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Lin H, Friedman M, Chang H, et al. Minimally Invasive, Single-Stage, Multilevel Surgery for Obstructive Sleep Apnea in Asian Patients. JAMA Otolaryngol Head Neck Surg. 2017;143(2):147–154. doi:10.1001/jamaoto.2016.3103
What are the results of anatomy-based, minimally invasive, single-stage, multilevel surgery in the treatment of patients with obstructive sleep apnea (OSA)?
In this retrospective study of 47 Asian adults with OSA, the Epworth Sleepiness Scale and patient’s snoring severity significantly decreased 3 months after surgery. However, the preoperative and postoperative apnea-hypopnea index did not differ significantly.
Minimally invasive, single-stage, multilevel surgery for patients with OSA could improve the 2 relevant clinical outcomes for snoring severity and daytime sleepiness but may have limited effects on polysomnographic results.
This study adds to the literature on the efficacy and low complication rates associated with minimally invasive, single-stage, multilevel surgery for Asian adults with obstructive sleep apnea (OSA) for whom conservative treatment had failed. Overall, our experience has produced results that make this procedure an option for select patients with snoring and OSA.
To investigate the effectiveness and safety of anatomy-based, minimally invasive, single-stage, multilevel surgery in the treatment of OSA in an Asian population.
Design, Setting, and Participants
This retrospective study enrolled 59 consecutive patients with OSA from a tertiary academic medical center who had multilevel obstruction and unsuccessful conservative therapy and then underwent minimally invasive, single-stage, multilevel surgery. The subjective symptoms and objective polysomnographic findings were collected preoperatively and at a minimum of 3 months postoperatively. The Global Patient Assessment questionnaire was used to assess patient satisfaction after minimally invasive, single-stage, multilevel surgery.
Main Outcomes and Measures
Scores on the Epworth Sleepiness Scale and bed partner evaluation of patient’s snoring on a visual analog scale (scale of 0-10, with 0 indicating no snoring and 10 indicating the bed partner to leave the room or sleep separately, as assessed by the bed partner). The primary outcomes are a 50% decrease in bed partner’s snoring visual analog scale level postoperatively and an improvement of 50% or more in apnea-hypopnea index by an at least 3-month follow-up. Adverse events and patient-reported quality measures were also assessed.
Forty-seven patients (36 men and 11 women; mean [SD], 47.3 [10.9] years) with a minimum 3-month follow-up and complete data were included in the analysis. None of the patients had serious perioperative or postoperative complications. Three months postoperatively, the mean (SD) scores on the Epworth Sleepiness Scale and bed partner evaluation of patient’s snoring on the visual analog scale decreased from 11.6 (4.3) to 9.2 (3.1), with a mean (SD) difference of −2.4 (3.7) (95% CI, −3.5 to −1.3), and 9.4 (1.5) to 3.9 (1.9), with a mean (SD) difference of −5.6 (2.0) (95% CI, −6.2 to −5.0), respectively. The mean (SD) apnea-hypopnea index and lowest oxygen saturation changed from 30.5 (18.8) to 26.0 (16.5), with a mean (SD) difference of −4.5 (14.1) (95% CI, −8.6 to −0.3), and 78.2% (9.9%) to 80.8% (8.2%), with a mean (SD) difference of +2.6 (8.7) (95% CI, 0-5.1), respectively. The surgical response rate was 46.8% (22 of 47 patients) (95% CI, 32.5%-61.1%). The success rate by the classic definition was 14.9% (7 of 47 patients) (95% CI, 6.2%-28.3%).
Conclusions and Relevance
This study reveals the improvement of the 2 relevant clinical outcomes in snoring severity and daytime sleepiness after minimally invasive, single-stage, multilevel surgery for patients with OSA but the limited effects on the polysomnographic parameters. Although the current role of minimally invasive, single-stage, multilevel surgery for Asian adults with OSA remains to be established, it is hoped that ongoing and future studies will solidify their role in the treatment of OSA.
