MedNexus
Volume 33 · Issue 10 · 2017
MedNexus
Moyamoya disease is a chronic ischemic cerebrovascular disease characterized by progressive stenosis or occlusion of multiple large intracranial arteries with the formation of moyamoya-like compensatory vessels at the base of the brain and the pial meninges. Moyamoya disease mostly occurs in East Asian populations, and the prevalence rates in Japan and South Korea are lower than 7/100,000. Although there is no national census data for this disease in China, the regional reports are basically similar[
After a century of development, neuroendoscopic technology has been widely used in many sub-specialties of neurosurgery. Currently, endoscopic neurosurgery is one of the most important and active subspecialties in minimally invasive neurosurgery. It mainly covers ventriculoscopic surgery characterized by third ventriculostomy (ETV) for the treatment of hydrocephalus and various types of cyst fistula, endoscopic nasal skull base surgery to remove skull base lesions, endoscopic transcranial keyhole approach, endoscopic trans-channel (endoport) surgery, endoscopic spinal surgery and endoscopic combined microscopic surgery. Among them, ventriculoscopic surgery and endoscopic transnasal skull base surgery are currently the most widely carried out. Endoscopic transcranial keyhole approach, endoscopic transcanal surgery and endoscopic spinal surgery are already being carried out gradually and orderly and will become important subspecialties. In this paper, the present situation, existing problems and prospects of the application of endoscopy in various subspecialties of neurosurgery are discussed, in order to promote the application of neuroendoscopy in neurosurgery.
To explore the surgical method and clinical effect of endoscopic endonasal approach for the treatment of invasive pituitary adenomas (IPA).
A retrospective analysis was conducted on the clinical data of 49 patients (50 procedures) with IPA treated through endoscopic endonasal approach at Department of Neurosurgery, the First Affiliated Hospital of Shenzhen University, from May 2014 to September 2017. Among them, the trans-cavernous approach was taken in 29 patients, the lateral-cavernous approach in 9 patients, the tuberculum sella planum approach in 7 patients and the diaphragma-sellae-cut and (or) dorsum-sellae-removal approach in 5 patients. The following aspects were investigated including extent of resection, curing rate and complications in patients with varying Knosp classifications and Hardy stages.
Among all 50 procedures, gross total resection (GTR) was achieved in 34 cases (68.0%). Subtotal resection was in 10 case(20.0%) and 6 cases(12.0%) of partial resection. Biology cured 28 cases(57.1%, 28/49). The GTR rate for pituitary adenoma was 10/11 for grade 3 and 4/16 for grade 4 based on Knosp classification. The GTR rate was 9/10 for Hardy stage C, 10/12 for stage D and 6/19 for stage E. The rate of biology cure was 8/10 for stage C, 8/12 for stage D and 4/19 for stage E. Postoperative complications included 7 (14.3%) cases of cerebrospinal fluid leaks, 16 (32.7%) cases of electrolyte imbalance, 23 (46.9%) cases of transient diabetes insipidus, 16 (32.7%) cases of hypopituitarism, 2 (4.1%) cases of permanent hypopituitarism, and 1 (2.0%) case of epistaxis. The follow-up lasted 4-31 months with an average of 16 months. None reported recurrence in the group of GTR. One undergoing subtotal resection reported recurrence and received a second operation. Three patients underwent postoperative Gamma knife radiosurgery. Two patients with refractory IPA were administered temozolomide and metformin chemotherapy.
Based on the invasiveness of IPA, proper choice of endoscopic surgical approach could help with tumor resection and complication reduction.
