Abstract
Since the introduction of rigid internal fixation devices, more and more surgeons favour an open approach to treating condylar fractures of the mandible in adult patients. Different indications for open treatment have been published. Open treatment is associated with surgical complications because of the technique employed. The aim of this systematic review was to provide an overview of the studies published exclusively on open treatment, and to summarize the existing open treatment modalities and their clinical outcomes. A total of seventy studies were selected for detailed analysis. Most studies reported good results with regard to the outcome measures of open treatment. Surgical complications including hematoma, wound infection, weakness of the facial nerve, sialocele, salivary fistula, sensory disturbance of the great auricular nerve, unsatisfactory scarring, and fixation failure were reported in the studies. This review suggests that because of the high level of methodological variance in the relevant studies published to date, among other factors, there are currently no evidence-based conclusions or guidelines that can be formulated with regard to the most appropriate open treatment. Establishment of such standards could potentially improve treatment outcomes.
Since the introduction of rigid internal fixation devices, more and more surgeons favour an open approach to treating condylar fractures of the mandible in adult patients . Different indications for open treatment have been published . Based on the literature, strong indications for open treatment are, for example, displacement into the middle cranial fossa, inappropriate occlusal restoration by closed reduction, lateral extracapsular displacement, and foreign material at the fracture site. Although there are other indications, such as bilateral mandibular condyle fracture in edentulous patients who cannot have a splint, where intermaxillary fixation and physical therapy are not possible because of internal disease, bilateral mandibular condyle fracture with comminuted fracture of other facial bones, bilateral mandibular condyle fracture with jaw deformities, and a certain amount of shortening of the ramus and angulation of the condyle, controversies regarding open and closed treatment exist .
The main advantages of open treatment are the ability to restore the most ideal anatomical position. Further, open treatment can prevent complications, such as breathing problems, a pronunciation disorder, or severe nutritional imbalance because of the shorter duration of maxillomandibular fixation (MMF). This will also potentially allow immediate mobilization of the joint, leading to more efficient functioning of the joint .
Because of the technique employed, open treatment is associated with surgical complications. The most concerning complication is permanent damage to the facial nerve. Other surgical complications include malocclusion, pain, reduced mouth opening, restricted range of motion (ROM) of the mandible, weakness of the facial nerve, infection, haemorrhage, Frey syndrome, sialocele/sialofistula, damage of the great auricular nerve, plate fracture and screw loosening, and a visible scar .
In this systematic review, studies published on endoscopic or transoral approaches were excluded. Despite the advantages, including absence of scarring (if no transcutaneous trocars are used) and not crossing the facial nerve , it has been found that these intra- and transoral approaches are technically demanding, especially for fractures at higher levels or with medial luxation of the proximal stump . Therefore, in most cases, the intraoral approach is too difficult for both stabilization of fractures and screw fixation. Thus, some say that the intraoral approach can only be used in select cases of low subcondylar fractures, and that this approach requires special instruments, additional training, and a longer operative duration . Therefore, we only addressed transcutaneous approaches in this review.
To date, controversies regarding the indications for the open treatment exist. Consequently, this systematic review focuses on the existing open treatment modalities and defines the outcome measures in accordance with our recently published review on closed treatment of mandibular condyle fractures .
Methods
A systematic literature search was performed on April 29, 2016 using PubMed (all indexed years), MEDLINE (all indexed years), and Embase (all indexed years) with multiple search terms ( Appendix A ). The search excluded case reports with 10 or fewer subjects, endoscopic or transoral treatment modalities, and studies in which stainless steel wires for osteosynthesis were used. Reports published in English, German, or Dutch were considered for inclusion. All prospective and retrospective human clinical studies that reported data relating to any form of open treatment of unilateral fractures of the mandibular condyle and the outcome of that treatment were included.
The following data were extracted from the selected studies: study design, period of follow-up, patient characteristics (age, gender), details of the fracture, details of the surgical approach, use of MMF, complications of the surgical approach and osteosynthesis material, and treatment outcomes.
Some studies included data on bilateral fractures and children; these data were excluded during data analysis.
