage and then decreasing in group A. CONCLUSION: Metal stents can cause different degrees of stent-related complications in rabbits with benign tracheal stenosis. The incidence of stent-induced tracheomalacia and scar contracture were higher in Group B than that in Group A. IL-1RA, IL-8 and MMP9 may be involved in the development of complications after stentimplantation and peak value of group B movered backward. ing.

Frequency and Risk Factors of Tracheomalacia in Patients Undergoing Thyroidectomy.

It was a descriptive cross-sectional study to determine the frequency and risk factors of tracheomalacia in patients undergoing thyroidectomy. One hundred and forty-nine patients underwent thyroidectomy at MTI-Khyber Teaching Hospital Peshawar between 1st January 2021 and 1st March 2022. The frequency of post-thyroidectomy tracheomalacia and possible associated factors were determined. The inclusion criteria were patients of either gender, between 18 to 70 years fulfilling criteria of clinically diagnosed cases of thyroid disorders who underwent subtotal, hemi, near or total thyroidectomy for their respective thyroid diseases. Post-thyroidectomy tracheomalacia was recorded in 18 patients (12.1%): Seventeen patients were aged less than 30 (p-value 0.038) and 14 (77.8%) patients had a duration of surgery > three hours (p-value <0.001). Young female patients with multinodular goitre who had a longer duration of surgery developed post-thyroidectomy tracheomalacia more frequently. Hence, the incidence of post-thyroidectomy tracheomalacia can be markedly reduced with proper preoperative assessment and postoperative measures. Key Words: Thyroid gland, Thyroid disorders, Tracheomalacia, Thyroidectomy.

Dynamic airway computed tomography and flexible bronchoscopy for diagnosis of tracheomalacia in children: A comparison study.

INTRODUCTION: Tracheomalacia (TM) is an important cause of respiratory morbidity. Dynamic flexible bronchoscopy is considered the gold standard for diagnosis. Dynamic airway computed tomography (DACT) is a low radiation, noninvasive diagnostic tool utilizing images obtained continuously over several respiratory cycles. We aimed to assess the accuracy of DACT in TM diagnosis. METHODS: Retrospective analysis of all patients who underwent both DACT and flexible bronchoscopy within 6 months. Airway anterior-posterior (AP) diameter was measured on multiplanar reconstructions CT in both the inspiratory and expiratory phases. Using still images from the bronchoscopy videos, the AP diameter of the trachea was measured at points of maximal and minimal diameter during tidal breathing. Degree of TM on both DACT and flexible bronchoscopy were graded using a scaling system of 50%-74%, 75%-89%, and 90%-100% as described by the European Respiratory Society. RESULTS: Twenty-four patients met inclusion criteria with an average time of 19.5 days between CT and bronchoscopy. The specificity and sensitivity of DACT for the overall diagnosis of TM was 100% and 68%, respectively, with a positive predictive value of 100% and a negative predictive value of 62%. There was a strong positive correlation between DACT and flexible bronchoscopy in the measurement of tracheal AP diameter changes (ρ = 0.773, R2 0.597, p = 0.00001). Mean effective radiation dose for DACT was 0.1 mSv. CONCLUSION: Ultralow dose DACT has excellent specificity and positive predictive value for both detection of TM and categorizing severity of tracheal collapse but is not sufficiently sensitive to rule it out.

Flexible bronchoscopy findings and management impact in children with oropharyngeal dysphagia.

INTRODUCTION: Flexible bronchoscopy (FB) and bronchoalveolar lavage (BAL) are frequently performed in children with known or suspected aspiration, however, the additive value of FB in conjunction with direct laryngoscopy and rigid bronchoscopy (DLB) has not been previously quantified. This study details the common endoscopic/cytological findings and associated management impact of FB and BAL in pediatric Aerodigestive patients undergoing combined airway evaluation (FB and DLB) for oropharyngeal dysphagia. MATERIALS AND METHODS: A retrospective chart review was performed in children <3 years of age followed through a large Aerodigestive center undergoing outpatient, combined airway endoscopy for dysphagia. Patient and procedural characteristics, endoscopic and BAL findings, and management metrics were collected and analyzed. A secondary analysis evaluated the association between endoscopic findings and medication changes. RESULTS: Ninety-one procedures (median patient age, 15 months) were identified. All procedures included both FB and DLB, and just over half (52.7%) included esophagogastroduodenoscopy. Common endoscopic findings included bronchitis (73.6%), adenoidal hypertrophy (31.9%), and tracheomalacia (10.8%). BAL cytology frequently identified neutrophilic inflammation (mean 39.6% neutrophils [interquartile range 6.5%-71%)]. Cultured pathogens commonly included Streptococcus viridans (46.6%), Hemophilus influenzae (36.3%), Moraxella catarrhalis (30.1%), and Streptococcus pneumoniae (25.0%). FB and BAL results contributed to clinical decisions in 65 of 91 (71.4%) patients. Endoscopically-diagnosed bronchitis (odds ratio [OR] 7.27, 95% confidence interval [CI] 2.4-21.99) and tracheomalacia (OR 5.79, 95% CI 1.20-27.85) were significantly associated with increased odds of medication adjustments following FB. CONCLUSION: In pediatric Aerodigestive patients undergoing combined airway evaluation for oropharyngeal dysphagia, FB and BAL are high-yield and clinically impactful procedures.

