Indian Journal of Dental Research

ORIGINAL RESEARCH
Year
: 2011  |  Volume : 22  |  Issue : 6  |  Page : 739--748

Evaluation of craniofacial morphology in patients with obstructive sleep apnea using lateral cephalometry and dynamic MRI


Rekha Bharadwaj1, A Ravikumar2, NR Krishnaswamy1,  
1 Department of Orthodontics, Ragas Dental College and Hospitals, Chennai, India
2 Department of ENT, Sri Ramachandra Medical College and Research Institute, (Deemed University), Chennai, India

Correspondence Address:
Rekha Bharadwaj
Department of Orthodontics, Ragas Dental College and Hospitals, Chennai
India

Abstract

Context: Obstructive sleep apnea (OSA) is a potentially life-threatening disorder, characterized by repeated collapse of the upper airway during sleep with cessation of breathing. The altered mouth breathing produces morphological changes in craniofacial region. Aim: This study was designed to compare and validate the craniofacial morphological characteristics in patients with OSA using lateral cephalometry and to investigate the dentofacial characteristics of patients with OSA with respect to the obstructive sites determined by dynamic magnetic resonance imaging (MRI) to more accurately clarify the pathophysiological features. Materials and Methods: 10 patients with OSA were divided into two groups of five each according to their obstructive site determined by dynamic MRI. (1) Obstruction at the retropalatal and retroglossal region (Rp + Rg group) and (2) obstruction at the retropalatal region (Rp group). Lateral cephalogram both in upright and supine position was taken for all the subjects. In addition, dynamic MRI was performed to identify the sites of obstruction of the upper airway. Statistical analysis used: Independent t-test was performed to evaluate the significant difference in the upright cephalometric variables between the study and control group and between the two groups. The changes in skeletal and soft tissue parameters with change in posture was assessed within the study and control group by paired t test. P value of ≤0.05 was considered as statistically significant. Results: The study indicated that the first group of patients with both retropalatal and retroglossal obstruction showed signs of skeletal discrepancy that predisposed to obstruction at the retroglossal level and the soft tissue components like the soft palate and tongue that contributed to retropalatal obstruction. However, the second group of patients with only retropalatal obstruction had primarily soft tissue components associated with increased BMI that contributed to retropalatal obstruction. Conclusion: Evaluation of craniofacial morphology in OSA patients is bound to help the concerned specialist in recognizing the morphological changes induced by altered sleep pattern so as to provide the appropriate treatment.



How to cite this article:
Bharadwaj R, Ravikumar A, Krishnaswamy N R. Evaluation of craniofacial morphology in patients with obstructive sleep apnea using lateral cephalometry and dynamic MRI.Indian J Dent Res 2011;22:739-748


How to cite this URL:
Bharadwaj R, Ravikumar A, Krishnaswamy N R. Evaluation of craniofacial morphology in patients with obstructive sleep apnea using lateral cephalometry and dynamic MRI. Indian J Dent Res [serial online] 2011 [cited 2014 Oct 25 ];22:739-748
Available from: http://www.ijdr.in/text.asp?2011/22/6/739/94566


Full Text

Obstructive sleep apnea (OSA) is a potentially life-threatening disorder, characterized by repeated collapse of the upper airway during sleep with cessation of breathing. [1] The etiology is multifactorial, with decreased airway muscle tone and the gravitational pull in supine position that decreases the airway size, thereby impeding airflow during respiration. [2] Nocturnal polysomnography is the gold standard for diagnosing OSA. Several advanced technologies like computerized tomography (CT), magnetic resonance imaging (MRI), etc. are being used to evaluate the anatomical characteristics of the upper airway and craniofacial structures and/or to determine the site (s) of obstruction. However, the traditional cephalometric method has been the most practical and commonly used. [3] The cephalometric method despite being a static, two-dimensional evaluation of the dynamic three-dimensional anatomical structures of the head and neck is useful, as they have shown that significant differences exist between asymptomatic controls and patients with OSA. The primary advantages of cephalometry are its easy access, low cost and minimal radiation exposure. In addition to conventional upright cephalometry, supine cephalometry has been introduced to examine the effect of change in body position on the anatomy and function of the upper airway in patients with OSA. Abnormal cephalometric dentofacial morphologies such as retrognathia, micrognathia, long face, large ANB angle, inferior positioning of the hyoid bone, steep mandibular plane, narrowing of the upper airway, long and large soft palate and large tongue have been reported. [4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17]