Looking back on the history of obstructive sleep apnea (OSA) and hypopnea syndrome surgery, we discovered that the aspiration of surgeons is to do their best to reduce morbidity and decrease complications after surgery. In recent years, advancements in technology have allowed sleep surgeons to use minimally invasive techniques to offer this kind of benefit to patients with sleep-disordered breathing. Compared with traditional snoring and OSA operations, the main advantages of minimally invasive upper airway surgery include the sparing of the overlying mucosa and decreased operative morbidity and postoperative complications. Because a subset of patients with OSA cannot tolerate the treatment of continuous positive airway pressure or oral appliances and are also often not willing to undergo traditional invasive surgical correction, the options are limited to minimally invasive upper airway techniques.
Clinically, many modifications of palatal operations for OSA with minimally invasive techniques have been reported, and considerable interest has developed with recent nuances in the last decade.1-4 Pillar implants (PIs) (Pillar Palatal Implant System; Medtronic) treat socially disruptive snoring and OSA in patients with obvious soft palate flutter and collapsibility. The use of PIs has demonstrated clinical benefits with minimal postoperative morbidity and complications.3-5 These benefits, along with acceptable surgical results of the PIs for patients with OSA, make it a possible option that can be offered to properly selected patients with OSA and obvious palatal vibration.6
Traditionally, hypopharyngeal procedures for OSA are generally more technically challenging and time consuming. Conventional traditional tongue base operations, such as carbon dioxide midline laser glossectomy, tongue base suspension, genioglossus advancement, and hyoid suspension, are effective to a certain degree. However, these operations are invasive and associated with severe complications, such as edema, infection, bleeding, lingual paralysis, and persistent odynophagia, resulting in limited patient and physician acceptance.7-13
Temperature-controlled radiofrequency tissue volume reduction uses a probe to deliver energy to stiffen the redundant upper airway soft tissue while sparing the mucosa and adjacent tissue. This results in less pain than conventional methods, quicker patient recovery, and significantly less morbidity. The value of radiofrequency for OSA treatment has been well demonstrated, especially in the tongue base region.2,14 Radiofrequency base of tongue (RFBOT) surgery can be performed in an office-based setting. It can be repeated as needed and can ameliorate the operation time, the possible postoperative complications, and the risk of a compromised airway in patients with OSA.
Because most OSA is caused by multilevel obstructions of the upper airway, the appropriate treatment should be a multilevel approach. Many studies15-18 have found that treatment of all sites of obstruction can lead to better surgical outcomes.
The purpose of this study was to investigate the effectiveness and safety of anatomy-based, minimally invasive, single-stage, multilevel surgery in the treatment of OSA in an Asian population. To our knowledge, this is the first report on minimally invasive, single-stage, multilevel surgery for OSA in Asian patients in the literature.
Approval for this retrospective study was obtained from the Chang Gung Medical Foundation Institutional Review Board to review the medical records of these enrolled patients, who provided oral informed consent. The deidentified data were collected for all cases of minimally invasive, single-stage, multilevel surgery by one of us (H.-C.L.).
The medical records of 59 patients with OSA at the Sleep Center of the Kaohsiung Chang Gung Memorial Hospital who refused or in whom continuous positive airway pressure therapy failed and who then underwent minimally invasive, single-stage, multilevel surgery were reviewed. Only patients with complete data were included in this study.
Full-night attended, comprehensive diagnostic sleep studies were performed at the sleep center of the Kaohsiung Chang Gung Memorial Hospital in a temperature-controlled and sound-attenuated room. Electroencephalography, submental electromyography, and electro-oculography were performed with surface electrodes by standard techniques. Nasal and oral airflow were recorded by thermistors. Oxygen saturation was measured by pulse oximetry. Sleep stage scoring was performed for 30-second intervals by experienced sleep physicians (K.-T.H.) according to the standard criteria.19
The severity of sleep-disordered breathing was classified according to the number of apneas and hypopneas during sleep. By definition, OSA is a cessation of airflow for at least 10 seconds with effort to breathe during the event. Obstructive hypopnea is defined as an abnormal respiratory event with at least a 30% reduction in thoracoabdominal movement or airflow when compared with the baseline, lasting at least 10 seconds, and with 4% or more oxygen desaturation.20 The apnea-hypopnea index (AHI) is defined as the total number of apneas and hypopneas per hour of electroencephalographic sleep. Obstructive sleep apnea is a severe type of sleep-disordered breathing and is defined as an AHI greater than 5.21 All polysomnograms were scored and read by a board-certificated physician (K.-T.H.) who was unaware of the study and, therefore, masked to the patients’ participation in the study.
