Anterior lumbar interbody fusion (ALIF)

Anterior lumbar interbody fusion (ALIF)

ALIF is an effective treatment for degenerative disc disease (with and without radiculopathy) and spondylolisthesis. Although results were promising for scoliosis, failed posterior fusion, and adjacent segment disease, further studies are necessary to establish the effectiveness of ALIF in these conditions 1).

Radiographic adjacent segment disease ASD is relatively common long-term finding associated with instrumented lumbar fusion. However, radiographic evidence of ASD does not necessarily correlate with a poor outcome. Results suggest that advanced age, anterior lumbar interbody fusion, and the restoration of the preoperative standing lumbar lordosis may have a protective effect against the development of ASD 2).

In degenerative disc disease, if conservative extensive care fails, anterior lumbar interbody fusion has proven to be an alternative form of surgical management.

Best for L5–1 (where the great vessels tend not to interfere with the access, and where every degree of correction produces a more significant amount of improvement in SVA than at other levels as a result of being at the lowest point in the spine).

Amount of lumbar lordosis that can be obtained (6º) 3)

Retroperitoneal usually through a Pfannenstiel’s abdominal incision.

Relatively contraindicated in males because of risk of retrograde ejaculation in 1–2% (as high as 45% in some reviews). Other risks: injury to great vessels, especially with calcified arteries, especially at L4–5. Bowel prep the day before surgery for complex cases.

Trendelenburg position, place the level of the iliac crests over the kidney rest, or use a sacral bump to increase lordosis. As a result of the bifurcation of the great vessels (aorta and inferior vena cava) which ranges from just above to just below the L4–5 disc space, this approach is best suited for access to L5–1. At L5–1, the anterior sacral artery runs down the midline of the VB and has to be sacrificed to do an ALIF.

Continuous wound infiltration with ropivacaine using an On-Q system may be effective for controlling postoperative pain after ALIF surgery 4).

see ALIF Cage

Anterior lumbar interbody fusion (ALIF) with percutaneous pedicle screw fixation (PPF) provides successful surgical outcomes to isthmic spondylolisthesis patients with indirect decompression through foraminal volume expansion. However, indirect decompression through ALIF followed by PPF may not obtain a successful surgical outcome in patients with isthmic spondylolisthesis accompanied by foraminal stenosis caused by a posterior osteophyte or foraminal sequestrated disc herniation. The microscopic anterior foraminal approach provides successful foraminal decompression. Combined with ALIF and PPF, this approach shows a good surgical outcome in patients with isthmic spondylolisthesis accompanied by foraminal stenosis caused by a posterior osteophyte or those with foraminal sequestrated disc herniation 5).

Posterior pedicle screw supplementation without posterolateral fusion improves the fusion rate of ALIF when using anterior cage and screw constructs 6).

The procedure is performed in close proximity to the large blood vessels.

Damage to these large blood vessels may result in excessive blood loss. Quoted rates in the medical literature put this risk at 1% to 15%, although this should be an uncommon complication in the hands of experienced vascular and spine surgeons.

Retrograde Ejaculation after ALIF Surgery

For males, another risk unique to this approach is that approaching the L5-S1 (lumbar segment 5 and sacral segment 1) disc space from the front has a risk of creating a condition known as retrograde ejaculation.

There are very small nerves directly over the disc interspace that control a valve that causes the ejaculate to be expelled outward during intercourse. By dissecting over the disc space, the nerves can stop working, and without this coordinating innervation to the valve, the ejaculate takes the path of least resistance, which is up into the bladder.

With retrograde ejaculation, the sensation of ejaculating is largely the same, but it makes conception very difficult (special harvesting techniques can be utilized). Fortunately, retrograde ejaculation happens in less than 1% of cases and tends to resolve over time (a few months to a year). This complication does not result in impotence as these nerves do not control erection.

Sixty-one patients who underwent ALIF surgery were enrolled. For thirty-one of them, a continuous local anesthetics infiltration system was used at the abdominal site. They collected data regarding the patients’ sleep quality; satisfaction with pain control after surgery; abilities to perform physical tasks and the additional application of opioids in the postoperative 48 hours.