With the development of neuroendoscopic technique, endoscopic transnasal sphenoidal enlargement approach for the treatment of skull base tumors has gradually been adopted clinically. However, postoperative cerebrospinal fluid leakage is the most common complication of this approach, and reliable skull base reconstruction techniques are necessary for successful surgery[
tethered cord syndrome (TCS) is a syndrome in which various factors cause longitudinal traction of the spinal cord, low cone position, pathophysiological changes of the spinal cord, and neurological dysfunction and deformity. Surgery is its most effective treatment. With the advancement of technology, the surgery for TCS presents a trend of transformation from classical surgery to microsurgery and endoscopic surgery[
In the past, many scholars have reported the anatomical studies of vascular nerves in the skull base, but most of them are studied from the perspective of microscopic craniotomy, and the anatomical features of the skull base observed by naked eye or microscope are reported. In recent years, extended endoscopic endonasal approach (EEEA) skull base surgery has shown many advantages[
Cerebrospinal fluid rhinorrhea is a fracture of the skull base or skull defect caused by various reasons, resulting in the outflow of cerebrospinal fluid from the nasal cavity with rupture of the dura and arachnoid membranes. The leakage has different clinical manifestations with different sizes, and can be divided into spontaneous, iatrogenic, traumatic and neoplastic cerebrospinal fluid rhinorrhea. With the increasing application of neuroendoscopic nasal treatment of sellar region diseases, the incidence of iatrogenic cerebrospinal fluid rhinorrhea has also increased. Cerebrospinal fluid rhinorrhea can be treated by craniotomy and skull base repair, neuroendoscopic nasal repair or a combination of two methods. Craniotomy for skull base repair is more invasive, slow postoperative recovery and high failure rate. The advantage of neuroendoscopic nasal repair is that it can look for leaks under direct vision. Compared with craniotomy and tile surgery, its repair is more accurate and the success rate of surgery is higher. From January 2012 to June 2016, the Department of Neurosurgery of the First Affiliated Hospital of Shenzhen University treated 17 patients with cerebrospinal fluid rhinorrhea nasally under neuroendoscopy, and the curative effect was good, which is reported below.
To investigate the significance of the concept of the pseudocapsule-based extra-capsular dissection technique in endoscopic transsphenoidal surgery for pituitary adenomas.
We performed a retrospective analysis on clinical data of 287 patients with pituitary adenomas who underwent endoscopic endonasal transsphenoidal surgeries at Neurosurgery Department of Zhongshan Hospital, Fudan University from October 2011 to December 2015. Patients were divided into two groups: pseudocapsule-based extra-capsular dissection group (157 cases) and intra-capsular resection group (130 cases). We compared their surgical and endocrinological outcomes and complications.
The total resection rate in pseudocapsule-based extra-capsular dissection group was 89.8% (141/157) while that in intra-capsular resection group was 81.5% (106/130) (P=0.044). Furthermore, the recurrence rates in the extra-capsular and intra-capsular resection groups were 1.9% (3/157) and 6.9% (9/130), respectively (P= 0.035). Besides, with the application of extra-capsular dissection technique, the remission rate of functional adenoma in terms of biochemical parameters increased [56.5% (26/46) vs. 86.2% (50/58), P=0.001]. In addition, there was no difference in the rate of hypopituitarism, CSF leakage, intracranial infection or temporary polyuria (P>0.05).
The application of pseudocapsule-based dissection technique in endoscopic transsphenoidal surgery for pituitary adenomas could lead to a high rate of gross total tumor resection and endocrinological remission. Extra-pseudocapsular resection does not seem to cause additional postoperative complications.
To present our experience in surgical treatment of recurrent or residual craniopharyngiomas through extended endoscopic endonasal approach.
A retrospective review of clinical data of 12 patients who were treated for recurrent or residual craniopharyngiomas through extended endoscopic endonasal approach by the Deparment of Neurosurgery, the First Affiliated Hospital of Nanchang University from April 2012 to May 2016. All patients were analyzed in terms of the treatment effect, complications, and follow-up results.
Total removal of the tumors were achieved in 9 cases and subtotal removal in 3 cases. The pituitary stalks were identified in 8 cases during operations and secured in 7 cases. Postoperative visual acuity was improved in 8 cases and remained at the preoperative level in the other 4 cases. There was no significant difference between pre- and postoperative endocrine function, except for 1 patient with normal preoperative endocrine function who developed panhypopituitarism post surgery. Postoperative diabetes insipidus occurred in 11 patients including 1 patient who had long-term diabetes insipidus and others reporting transient postoperative diabetes insipidus. No cerebrospinal fluid (CSF) leak was identified. Intracranial infection was observed in 1 case and resolved with enhancement of anti-infection medication and extension of CSF drainage time. One case was lost to follow-up. There were no deaths or recurrence reported during the follow-up (3-45 months). Obesity developed in 2 patients. The cases with preoperative hypopituitarism were not improved.
