Choroid plexus hyperplasia

Choroid plexus hyperplasia

Choroid plexus hyperplasia (CPH), also known as villous hypertrophy of the choroid plexus, is a rare benign condition that is characterized by bilateral enlargement of the entire choroid plexus in lateral ventricles without any discrete masses. This can result in overproduction of CSF and communicating hydrocephalus.

Despite the current knowledge about hydrocephalus, we remain without a complete understanding of the pathophysiology of this condition. glymphatic system (GS) could be more important than the conventional concept of reabsorption of CSF in the arachnoid villi, therefore GS could be a new key point, which will guide future investigations 1).

Histology shows an increased number of normal-sized cells.

This is best diagnosed by MRI which demonstrates a diffuse enlargement and homogeneous enhancement of choroid plexuses in a patient with communicating hydrocephalus 2).

It is a rare condition that may necessitate unusual treatment paradigms.

Although some authors recommend choroid plexus excision or coagulation, ventriculoatrial shunt insertion is a simple and effective treatment modality in cases of diffuse villous hyperplasia of the choroid plexus 3).

It can be seen in trisomy 9p where coexisting congenital heart disease additionally may complicate the therapeutic approach 4).

At 20 months of age, a Caucasian girl with trisomy 9 and a family history of an older brother and twin sister having the same syndrome displayed signs of congenital hydrocephalus due to increasing head circumferenceMagnetic resonance imaging revealed enlarged lateral ventricles and a prominent choroid plexus and the girl was treated with a ventriculoperitoneal shunt, which 2 days later had to be replaced with a ventriculoatrial shunt as cerebrospinal fluid production greatly exceeded the ability of the patient’s abdominal absorptive capability. At 16 years of age, the patient was diagnosed with cardiomyopathy and diminished ejection fraction. Some months later, she was admitted to the neurosurgical ward showing signs of shunt dysfunction due to a colloid cyst in the third ventricle. Cystic drainage through endoscopic puncture only helped temporarily. Revision of the shunt system showed occlusion of the ventricular drainage, and replacement was merely temporary alleviating. Intracranial pressure was significantly increased at around 30 mmHg, prompting externalization of the drain, and measurements revealed high cerebrospinal fluid production of 60-100 ml liquor per hour. Thus, endoscopic choroid plexus coagulation was performed bilaterally leading to an immediate decrease of daily cerebrospinal fluid formation to 20-30 ml liquor per hour, and these values were stabilized by pharmaceutical treatment with acetazolamide 100 mg/kg/day and furosemide 1 mg/kg/day. Subsequently, a ventriculoperitoneal shunt was placed. Follow-up after 1 and 2 months displayed no signs of hydrocephalus or ascites.

High cerebrospinal fluid volume load and coexisting heart disease in children with trisomy 9p may call for endoscopic choroid plexus coagulation and pharmacological therapy to diminish the daily cerebrospinal fluid production to volumes that allow proper ventriculoperitoneal shunting 5).

A 1-year-old patient was diagnosed with communicating hydrocephalus; ventricle peritoneal shunt (VPS) is installed and ascites developed. VPS is exposed, yielding volumes of 1000-1200ml/day CSF per day. MRI is performed showing generalized choroidal plexus hyperplasia. Bilateral endoscopic coagulation of thechoroid plexus was performed in 2 stages (CPC) however the high rate of CSF production persisted, needing a bilateral plexectomy through septostomy, which finally decreased the CSF outflow.

New knowledge about CSF physiology will help to propose better treatment depending on the cause of the hydrocephalus. The GS is becoming an additional reason to better study and develop new therapies focused on the modulation of alternative CSF reabsorption. 6).

In these patients, intractable ascites can occur after a ventriculoperitoneal (VP) shunting operation. However, shunt-related hydrocele is a rare complication of VP shunting. Previous reports have indicated catheter-tip migration to the scrotum as a cause of hydrocele. Here, we present the first documented case of choroid plexus hyperplasia that led to intractable ascites after shunting and a resulting hydrocele without catheter-tip migration into the scrotum 7).