Figure 1 shows a flow diagram of the inclusion process. First, two authors (R.B., A.R.) screened titles and abstracts for the potential relevance of the retrieved articles in a primary review process conducted in accordance with PRISMA criteria . Second, full articles were retrieved and relevant articles were designated for inclusion. Disagreement was resolved via discussion with a third person (L.D.). The included articles were critically appraised using a checklist with key criteria ( Table 1 – available online) . Table 1
Results
A total of 70 studies with a combined total of 3,052 patients, ranging from 11 to 230 patients in each study (with a male to female ratio of 2.7:1), were selected . The year of publication of the selected studies ranged from 1980 to 2016. The sample size in almost 50% of the studies was fewer than 100 patients. The mean age of the patients was 32.2 years, with a range of 4–91 years. In 19% of cases, both mandibular joints were fractured, and in 81% of cases, the fractures were unilateral. Of these fractures, 9% were located intracapsularly and 91% extracapsularly. The period of follow-up varied widely, from 5 days to 119 months. Yabe et al. reported the longest period of follow-up at 119 months.
Retrospective studies
Of the assessed studies, 38 (54.3%) were retrospective in nature, and included a heterogeneous series of mandibular condyle fractures and treatment modalities. The clinical outcome measurements in these studies were diverse and the follow-up periods were variable (range 5 days to 119 months). Of all the included studies, Eckelt and Hlawitschka had the largest sample size (230 patients).
Prospective studies
Thirty-two (45.7%) prospective studies were identified. There were two randomized clinical trials, both comparing different osteosynthetic materials. Rai compared the use of single and double non-compression miniplates and Seemann et al. compared the use of locking and non-locking plates. The follow-up duration ranged from 1 month to 66 months.
Overview of treatment modalities applied in the included studies
The treatments varied in the approach and material used for osteosynthesis. In the order of most frequently employed to the least frequently employed, the treatment approaches were as follows: retromandibular (31.4%), pre-auricular (12.9%), submandibular (7.1%), periangular (8.6%), and other (8.6%). In some studies, more than one approach was employed (22.9%; of these, retromandibular 30.3%, pre-auricular 36.4%, submandibular 21.2%, and other 12.1%), and in some studies the approach was not described (8.6%). Retroauricular, extended bicoronal, anteroparotid, rhytidectomy/facelift was also noted to have been employed along with a supratemporal approach, a curved incision in the ear lobule area, or a parotid mini-incision.
The approach was transparotid in 37.1% of the studies, non-transparotid in 21.4%, both transparotid and non-transparotid in 7.1%, and 34.3% of the studies did not describe whether the approach was transparotid. Focusing on the individual approaches, 56.3% of the retromandibular approaches were transparotid, 12.5% were non-transparotid, 9.4% described both transparotid and non-transparotid, and in 21.9% it was not described whether the approach involved the parotid gland. Where the pre-auricular approach was used, 14.3% of the studies reported the involvement of the parotid gland, 19% did not, and in 66.7% of studies involvement of the parotid gland was not defined.
In most studies, osteosynthesis (plates) were used for fixation (80.6%; 5.2% resorbable and 94.8% titanium). Lag screws were used in 6.9% of the studies and a combination of plates and lag screws was used in another 6.9% of the studies. In 5.6% of the studies, the method of fixation was not described ( Table 2 – available online). Table 2
In 34.3% of the studies, MMF was applied during surgery, but in 60% of the studies, the use of MMF during surgery was not reported. In 26.4% of the studies, MMF was continued after surgery as a standard postoperative therapy. In 22.2% of the studies, MMF was only used in the event of a malocclusion (22.2%). In 16.7%, no MMF was used postoperatively or was not described (34.7%).
The duration of postoperative MMF varied from 3 days to a maximum of 4 weeks. The most commonly used method of fixation was guiding elastics; however, Narayanan et al. used stainless steel wires. Most studies recommended a soft diet for 3–6 weeks and mouth opening exercises or physiotherapy after open reduction.
Indications mentioned for open treatment included malocclusion, inability to restore occlusion with closed treatment, patient not willing to have MMF, fracture displacement, and shortening of the ramus. Exclusion criteria for open treatment included undisplaced intracapsular and/or comminuted fractures, paediatric patients, or the patient being unfit for surgery.
