|
 
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| REVIEW ARTICLE |
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| Year : 2013 | Volume
: 3
| Issue : 1 | Page : 16-25 |
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Current concepts and guidelines in chin graft harvesting: A literature review
Ankit Jivan Desai, Raison Thomas, AB Tarun Kumar, DS Mehta
Department of Periodontics, Bapuji Dental College and Hospital, Davangere, Karnataka, India
| Date of Web Publication | 26-Nov-2013 |
Correspondence Address:
Ankit Jivan Desai
Room-5, Department of Periodontics, Bapuji Dental College and Hospital, Davangere - 577 004, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2231-6027.122094
After tooth loss, alveolar ridge resorption is a common phenomenon, which alters the size and shape of the host bone available for the dental implant placement. In the era of prosthetic driven implant dentistry, the final prosthesis type and design dictates the number, size and the ideal implant position. In clinical practice, though patients often demand osseointegrated implants to replace their missing teeth; the deficiency of bone volume is the primary reason for avoiding such treatment options. The solution to such situations lies in the re-establishment of the ridge height consistent with prosthetic design and with suitable load-bearing lamellar bone for implant placement and long-term stability. Despite recent advances in bone grafts and bone-substitute technology, the use of autogenous bone grafts continues to represent the "gold standard" in implant site reconstructive surgery. The mandibular symphysis (chin bone in interforaminal region) is a favorable donor site as it has an excellent risk-benefit ratio. Several reconstruction procedures by using chin graft have been proposed to increase alveolar bone volume both vertically and laterally to prepare the ridge for a correct placement of oral implants. This article reviews the various aspects of chin grafts, wherein the regional surgical anatomy, various incision designs, surgical protocols for harvesting and the possible clinical and esthetic complications of chin grafts have been discussed. Keywords: Autogenous graft, chin graft, mandibular incisive canal, ridge augmentation
How to cite this article:
Desai AJ, Thomas R, Tarun Kumar A B, Mehta D S. Current concepts and guidelines in chin graft harvesting: A literature review. Int J Oral Health Sci 2013;3:16-25 |
How to cite this URL:
Desai AJ, Thomas R, Tarun Kumar A B, Mehta D S. Current concepts and guidelines in chin graft harvesting: A literature review. Int J Oral Health Sci [serial online] 2013 [cited 2023 Jun 7];3:16-25. Available from: https://www.ijohsjournal.org/text.asp?2013/3/1/16/122094 |
| Introduction | |  |
Dental implantology has evolved into an accepted, predictable treatment for restoring lost teeth. In the era of prosthetic driven implant dentistry, the final prosthesis type and design dictates the number, size and the ideal implant position. Often in clinical practice, the deficiency of bone volume is shown to be the primary reason for avoiding implant treatment. [1] The solution lies in re-establishing the ridge volume consistent with prosthetic design and with suitable load-bearing lamellar bone for long-term stability of the implant therapy. [2]
Despite recent advances in bone grafts and bone-substitute technology, intramembranous autogenous osseous transplants are regarded as the gold standard for reconstruction of the deficient alveolar ridge. [3] If the amount of bone necessary for augmentation is modest, intramembranous autografts can be easily obtained from regional intraoral sites such as maxillary palate and tuberosity, mandibular symphysis, angle of the mandible, ramus and bony exostosis. [3]
Chin offers a large amount of cortico-cancellous autograft and easy access among all the intraoral sites. [4] It can be easily harvested in the office settings under local anesthesia on an out-patient basis. Proximity of the donor and recipient sites reduce operative time and cost. Convenient surgical access, low morbidity, elimination of hospital stay, minimal donor site discomfort and avoidance of cutaneous scars are the added advantages.
| Indication | | |
Chin bone block can be used for predictable bone augmentation of up to 6 mm in horizontal and vertical dimensions. Cortico-cancellous graft ranging from 3 mm to 11 mm thickness, with most of the sites providing 5-8 mm can be harvested from symphysis. Up to three teeth edentulous site can be augmented. It provides D-1 (>1250 HU) or D-2 (850-1250 HU) density bone for augmentation. [5]
| Presurgical Considerations | | |
Correct patient selection is the paramount for the success of the osseous transplant procedures. Complete medical and dental evaluation should be done to prevent surgical complications.