1) , 6)

Paez-Nova M, Andaur K, Campos G, Garcia-Ballestas E, Moscote-Salazar LR, Koller O, Valenzuela S. Bilateral hyperplasia of choroid plexus with severe CSF production: a case report and review of the glymphatic system. Childs Nerv Syst. 2021 Nov;37(11):3521-3529. doi: 10.1007/s00381-021-05325-2. Epub 2021 Aug 19. PMID: 34410450.

Iplikcioglu AC, Bek S, Gökduman CA, Bikmaz K, Cosar M. Diffuse villous hyperplasia of choroid plexus. Acta Neurochir (Wien). 2006 Jun;148(6):691-4; discussion 694. doi: 10.1007/s00701-006-0753-1. Epub 2006 Mar 8. PMID: 16523225.
4) , 5)

Henningsen MB, Gulisano HA, Bjarkam CR. Congenital hydrocephalus in a trisomy 9p gained child: a case report. J Med Case Rep. 2022 May 27;16(1):206. doi: 10.1186/s13256-022-03424-5. PMID: 35619116.

Hori YS, Nagakita K, Ebisudani Y, Aoi M, Shinno Y, Fukuhara T. Choroid Plexus Hyperplasia with Intractable Ascites and a Resulting Communicating Hydrocele following Shunt Operation for Hydrocephalus. Pediatr Neurosurg. 2018;53(6):407-412. doi: 10.1159/000492333. Epub 2018 Aug 29. PMID: 30157489.

Cervical juxtafacet cyst

Cervical juxtafacet cyst

A literature review till 2010 described only 28 symptomatic cervical synovial cyst cases 1)

A literature review till 2013 identified 35 studies with 89 previously reported cases of surgically treated subaxial juxtafacet cysts (JFCs) 2).

Attwell et al. presented an unusual case of acute symptomatology secondary to spontaneous haemorrhage into a cervical facet joint cyst 3)

Sasamori et al. report a case of cervical juxtafacet cyst with extensive rim enhancement on magnetic resonance imaging 4).

see atlantoaxial juxtafacet cyst

Juxtafacet cysts (JFCs) seem to be a degenerative change of the cervical spine rather than a traumatic event. Similar to their counterparts in the lumbar spine, they tend to arise in segments with increased mobility.

Sivakumar et al. have reported on the development of JFCs adjacent to anterior cervical fusion constructs, and consideration of JFCs as a form of adjacent level disease (ALD) has been hypothesized 5).

Moon et al. reported one patient that developed a C5/6 JFC 20 months after C4/5 anterior fusion and C5/6 anterior foraminotomy. In this case, despite progressive subluxation at C5/6 and solid C4/5 fusion demonstrated on flexion films 20 months after the original surgery, the patient underwent partial hemilaminectomy alone for cyst decompression. Outcome was favorable at 4 months follow-up 6)


After a cervical spine fracture and, hence, was probably related to trauma. Surgical therapy resulted in a satisfactory recovery 7).

Chronic expansion of the extradural mass may lead to compression of the nerve root, thecal sac, or both, and may follow long periods of axial back pain without neurological deficit 8).

They are rare causes of neurological deficits. Their imaging characteristics, relationship to segmental instability, and potential for inducing acute symptomatic deterioration have only been described in a few case reports and small case series 9).

Less commonly, neurological deterioration has been attributed to rapid cystic growth with hemorrhage 10) 11)

Attwell et al., reported acute symptomatology secondary to spontaneous haemorrhage into a cervical facet joint cyst 12).

Combination with discal herniation and spina bifida occulta was diagnosed with computed tomography (CT) and magnetic resonance imaging (MRI) in one case 13).


In the series of Christophis all cervico-thoracic or thoracic cysts presented myelopathy 14).

Till 1999 there have been only two previously reported cases of subaxial degenerative synovial cysts of the cervical spine in patients who presented with a clinical picture of spinal cord compression. Cudlip et al. report three additional patients treated for degenerative cervical synovial cysts who presented with myelopathy. In all three patients the cyst was successfully excised and a good clinical outcome achieved 15).