The On-Q system group showed reduced visual analog scale scores for pain at the surgical site during rest and movement at 0, 12, 24, and 48 hours; and more were satisfied with pain control management at the first postoperative day (7.0 ± 1.2 vs. 6.0 ± 1.4; P = 0.003) and week (8.1 ± 1.6 vs. 7.0 ± 1.8; P = 0.010) than the control group. The number of additional patient-controlled analgesia (PCA) bolus and pethidine injections was lower in the On-Q group (PCA: 3.67 ± 1.35 vs. 4.60 ± 1.88; P = 0.049 and pethidine: 2.09 ± 1.07 vs. 2.73 ± 1.38; P = 0.032). Patients who used the On-Q system performed more diverse activity and achieved earlier ambulation than those in the control group.

Continuous wound infiltration with ropivacaine using an On-Q system may be effective for controlling postoperative pain after ALIF surgery 7).


study retrospectively reviewed 82 patients who underwent MO-ALIF with self-anchored standalone cages (n = 42) or TLIF (n = 40) for the treatment of lumbar disc herniation between April 2013 and October 2014. Patient demographics, intraoperative parameters, and perioperative complications were collated. Clinical outcomes were evaluated using the visual analog scale (VAS) scoring, the Oswestry Disability Index (ODI) for pain in the leg and back, and radiological outcomes, including fusion, lumbar lordosis (LL), disc height (DH), and cage subsidence were evaluated at each follow-up for up to 2 years.

Patients who underwent TLIF had a significantly higher volume of blood loss (295.2 ± 81.4 vs. 57.0 ± 15.2 mL) and longer surgery time (130.7 ± 45.1 vs. 60.4 ± 20.8 min) than those who had MO-ALIF. Compared with baseline, both groups had significant improvements in the VAS and ODI scores and DH and LL postoperatively, though no significant difference was found between the two groups regarding these indexes. All patients reached solid fusion at the final follow-up in both groups. Three patients (3/42) with three levels (3/50) suffered from cage subsidence in the MO-ALIF group; meanwhile, no cage subsidence occurred in the TLIF group.

MO-ALIF with self-anchored stand-alone cages is a safe and effective treatment of lumbar disc herniation with less surgical trauma and similar clinical and radiological outcomes compared with TLIF 8).


84 consecutive patients who underwent anterior lumbar interbody fusion from 2004 to 2009 were reviewed. The operative time, intraoperative blood loss, hospital stay, Oswestry Disability Index (ODI), visual analog scale (VAS) results, and complication rate were recorded separately.Medical indications were degenerative disc disease (73.8%), postdiscectomy disc disease (16.1%), and disc herniation (9.5%). Patients with severe spondylolysis or disc degeneration, with more than 3 or multilevel lesions, were excluded.The mean operative time was 124.5 ± 10.9 min (range 51-248 min), the mean intraoperative blood loss was 242.1 ± 27.7 mL (range 50-2700 mL), the mean hospital stay was 3.9 ± 1.1 days (range 3-6 days), the mean preoperative VAS score was 7.5 ± 1.4, and the mean preoperative ODI score was 60.0 ± 5.7. At the 1-year follow-up, the mean postoperative VAS score was 3.3 ± 1.3 and the mean postoperative ODI score was 13.6 ± 3.4 (P < 0.05). L4-L5 disc fusion led to better clinical results than 2-level L4-L5/L5-S1 disc fusion. Additionally, the 2-level fusion of L4-L5/L5-S1 had better clinical results than the L5-S1 disc fusion at both the 1 and 2-year postoperative follow-ups regarding the VAS score and the ODI score. The rate of complications was more frequent in the 2-level L4-L5/L5-S1 group (27.3%) (group C) than in the L4-L5 group (9.1%) (group A) and the L5-S1 group (12.5%) (group B). There was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%). A venous tear occurred during surgery and was successfully repaired in 6 of the 84 patients. Also, out of the 84 patients, 6 were found with pseudarthrosis during the follow-up, and these patients underwent a spinal fusion with instrumentation, with a posterior approach after a mean of 1 year. The complications secondary to the surgical approach were persistent abdominal pain (1/84, 1.2%) and wound dehiscence (1/84, 1.2%). Anterior lumbar interbody fusion for L4-L5 had better clinical results than the 2-segmental L4-L5/L5-S1 disc fusion, and the 2-segmental L4-L5/L5-S1 disc fusion had better clinical results than the L5-S1 disc fusion. Also, the 2-segmental L4-L5/L5-S1 disc fusion had a higher complication rate (27.3%), but there was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%) 9).