The symphyseal site must be clinically evaluated for hard and soft-tissue deficiencies, ridge morphology, vestibular depth, width of the attached gingiva, periodontal and endodontic health of the lower anteriors and premolars; and also location of the neurovascular bundle. Diagnostic cast can be prepared to do ridge mapping. Wax-up of the reconstructed defect can be done to determine graft requirements and to prepare surgical template for precise placement of the transplant. [3]
Radiographic examination with the periapical, panoramic, lateral cephalogram, conventional or cone-beam computed tomography (CBCT) scan should be conducted according to need. Periapical radiograph should be done to check periapical pathology if present and also to check the length of the roots of lower anterior tooth. Panoramic view can be taken to trace location of the mental foramen and mandibular canal. Lateral cephalogram is done to determine width, bone quality at chin area and its relation to neighboring teeth. Computed tomography (CT)/CBCT scan should be done for accurate treatment planning, to determine the quantity and quality of the graft at the donor site and to see the neurovascular components, which can affect the surgical design.
| Anatomical Considerations | | |
Musculature
The chin musculature is composed of three muscle groups: mentalis, orbicularis oris and depressors (anguli oris and labii inferiori). Orbicularis oris and depressors have little effect on the chin position and of not so much surgical concern.
A mentalis muscle is a short, stout and paired muscle; usually separated by a small column of adipose tissue in the midline. It originates from the incisive fossa of the mandible at the level of the root of the lower lateral incisors, just below the attached gingiva and insert into the integument of the chin [Figure 1]. [6] It is innervated by the marginal mandibular branch of the facial nerve. [6],[7] Over-reflection of the mentalis muscle may lead to loss of facial contour by inversion of the lower lip and flattening of the labiomental fold (pseudoprognatism). [3]
Mental nerve, foramen and anterior loop
The inferior alveolar nerve usually divides into two anterior terminal branches, the mental and incisal nerves. [8] In the molar-premolar region, mental nerve continues upward in the mental canal and normally, three nerve branches come out of the mental foramen in conjunction with blood vessels. The mental foramen may be oval or round in shape and is usually located apical to the second mandibular premolar or between apices of the premolars. However, its location can vary from the mandibular canine to the first molar with the mean height of 3.47 mm (range: 2.5-5.5 mm) and the average width of 3.59 mm (range: 2-5.5 mm). [9]
The mental nerve can present a loop, an anterior extension of the inferior alveolar nerve mesial to the mental foramen, prior to exiting the canal. There are discrepancies between the data of radiographic and cadaveric dissection studies regarding the prevalence and length of the loop. Panoramic radiography may not be a very reliable imaging modality for identifying the presence and length of the anterior loop. [10],[11] The length ranging from 0.0 to 5.9 mm is found on CBCT and a distance of 6 mm between the anterior border of the mental foramen and the most distal interforaminal implant fixture is recommended. [12]
Sensory dysfunction may occur due to direct nerve damage or due to traumatic edema of the epineurium during preparation of an osteotomy. The foramen and the anterior loop may not appear on conventional radiographs and linear measurements need to be adjusted to account for radiographic errors. For detection, CT/CBCT scans are more accurate than conventional radiographs. Its presence should be verified surgically by using curved probes to prevent nerve injury [9] [Figure 2]. [13] | Figure 2: Computed tomography scan image showing Anatomical structures related to mandibular symphysis. (a) Inferior alveolar nerve, (b) Mental foramen, (c) Anterior loop, (d) Mandibular incisive nerve
Click here to view |
Mandibular incisive canal (MIC)
Olivier was the first anatomist to define the mandibular incisive nerve as a terminal branch of the inferior alveolar nerve, which extends anteriorly within the mandible, mesially to the mental foramen. [14] Various cadaver dissection studies done by De Andrade et al. in 2001 [15] and Mraiwa et al. in 2003 [16] showed almost 100% of existence of the incisive canal [Figure 3]. [15] The conventional two-dimensional radiographs (intraoral periapical, orthopantomographs) are of limited value as they often fail to show MIC [16],[17] while the spiral CT and CBCT based studies showed 83-100% of its existence. [13],[16],[17],[18],[19] | Figure 3: Cadaver dissection studies demonstrating the course of mandibular incisive nerve
Click here to view |
Most of the time, the incisive nerve did not reach the area below the central incisors. The mean length of the incisive nerve to the midline was 8.9 mm (range: 0-24.6 mm). The mean distances of the canal from the root tips of the premolars, canines and incisors were 6.9 mm, 7.3 mm and 10.4 mm, respectively. The mean distances from the canal to the buccal cortical border in the same tooth positions were 2.8 mm, 4.4 mm and 4.8 mm, respectively. [20] It is located closer to buccal cortex than the lingual cortical plate and curves toward the lingual side at the symphysis menti.