Cho el al. describe a case of an 80-year-old man with a gradual weakness of the lower extremities not linked to any known traumatic episode over the 2 weeks before admission. CT scan and MRI of the spine revealed a cystic formation, measuring about 1 cm in diameter, at C7-T1 at the left posterolateral site at the level of the articular facet. During surgery, the mass appeared to be in the ligamentum flavum at the level of the articular facet and was in contact with the dura mater. After the removal of the mass, there was an immediate and significant improvement of the patient’s symptoms. Histopathologic examination showed the cyst to be composed of nonspecific degenerative fibrous tissue with mild inflammatory change and confirmed the cyst as a synovial cyst. Synovial cyst in the cervical region is a very rare lesion causing myelopathy. Surgical removal of the cyst and decompression of the spinal cord results in good neurological recovery 16).

Brown-Sequard syndrome

Cheng et al. published a rare case of a patient with a ganglion cyst of the lower cervical spine presenting with acute Brown-Sequard syndrome. The patient had no history of trauma. Magnetic resonance imaging of the cervical spine showed a cystic lesion connecting to the synovial joint C6-7 and compressing the posterior aspect of the spinal cord. The patient underwent emergent C6-7 laminectomy with total removal of the cyst. Neurological function recovered completely 4 months after operation 17).

Magnetic resonance imaging reveal an intraspinal extradural cystic lesion in contact with the facet joint. The spinal cord can severely compressed by this lesion which is hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging and short T1 inversion recovery. The cyst wall can strongly enhance after contrast injection 18).

Sasamori et al. report a case of cervical juxtafacet cyst with extensive rim enhancement on gadolinium-diethylenetriamine pentaacid magnetic resonance imaging.

Operative finding revealed the epidural space around the mass filled with abundant venous plexus. Histological examination demonstrated that cyst wall was composed of the well-vascularized fibrous connective tissue with some inflammatory changes. They speculate that extensive rim enhancement of juxtafacet cyst may be attributed not only to the chronic inflammatory changes of cyst wall, but to engorged venous plexus within the widened epidural space 19)

Surgical treatment is effective 20).

Colen and Rengachary report a spontaneous resolution of a cervical synovial cyst 21)


The head is positioned in Mayfield pins under gentle capital flexion, and the patient was positioned prone on gel rolls. Dissection proceeded in the subperiosteal plane, either unilaterally (e.g., hemilaminectomy) or bilaterally, depending on the goals of the decompression and the extent of spinal canal compromise. During resection of the lesion, the lateral facet and capsule were preserved as much as possible. When deemed necessary for complete decompression or visualization of the lesion, the laminectomy was extended to include a conservative medial facetectomy on the affected side.

The putative medial facet joint is carefully cauterized to minimize risk of cyst regrowth.

Instrumentation and fusion can be performed at the discretion of the operating surgeon. Loss of cervical lordosis, spondylolisthesis, hypermobility, index level neck pain, and iatrogenic instability following decompression are each relative indications for fusion.

Fixation can be accomplished using bilateral lateral mass/pedicle screw and rod constructs. Fusion can be augmented with morselized local autograft, with or without bone allograft.

12 consecutive patients (mean age 63.4 years, range 52-83 years) harboring 14 JFCs treated across 9 years was retrospectively reviewed. Clinical history, neurological status, preoperative imaging, operative findings, pathology, and postoperative outcomes were obtained from medical records. The mean follow up was 9.2 ± 7.8 months.

Most JFCs in this series involved the C7/T1 level. Nine patients reported axial neck pain, 12 patients had radicular symptoms, four patients had myelopathy, and one patient experienced rapid neurological decline attributable to cystic hemorrhage. Cyst expansion without hemorrhage caused subacute deterioration in one patient. All patients experienced sensory and/or motor improvement following surgical decompression. Preoperative axial neck pain improved in eight of nine patients (89 %). Seven out of 12 patients (58 %) underwent fusion either at the time of decompression (six patients) or at a delayed timepoint within the follow-up period (one patient). Prior history of cervical instrumentation, hypermobility on dynamic imaging, and other risk factors for segmental instability were more common in this series than in previous reports 22).