Rao PJ, Loganathan A, Yeung V, Mobbs RJ. Outcomes of anterior lumbar interbody fusion surgery based on indication: a prospective study. Neurosurgery. 2015 Jan;76(1):7-24. doi: 10.1227/NEU.0000000000000561. PubMed PMID: 25255259.

Min JH, Jang JS, Jung Bj, Lee HY, Choi WC, Shim CS, Choi G, Lee SH. The clinical characteristics and risk factors for the adjacent segment degeneration in instrumented lumbar fusion. J Spinal Disord Tech. 2008 Jul;21(5):305-9. doi: 10.1097/BSD.0b013e318142b960. PubMed PMID: 18600137.

Hsieh PC, Koski TR, O’Shaughnessy B A, et al. Anterior lumbar interbody fusion in comparison with transforaminal lumbar interbody fusion: implications for the restoration of foraminal height, local disc angle, lumbar lordosis, and sagittal balance. J Neurosurg Spine. 2007; 7:379–386
4) , 7)

Lee SM, Yun DJ, Lee SH, Lee HC, Joeng KH. Continuous wound infiltration of ropivacaine for reducing of postoperative pain after anterior lumbar fusion surgery: a clinical retrospective comparative study. Korean J Pain. 2021 Apr 1;34(2):193-200. doi: 10.3344/kjp.2021.34.2.193. PMID: 33785671.

Shin SH, Choi WG, Hwang BW, Tsang YS, Chung ER, Lee HC, Lee SJ, Lee SH. Microscopic anterior foraminal decompression combined with anterior lumbar interbody fusion. Spine J. 2013 Oct;13(10):1190-9. doi: 10.1016/j.spinee.2013.07.458. Epub 2013 Oct 2. PubMed PMID: 24094988.

McCarthy MJ, Ng L, Vermeersch G, Chan D. A radiological comparison of anterior fusion rates in anterior lumbar interbody fusion. Global Spine J. 2012 Dec;2(4):195-206. doi: 10.1055/s-0032-1329892. Epub 2012 Nov 19. PubMed PMID: 24353968; PubMed Central PMCID: PMC3864421.

Kuang L, Wang B, Lü G. Transforaminal Lumbar Interbody Fusion Versus Mini-open Anterior Lumbar Interbody Fusion With Oblique Self-anchored Stand-alone Cages for the Treatment of Lumbar Disc Herniation: A Retrospective Study With 2-year Follow-up. Spine (Phila Pa 1976). 2017 Nov 1;42(21):E1259-E1265. doi: 10.1097/BRS.0000000000002145. PubMed PMID: 28277385.

Ni J, Fang X, Zhong W, Liu N, Wood KB. Anterior Lumbar Interbody Fusion for Degenerative Discogenic Low Back Pain: Evaluation of L4-S1 Fusion. Medicine (Baltimore). 2015 Oct;94(43):e1851. doi: 10.1097/MD.0000000000001851. PubMed PMID: 26512594.

Lateral lumbar interbody fusion (LLIF)

Lateral lumbar interbody fusion (LLIF)

E.g. XLIFDLIFOLIF. Approach through psoas muscle (XLIF, DLIF) or anterior to psoas muscle (OLIF) through a lateral or anterolateral approach. Can distract the vertebral bodies by increasing the height of the disc space and thereby indirectly decompressing the neural elements. If bone quality is good, and there is no instability nor spondylolisthesis > Grade I, a standalone procedure (i.e. without screw instrumentation) may be an option if cage width of at least 22 mm (or preferably 26 mm) in the AP dimension is used.

LLIF was more effective than TLIF for spondylolisthesis reduction, likely due to the higher profile cage and ligamentotactic effect. In addition, LLIF showed mechanical stability of the reduction level by using a cage with a larger footprint. Therefore, LLIF should be considered a surgical option before TLIF for patients with unstable DS 1).


Lateral lumbar interbody fusion (LLIF) is a minimally invasive technique first described by Ozgur et al. 2). LLIF allows the surgeon to access the intervertebral space via a minimally invasive direct lateral approach through the psoas muscle. The advantage of LLIF over the traditional anterior approach is the avoidance of exposure of the abdominal viscera, large vessels, and sympathetic plexus. Injury to the nerve roots and dura, and perineural fibrosis, which can occur after PLIF or TLIF, are minimized with this technique 3)4).