It gives neurovascular supply to the lower incisors, canine and first premolar. Several procedures such as endosseous implant placement, genioplasty, autograft harvesting for ridge and sinus augmentations, screws and/or plate fixation in symphysial and parasymphysial fractures are performed in this interforaminal region. It is one of the important vital structures to keep in mind to avoid neurosensory disturbances and also to avoid failures of osseointegration of implants. The large variation in the spatial relationship of the canal indicates case-by-case pre-operative radiographic evaluation by CBCT.
Mandibular anterior teeth
Cuspids have the longest root in the mandibular anterior sextant followed by lateral incisors and central incisors [Table 1]. [20],[21] To preserve tooth vitality, a minimum clearance of 5 mm from apices seems reasonable. [22]
Osseous quality and quantity of mandibular symphysis
The maximum volume of block graft that can be harvested as a rectangular graft block from the mandibular symphysis is around 1-1.5 cm in height and around 4.0 cm in width, centred at the midline of the mandible. [23]
A CT Scan based radiographic study by Yavuz et al. in 2009, calculated the 3491.08 ± 772.12 mm 3 and average sized cortico-cancellous chin bone block graft of around 38.75 mm ×11.05 mm × 7.80 mm. The mean bone density was found to be 958.95 ± 98.11 HU indicating D2 type bone. [24] Symphysis provides dense cortical D-1 (>1250 HU) bone or 2 mm thick porous cortical D-2 (850-1250 HU) bone with coarse trabeculae type density of the bone graft. [25]
| Surgical Harvest | | |
Anesthesia
Several injections are required as the anterior symphyseal region of the mandible is innervated by the mandibular branch of the fifth cranial nerve (V3) and cervical nerves from C-3 and C-4. Bilateral mandibular block with 2% lidocaine HCL (1:100,000 epinephrine) accomplish anesthesia for V3 innervation. One-third-carpule of infiltration in front and below each mental foramen and also in the midline at the base of the mental protuberance should be given. Another carpule of anesthetic is divided in half and an infiltration injection on each side of the superior genial tubercle near the base of the mandible should be given. [26]
Incision design for surgical access to symphysis
Assessment of the periodontal status of lower anteriors, amount of bone loss, periodontal risk of root fenestration, amount of keratinized gingiva, subgingival margins of the restoration and local musculature should be done to indicate the best possible incision design. Depending on anatomy, surgical access to symphysis area can be obtained via a crestal incision, vestibular incision, mid-keratinized tissue incision, or sulcular approach [Figure 4].
Vestibular/alveolar mucosa incision
Horizontal incision should be made 1 cm beyond MGJ and extends to each distal region of the canines. Vertical incision is given anterior and above the mental foramen, between canine and premolar. Horizontal incision should be given in apicolingual direction toward the bone to incise through the mentalis muscle. It will preserve 3 mm of periosteum and mentalis muscle, which will later be used for reattachment of mentalis muscle. Below this point a full thickness incision is made and a full thickness mucoperiosteal flap is reflected toward the base of the mandible to the level of the pogonion. [26],[27] Keep the most inferior aspect of periosteal attachment of mentalis muscle intact [Table 2] and [Figure 5]. | Figure 5: Vestibular approach to mandibular symphysis and a trephine core harvest procedure
Click here to view |
Sulcular approach
The incision begins in the sulcus from second bicuspid of one side to another side. An oblique releasing incision is made at the distal buccal line angle of these teeth and continues into the depth of the buccal vestibule. A full thickness mucoperiosteal flap is reflected up to the inferior border to expose the symphysis. [26],[27] Short duration of bone exposure (15-30 min) and frequent irrigation should be done with saline to prevent dehydration. planing of root surface should not be done to achieve "reattachment" instead of "new attachment" [Table 3] and [Figure 6]. | Figure 6: Sulcular approach to mandibular symphysis and a trephine core harvest procedure
Click here to view |
Submarginal/attached gingiva incision
It is the incision line of choice whenever possible. The horizontal or parasulcular, scalloped incision [26],[27],[28] should be given in the attached gingiva at least 1 mm above the mucogingival junction. If >3 mm keratinized gingiva present, Beveled incision More Details in apical direction is given. If >3 mm of keratinized gingiva present, perpendicular incision to the underlying bone is given to gain a butt joint for facilitation of tissue adaptation during the suturing. [28] The vertical incision can be given between canine and first premolar or at the midline, from a safe distance of a local neurovascular bundle. The midline vertical release can be given when the harvest is for the span of 3 teeth or less and it often extends to within 5 mm of the inferior aspect of the mandible [Table 4].