Inclusion criteria include the following: age of 20 years or older; significant symptoms of habitual snoring and/or excessive daytime somnolence; no previous upper airway surgical treatment for sleep-related breathing; AHI greater than 5 with full-night polysomnography; failure or refusal of conservative treatments, such as oral appliances or continuous positive airway pressure; Friedman tongue position less than III and small tonsils (grade I or II)22-24; and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) less than 30.
The site of airway obstruction was confirmed by a flexible fibroscope with the Müller maneuver and an endoscope with a target-controlled infusion of propofol with the patient under drug-induced sedative sleep. In this study, the estimated degree of the airway collapse by a fiber optic nasal endoscope with the Müller maneuver at the retropalatal and retrolingular levels should be a more than 50% change in cross-sectional airway area. The severity of airway collapse during the drug-induced sleep endoscopy with VOTE classification should be as follows: V, degree 1 and 2 and anteroposterior configuration; O, degree 0 and 1 (absolutely exclude degree 2 or tonsil size grades 3 and 4); T, degree 1 and A-P configuration; and E, degree 0. Patients who had palatal lengths less than 2.5 cm, severe redundant parapharyngeal tissues, and/or pillar webbing were also excluded.
All surgical procedures were performed by one of us (H.-C.L.) with the patients under local anesthesia or general anesthesia with transoral endotracheal intubation, depending on the severity of patient’s gag reflex and tolerance. The inferior turbinate reduction, PI procedure, and RFBOT surgery were performed in the same manner as previously described.3,6,17,25-28 Only patients who experienced nasal congestion symptoms or had a positive response to decongestant or corticosteroid nasal spray were treated with nasal surgery. Surgical techniques performed in the nose include a resection of septal spur endoscopically or endoscopic septoplasty when appropriate and/or turbinate tissue volume reduction by radiofrequency or submucosal resection with bipolar electrocautery when indicated. The soft palatal stiffening technique with the 3 soft palate PIs was then performed. All patients then underwent RFBOT surgery (Somnoplasty System; Gyrus Inc) as adjunctive treatment for tongue base obstruction. The patients received 4500 to 7500 J distributed to 6 to 10 points along the midline of the tongue behind the circumvallate papillae.
Oral antibiotics (cefadroxil) were prescribed for 1 week, and low-dose steroids were prescribed for 3 days. Nonsteroidal anti-inflammatory drugs (ibuprofen), proton pump inhibitors, or histamine2-receptor antagonists and chlorhexidine mouth rinses were prescribed for 1 week. A liquid or soft diet was started 6 hours after surgery based on the recovery status of each patient.
The subjective assessment was based on symptoms of daytime somnolence as measured by the Epworth Sleepiness Scale and bed partner evaluation of patient’s snoring on the visual analog scale (scores of 0-10, with 0 indicating no snoring and 10 indicating the bed partner to leave the room or sleep separately, as assessed by the bed partner). The subjective symptoms and objective polysomnographic parameters were collected preoperatively and at a minimum of 3 months postoperatively. Complications that occurred between postoperative recovery and the follow-up period were recorded. At the 3-month postoperative follow-up, patients also completed a Global Patient Assessment questionnaire,29 which was designed to assess patient satisfaction after undergoing a procedure by asking, if given the choice, whether the patient would choose to undergo the same procedure (yes, not sure, or no) and having the patient to rank the overall experience on a scale of +5 to −5 (+5 being the best outcome possible and −5 being the worst outcome possible). Although the Global Patient Assessment questionnaire contained additional parameters, we arbitrarily selected these 2 for the study before data collection and analysis. All patients with complete data were included.
Statistical analysis was performed using the Wilcoxon signed rank test for paired data. P < .05 was considered statistically significant.