Tracheomalacia Reduces Aerosolized Drug Delivery to the Lung.

Rationale: Neonates with respiratory issues are frequently treated with aerosolized medications to manage lung disease or facilitate airway clearance. Dynamic tracheal collapse (tracheomalacia [TM]) is a common comorbidity in these patients, but it is unknown whether the presence of TM alters the delivery of aerosolized drugs. Objectives: To quantify the effect of neonatal TM on the delivery of aerosolized drugs. Methods: Fourteen infant subjects with respiratory abnormalities were recruited; seven with TM and seven without TM. Respiratory-gated 3D ultrashort echo time magnetic resonance imaging (MRI) was acquired covering the central airway and lungs. For each subject, a computational fluid dynamics simulation modeled the airflow and particle transport in the central airway based on patient-specific airway anatomy, motion, and airflow rates derived from MRI. Results: Less aerosolized drug reached the distal airways in subjects with TM than in subjects without TM: of the total drug delivered, less particle mass passed through the main bronchi in subjects with TM compared with subjects without TM (33% vs. 47%, p = 0.013). In subjects with TM, more inhaled particles were deposited on the surface of the airway (48% vs. 25%, p = 0.003). This effect becomes greater with larger particle sizes and is significant for particles with a diameter >2 µm (2-5 µm, p ≤ 0.025 and 5-15 µm, p = 0.004). Conclusions: Neonatal patients with TM receive less aerosolized drug delivered to the lungs than subjects without TM. Currently, infants with lung disease and TM may not be receiving adequate and/or expected medication. Particles >2 µm in diameter are likely to deposit on the surface of the airway due to anatomical constrictions such as reduced tracheal and glottal cross-sectional area in neonates with TM. This problem could be alleviated by delivering smaller aerosolized particles.

Open and Thoracoscopic Aortopexy for Airway Malacia in Children: 15 Year Single Centre Experience.

OBJECTIVES: The objective was to report and analyse the characteristics and results of open aortopexy and thoracoscopic aortopexy for the treatment of airway malacia in a paediatric population. METHODS: We report a retrospective consecutive case series of paediatric patients undergoing aortopexy for the treatment of airway malacia at a quaternary referral centre between December 2006 and January 2021. Outcome measures included days to extubation, continued need for non-invasive ventilation, further intervention in the form of tracheostomy and death. RESULTS: 169 patients underwent aortopexy: 147 had open procedures (135 via median/limited median sternotomy and 12 thoracotomy) and 22 thoracoscopic. Mean follow up was 8.46 yrs (range 1-20 yrs). Most common site of airway malacia was the trachea (n = 106, 62.7 %), and 48 (28.4 %) had additional involvement at the bronchi with tracheobronchomalacia (TBM). 15 (8.9 %) had bronchomalacia (BM) only. Incidence of bronchial disease was lower in the thoracoscopic than open group (13.6 % vs 40.82 %; p < 0.0001). Mean time to extubation was 1.45 days, 2.59 days, 5.23 days in tracheomalacia, TBM and BM groups, respectively (p = 0.0047). Mean time to extubation was 1.35 days, 2 days, 3.67 days, and 5 days in patients with external vascular compression, TOF/OA, primary airway malacia, and laryngeal reconstruction, respectively (p = 0.0002). There were 21 deaths across the cohort, and all were in the open group. 71.4 % (n = 15) had bronchial involvement of their airway malacia. CONCLUSIONS: Open and thoracoscopic aortopexy are effective treatments for airway malacia in children. We have identified that involvement of the bronchi is a risk factor for adverse outcomes, and the optimum treatment for this patient cohort is still debatable. LEVEL OF EVIDENCE: IV. TYPE OF STUDY: Retrospective Study.