Among patients with OSA, however, the sites of obstruction and the narrowing of the upper airway differ greatly. Detection and characterization of the sites of obstruction and narrowing of the upper airway are of particular clinical importance in understanding the pathophysiology of OSAS as well as in the planning of therapy. Since the shape of upper respiratory tract continuously changes with the respiratory movement, conventional CT or MRI lacks sufficient temporal resolution to diagnose the severity of obstruction. In this respect, dynamic MRI [18],[19],[20] provides excellent temporal resolution to define dynamic changes of the upper airway, requires no exposure to ionizing radiation and provides a pharyngeal airway view on the sagittal plane.

This study was designed to compare and validate the craniofacial morphology in patients with OSA using lateral cephalometry in both upright and supine position and to investigate the dentofacial characteristics of patients with OSA with respect to the obstructive sites determined by dynamic MRI to more accurately clarify the pathophysiological features and the proper modalities for the correction of OSAS.

 Materials and Methods



Twenty subjects participated in the study of which 10 were patients with OSA and the other 10 were healthy control group diagnosed by polysomnography. Mean age of the study group was 45.9 years (range 25-65 years), and control group was 35.40 years (range 25-50 years). Patients were considered to have OSA if they had an apnea and hypopnea index (AHI) of more than 10 apneas and/or hypopneas per hour of total sleep time during an overnight polysomnographic study. An apnea was defined as a cessation of airflow for more than 10 seconds and a hypopnea was defined as a decrease in airflow with a 50% decrease in respiratory effort.

Patients selected for the study had one or more of the following signs and symptoms of OSA:



SnoringDaytime sleepiness and fatigueIncreased body mass index (BMI)Increased neck circumferenceMicrognathic jaw, retrognathic mandible, enlarged soft palate or tonsillar hypertrophy, macroglossia or any other structural/morphological abnormality that contributes to restricted upper airway.

The 10 patients with OSAS were divided into two groups of five each according to their obstructive site determined by dynamic MRI (1) obstruction at the retropalatal and retroglossal region (Rp + Rg group) and (2) obstruction at the retropalatal region (Rp group). The control subjects showed no symptoms or features suggestive of OSAS such as snoring, nocturnal apnea or excessive daytime sleepiness.

Polysomnography

The selected subjects were evaluated by an overnight polysomnographic sleep study to assess the severity of the OSA.

This study monitored the following:



Electroencephalogram (EEG).Bilateral electrooculograph (EOG).Submental, intercostal and anterior tibialis electromyogram (EMG).Oronasal flow recorded by an infrared CO 2 analyzer.Arterial Oxygen saturation (SaO 2 ) recorded simultaneously with a pulse oximeter.

The severity of sleep apnea was assessed in terms of AHI numbers.

Identification of the obstructive site

To identify the site of obstruction (Rp, Rp+Rg), patients were scanned by dynamic MRI. The patients were supine with the head placed in a neutral position to ensure consistent positioning. MRI was performed with a 1.5-T MR imager with a quadrature head coil [General Electric (GE), Signa Excitte]. The pharyngeal airway was imaged in a median sagittal plane. Two transverse plane sections one at the retropalatal (posterior to the soft palate) level and other at retroglossal (posterior to the tongue base) level were obtained. Fifty images taken during 50 seconds were obtained at each location for the midsagittal and two transverse plane sections of the pharynx and were viewed as a cineloop display. Patients whose sagittal images showed complete obstruction or remarkable narrowing at the retropalatal and retroglossal regions were assigned to the Rp+Rg (Group A) group. Patients whose sagittal images showed obstruction only at the retropalatal region, but no obstruction or narrowing at the retroglossal region were assigned to the Rp (Group B) group. From the transverse axial image, the minimal cross-sectional areas of the airway at the retropalatal and retroglossal levels were measured with the aid of Advanced Workstation software. For this study, obstruction was defined as a cross-sectional area at each level of the airway of less than 20 mm2, and non-obstruction was defined as a cross-sectional area greater than 100 mm2. Thus, the minimal cross-sectional area at the retroglossal level of the retropalatal obstruction group was at least 100 mm2.