Used to treat leg pain or back pain generally caused by degenerative disc disease.

LLIF has been utilized to treat a variety of pathologies including adult degenerative scoliosis, central and foraminal stenosis, spondylolisthesis, and adjacent segment degeneration

They have become an increasingly popular surgical technique due to the benefits of minimal tissue disruption, excellent disc visualization, ability to insert a large intervertebral cage to lessen subsidence, and faster recovery times 5) 6).


The LLIF procedure differs from other lumbar procedures in that the patient is positioned in the lateral decubitus position, often times utilizing bending the bed near the iliac crest region in order to facilitate access to the L4-5 disc space.

In awake volunteers, the pressure at the iliac crest or greater trochanter at the break of the bed increases by increasing the bed angle. Women with a lower BMI had high VAS pain scores when their greater trochanter was at maximal bed break. Men with higher BMI had high VAS pain scores when their iliac crest was at maximal bed break. An awareness of the iliac crest or greater trochanter at the break of the bed should be considered to prevent pain and increased pressure based on the patient’s sex and BMI 7).

As with most minimally invasive spine procedures, lateral lumbar interbody fusion (LLIF) requires the use of biplanar fluoroscopy for localization and safe interbody cage placement. Computed tomography (CT)-based intraoperative spinal navigation has been shown to be more effective than fluoroscopic guidance for posterior-based approaches such as pedicle screw instrumentation.

Use of an intraoperative cone-beam CT with an image-guided navigation system is feasible and safe and appears to be accurate, although a larger study is required to confirm these results 8).


Cost effectiveness

TLIF and LLIF produced equivalent 2-year patient outcomes at an equivalent cost-effectiveness profile 9).

Systematic reviews

Transpsoas lateral interbody fusion is one of the Lateral Lumbar Interbody Fusion minimally invasive approaches for lumbar spine surgery. Most surgeons insert the interbody cage laterally and then insert pedicle or cortical screw and rod instrumentation posteriorly. However, standalone cages have also been used to avoid posterior instrumentation.

The literature on comparison of the two approaches is sparse.

Alvi et al., performed a systematic review and meta-analysis of the available literature on transpsoas lateral interbody fusion by an electronic search of the PubMedEMBASE, and Scopus databases using PRISMA guidelines. They compared patients undergoing transpsoas standalone fusion (TP) with those undergoing transpsoas fusion with posterior instrumentation (TPP).

A total of 28 studies with 1462 patients were included. Three hundred and seventy-four patients underwent TPP, and 956 patients underwent TP. The mean patient age ranged from 45.7 to 68 years in the TP group, and 50 to 67.7 years in the TPP group. The incidence of reoperation was found to be higher for TP (0.08, 95% confidence interval [CI] 0.04-0.11) compared to TPP (0.03, 95% CI 0.01-0.06; p = 0.057). Similarly, the incidence of cage movement was found to be greater in TP (0.18, 95% CI 0.10-0.26) compared to TPP (0.03, 95% CI 0.00-0.05; p < 0.001). Oswestry Disability Index (ODI) and visual analog scale (VAS) scores and postoperative transient deficits were found to be comparable between the two groups.

These results appear to suggest that addition of posterior instrumentation to transpsoas fusion is associated with decreased reoperations and cage movements. The results of previous systematic reviews and meta-analysis should be reevaluated in light of these results, which seem to suggest that higher reoperation and subsidence rates may be due to the use of the standalone technique 10).