A subset of 47 patients with OSA had complete preoperative and postoperative subjective and objective data with a minimum follow-up of 3 months to assess efficacy of the procedure (Table 1). This population consisted of 11 women and 36 men, with a mean (SD) age of 47.3 (10.9) years and a mean (SD) BMI of 24.2 (2.6). All patients underwent PI and RFBOT surgery, and 36 patients underwent additional nasal surgery. Three months after the treatment, the mean (SD) Epworth Sleepiness Scale scores and bed partner evaluations of patient’s snoring on the visual analog scale decreased from 11.6 (4.3) to 9.2 (3.1), with a mean (SD) difference of −2.4 (3.7) (95% CI, −3.5 to −1.3), and 9.4 (1.5) to 3.9 (1.9), with a mean (SD) difference of −5.6 (2.0) (95% CI, −6.2 to −5.0), respectively. The AHI and lowest oxygen saturation changed from 30.5 (18.8) to 26.0 (16.5), with a mean (SD) difference of −4.5 (14.1) (95% CI, −8.6 to −0.3), and 78.2% (9.9%) to 80.8% (8.2%), with a mean (SD) difference of +2.6 (8.7) (95% CI, 0-5.1), respectively. The preoperative and postoperative BMIs did not differ significantly.
Because most of the patients originally sought treatment for loud snoring, we defined subjective improvement by strict criteria, which required a 50% decrease in bed partner’s snoring visual analog scale score postoperatively. Subjective improvement of postoperative snoring severity was encountered in 37 of 47 patients (78.7%) (95% CI, 64.3%-89.3%).
Objective measures of clinical improvement of OSA were based on data collected during polysomnography. The classic definition5 of surgical success requires a 50% or greater reduction in postoperative AHI compared with the preoperative value and a postoperative AHI of less than 20. The success rate in this study was 14.9% (7 of 47 patients) (95% CI, 6.2%-28.3%). If we define the surgical response group as including a 25% or greater reduction in postoperative AHI and the bed partner’s satisfaction with the patient’s reduction in snoring, the response rate was 46.8% (22 of 47 patients) (95% CI, 32.1%-61.9%). Subset analysis of the changes in clinical outcomes after minimally invasive, single-stage, multilevel surgery is given in Table 2. The correlation of changes of subjective estimates of symptoms and important polysomnographic data before and after surgery is given in Table 3. Although 6 patients (12.8%) (95% CI, 4.8%-25.7%) had increased postoperative AHIs, all still reported subjective improvement in daytime sleepiness and snoring intensity.
The status of patient satisfaction with minimally invasive, single-stage, multilevel surgery was evaluated with the Global Patient Assessment. Forty-one of 47 patients (87.2%) (95% CI, 74.3%-95.2%) reported that they would undergo the same procedure again as needed in the future. Sixteen of 47 patients (34.1%) (95% CI, 20.9%-49.3%) ranked the overall experience with their procedure as +5, 23 of 47 (48.9%) (95% CI, 34.1%-63.9%) as +4, and only 2 patients ranked a negative experience with −1 and −2, respectively.
No life-threatening perioperative complications or cases of immediate postoperative airway obstruction occurred in this study. The durations of reducing pain medication (400 mg of ibuprofen 4 times daily) use were used as an index of recovery from surgery and ranged from 3 to 7 days, with a mean (SD) of 4.2 (3.1) days. Two patients had extrusion of 1 PI at 1 month and 6 months postoperatively, respectively. Temporary postoperative velopharyngeal insufficiency was reported in 8 patients (17.0%) (95% CI, 7.7%-30.8%), and the postoperative velopharyngeal insufficiency lasted between 2 and 6 days after surgery. No cases of permanent postoperative velopharyngeal insufficiency were encountered in this study. Most minor complications encountered were related to postoperative throat discomfort, such as pain, sensation of a lump in the throat, dry throat, and frequent throat clearing. However, the severity reduced, typically within a week, and patients reported that the change did not affect their social activities. One patient developed temporary hypoglossal nerve paralysis for 3 months after surgery. No postoperative bleeding, infection, or tongue base abscess formation after surgery that required surgical intervention was encountered in the follow-up period.