Lateral cephalometry

Two lateral cephalometric radiograph one upright and one supine posture was taken for each of the subjects [Figure 1]. Two lead markers, one at the inferior border of orbit after palpating for it and one in front of the tragus of ear representing porion were placed and joined together by a line on the cephalogram that formed the Frankfurt Horizontal plane for the patient. The subject was seated in an upright position with the Frankfort horizontal plane parallel to the floor, and was instructed to lightly contact the back teeth. For the supine cephalogram, the subject was instructed to lie down on a stretcher, and to maintain their teeth slightly apart in the rest position. The patients head was fixed with ear rods and two pointers were placed at nasion and orbitale respectively for proper orientation of the head. The dorsum of the tongue was coated with barium sulfate contrast to enhance the outline of the tongue and pharyngeal soft tissues. While taking the cephalograms, the distance between the midsagittal plane of the subject and the X-ray source was fixed at 5 feet and the median plane to film distance was 15 cm and thus the constant enlargement was 10%. All the X-rays were taken on a Kodak T Matte -En in an 8 × 10 inch cassette exposed for 1 sec, at 10 milliamperes and 75 kvp. All the films were manually developed under controlled conditions and cephalograms were traced on matt acetate film of 50-micron thickness by the same operator using a 0.5 mm 2 H lead pencil.{Figure 1}

Statistical analysis

All the values obtained were evaluated for statistics using SPSS software. Independent t-test was performed to determine the difference in the age between study and control group and the difference in AHI between Group A and Group B. Analysis of variance (ANOVA) was performed to determine the difference in the BMI between control group, Group A and Group B. Independent t-test was performed to evaluate the significant difference in the upright cephalometric variables between the study and control group and between the two groups (Groups A and B). The changes in skeletal and soft tissue parameters with change in posture were assessed within the study and control group by paired t-test. Pearson's correlation coefficient was performed to determine if there was a significant correlation for the skeletal and soft tissue parameters between upright and supine cephalometric variables within the study and control group. P value of ≤0.05 was considered as statistically significant.

 Results



Demographic and sleep data are shown in [Table 1]. The mean age in study group was 45.90 years and control group was 35.40 years. The mean BMI of the control group was 23.94 kgm/m2. The patients with both Rp + Rg (Group A) obstruction had a mean BMI of 37.68 kgm/m2 and those with only retropalatal (Rp) (Group B) obstruction had a mean BMI of 55.68 kgm/m2. This indicated that the mean BMI of the OSA patients were considerably higher than the control group and the mean BMI was also greater for patients with only Rp obstruction compared to Rp + Rg obstruction group. All these parameters were statistically significant. The mean AHI in both group A and B was, however, greater than 35 per hour. With dynamic MRI, both sagittal and axial images were obtained. The levels of obstruction in sagittal images and the minimal cross-sectional area of retropalatal and retroglossal obstruction in axial images were tabulated [Table 2].{Table 1}{Table 2}

Cephalometric analysis

The results of the cephalometric variables were tabulated.

Comparison of upright cephalogram between the study and the control group

The results of the cephalometric variables in [Table 3] showed a significant difference in the skeletal and soft tissue parameters between study and the control group. The study group revealed retropositioned mandible with large ANB angle and an extended cervical posture. Soft tissue morphology was characterized by elongated tongue and soft palate with reduced anteroposterior pharyngeal space at the superior, middle and inferior levels; the cross-sectional areas of soft palate were enlarged.{Table 3}

Comparison of upright and supine cephalogram in the study and control group

The present study demonstrated the soft tissue changes that occurred from upright to supine posture in study and control [Table 4], [Table 5], [Table 6] and [Table 7]. The study group showed that with change in posture, soft palate length decreased, thickness increased, tongue length decreased with no significant change in tongue height. However, correlation coefficient test showed that with change in posture, there was a positive correlation for soft palate length and thickness and tongue length in both the groups, but change in tongue height was evident only in study group. There was a significant reduction in the superior posterior airway space behind the soft palate with change in posture in both the groups with no significant change in middle and inferior posterior airway space. However, a positive correlation for the superior and inferior posterior airway space was evident in the control group and not in study group. Cranio-cervical angulation (NSL-OPT; NSL-CVT) showed no significant difference with change in posture in study group, while in control group, NSL-OPT were significantly different and positively correlated.{Table 4}{Table 5}{Table 6}{Table 7}