A systematic and critical review of recent literature was conducted in accordance with PRISMA guidelines. The sources of the data were PubMed, MEDLINE, Embase, Cochrane and Scopus. Key search terms were “transpsoas”, “interbody fusion”, “LLIF”, “XLIF” and “spondylolisthesis”. Papers included in the review were original research articles in peer-reviewed journals. The articles were thoroughly examined and compared on the basis of study design, outcomes, and results. Only studies which met the eligibility criteria were included. Eight studies were included in the qualitative and quantitative analysis (three retrospective, four prospective, one randomized controlled trial). A total of 308 patients (227 females) (pooled age 64.5 years) and a total of 353 operated levels were analyzed. Mean follow up time ranged from 6.2 to 24 months. There were no reported cases of durotomies or pseudarthrosis in any study. All neurologic complications were reported to be transient with no permanent deficits. Mean improvement in ODI scores ranged between 19.5 (38.6%) to 36 (54.5%). Mean improvement in slip ranged from 47 to 67.5%. Three studies also reported that patient satisfaction and willingness to undergo the procedure again approached 90%. Minimally invasive transpsoas interbody fusion possibly leads to favorable clinical and radiological outcomes while avoiding the possible complications of its more traditional open and minimally invasive counterparts. Further studies are needed to better establish its role in the management of low grade degenerative lumbar spondylolisthesis 11).

Case series



Ko MJ, Park SW, Kim YB. Correction of Spondylolisthesis by Lateral Lumbar Interbody Fusion Compared with Transforaminal Lumbar Interbody Fusion at L4-5. J Korean Neurosurg Soc. 2019 May 8. doi: 10.3340/jkns.2018.0143. [Epub ahead of print] PubMed PMID: 31064044.
2) , 3)

Ozgur BM, Aryan HE, Pimenta L, Taylor WR. Extreme lateral interbody fusion (XLIF): a novel surgical technique for anterior lumbar interbody fusion. Spine J. 2006;6:435–443.

Rodgers WB, Gerber EJ, Patterson J. Intraoperative and early postoperative complications in extreme lateral interbody fusion: an analysis of 600 cases. Spine (Phila Pa 1976) 2011;36:26–32.

Rodgers WB, Gerber EJ. Outcomes of MIS spinal fusion: 12 and 24 months. The Spine Journal. 2010;10(9):S141.

Isaacs RE, Hyde J, Goodrich JA, et al. A prospective, nonrandomized, multicenter evaluation of extreme lateral interbody fusion of the treatment of adult degenerative scoliosis: perioperative outcomes and complications. Spine. 2010;15(35):S322–30.

Tatsumi RL. Lateral Pressure and VAS Pain Score Analysis for the Lateral Lumbar Interbody Fusion Procedure. Int J Spine Surg. 2015 Sep 28;9:48. doi: 10.14444/2048. eCollection 2015. PubMed PMID: 26512342; PubMed Central PMCID: PMC4610324.

Park P. Three-Dimensional Computed Tomography-Based Spinal Navigation in Minimally Invasive Lateral Lumbar Interbody Fusion: Feasibility, Technique, and Initial Results. Neurosurgery. 2015 Mar 23. [Epub ahead of print] PubMed PMID: 25812070.

Gandhoke GS, Shin HM, Chang YF, Tempel Z, Gerszten PC, Okonkwo DO, Kanter AS. A Cost-Effectiveness Comparison Between Open Transforaminal and Minimally Invasive Lateral Lumbar Interbody Fusions Using the Incremental Cost-Effectiveness Ratio at 2-Year Follow-up. Neurosurgery. 2016 Apr;78(4):585-95. doi: 10.1227/NEU.0000000000001196. PubMed PMID: 26726969.

Alvi MA, Alkhataybeh R, Wahood W, Kerezoudis P, Goncalves S, Murad MH, Bydon M. The impact of adding posterior instrumentation to transpsoas lateral fusion: a systematic review and meta-analysis. J Neurosurg Spine. 2018 Oct 1:1-11. doi: 10.3171/2018.7.SPINE18385. [Epub ahead of print] Review. PubMed PMID: 30485206.

Goyal A, Kerezoudis P, Alvi MA, Goncalves S, Bydon M. Outcomes following minimally invasive lateral transpsoas interbody fusion for degenerative low grade lumbar spondylolisthesis: A systematic review. Clin Neurol Neurosurg. 2018 Apr;167:122-128. doi: 10.1016/j.clineuro.2018.02.020. Epub 2018 Feb 16. Review. PubMed PMID: 29476935.

Intraoperative neurophysiological monitoring for anterior cervical discectomy and fusion

Intraoperative neurophysiological monitoring for anterior cervical discectomy and fusion

Although Intraoperative neurophysiological monitoring has been shown to decrease the risk of neurological injury in deformity surgery, its utility in anterior cervical spine surgery (ACSS) remains controversial 1) 2) 3) 4) 5) 6)7) 8).