Update on aortopexy and posterior tracheopexy for tracheomalacia in patients with esophageal atresia.

Despite improving the survival after repair of esophageal atresia (EA), the morbidity of EA repair remains high. Specifically, tracheomalacia (TM) is one of the most frequent complications of EA repair. Continuous positive airway pressure is generally applied for the treatment of TM. However, surgical intervention is required against an apparent life-threatening event or inability to perform extubation for a long period. According to our review, most cases of TM showed symptom improvement after aortopexy. The ratio of the trachea's lateral and anterior-posterior diameter at the brachiocephalic artery crossing the trachea, which reflects the compression of the trachea by the brachiocephalic artery, is a good indicator of aortopexy. Our finding suggests that most TM cases associated with EA may not be caused by tracheal fragility alone, but may involve blood vessel compression. Posterior tracheopexy (PT) is also an effective treatment for TM. Recently, open or thoracoscopic PT was able to be performed simultaneously with EA repair. In many cases, aortopexy or PT is a safe and effective surgical treatment for TM with EA. Other surgical procedures, such as external stenting, should be considered for patients with diffuse-type TM for whom aortopexy and PT appear relatively ineffective.

Predictors of response to endoscopic management of subglottic/tracheal stenosis in patients without tracheostomy.

INTRODUCTION: Subglottic and tracheal stenosis (SGTS) in adults is an acquired or idiopathic condition that can lead to dyspnea, and even life-threatening airway obstruction. Endoscopic techniques have advanced and largely eclipsed open surgery, with open surgery now reserved for refractory cases (Hseu et al., 2013; Feinstein et al., 2017). Currently, there is no accepted guideline for the endoscopic treatment of SGTS. Thus, the aim of the present study is to examine the impact of various clinical and pathological characteristics on outcomes to endoscopic treatment in a cohort of SGTS patients. DISCLOSURE: None of the authors have any financial or personal relationship that could cause a conflict of interest regarding this article. METHODS: Retrospective chart review was performed for 41 patients presenting with SGS without a tracheostomy over a 4-year-period (2018-2022), within a single tertiary care center. Quantitative outcomes including number of dilation procedures undergone and need for open procedures were examined. The qualitative variables included a history of pulmonary disease, prior tracheostomy/tracheal resection, presence of tracheomalacia, granulation tissue, excessive dynamic airway collapse (EDAC), and etiology of idiopathic subglottic stenosis. RESULTS: The presence of granulation tissue seen on tracheoscopy was associated with a higher number (4+) of dilation procedures (p = 0.01). A history of pulmonary disease (p = 0.037), the presence of tracheomalacia (p = 0.039), and the presence of granulation tissue (0.003) were all associated with a need for open procedures. CONCLUSION: Patients with the presence of granulation tissue, tracheomalacia, and a history of pulmonary disease were more associated with more severe disease requiring either a higher number of endoscopic procedures or need for open procedures.

A case report of tracheal tenting to the skin: An option to tracheostomy for post-thyroidectomy tracheomalacia.

Operating on a huge and long-standing goiter is challenging to the surgeon and anesthetist because of the possibility of tracheomalacia and collapse of the tracheal rings after extubation. We report our innovation of tenting the trachea to the skin using sutures (passed through the strap and sternocleidomastoid muscles) to prevent post-thyroidectomy tracheomalacia.

Prevalence of symptomatic tracheal morbidities after fetoscopic endoluminal tracheal occlusion: a systematic review and meta-analysis.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been shown to improve survival of infants with congenital diaphragmatic hernia (CDH). However, there are concerns that FETO may lead to tracheomegaly, tracheomalacia and related complications. METHODS: A systematic review was conducted to estimate the prevalence of symptomatic tracheal complications in infants who underwent FETO for CDH. Presence of one or more of the following was considered as tracheal complication: tracheomalacia, stenosis, laceration or tracheomegaly with symptoms such as stridor, effort-induced barking cough, recurrent chest infections or the need for tracheostomy, tracheal suturing, or stenting. Isolated tracheomegaly on imaging or routine bronchoscopy without clinical symptoms was not considered as tracheal morbidity. Statistical analysis was performed using the metaprop command on Stata V.16.0. RESULTS: A total of 10 studies (449 infants) were included (6 retrospective cohort, 2 prospective cohort and 2 randomised controlled trials). There were 228 infants who survived to discharge. Prevalence rates of tracheal complications in infants born alive were 6% (95% CI 2% to 12%) and 12% (95% CI 4% to 22%) in those who survived to discharge. The spectrum of severity ranged from relatively mild symptoms such as effort-induced barking cough to the need for tracheostomy/tracheal stenting. CONCLUSION: A significant proportion of FETO survivors have symptomatic tracheal morbidities of varying severity. Units that are planning to adopt FETO for managing CDH should consider ongoing surveillance of survivors to enable early identification of upper airway issues. Inventing FETO devices that minimise tracheal injury is needed.