Outcome measures
Table 3 gives an overview of the most uniformly reported outcome measures: occlusion, mouth opening, ROM of the mandible, and pain. In the studies that reported these outcome measures, 72.7–100% of the patients had no occlusal disturbances at the end of the follow-up period. The presence of some form of malocclusion ranged from 0% to 27.3%. Nonetheless, the need to perform orthognathic surgery was not described. The degree of mouth opening considered to constitute a “good” outcome varied. Some authors reported that it was equivalent to that of more than 30 mm, some used a threshold of more than 35 mm, and others used a threshold of more than 40 mm. Overall, limited mouth opening was reported in 0–27.3% of patients and a reduced ROM of the mandible in 0–42.1% of patients. No cases of ankylosis were reported. The reported incidences of persistent pain ranged from 0 to 42.1%.
| Authors | Occlusion % no malocclusion | Mouth opening good (%) | Range | Mean (mm) | ROM (% unlimited) | Pain (% free of pain) |
|---|---|---|---|---|---|---|
| Baek | 100 | 100 | >30 mm | ND | 100 | NCD |
| Benech | 100 | ND | ND | 38 | ND | ND |
| Bhutia | 100 | 100 | ND | ND | 100 | ND |
| Biglioli | 95.2 | ND | ND | ND | ND | ND |
| Biglioli | 100 | ND | ND | ND | ND | ND |
| Bindra | 100 | ND | ND | 34 | 100 | 100 |
| Bouchard | ND | ND | ND | ND | ND | ND |
| Chossegros | 79 | 100 | >35 mm | ND | Numbers given | 100 |
| Colletti | 100 | 99 | >38 mm | ND | 100 | 100 |
| Croce | 100 | 100 | ≥40 mm | ND | 100 | 100 |
| Dalla Torre | 100 | ND | 42–58 mm | 44 | ND | ND |
| Downie | 100 | ND | ND | ND | ND | ND |
| Dunaway | 96 | ND | 37–50 mm | 43 | ND | ND |
| Ebenezer | 100 | ND | ND | ND | ND | 100 |
| Girotto | ND | ND | ND | ND | ND | ND |
| Hou | 100 | 100 | ND | ND | ND | ND |
| Kanno | 100 | 100 | >40 mm | ND | 100 | 100 |
| Kim | 100 | 100 | >40 mm | ND | ND | 78.57 |
| Klatt | 84 | ND | 33–59 mm | 42.37 | Numbers given | ND |
| Kumaran | 100 | ND | ND | 44.84 | Numbers given | ND (VAS) |
| Li | 100 | ND | ND | 34.15 | ND | ND |
| Manisali | ND | ND | ND | ND | ND | ND |
| Nam | 100 | ND | 38–56 mm | 46.6 | ND | ND |
| Narayanan | 100 | ND | ND | 45 | Numbers given | ND |
| Narayanan | 100 | ND | ND | 44 | Numbers given | ND |
| Pilanci | ND | ND | 40–50 mm | 46 | Numbers given | 100 |
| Rao | 100 | ND | 30–44 mm | 38.33 | 100 | ND |
| Saikrishna | 76.7 | 100 | >40 mm | ND | ND | 100 |
| Salgarelli | 92.3 | ND | 30–60 mm | ND | ND | 92.3 |
| Shi J | 100 | ND | 30–48 mm | 40 | ND | 100 |
| Sikora | 100 | ND | 45–54 mm | 48 | ND | ND |
| Tang | 88.2 | 86.1 | >37 mm | ND | ND | ND |
| Trost | 80 | 97.1 | to 40 mm | ND | 97.1 | 100 |
| Vesnaver | 94 | ND | 30–61 mm | 44 | ND | 59 |
| Vogt | 100 | ND | ND | ND | ND | ND |
| Yabe | 100 | ND | ND | ND | ND | ND |
| Yang | 93 | ND | 32–61 mm | 44 | ND | 100 |
| Zhou | 92 | ND | +/− 40 mm | ND | ND | 94 |
| Alexander | 100 | ND | 16–50 mm | 30 | ND | 100 |
| Choi | 80 | 96 | ≥40 mm | ND | ND | 80 |