13 patients with synovial or ganglion cysts of the spinal facet joints causing nerve root compression. These cysts were found in both the cervical and the lumbar spine, and the anatomical location of each cyst corresponded to the patient’s signs and symptoms. In no case was there evidence of intervertebral disc abnormality found at operation. The patients ranged from 49 to 77 years of age and included 4 men and 9 women. Radiographic evidence of facet degenerative change and degenerative spondylolisthesis was frequently but not invariably noted. The extradural defects defined with positive contrast myelography or postmyelography computed tomographic scanning were usually posterior or posterolateral to the common dural sac and were misinterpreted as extruded discs in the majority of cases. Treatment consisted of laminectomy and surgical excision of cysts. All patients reported improvement or resolution of their presenting symptoms 23).

Chun et al. described an interesting case of cervical juxtafacet that developed outside the intervertebral foramen, compressing the cervical medial branch and causing neuropathic pain in the posterior inferior neck pain. A 61-year-old woman visited a local pain clinic due to neuropathic pain with a tingling and burning nature (numeric rating scale [NRS]: 5 out of 10) on the left posterior inferior neck area for 4 months. Paresthesia was observed in the left posterior inferior neck area. On cervical radiography, segmental instability was observed at the C3-4 and C4-5 levels. Moreover, on the magnetic resonance imaging (MRI) of the cervical spine, a cyst (size: 1.3 cm × 0.7 cm × 1 cm) was outside the intervertebral foramen, contacting the left C4-5 facet joint and left C5 articular pillar. We thought that compression of the left C5 medial branch by the cyst could cause the patient’s pain. We conducted computed tomography (CT)-guided percutaneous needle aspiration of a cervical juxtafacet cyst. An 18-gauge needle was advanced under the guidance of CT into the largest portion of the cyst through a posterolateral oblique approach. Gelatinous mucoid fluid (approximately 0.5 cc) was aspirated. Immediately after the aspiration, 80% of the patient’s pain was disappeared, and dysesthesia was completely disappeared. At the 1-, 3-, and 6-month follow-ups, the patient reported slight pain (NRS: 1) on the left posterior inferior neck. Cervical juxtafacet cysts can develop outside of the intervertebral foramen and spinal canal. Percutaneous needle aspiration can be a useful therapeutic tool for the treatment of such cysts 24)

Third reported case of a degenerative articular cyst of the upper cervical spine, involving the quadrate ligament of the odontoid process. Magnetic resonance examination reveals typical images. A new, more general terminology is proposed 25).


Costa F, Menghetti C, Cardia A, Fornari M, Ortolina A. Cervical synovial cyst: case report and review of literature. Eur Spine J. 2010 Jul;19 Suppl 2:S100-2. doi: 10.1007/s00586-009-1094-6. Epub 2009 Jul 15. Review. PubMed PMID: 19603197; PubMed Central PMCID: PMC2899642.
2) , 9) , 22)

Uschold T, Panchmatia J, Fusco DJ, Abla AA, Porter RW, Theodore N. Subaxial cervical juxtafacet cysts: single institution surgical experience and literature review. Acta Neurochir (Wien). 2013 Feb;155(2):299-308. doi: 10.1007/s00701-012-1549-0. Epub 2012 Nov 17. Review. PubMed PMID: 23160630.
3) , 12)

Attwell L, Elwell VA, Meir A. Cervical synovial cyst. Br J Neurosurg. 2014 Dec;28(6):813-4. doi: 10.3109/02688697.2014.913782. Epub 2014 May 6. PubMed PMID: 24801806.
4) , 19)

Sasamori T, Hida K, Anzai K, Yano S, Kato Y, Tanaka S, Saito H, Houkin K. A case of cervical juxtafacet cyst with extensive rim enhancement on Gd-DTPA MRI. Clin Imaging. 2014 Mar-Apr;38(2):199-201. doi: 0.1016/j.clinimag.2013.10.002. Epub 2013 Nov 7. PubMed PMID: 24332973.