External airway splint placement for severe pediatric tracheobronchomalacia.

OBJECTIVE: To present external airway splinting with bioabsorbable airway supportive devices (ASD) for severe, life-threatening cases of pediatric tracheomalacia (TM) or tracheobronchomalacia (TBM). METHODS: A retrospective cohort was performed for 5 pediatric patients with severe TM or TBM who underwent ASD placement. Devices were designed and 3D-printed from a bioabsorbable material, polycaprolactone (PCL). Pre-operative planning included 3-dimensional airway modeling of tracheal collapse and tracheal suture placement using nonlinear finite element (FE) methods. Pre-operative modeling revealed that triads along the ASD open edges and center were the most effective suture locations for optimizing airway patency. Pediatric cardiothoracic surgery and otolaryngology applied the ASDs by suspending the trachea to the ASD with synchronous bronchoscopy. Respiratory needs were trended for all cases. Data from pediatric patients with tracheostomy and diagnosis of TM or TBM, but without ASD, were included for discussion. RESULTS: Five patients (2 Females, 3 Males, ages 2-9 months at time of ASD) were included. Three patients were unable to wean from respiratory support after vascular ring division; all three weaned to room air post-ASD. Two patients received tracheostomies prior to ASD placement, but continued to experience apparent life-threatening events (ALTE) and required ventilation with supraphysiologic ventilator settings. One patient weaned respiratory support successfully after ASD placement. The last patient died post-ASD due to significant respiratory co-morbidity. CONCLUSION: ASD can significantly benefit patients with severe, unrelenting tracheomalacia or tracheobronchomalacia. Proper multidisciplinary case deliberation and selection are key to success with ASD. Pre-operative airway modeling allows proper suture placement to optimally address the underlying airway collapse.

Acquired Tracheomalacia Requiring Urgent Tracheostomy Exchange in Patients With COVID-19.

Tracheostomy for prolonged ventilation of patients with COVID-19 was often delayed due to high viral loads and persistent high ventilatory requirements. With prolonged intubation and significant dose corticosteroid use, patients with COVID-19 are at risk for tracheomalacia, and urgent tube exchange may be required to address persistent cuff leak and to maintain adequate mechanical ventilation. We sought to describe our single center experience with COVID-19 patients requiring tracheostomy and the tracheal complications that followed. We performed a review of patients with COVID-19 who underwent tracheostomy from June 2020 to October 2021. 45 patients were identified; 82.2% survived their index hospitalization. Tracheostomy was performed after 16.4 days of mechanical ventilation. 22.2% required urgent exchange to an extended length tracheostomy tube after 7.2 days from initial tracheostomy. Placement of an extended length tracheostomy tube can reduce cuff leak in ventilated COVID-19 patients and may be considered during initial tracheostomy placement.

Automatic segmentation and measurement of tracheal collapsibility in tracheomalacia.

PURPOSE: To assess feasibility of automated segmentation and measurement of tracheal collapsibility for detecting tracheomalacia on inspiratory and expiratory chest CT images. METHODS: Our study included 123 patients (age 67 ± 11 years; female: male 69:54) who underwent clinically indicated chest CT examinations in both inspiration and expiration phases. A thoracic radiologist measured anteroposterior length of trachea in inspiration and expiration phase image at the level of maximum collapsibility or aortic arch (in absence of luminal change). Separately, another investigator separately processed the inspiratory and expiratory DICOM CT images with Airway Segmentation component of a commercial COPD software (IntelliSpace Portal, Philips Healthcare). Upon segmentation, the software automatically estimated average lumen diameter (in mm) and lumen area (sq.mm) both along the entire length of trachea and at the level of aortic arch. Data were analyzed with independent t-tests and area under the receiver operating characteristic curve (AUC). RESULTS: Of the 123 patients, 48 patients had tracheomalacia and 75 patients did not. Ratios of inspiration to expiration phases average lumen area and lumen diameter from the length of trachea had the highest AUC of 0.93 (95% CI = 0.88-0.97) for differentiating presence and absence of tracheomalacia. A decrease of ≥25% in average lumen diameter had sensitivity of 82% and specificity of 87% for detecting tracheomalacia. A decrease of ≥40% in the average lumen area had sensitivity and specificity of 86% for detecting tracheomalacia. CONCLUSION: Automatic segmentation and measurement of tracheal dimension over the entire tracheal length is more accurate than a single-level measurement for detecting tracheomalacia.