| Eckelt | 100 | 4 | <35 mm | ND | 95.5 | 90.9 |
| Hammer | ND | 90 | ≥35 mm | ND | ND | 99.7 |
| Hyde | 100 | ND | 37–52 mm | 42 | ND | 100 |
| Iizuka | 100 | 89 | >40 mm, 27–74 mm | 44 | ND | 89.2 |
| Iizuka | ND | ND | 22–50 mm | 39 | Numbers given | 76.9 |
| Lima | ND | ND | ND | ND | ND | ND |
| Petzel | 100 | ND | ND | ND | ND | ND |
| Raveh | 100 | ND | ND | >40 mm | ND | ND |
| Sargent | 92 | ND | 35–56 mm | 45 | ND | 92.9 |
| Spinzia | 80 | 62.5 | >40 mm, 18–50 mm | 35.48 | Numbers given | 72 |
| Widmark | 89.50 | ND | 40–67 mm | 51 | 57.9 | 57.9 |
| Zrounba | 99.3 | ND | 21–56 mm | 42.10 | Numbers given | ND |
| Chaithanyaa | 80 | ≥86.7 | (≥46.7: 38–40 mm, 40: 30–35 mm) | ND | ND | ND |
| Chaudhary | 100 | ND | 34–42 mm | 36.13 | ND | 100 |
| Choi | 83.8 | ≤91.9 | (75.7 > 38 mm) | ND | ND | ND |
| Cortelazzi | 100 | ND | 35–48 mm | 41 | ±100 | ±100 |
| Derfoufi | ND | ND | ND | ND | ND | ND |
| Eckelt | ND | 100 | ≥30 mm | ND | 92.2 | 85.4 |
| Eckelt | 99.1 | 91.7 | ≥35 mm | ND | 88.7 | ND |
| Hachem | ND | 100 | ≥30 mm, 68.2 > 40 mm | ND | 90.9 | 90.9 |
| Kallela | 72.7 | 90.9 | (82 > 40 mm) | ND | 100 | 90.9 |
| Meyer | 94 | 100 | >40 mm | 49.5 | 100 | 100 |
| Petzel | ND | ND | 32–51 mm | ND | Numbers given | ND |
| Rai | 93.3 | ND | ND | ND | ND | ND |
| Rallis | ND | 93.6 | >40 mm, (6.4 < 35 mm (28–34 mm) | ND | ND | ND |
| Seemann | ND | ND | ND | ND | ND | ND |
| Singh | ND | ND | ND | ND | ND | ND |
| Sugiura | 94.4 | ND | ND | 42.8 | Numbers given | 96.3 |
| Xie | 80.6 | ND | ND | 38.3 | ND | 94.4 |
| Zhang | 100 | ND | ND | ND | ND | ND |
Surgical complications were observed ( Table 4 ), including weakness of the facial nerve (12%; of which approximately 5% of cases were permanent), hematoma (1.7%), wound infections (≥2.9%), Frey syndrome (1.1%), sialocele (2.6%), salivary fistula (≥4.8%), disturbance of the sensory component of the great auricular nerve (7.9%), and unsatisfactory scarring (≥1.6%). Fifty-seven per cent of the studies investigated the incidence of fixation failure as an outcome measure (Table 2). In these studies, 5.5% of the patients experienced some form of fixation failure, i.e. plate or screw breakage/loosening.
| Wound infection | Hematoma formation | Sialocele | Salivary fistula | Scar | Facial nerve (total) | Percentage | Recovery | Permanent | Auricular anesthesia | Frey syndrome | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Baek | None | NCD | ND | 1 (5.3%) | Not disturbing | 2 | 11.8 | 3 months | None | None | ND |
| Benech | None | None | None | None | Not disturbing | 1 | 7.1 | 1.6 months | None | None | None |
| Bhutia | None | ND | ND | 3 (6.8%) | Not disturbing | 9 | 21.9 | 3–6 months | None | ND | ND |
| Biglioli | 2 (8%) | ND | ND | ND | 2 (8%) unsatisfactory | None | 0 | NA | None | ND | ND |
| Biglioli | 2 (5.3%) | ND | ND | ND | 2 (5.3%) unsatisfactory | None | 0 | NA | None | ND | ND |
| Bindra | None | ND | ND | None | Not disturbing | None | 0 | NA | None | ND | None |