Crestal incision
It can be given when single or multiple lower anterior teeth are missing. The crestal incision on the edentulous span will be continued with the sulcular incision on the adjacent dentate area if present. [29]
| Harvesting Rules | | |
Rule of 5's
Misch in 1992, proposed a safe surgical technique to harvest a bone block graft from symphysis which help to prevent injury to neuro-vascular components of mandibular symphysis region. All the bone cuts should be perpendicular to the cortex in a right angle to the vestibular plain of the symphysis. The superior cut should be 5 mm below root apices to prevent injury to tooth roots and MIC. The inferior cut should be 5 mm above the lower border [Figure 7]. Vertical cuts should be at least 5 mm away from the mental foramen. Depth of the cut should be at least through the outer cortex and to the opposite cortical plate to obtained monocortical graft. Lingual cortex should not be perforated. [22]
New safety guidelines
Misch et al.'s safety rules [22] are not possible in all patients (due to insufficient bone height) and it endangered the contents of MIC in 57% of the patients. If the new safety margins proposed by Pommer et al. in 2008, [30] for chin bone harvesting are respected, the risk of injury to the MIC can be lowered to 16%. If proper patient selection is applied additionally, a residual risk of only 6% remains.
The new safety margins are, depth of the bone graft should be 4 mm and the distance to the tooth apices should be kept at least 8 mm. The lower border should be kept intact with the 5 mm safety distance from the mental foramen [30] [Figure 8] and [Figure 9].
According to new safety guidelines of Pommer et al., the symphysis can be used as a donor site in 56% of patients to harvest a graft of 10 mm diameter, in 74% of patients for a graft of 8 mm diameter and in 90% of patients for a graft of 6 mm diameter. The residual 10% of the population are not suitable for chin bone harvesting. [30]
Armamentarium for chin graft harvesting
The ideal bone cutting instrument should be easy to handle, less time consuming as atraumatic as possible and should prevent more amount of bone loss during harvesting.
- Reciprocating and oscillating saws allow thin cuts and prevent bone loss
- Fissure bur no. 702 is very effective and cheap instrument. It leads to more amount of heat generation and additional bone loss of around 1 mm
- Trephines are used when small cores of cortico-cancellous bone are needed. Depending in the diameter of the trephine bur, cores of 4-10 mm can be harvested. It is very easy, atraumatic and less time consuming procedure
- Disc acts as a saw and makes very thin cuts. A soft-tissue guard is must to prevent damage to the surrounding tissues
- Piezotomed instruments are preferred over any other instruments as they allow for maximum intra-operative precision and minimal tissue damage. It reduce the bone loss during osteotomy and gives precise cut of only 0.5-0.7 mm in width. The selective frequency of 25-30 KHz cuts only the bone as to cut the soft-tissue, ideally a frequency of 50 KHz is needed. Thus, it is atraumatic to the soft-tissues, nerves, periosteum and the schneiderian membrane.
Patterns of harvesting
Different patterns such as J-graft, ring graft, rectangular blocks or cylindrical bone cores can be harvested from chin. Pikos [5] recommended 2 mm larger block outline than the target size to allow for contouring of the block after removal. Furthermore, leave a 3 mm midline strut of mental protuberance to retain support for the chin profile. More than one piece of bone block can be harvested from symphysis. Two bone blocks are often easier to harvest and provide good access to the second larger block. [28] Particulate grafts can be harvested from chin by using bone scraper or bone crusher.