Considering the adhesion of recurrent or residual craniopharyngiomas to their surrounding structures, extended endoscopic endonasal approach could be safe and effective with minimally invasiveness owing to its advantages including wide-angle view, close observation, and less traction and dissection of brain tissues.
To discuss and analyze the outcomes, complications and progression-free survival of craniotomy and expanded endoscopic endonasal transsphenoidal surgery (EETS) of craniopharyngioma.
Clinical data of 58 patients with craniopharyngiomas were analyzed retrospectively who underwent 68 surgical operations at Department of Neurosurgery, Tangdu Hospital of the Air Force Medical University, from January 2006 to December 2015. Patients were separated into two groups including one group of patients underwent craniotomy (38 cases) and EETS was performed in the other group (30 cases). Intra-group comparison was conducted regarding the resection extent, complications, recurrence rate and progression-free survival.
No significant difference was identified in the patient's age, gender, pathological classification, texture or preoperative volume of tumor between the two groups. The total resection rate of craniopharyngiomas in craniotomy group was 81.6% and 80.0% in EETS group (P=0.927). There was no significant difference in the incidence rate of panhypopituitarism (36.8% vs. 40.0%, P=0.81), diabetes insipidus (47.4% vs. 33.3%, P=0.32) or hydrocephalus (10.5% vs. 13.3%, P=0.53) between craniotomy and EETS groups. Cranial nerve injures were more commonly reported in craniotomy group than in EETS group (21.1% vs. 0%, P=0.007). The incidence rate of cerebrospinal fluid (CSF) leakage was significantly higher in EETS group than that in craniotomy group (23.3% vs. 0%, P=0.002). All patients were followed up for 19-94 months. There was no significant difference in the recurrence rate [18.4% (7/38) vs. 20.0% (6/30)], median time to recurrence (10.3 months vs. 10.8 months) or progression-free survival (25.4 months vs. 26.4 months) between the craniotomy and EETS groups (all P>0.05).
The extent of craniopharyngioma resection and outcomes of patients in EETS are comparable to those in craniotomy. EETS seems to be associated with a lower incidence rate of cranial nerve injures and a higher incidence rate of CSF leakage.
To explore the safety and efficacy of the treatment of trigeminal neuralgia and hemifacial spasm via fully neuroendoscopic microvascular decompression (MVD).
The clinical data of 32 patients underwent fully neuroendoscopic MVD during the period from November 2014 to June 2016 and were enrolled into this retrospective study. Among them, 11 cases were trigeminal neuralgia (TN) and 21 cases were hemifacial spasm (HFS).
The offending vessels were identified under endoscope in all cases. Among them, arterial compression was found in 28 cases, venous compression in 1 case, and both arterial and venous compression in 3 cases. In all 11 cases of trigeminal neuralgia, the symptom disappeared in 10 cases and was relieved in 1 case post surgery. Facial numbness occurred in 2 cases. In all 21 cases of hemifacial spasm, 20 cases obtained complete symptomatic relief and 1 case gained partial relief postoperatively. There was 1 case of hearing impairment and 1 case of mild facial paralysis reported post operation. No severe complications or death occurred. All cases were followed up for 6-24 months with a median period of 10.0±2.3 months. During the follow-up periods, none of the cases reported recurrence or aggravation.
Fully neuroendoscopic MVD, applied to treatment of TN and HFS, could help facilitate clear exposure of small vessels, avoid missing the offending vessels and reduce retraction of the cerebellum. Fully endoscopic MVD seems to be a safe and effective procedure and warrants further study and exploration.
To evaluate the effect of varying duration of prophylactic antibiotics on the incidence of postoperative intracranial infection in neurosurgeries with Class Ⅰ wound.