| Bouchard | 14 (11.9%) | ND | 2 (1.7%) | 4 (3.4%) | ND | 35 | 29.7 | NA | 1 (0.8), (6.8 unknown) | ND | 1 (0.9%) |
| Chossegros | 1 (5.2%) | ND | ND | ND | 2 (11%) unsatisfactory | 2 | 10.5 | 3.6 weeks | None | 2 (10.5%) transient | ND |
| Colletti | 3 (3%) | ND | 1 (1%) (trans) | ND | 2 (2%) unsatisfactory | 4 (ND) | 4.6 | 2 months | None | ND | ND |
| Croce | ND | None | None | 4 (22.2%) | Not disturbing | 6 | 46.2 | 4–8 weeks | None | ND | 1 (5.6%) |
| Dalla Torre | ND | ND | 7 (6.8%) | None | Not disturbing | 4 | 3.9 | 3–6 months | None | ND | ND |
| Downie | 1 (2%) | ND | 1 (2%) | 1 (2%) | ND | 7 | 14 | NA | None | ND | ND |
| Dunaway | ND | 1 (3.4%) | ND | ND | Not disturbing | 3 | 12 | 6 weeks | None | ND | ND |
| Ebenezer | None | ND | ND | 3 (15%) (trans) | 4 (20%) unsatisfactory (1 sub, 3 after fistula) | NCD | NCD | NCD | NCD | ND | None |
| Girotto | None | ND | ND | None | Not disturbing | 2 | 8 | 1–2 weeks | None | None | ND |
| Hou | None | ND | ND | 3 (4.2%) (1 min, 2 ret) | ND | 4 (retro) | 6.7 | ND | 1 (1.7) | ND | ND |
| Kanno | None | ND | ND | 1 (5.3%) | Not disturbing | 2 | 11 | 3 months | None | ND | None |
| Kim | None | ND | ND | 3 (10.7%) | Not disturbing | 9 | 32.1 | 6–20 weeks | None | 1 (3.57%) transient | ND |
| Klatt | None | None | ND | 2 (4%) | ND | 4 | 10 | 6 weeks | None | 5 (16%) lasting > 6 months | ND |
| Kumaran | ND | ND | 1 (2.9%) (retro) | ND | Disturbing in preauricular group (n = 12) | 4 (3 pre, 1 retro) | 12.9 | ND | ND | ND | ND |
| Li | None | ND | ND | ND | ND | 7 | 8.3 | ND | 2 (2.4) | ND | None |
| Manisali | ND | ND | 1 (4%) | ND | 2 (8%) unsatisfactory | 6 | 30 | 3 months | None | 2 (8%) transient | ND |
| Nam | ND | ND | ND | ND | ND | 4 | 16 | 1–2 months | None | ND | ND |
| Narayanan | 2 (5.7%) | ND | ND | 4 (11.4%) | 2 (5.7%) unsatisfactory | 1 | 32.3 | 2 weeks | None | ND | None |
| Narayanan | 1 (0.7%) | ND | None | None | ND | None | 0 | NA | NA | ND | None |
| Pilanci | 1 (5%) | None | None | None | Not disturbing | 1 | 6.3 | 6 weeks | None | None | ND |
| Rao | None | ND | ND | 3 (17.6%) | Not disturbing | 2 | 13.3 | 4–3 months | None | ND | None |
| Saikrishna | None | 1 (3.3%) | 3 (10%) | ND | 6 (40%), 1 hypertrophic (3.3%) unsatisfactory (retro) | 4 | 13.3 | ND | None | 1 (3.3%) transient | ND |
| Salgarelli | ND | ND | ND | ND | Not disturbing | 1 | 7.7 | 1 week | None | ND | ND |
| Shi J | ND | 1 (2.8%) | 1 (2.8%) | ND | Not disturbing | None | 0 | NA | NA | ND | ND |
| Sikora | ND | ND | ND | ND | Not disturbing | 3 | 7.9 | 3 months | None | ND | ND |
| Tang | ND | ND | ND | None | ND | 4 | 7.8 | 1–3 months | None | ND | ND |
| Trost | 1 (2.6%) | ND | ND | ND | 1 (2.6%) unsatisfactory | None | 0 | NA | NA | ND | ND |
| Vesnaver | ND | 2 (6%) | ND | 5 (14%) | Not disturbing | 8 | 22 | 4–8 weeks | 1 (2.8) | 5 (14%) transient | ND |
| Vogt | None | ND | ND | 4 (7.8%) | Not disturbing | 10 | 19.6 | 6 months | None | ND | ND |