Sivakumar W, Elder JB, Bilsky MH. Cervical juxtafacet cyst after anterior cervical discectomy and fusion. Neurosurg Focus. 2011 Oct;31(4):E19. doi: 10.3171/2011.8.FOCUS11119. Review. PubMed PMID: 21961863.

Moon HJ, Kim JH, Kim JH, Kwon TH, Chung HS, Park YK. Cervical juxtafacet cyst with myelopathy due to postoperative instability. Case report. Neurol Med Chir (Tokyo). 2010;50(12):1129-31. PubMed PMID: 21206195.

Cartwright MJ, Nehls DG, Carrion CA, Spetzler RF. Synovial cyst of a cervical facet joint: case report. Neurosurgery. 1985 Jun;16(6):850-2. PubMed PMID: 4010912.

Boviatsis EJ, Stavrinou LC, Kouyialis AT, Gavra MM, Stavrinou PC, Themistokleous M, Selviaridis P, Sakas DE (2008) Spinal synovial cysts: pathogenesis, diagnosis and surgical treatment in a series of seven cases and literature review. Eur Spine J 17:831– 837

Akhaddar A, Qamouss O, Belhachmi A, Elasri A, Okacha N, Elmostarchid B, Boucetta M (2008) Cervico-thoracic juxtafacet cyst causing spinal foraminal widening. Joint Bone Spine 75:747–749

Jabre A, Shahbabian S, Keller JT (1987) Synovial cyst of the cervical spine. Neurosurgery 20:316–318

Vastagh I, Palásti A, Nagy H, Veres R, Bálint K, Karlinger K, Várallyay G. Cervical juxtafacet cyst combined with spinal dysraphism. Clin Imaging. 2008 Sep-Oct;32(5):387-9. doi: 10.1016/j.clinimag.2008.02.034. PubMed PMID: 18760727.

Christophis P, Asamoto S, Kuchelmeister K, Schachenmayr W. “Juxtafacet cysts”, a misleading name for cystic formations of mobile spine (CYFMOS). Eur Spine J. 2007 Sep;16(9):1499-505. Epub 2007 Jan 4. PubMed PMID: 17203271; PubMed Central

Cudlip S, Johnston F, Marsh H. Subaxial cervical synovial cyst presenting with myelopathy. Report of three cases. J Neurosurg. 1999 Jan;90(1 Suppl):141-4.Review. PubMed PMID: 10413141.

Cho BY, Zhang HY, Kim HS. Synovial cyst in the cervical region causing severe myelopathy. Yonsei Med J. 2004 Jun 30;45(3):539-42. PubMed PMID: 15227744.

Cheng WY, Shen CC, Wen MC. Ganglion cyst of the cervical spine presenting with Brown-Sequard syndrome. J Clin Neurosci. 2006 Dec;13(10):1041-5. PubMed PMID:17113987.

Cheng YY, Chen CC, Yang MS, Hung HC, Lee SK. Intraspinal extradural ganglion cyst of the cervical spine. J Formos Med Assoc. 2004 Mar;103(3):230-3. PubMed PMID: 15124052.

Krauss WE, Atkinson JL, Miller GM. Juxtafacet cysts of the cervical spine.Neurosurgery. 1998 Dec;43(6):1363-8. Review. PubMed PMID: 9848850.

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Chun YM, Boudier-Revéret M, Lee SH, Chang MC. Neuropathic Pain due to Compression of Cervical Medial Branch by Cervical Juxtafacet Cyst: A Case Report. Pain Pract. 2022 May 24. doi: 10.1111/papr.13129. Epub ahead of print. PMID: 35607892.

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Avelumab, sold under the brand name Bavencio, is a fully human Monoclonal antibody therapy for Merkel cell carcinoma, urothelial carcinoma, and renal cell carcinoma.