Proponents of intraoperative neurophysiological monitoring for ACSS claim that it improves patient safety and functional outcome whereas opponents refute this claim by citing increased cost and the lack of correlation between intraoperative neurophysiological monitoring abnormalities and postoperative neurological deficits especially with anterior cervical discectomy and fusions (ACDFs) 9) 10) 11) 12).

In a systematic review and meta-analysis from 2017, the risk of neurological injury after ACSS was low although procedures involving a corpectomy may carry a higher risk. For ACDFs, there is no difference in the risk of neurological injury with or without ION use. Unimodal ION has a higher specificity than multimodal ION and may minimize “subclinical” intraoperative alerts in ACSS 13)

A analysis of over 140,000 cases from the National Inpatient Sample data set, found that the use of intraoperative neurophysiological monitoringfor anterior cervical discectomy and fusion was not associated with a reduced rate of neurological complication14).



Dawson EG, Sherman JE, Kanim LE, et al. Spinal cord monitoring. Results of the Scoliosis Research Society and the European Spinal Deformity Society survey. Spine. 1991;16:S361–4.

Diab M, Smith AR, Kuklo TR. Neural complications in the surgical treatment of adolescent idiopathic scoliosis. Spine. 2007;32:2759–63.

Eggspuehler A, Sutter MA, Grob D, et al. Multimodal intraoperative monitoring during surgery of spinal deformities in 217 patients. Eur Spine J. 2007;16:S188–96.

Forbes HJ, Allen PW, Waller CS, et al. Spinal cord monitoring in scoliosis surgery. Experience with 1168 cases. J Bone Joint Surg Br. 1991;73:487–91.

Kamerlink JR, Errico T, Xavier S, et al. Major intraoperative neurologic monitoring deficits in consecutive pediatric and adult spinal deformity patients at one institution. Spine. 2010;35:240–5.

Nuwer MR, Emerson RG, Galloway G, et al. Evidence-based guideline update: intraoperative spinal monitoring with somato-sensory and transcranial electrical motor evoked potentials*. J Clin Neurophysiol. 2012;29:101–8.

Resnick DK, Choudhri TF, Dailey AT, et al. Guidelines for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 15: electrophysiological monitoring and lumbar fusion. J Neurosurg Spine. 2005;2:725–32.

Zhuang Q, Wang S, Zhang J, et al. How to make the best use of intraoperative motor evoked potential monitoring? Experience in 1162 consecutive spinal deformity surgical procedures. Spine. 2014;39:E1425–32.

Engler GL, Spielholz NJ, Bernhard WN, et al. Somatosensory evoked potentials during Harrington instrumentation for scoliosis. J Bone Joint Surg Am. 1978;60:528–32.

Epstein NE, Danto J, Nardi D. Evaluation of intraoperative somatosensory-evoked potential monitoring during 100 cervical operations. Spine. 1993;18:737–47.

Taunt CJ, Jr, Sidhu KS, Andrew SA. Somatosensory evoked potential monitoring during anterior cervical discectomy and fusion. Spine. 2005;30:1970–2.

Traynelis VC, Abode-Iyamah KO, Leick KM, et al. Cervical decompression and reconstruction without intraoperative neurophysiological monitoring. J Neurosurg Spine. 2012;16:107–13.

Ajiboye RM, Zoller SD, Sharma A, Mosich GM, Drysch A, Li J, Reza T, Pourtaheri S. Intraoperative Neuromonitoring for Anterior Cervical Spine Surgery: What Is the Evidence? Spine (Phila Pa 1976). 2017 Mar 15;42(6):385-393. doi: 10.1097/BRS.0000000000001767. Review. PubMed PMID: 27390917; PubMed Central PMCID: PMC5552368.

Badhiwala JH, Nassiri F, Witiw CD, Mansouri A, Almenawer SA, da Costa L, Fehlings MG, Wilson JR. Investigating the utility of intraoperative neurophysiological monitoring for anterior cervical discectomy and fusion: analysis of over 140,000 cases from the National (Nationwide) Inpatient Sample data set. J Neurosurg Spine. 2019 Mar 29:1-11. doi: 10.3171/2019.1.SPINE181110. [Epub ahead of print] PubMed PMID: 30925481.
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