Trephine technique
In 1999, Hunt and Jovanovic [4] followed Misch's safety margins to harvest a trephine based bone cylinders or particulate bone. They proposed 2 designs to harvest trephine cores which are:
- "Audi design", pattern of 4 trephine cuts, can be used when moderate harvesting is needed. It consists of 4 overlapping 8-mm rings in the mid-symphyseal region [Figure 10] [4]
- "Reverse-olympic design" can be used when a large amount of bone is needed. 4-5 large 8-mm trephine rings in the midline of the symphysis and 2 separate small 6-mm trephine rings on the superior and lateral borders [Figure 11]. [4]
Donor site management after graft harvest
Hemostatic material such as collagen, gelatin, sponge or oxidized regenerated cellulose can be placed into the symphysis area after bone harvest. Natural dressing with platelet-rich fibrin (PRF) enriched with growth factors can also be done. Bone wax should be used to stop heavier osseous bleeding. Larger bone defects should be grafted with allogenic bone or resorbable hydroxyapatite.
Donor site suturing
- Intrasulcular incision can be sutured with resorbable/non-resorbable sutures with interrupted suturing techniques [26],[27],[28]
- Suturing for vestibular incision is done in two levels: the muscle is sutured first, followed by the mucosal tissue suturing. The soft-tissue superior to the initial access incision should be elevated by few millimeters to reduce tension on the flap from edema and lip movement. Internal suturing involving the periosteum and muscle layers is done with a 4-0 resorbable Vicryl with a mattress or interrupted technique. Suturing of the external flap begins with several horizontal mattress sutures followed by a continuous locking suture. This technique promotes rapid healing and low morbidity [26],[28]
- Suturing of mid-keratinized tissue incision can be done in two layers. The detached mentalis muscle is sutured first with a sling suture around the mandibular incisors. The purpose of sling suture is to release tension for the closing sutures. External flap can be sutured with a sling or multiple interrupted sutures. Bio-absorbable sutures are preferred materials for wound closure [26],[28]
- Mid-crestal incision can be sutured with multiple interrupted sutures or combination of interrupted and mattress sutures. [26],[28]
Complications and post-operative morbidity
Intra-operative complications includes bleeding, soft-tissue injury of cheeks, lips and tongue, incisive and mental nerve injury, potential bicortical harvest and block graft fracture.
- Intrabony bleeding episodes can be taken care with the use of cautery, local anesthesia and collagen plugs [5],[25]
- Injury to the mental neurovascular bundle is avoidable with proper surgical technique, especially the use of the sulcular approach for bone harvesting
- Injury to incisive nerve occurs when deep cancellous bone is harvested and it can be prevented by careful radiographic examination with CT scan and by using new safety guidelines of harvesting symphysial graft [30]
- Block fracture and bicortical block harvest also can be prevented by following a good surgical technique
- There is a potential risk of damaging mandibular tooth roots during osteotomy, which can be prevented by careful radiographic examination with panoramic/CT scan and by keeping minimum of 5 mm safety distance between the apex of the canine and the upper osteotomy cut.