AMPLIFY-NEOVAC is a randomized 3-arm, window-of-opportunity, multicenter national phase 1 trial to assess the safety, tolerability, and immunogenicity of IDH1-vac combined with avelumab (AVE), an immune checkpoint inhibitor (ICI) targeting programmed death-ligand 1 (PD-L1). The target population includes patients with resectable IDH1R132H-mutant recurrent astrocytoma or oligodendroglioma after standard of care (SOC). Neoadjuvant and adjuvant immunotherapy will be administered to 48 evaluable patients. In arm 1, 12 patients will receive IDH1-vac; in arm 2, 12 patients will receive the combination of IDH1-vac and AVE, and in arm 3, 24 patients will receive AVE only. Until disease progression according to immunotherapy response assessment for neuro-oncology (iRANO) criteria, treatment will be administered over a period of a maximum of 43 weeks (primary treatment phase) followed by facultative maintenance treatment.

Perspective: IDH1R132H 20-mer peptide is a shared clonal driver mutation-derived neoepitope in diffuse gliomas. IDH1-vac safely targets IDH1R132H in newly diagnosed astrocytomas. AMPLIFY-NEOVAC aims at (1) demonstrating the safety of enhanced peripheral IDH1-vac-induced T cell responses by combined therapy with AVE compared to IDH1-vac only and (2) investigating intra-glioma abundance and phenotypes of IDH1-vac induced T cells in exploratory post-treatment tissue analyses. In an exploratory analysis, both will be correlated with clinical outcome 1).

The combination of avelumab plus axitinib has an acceptable toxicity profile but did not meet the prespecified threshold for activity justifying further investigation of this treatment in an unselected population of patients with rGB 2).

To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs 3).

Giles et al. found that programmed cell death ligand 1 (PD-L1) was highly expressed in multiple human malignant meningioma cell lines and patient tumor samples. PD-L1 was targeted with the anti-PD-L1 antibody avelumab and directed natural killer cells to mediate antibody-dependent cellular cytotoxicity (ADCC) of PD-L1-expressing meningioma tumors both in vitro and in vivo. ADCC of meningioma cells was significantly increased in target cells that upregulated PD-L1 expression and, conversely, abrogated in tumor cells that were depleted of PD-L1. Additionally, the high-affinity natural killer cell line, haNK, outperformed healthy donor NK cells in meningioma ADCC. Together, these data support a clinical trial designed to target PD-L1 with avelumab and haNK cells, potentially offering a novel immunotherapeutic approach for patients with malignant meningioma 4).


Bunse L, Rupp AK, Poschke I, Bunse T, Lindner K, Wick A, Blobner J, Misch M, Tabatabai G, Glas M, Schnell O, Gempt J, Denk M, Reifenberger G, Bendszus M, Wuchter P, Steinbach JP, Wick W, Platten M. AMPLIFY-NEOVAC: a randomized, 3-arm multicenter phase I trial to assess safety, tolerability and immunogenicity of IDH1-vac combined with an immune checkpoint inhibitor targeting programmed death-ligand 1 in isocitrate dehydrogenase 1 mutant gliomas. Neurol Res Pract. 2022 May 23;4(1):20. doi: 10.1186/s42466-022-00184-x. PMID: 35599302.

Awada G, Ben Salama L, De Cremer J, Schwarze JK, Fischbuch L, Seynaeve L, Du Four S, Vanbinst AM, Michotte A, Everaert H, Rogiers A, Theuns P, Duerinck J, Neyns B. Axitinib plus avelumab in the treatment of recurrent glioblastoma: a stratified, open-label, single-center phase 2 clinical trial (GliAvAx). J Immunother Cancer. 2020 Oct;8(2):e001146. doi: 10.1136/jitc-2020-001146. PMID: 33067319; PMCID: PMC7570224.

Wang S, Hu C, Xie F, Liu Y. Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer. Onco Targets Ther. 2020 Jan 23;13:667-683. doi: 10.2147/OTT.S235714. PMID: 32158220; PMCID: PMC6986404.

Giles AJ, Hao S, Padget M, Song H, Zhang W, Lynes J, Sanchez V, Liu Y, Jung J, Cao X, Fujii R, Jensen R, Gillespie D, Schlom J, Gilbert MR, Nduom EK, Yang C, Lee JH, Soon-Shiong P, Hodge JW, Park DM. Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. JCI Insight. 2019 Oct 17;4(20):e130688. doi: 10.1172/jci.insight.130688. PMID: 31536478; PMCID: PMC6824312.
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