The PIs, consisting of three 18-mm polyethylene terephthalate fibers, are designed to be permanently inserted into the palatal muscular layer at the hard palate junction. The cold technique and miniscule size of the PIs could preserve the contour and superficial mucosa of the soft palate. Furthermore, the material of the PIs, polyethylene terephthalate, has good biocompatibility. Therefore, the risk of possible complications is minimized. Tongue base procedures include tissue volume reduction and suspension techniques. The tongue base suspension may need additional devices, and relapse is a clinical concern. Thus, most studies focus on tongue base tissue volume reduction with different devices, with RFBOT surgery being the most common modality reported in the literature.
In this series, the classic success rate was relatively low at only 14.9% (7 of 47 patients) and the surgical response rate was 46.8% (22 of 47 patients). The structural support of the PIs works together with the fibrotic reaction to stiffen the soft palate and decrease palatal fluttering, which might induce secondary tongue base collapse attributable to loss of some support from the original soft palate or oropharyngeal framework, especially in the lateral pharyngeal walls, in sleep.
Because OSA is usually caused by multilevel obstruction during sleep and single-level OSA surgery alone has limited success, the true focus of treatment should be on multilevel surgical intervention. Clinically, sleep surgeons are increasingly using various adjunctive procedures to improve the surgical response rate. In this study, we treated the patients with PIs combined with RFBOT surgery. The advantage of these minimally invasive procedures for snoring and OSA is that they can be performed again if the physician or patient is not satisfied with the preliminary results and can be salvaged with traditional palatal and tongue base techniques. In this present report, RFBOT surgery was performed only once, and only 3 PIs were used in this follow-up period, which may have limited the results. Another extended study could be performed on surgical outcomes after adding additional RFBOT surgery or an additional PI procedure.
In recent years, planned multilevel surgery has become standard in many centers.18 To the best of our knowledge, published data on multilevel OSA surgery can be divided into the following groups. First, traditional uvulopalatopharyngoplasty or modified uvulopalatopharyngoplasty as a basic technique or a procedure designed to improve the hypopharyngeal airway can be performed. The most common hypopharyngeal operations include genioglossus advancement, thyrohyoid advancement, RFBOT surgery, and, in some cases, tongue base suspension. The success rates for these procedures have been reportedly between 20% and 100%. The second group of patients who have undergone multilevel treatment include those who previously had more invasive and more radical hypopharyngeal operations, such as open tongue base resection. The aggressive nature of these procedures resulted in temporary tracheotomy for some patients. The success rates in this group vary from 44% to 100%. The third group is multilevel, minimally invasive techniques. Steward30 studied 22 patients who underwent combined radiofrequency reduction of the palate and base of tongue and reported a success rate of 59%. None of their patients underwent concomitant nasal surgery. Fischer et al31 presented a similar study about multilevel, minimally invasive surgery with radiofrequency on the palate, tonsil, and tongue base for 15 patients with OSA with a success rate of 33.3%. Stuck et al32 published their surgical results with radiofrequency on the palate and base of the tongue for 18 patients with mild to moderate OSA. Six of 18 patients (33%) were cured after a mean of 2.7 treatment sessions. In 2007, Friedman et al6 presented their results regarding minimally invasive, multilevel surgery for patients with mild to moderate OSA, and classic success was achieved in 54 of 122 patients (47.5%). In 2009, Ceylan et al33 studied 26 patients with OSA who underwent combined radiofrequency reduction of the palate and the base of tongue and reported a success rate of 53.8%. Neruntarat and Chantapant34 also described 72 patients who underwent combined radiofrequency reduction of the palate and the base of tongue and reported a success rate of 55.6%. Although our results in Asian patients revealed a lower success rate compared with the previous literature in Western countries with minimally invasive techniques for OSA, the significant improvement in the severity of snoring severity and daytime sleepiness status produced a relatively high satisfaction level in patients and their bed partners after surgery (using the GPA questionnaire). Thus, we believe that minimally invasive, single-stage, multilevel surgery could be a viable option in select patients with OSA who refused invasive airway surgery, especially in the patients with major symptoms of snoring and hypersomnia.