Dynamic MRI for OSA patients

The present study used a dynamic MRI to identify the retropalatal and retroglossal obstruction [Figure 2]. Among the total of 10 patients, five patients had obstruction at both retropalatal and retroglossal (Rp + Rg) level (Group A) and other five patients had obstruction only at retropalatal (Rp) level (Group B). The skeletal and soft tissue parameters of Group A and Group B are shown in [Table 8]. The first group who had obstruction at both retropalatal and retroglossal level (Group A) showed retrognathic maxilla and mandible in relation to the cranial base, high mandibular plane angle and increased lower anterior face height. The head posture was, however, insignificant between the two groups. Likewise, the soft tissue components namely the soft palate, tongue and posterior airway space was also not significantly different between the two groups.{Figure 2}{Table 8}

 Discussion



The orthodontic relevance of naso-respiratory obstruction and its effect on facial growth continues to be debated after almost a century of controversy. There are numerous studies to support that there is a significant correlation between naso-respiratory function and craniofacial growth [21],[22],[23] although few of them refute such relationship. [24]

There are a host of studies concerning the craniofacial morphology and soft tissue measurements like tongue, soft palate and pharynx. [8],[9],[14],[15],[16],[17],[18],[25],[26] Some studies have shown that a change from upright to supine position altered the cross-sectional area of soft palate and tongue, [27],[28] while others [14] reported no such change. Among patients with OSA, however, the sites of obstruction and the narrowing of the upper airway differed greatly. The retropalatal (posterior to the soft palate) region and retroglossal (posterior to the base of tongue) region were commonly affected sites, and multiple sites of obstruction and narrowing were not rare. [18],[19],[20] However, there were few studies [18] that have assessed the relationship between the dentofacial characteristics and obstructive sites in patients with OSAS.

Thus the present study was aimed to compare and validate the craniofacial morphology in patients with OSA using lateral cephalometry in both upright and supine position and to investigate the dentofacial characteristics of patients with OSAS with respect to the obstructive sites determined by Dynamic MRI to more accurately clarify the pathophysiological features and the proper modalities for the correction of OSA.

Conventionally, patients with OSA are diagnosed based on their complaints and history. The routine diagnostic protocol that is followed is polysomnography. However, a few ENT surgeons prefer to perform a dynamic MRI if they feel the need to locate the site of obstruction. The present study being a prospective one and the cost of motion MRI being prohibitive limited the sample population to a total of 10 patients and 10 controls. Further, statistician of this study opinioned that the power of statistics and the results of the study would not be influenced because of the less number of samples that were used in this study.

Although lateral cephalometry is a two-dimensional representation of a three-dimensional structure, it has been extensively used to quantify the dental, skeletal and the soft tissue relationships of the craniofacial complex. Lead markers, one at the level of inferior border of the orbit and the other in front of tragus of the ear were placed to avoid error in locating porion in lateral cephalometry in closed mouth position. [21]

A variety of morphological characteristics specific to patients with OSA have been reported in studies that used upright cephalograms. [3],[4],[8],[14],[16],[17],[29],[30],[31] The present study showed retrognathic mandible, large ANB angle, increase in the soft palate length and thickness, increase in tongue length and decrease in posterior airway space in the study group. Similar findings have been reported in previous studies. [31],[32] Although the tongue height was greater in majority of patients in study group compared to the control, it was statistically insignificant. Extended cervical posture has been a compensatory adaptation in patients with airway obstruction. [33],[34] This study group demonstrated similar postural change that was significant.