| Yabe | 1 (6.7%) | ND | ND | None | Not disturbing | None | 0 | NA | NA | ND | None |
| Yang | None | 2 (4.2%) | ND | 3 (6.3%) | Not disturbing | 8 | 19 | 3–4 weeks | None | None | ND |
| Zhou | None | ND | ND | None | Not disturbing | 7 | 8 | 1 month | None | ND | ND |
| Alexander | None | ND | ND | ND | ND | 7 | 31.8 | 1–3 months | None | ND | ND |
| Choi | ≥2 (7.4%) | ND | ND | ≥2 (7.4%) | Not disturbing | 5 | 20 | 3 months | None | 5 (18.5%) transient | ND |
| Eckelt | ND | ND | ND | ND | ND | 2 | 9.1 | ND | ND | ND | ND |
| Hammer | ≥3 (10%) | ND | ND | ≥3 (10%) (ND) | ND | 1 | 0.3 | 8 weeks | None | ND | ND |
| Hyde | ND | ND | ND | ND | ND | 3 | 12 | 3 weeks | None | ND | ND |
| Iizuka | ND | ND | ND | ND | ND | 2 | 7.4 | 2–6 weeks | None | ND | ND |
| Iizuka | ND | ND | ND | ND | 1 (4.8%) unsatisfactory (sub) | 2 | 15.4 | 6 months | 1 (7.7) | ND | ND |
| Lima | 3 (4.6%) | ND | 1 (1.5%) | None | Not disturbing | 3 | 5.2 | 6 months | 1 (1.7) | ND | None |
| Petzel | ND | ND | ND | ND | ND | ND | ND | ND | None | ND | ND |
| Raveh | ND | ND | ND | ND | ND | None | 0 | NA | NA | ND | ND |
| Sargent | None | ND | ND | ND | ND | 1 | 7.1 | Weeks | None | ND | ND |
| Spinzia | 1 (3.8%) | ND | ND | None | 3 (12%) unsatisfactory (ND) | 22 | 12 | 3 years | None | ND | 3 (11.5%) |
| Widmark | 1 (5%) | ND | ND | ND | Not disturbing | 1 | 5.3 | 4 weeks | None | 3 (15%) | ND |
| Zrounba | ND | 1 (0.6%) | ND | ND | Not disturbing | 7 | 4.9 | ND | 1 (0.7) | ND | 1 (0.6%) |
| Chaithanyaa | 2 (13.3%) | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Chaudhary | ND | ND | ND | ND | ND | ND | ND | 1 month | None | ND | ND |
| Choi | ≥3 (7.5%) | ND | ND | ≥3 (7.5%) | ND | 7 | 18.9 | 3 months | None | ND | ND |
| Cortelazzi | 6 (9.7%) | ND | ND | 10 (16.1%) (retro trans) | ND | 18 (11 retro, 7 pre) | 29 | 3–4 weeks | None | ND | ND |
| Derfoufi | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Eckelt | ND | ND | ND | ND | ND | 8 | 7.8 | ND | 8 (7.8) | ND | ND |
| Eckelt | 3 (1.2%) | 1 (0.4%) | ND | ND | Few unsatisfactory | 54 | 21 | ND | 1 (0.4) | ND | ND |
| Hachem | ≥1 (3.3%) | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Kallela | ND | ND | ND | ND | 1 (7.7%) unsatisfactory | 3 | 27.3 | 1–5 months | None | ND | ND |
| Meyer | 1 (1.4%) | ND | ND | ND | 1 (1.4%) unsatisfactory | None | 0 | NA | NA | ND | ND |
| Petzel | ND | ND | ND | ND | ND | None | 0 | NA | NA | ND | ND |
| Rai | 2 (13.3%) | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Rallis | ND | ND | ND | ND | ND | 5 | 10.6 | 1–2 months | None | ND | ND |
| Seemann | 1 (0.8%) | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Singh | None | ND | ND | ND | ND | ND | ND | ND | ND | ND | ND |
| Sugiura | 1 (1.7%) | ND | ND | ND | ND | 6 | 11.1 | >6 months | ND | ND | ND |
| Xie | ND | ND | ND | ND | ND | 3 | 8.3 | ND | None | ND | ND |
| Zhang | ND | ND | ND | 1 (1%) | ND | 4 | 4 | 3 months | None | ND | ND |
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