In this series, 6 patients (12.8%) had obvious reduction of snoring intensity but had increased postoperative AHI. Minimally invasive, single-stage, multilevel surgery with PIs and RFBOT surgery theoretically creates submucosal fibrotic tissues that stabilize airway patency; this surgery may also induce secondary tongue base collapse attributable to loss of some physiologic support from original soft palate or oropharyngeal framework in sleep. The limitation of tongue base tissue volume reduction is the degree of tissue removed with RFBOT surgery. The planned ablated specimens cannot be accurately weighed perioperatively for prediction of surgical response. Although RFBOT surgery reduces the tongue base tissue volume, the postoperative scarring might gradually retract the tongue base in an unpredictable direction and/or induce the negative turbulence in the upper airway. Investigation using images or other technology may be necessary to overcome this issue. The patients should be well informed about this potential risk preoperatively. Furthermore, to solve this problem, subsequent studies with additional PIs, additional RFBOT surgery, and more invasive tongue base resection, such as coblation tongue base resection or oral tongue body tissue volume reduction, may be warranted.
This study has some limitations. First, the results reflect a single surgeon’s experience. Second, the study was retrospective, with the patients serving as their own controls with no control group. Third, the techniques used for this study were implemented on patients with specified anatomical conditions (with <3 of the Friedman tongue positions and relatively thin palate) and on patients with all levels of OSA disease severity; the study could be broadened to determine whether minimally invasive, single-stage, multilevel surgery is effective in treating patients with OSA with difficult upper airway anatomy, such as Friedman tongue position III/IV. Fourth, because there was no statistical difference in the BMI of these patients before and after the surgery, the results are independent of weight loss frequently encountered after OSA surgery. In patients with significant weight loss or gain, this may cause confounding results that would require reevaluation. Fifth, predictive factors for success and cure were not evaluated because of a small sample size that may not result in a meaningful analysis. Sixth, this study had a short follow-up period and a relatively small number of patients. Long-term outcomes and a larger case series should be studied. Seventh, these results are limited to Asian patients. It is important to further compare the effectiveness of minimally invasive, single-stage, multilevel surgery among different ethnic populations. Another disadvantage of minimally invasive surgery is the relatively high out-of-pocket expense.
It is important to consider the risks and subjective and objective outcomes when choosing operative procedures. In this study, minimally invasive, single-stage, multilevel surgery resulted in acceptable improvement of clinical OSA symptoms, but had limited effects on the polysomnographic parameters. No serious permanent complications occurred during the follow-up period. Overall, our experience has produced encouraging results, making this procedure an option for select patients with snoring and OSA. This study will add to the literature the reasonable efficacy and low complication rates associated with MISS MLS for OSA in Asian patients for whom conservative treatment had failed.
Corresponding Author: Hsin-Ching Lin, MD, Sleep Center, Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, 123, Ta-Pei Rd, Niao-Sung District, Kaohsiung City, Taiwan 833 (email@example.com).
Accepted for Publication: August 18, 2016.
Published Online: November 10, 2016. doi:10.1001/jamaoto.2016.3103
Author Contributions: Drs H.-C. Lin and Huang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: H.-C. Lin, Friedman, Salapatas, Huang.
Acquisition, analysis, or interpretation of data: H.-C. Lin, Friedman, Chang, Bonzelaar, Salapatas, Huang.
Drafting of the manuscript: H.-C. Lin, Bonzelaar, Salapatas, Huang.
Critical revision of the manuscript for important intellectual content: Friedman, Chang, Bonzelaar, Salapatas, M.-C. Lin, Huang.
Statistical analysis: H.-C. Lin, Chang, Bonzelaar, Salapatas.
Administrative, technical, or material support: H.-C. Lin, M.-C. Lin, Huang.
Study supervision: Friedman, M.-C. Lin.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
Funding/Support: This study was supported by grant MOST 103-2314-B-182A-060 from the Ministry of Science and Technology Research Project and grant CMRPG8D1331 from the Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.
Previous Presentation: This study was presented in part at the 2015 Annual Meeting of the American Academy of Otolaryngology–Head and Neck Surgery Foundation; September 30, 2015; Dallas, Texas.
Additional Contributions: Mao-Chang Su, MD, Chien-Hung Chin, MD, and Yung-Che Chen, MD, Sleep Center and the Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan, assisted in manuscript preparation. They received no financial compensation for their contributions.
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