Supine cephalometry seemed more relevant clinically to examine the airways and surrounding structures because all OSA patients had obstruction in this position. The study group showed that with change in posture, soft palate length decreased, thickness increased, tongue length decreased with no significant change in tongue height. Similar changes have been reported previously. [9],[15],[35] However, correlation coefficient test showed that with change in posture, there was a positive correlation for soft palate length and thickness and tongue length in both the groups, but change in tongue height was evident only in study group. There was a significant reduction in the superior posterior airway space behind the soft palate with change in posture in both the groups with no significant change in middle and inferior posterior airway space. However, a positive correlation for the superior and inferior posterior airway space was evident in the control group and not in study group. Similar results with significant change in the superior posterior airway space were demonstrated in previous studies. [14],[17],[35] Moreover, the head position was rigorously controlled by using the ear rods of the cephalostat to ensure bilateral symmetry of the radiographs as suggested by Pracharktam. [14] In contrast, Pae [28] asked the subjects to mimic their own natural sleeping position and pillow height and used the subject's comfortable, natural sleeping position. Thus, differences in upper airway dimensions, other than the superior-posterior pharyngeal space reported in the supine position may have related more to differences in head and neck angulation and cephalometric technique rather than to the influences of gravitational pull, per se. In contrast, differences in the superior-posterior pharyngeal space in the supine position might depend more on the gravitational pull of the soft palate and the tongue backwards thereby increasing the chance of apnea in supine position. [9]

The change in cranio-cervical angulation with change in posture was inconsistent and not statistically significant in study group, while in control group, the angulation (NSL-OPT) increased from upright to supine posture in majority of patients and was positively correlated.

Dynamic MRI for OSA patients

The pathogenesis of OSA was complex associated with abnormal dentofacial pattern. Current approach using three-dimensional reconstruction of the airway space from cone beam CT have found to be a simple and effective method to accurately analyze the airway. [36] However, the lack of availability and cost factor is a limitation. The present study used a dynamic MRI to identify the retropalatal and retroglossal obstruction using both sagittal and transverse images, because sagittal images alone did not reveal the actual dimensions of the airway, such as asymmetric or vertical narrowing and occlusions. [19]

The present study showed that 50% of patients had obstruction at both retropalatal and retroglossal (Rp + Rg) level (Group A) with retrognathic maxilla and mandible in relation to the cranial base, high mandibular plane angle and increased lower anterior face height and the remaining 50% had obstruction only at retropalatal (Rp) level (Group B) associated with increased BMI of 55.68 kgm/m2. Subjects were categorized as mild obese when the BMI was between 25 and 40 kgm/m2, severe obese when the BMI was >40 kgm/ m2 and non-obese when the BMI was <25 kgm/m2. [37]

Thus, this study concluded that patients with both retropalatal and retroglossal obstruction showed signs of skeletal discrepancy that predisposed to obstruction at the retroglossal level and the soft tissue components like the soft palate and tongue that contributed to retropalatal obstruction and patients with only retropalatal obstruction had primarily soft tissue components associated with increased BMI that contributed to retropalatal obstruction. Similar results have been obtained in previous studies [18] where the craniofacial morphology determined by lateral cephalometry was significantly different for patients with different levels of obstruction diagnosed by dynamic MRI. Previous studies have shown that obese and non-obese individuals had different etiological basis [37],[38] and lateral cephalometry gave a clue to the site of obstruction and finally the appropriate treatment. Thus the role of lateral cephalometry, though two-dimensional, played a major role in diagnosis and treatment planning for OSA patients.

 Summary and Conclusions



The following conclusions could be made from the present study:

The OSA patients demonstrated retrognathic mandible, large ANB angle, extended cranio-cervical angulation, an elongated and thickened soft palate, decreased posterior airway space (superior, middle and inferior) and elongated tongue compared to the control group.

When subjects changed their posture from upright to supine, the soft palate was thickened and shortened, tongue length and superior posterior airway space was decreased in the study group with no significant change in tongue height in both the groups.

The site of obstruction demonstrated with dynamic MRI revealed that Group A had retrognathic maxilla and mandible, high mandibular plane angle and increased lower anterior face height that predisposed to obstruction at the retroglossal level and the soft tissue components like the soft palate and tongue that contributed to retropalatal obstruction while Group B had primarily soft tissue components associated with increased BMI that contributed to retropalatal obstruction.

Thus, lateral cephalometry served as an important tool in clinical diagnosis of obstructive sleep apnea patients demonstrating distinct cranio-facial morphological changes, thereby giving a clue to the site of obstruction based on specific skeletal and soft tissue components. [39]

Future

Future research with 3D imaging might provide better evaluation of the airway to understand and discriminate patients with potential airway problems and their consequences. Further studies with more number of patients might provide better understanding to discern the association between the facial morphology and site of obstruction in OSA patients.