Decannulation in Trisomy 21 patients undergoing laryngotracheal reconstruction.

BACKGROUND: Down Syndrome (DS) patients are more susceptible to either congenital or acquired subglottic stenosis (SGS). This often creates a multilevel airway obstruction and can lead to tracheostomy dependence early in life. As a result, they may require Laryngotracheal Reconstruction (LTR) to achieve decannulation. The primary objective of this study was to assess decannulation rates, time to decannulation and potential barriers to decannulation in DS patients undergoing LTR. METHODS: We performed a retrospective chart review from 2008 to 2021 of 193 children who underwent LTR for treatment for laryngotracheal stenosis at a stand-alone tertiary children's hospital. The relationship between clinical data and decannulation status was evaluated using multivariable logistic regression and Fisher exact tests. Time to decannulation analysis was performed using Kaplan Meier analysis and evaluated with log-rank and Cox proportional hazards regression. RESULTS: We determined that DS patients carry an inherit risk for decannulation failure compared to the general population (OR: 6.112, P = . 044, CI 1.046-35.730). Of the 8 patients with DS only three were decannulated. Overall, patients with Trisomy 21 had a significantly increased time to decannulation when compared to all LTR patients (P = .008, Log-rank). We found that these patients are more likely to have both suprastomal collapse (P = .0004, Fischer's Exact) and Tracheomalacia (P = .034, Fischer's Exact) compared to all other LTR patients. While post-operative tracheomalacia did not significantly affect decannulation failure (P = .056, Fischer's Exact) it did significantly prolong decannulation in all LTR patients (P = .018, Log-rank). CONCLUSION: Trisomy 21 patients are at an increased risk for decannulation failure. Our study illustrates that these poor outcomes are likely a result of conditions more commonly found in this cohort including: narrow tracheal caliber, tracheomalacia and hypotonia.

Unsuspected severe tracheal stenosis and tracheomalacia after correction surgery for congenital scoliosis: A case report.

Tracheal stenosis and tracheomalacia in patients with congenital scoliosis are serious and rare conditions caused by congenital dysplasia, postintubation injury, trauma, and tracheal tumor. Anesthesia of a child with tracheal stenosis is challenging for anesthesiologists. We describe an 8-year-old female patient developed severe tracheal stenosis and tracheomalacia after growing rod implantation for congenital scoliosis. Comprehensive assessment of preoperative pulmonary function and airway morphology, which can be neglected clinically, should be performed in congenital scoliosis patients.

Dynamic Volumetric Computed Tomography Angiography is an Effective Method to Evaluate Tracheomalacia in Children.

OBJECTIVE: Standard methods to evaluate tracheal pathology in children, including bronchoscopy, may require general anesthesia. Conventional dynamic proximal airway imaging in noncooperative children requires endotracheal intubation and/or medically induced apnea, which may affect airway mechanics and diagnostic performance. We describe a technique for unsedated dynamic volumetric computed tomography angiography (DV-CTA) of the proximal airway and surrounding vasculature in children and evaluate its performance compared to the reference-standard of rigid bronchoscopy. METHODS: Children who had undergone DV-CTA and bronchoscopy in one-year were retrospectively identified. Imaging studies were reviewed by an expert reader blinded to the bronchoscopy findings of primary or secondary tracheomalacia. Airway narrowing, if present, was characterized as static and/or dynamic, with tracheomalacia defined as >50% collapse of the tracheal cross-sectional area in exhalation. Pearson correlation was used for comparison. RESULTS: Over a 19-month period, we identified 32 children (median age 8 months, range 3-14 months) who had undergone DV-CTA and bronchoscopy within a 90-day period of each other. All studies were unsedated and free-breathing. The primary reasons for evaluation included noisy breathing, stridor, and screening for tracheomalacia. There was excellent agreement between DV-CTA and bronchoscopy for diagnosis of tracheomalacia (κ = 0.81, p < 0.001), which improved if children (n = 25) had the studies within 30 days of each other (κ = 0.91, p < 0.001). CTA provided incremental information on severity, and cause of secondary tracheomalacia. CONCLUSION: For most children, DV-CTA requires no sedation or respiratory manipulation and correlates strongly with bronchoscopy for the diagnosis of tracheomalacia. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:410-416, 2023.