- Post-operative complications include pain, swelling and bruising, ptosis of chin, infection, suture line opening and neurosensory deficits of the lower lip, chin and anterior mandibular dentition. [5],[25]
The most common concern of patients is the post-operative change in soft-tissue contour of chin. No evidence of dehiscence or chin ptosis was seen using the sulcular approach. Avoid degloving of facial and inferior aspects of mandible and exposure of the lingual aspect. To prevent reduction in the lower lip height and inversion of the vermilion zone, maintain the integrity of the periosteum attached to the inferior segment and flap reflection should not be deeper than one-third of the total distance from the vermilion border to mucogingival junction. Extra-oral pressure dressing (bandage) should be given for 3 days. In 1979 Hillerup [31] suggested the reflection of flaps no deeper than one-third of the total distance from the vermilion border to mucogingival junction to prevent reduction in the lower lip height and pseudoprognatism. However, when the entire symphyseal region is exposed, soft-tissue readaptation may improve if the integrity of the periosteum attached to the inferior segment is maintained [32]
Suture line opening can be seen more often in patients with thin gingival biotype, less vestibular depth and the vestibular incision approach to symphysis. The soft-tissue surgery to increase the width of the attached gingiva and/or vestibular deepening procedures can be performed prior to block harvesting surgery. The soft-tissue augmentation using acellular dermal matrix allograft seems to be a valid approach in soft-tissue preparation prior to mono-cortical block grafting
Pain, swelling and bruising occurred as normal postoperative sequelae and can be controlled by cold application, 1-time steroid therapy (dexamethasone sodium phosphate 8 mg injection) and/or elastic tape, proper usage of analgesic and anti-inflammatory drugs. Use of PRF has decreased overall soft-tissue morbidity
Infection rate is minimal (<1%) and can be prevented by proper aseptic surgical technique and post-operative course of antibiotics
Neurosensory deficits include altered sensation of the lower lip, chin (<1% permanent) and dysesthesia of the anterior mandibular dentition (transient, 53%; permanent, <1%). The dullness in sensation of the incisors usually resolves within 6-12 months. Pulp canal obliteration (12%) and negative pulp reaction (16%) was found in the study done by Hoppenreijs et al. Unless clinical signs of pulpal necrosis (discoloration, radiographic changes) become apparent, endodotic therapy is not indicated. Even if discoloration of a tooth is discovered, it may be closely followed because the return of vitality has been observed.
Healing at the donor site
A block leaves behind a five-wall defect with good potential to self-repair. [33],[34] Donor-site defects regenerate by a process similar to endosteal fracture healing. During bone wound healing, rapid vascularization of the defect site is paramount for successful neo-osteogenesis. [35],[36]
In the early stages, a vascular proliferation occurs within the medullary cavity. Blood vessels provide pluripotent perivascular cells that have the capability to become osteoblasts. Sides of the blood vessels carry osteoblasts, which help to repopulate the new bone. Monocytes in the blood forms osteoclasts, resorbs devital bone and help to grow the vessels. [36]
The normal cascade of physiologic healing events in response to surgical injury, a regionally accelerated process, favors the bone repair at the donor site. This phenomenon was proposed by Frost, [37] which is accelerated process of increased bone turnover in response to noxious stimuli. It causes osteoinduction by osteoclastic secretion of promoter proteins, like bone morphogenetic proteins and osteogenin, that will activate the transformation of pluripotent mesenchymal cells into osteoblasts. Thus, immature bone formation takes place and later a lamellar trabecular osseous structure gradually replaces the internal callus.
Montgomery and Moed [38] found the complete replacement of the cancellous bone after 1 year in the canine model. Bone turnover in canines is twice as fast as in humans. Therefore, the same donor sites in human may be a potential source of additional autogenous osseous transplant material after 24 months. A study done by Verdugo et al. [39] showed approximately 75% of filling of symphysis defect in around 27 months. This fill reached up to 89% in favorable conditions, such as defects (<0.5 cc), sulcular approach to symphysis and periosteal and midline preservation. Larger defects (>0.5 cc) may require longer healing time. Vestibular incision approach compromises the blood supply from the periosteum and leads to delayed healing.
Repair of mandibular symphysis defects is multifactorial and dependent on time and size of the harvested graft. [39] Preservation of the periosteum and symphysial midline and use of platelet-rich plasma (PRP)/PRF may positively influence the defect fill and reduce the healing period. Whenever short-term (<24 months) re-harvesting is expected, osteoconductive grafting of the donor site with/without PRP may benefit or accelerate the bone defect fill. Recently, a combination of bovine bone and PRP has shown such a rapid healing that it was possible to use the same site for graft re-harvesting after 5 months of the healing period. [40]
| Conclusion | | |
The intramembranous transplant like mandibular symphysis is a convenient source and provides a dense quality transplant. The thick cortical layer of the transplant prevents or reduces resorption and the cancellous part help to fasten the regeneration. It does not produce immune reactions and are incorporated by osteoclastic resorption with a shorter healing period compared with other methods of osseous repair. Proper case selection and accurate surgical planning is the prerequisite for successful graft harvesting. Applying the new safety recommendations and proper patient selection in chin bone harvesting could reduce the risk of altered post-operative tooth sensitivity due to injury of the mandibular incisive nerve.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11]
[Table 1], [Table 2], [Table 3], [Table 4]
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