Landmarks and measurements employed in the present cephalometric analysis

The following landmarks were identified on each X-ray film:

Hard tissue landmarks



S - sella turcica: It is defined as the midpoint of the hypophyseal fossa. It is a constructed point in the median plane.N - nasion: The anterior most point of the naso-frontal suture in the median plane.A - point A (subspinale): The deepest midline point in the curved bony outline from the base of the alveolar process of the maxilla i.e. the deepest point between the anterior nasal spine and prosthion. In anthropology it is known as subspinale.B - point B (supramentale): It is the most posterior point in the concavity between infradentale and pogonion, in the median plane. In anthropology it is called as supramentale. Go - gonion (anatomic): A point on the curvature of the angle of mandible located by bisecting the angle formed by lines tangent to the posterior ramus and the inferior border of the mandible.Go - gonion (constructed): A point at the intersection of the ramus tangent and tangent to the inferior border of mandible.Gn - Gnathion (anatomic): A point located by taking the midpoint between the anterior (pogonion) and the inferior (menton) points of the bony chin.Cd - condylion: Most superior point on the head of the condyle.ANS - anterior nasal spine: The anterior tip of the sharp bony process of the maxilla at the lower margin of the anterior nasal opening.PNS - the tip of the posterior nasal spine: The most posterior point at the sagittal plane on the bony hard palateMe - menton: The most caudal point in the outline of the symphysis.C3 - third cervical vertebra: The most inferior anterior point on the third cervical vertebra.CV2 ap: The apex of the odontoid process of the second cervical vertebra.CV2 ip: The most posterior and inferior point on the corpus of the second cervical vertebra.CV4 ip: The most posterior and inferior point on the corpus of the fourth cervical vertebra.

Soft tissue landmarks



SSP: Point in the nasal contour of velum - the most prominent point on the superior soft palate.ISP: Point on the oral contour of velum - The most prominent point on the inferior soft palate.U: The tip of the uvulaE: The most inferior and anterior point of the epiglottis.TT: Tip of the tongue

Reference lines and planes



SN/NSL: Line joining sella nasion.NA: Line joining nasion and Point A.NB: Line joining nasion and Point B.FH (Frankfurt horizontal): The line joining the marker placed in the inferior border of the orbit and the marker placed in front of the tragus of the ear representing porion.Go-Gn (anatomic) Mandibular plane: The line joining gonion and gnathion (Steiners).Go-Me (constructed) Mandibular plane: The line joining gonion and menton (McNamara) OPT - Odontoid process tangent: The line joining CV2 ap and CV2 ip.CVT - Cervical vertebra tangent: The line joining CV2 ip and CV4 ip.

Skeletal (linear and angular) measurements used in the study [Figure 3]



SNA: The postero-inferior angle between the lines SN and NA.SNB: The postero-inferior angle between the lines SN and NB.ANB: The difference between the angles SNA and SNB. Positive value- no spacing required.it is one complete sentencewhen SNA is greater than SNB and vice versa.Go-Gn - SN (Mandibular plane angle): The angle formed between Go-Gn and SN line.FH - MP (Mandibular plane angle): The angle formed between Frankfurt Horizontal and mandibular plane (Go-Me).Cd - Pt. A: Effective maxillary lengthCd - Gn: Effective mandibular lengthLAFH: Lower anterior face height: Linear distance between anterior nasal spine(ANS) to menton (Me).{Figure 3}

Soft tissue measurements and cranio-cervical angulation [Figure 4]



SP - T - Soft palate thickness: The linear distance between SSP and ISP.SP - L - Soft palate length: The linear distance between PNS and U.T - L - Tongue length: The linear distance from point E (epiglottis) and tongue tip (TT).T - H - Tongue height: The linear distance between the midpoint of E-TT (tongue length) and the most prominent point on the dorsum of the tongue.SPAS - Superior posterior airway space: The minimum distance between the posterior part of soft palate and posterior pharyngeal wall.MPAS - Middle posterior airway space: The minimum distance between the posterior pharyngeal wall and the tip of soft palate.IPAS - Inferior posterior airway space: The minimum distance of the posterior airway space at the angle of mandible measured along line Go-Pt B.NSL - OPT-Cranio-cervical angulation: The angle formed by the line sella nasion and odontoid process tangent.NSL - CVT-Cranio-cervical angulation: The angle formed by the line sella nasion and cervical vertebra tangent.{Figure 4}

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