A total of 1 130 patients were enrolled into this prospective study who underwent neurosurgeries with Class Ⅰ wound at Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from August 2015 to March 2016. Based on the risk-stratified scales for postoperative intracranial infection, all patients were classified into two groups: low-risk group (LRG, n=807) and high-risk group (HRG, n=323). The two groups were further randomized into subgroups with various duration of postoperative prophylactic antibiotics. Specifically, LRG was subdivided into 0 h and 24 h subgroups (n=414 and 393, respectively). HRG was subdivided into 24 h, 48 h and 72 h subgroups (n=116, 113 and 94, respectively). The incidence of postoperative intracranial infections were compared between subgroups using Chi-square test.
The incidences of intracranial infections were 2.9%(12/414) and 2.0%(8/393) in 0 h and 24 h subgroups within LRG, respectively; and they were 8.6%(10/116), 13.3%(15/113) and 11.7%(11/94) in 24 h, 48 h and 72 h subgroups within HRG, respectively. The incidence of intracranial infection was significantly higher in HRG than LRG among the patients who received prophylactic antibiotics for 24 h post operation (χ2=11.385, P=0.001). There was no significant difference in the incidence of postoperative intracranial infection between the subgroups within the same group (all P>0.05).
Patients undergoing neurosurgeries with Class Ⅰ wound could be divided into low-risk and high-risk groups. Extended or shortened postoperative prophylactic antibiotics may not be able to significantly affect the incidence of postoperative intracranial infection.
To investigate postoperative long-term efficacy in patients undergoing bilateral deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) for primary Meige syndrome.
We retrospectively studied 30 patients of Meige syndrome who underwent bilateral GPi-DBS at Neurosurgery Department of China-Japan Friendship Hospital from October 2014 to October 2016. All patients were postoperatively followed up at the outpatient clinic and their motor functions were assessed based on the globally accepted Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS).
The implanted stimulator was turned on at 1 month post surgery. All 30 patients received monopolar stimulation with the voltage of 2.5-3.5 V (average: 2.6 ± 0.8 V), frequency of 60-160 Hz (average: 88.0 ± 21.3 Hz) and pulse width of 60-185 μs (average: 90.0 ± 21.1 μs). The symptoms of most patients had significantly improved within 1 week of stimiulation. The patients were followed up for 6 to 24 months with an average of 15.0 ± 7.8 months. The clinical symptoms of all patients had significantly improved. Assessed at 6 months, 12 months and 24 months post operation, the BFMDRS subscores of eyes, mouth, speech and swallowing were significantly lower ( P<0.05), and the subscore of mouth movement demonstrated progressive decrease with the prolongation of stimulation time (P<0.05). The overall improvement rate was 72.5% (26/30,P<0.05).
Bilateral GPi-DBS seems to demonstrate satisfactory long-term efficacy in the treatment of primary Meige syndrome, which could serve as an effective and safe option.
To evaluate the application of preoperative diffusion tensor tractography (DTT) in the surgical management of brainstem cavernous malformation and its correlation with clinical outcomes.
The clinical data of 73 patients with brainstem cavernous malformations were analyzed retrospectively who were admitted to Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University from February 2013 to January 2016. Preoperatively, the bilateral corticospinal and medial lemniscus tracts of each patient were traced by DTT. The DTT scores were graded by the pattern of fiber tracts (1-4 scores). The surgical approach was determined according to the location of the fiber tracts and lesion. Intraoperatively, the lesion was resected by the fiber-merged navigation. Patients were postoperatively evaluated according to the modified Rankin scale (mRS) at different time points. The clinical factors were compared between the group with high DTT score and that with low DTT score. The relationship between the neurological function and preoperative DTT score was analyzed.
Gross total resection was achieved in 68 cases (93.2%) while subtotal resection in 5 cases (6.8%). The average DTT scores of corticospinal tract and medial lemniscus tract were 1.83±1.04 and 1.97±1.46, respectively. The location and size of the lesion between the group with high DTT score and that with low DTT score were significantly different (93.2%). The final mRS score was lower than the initial one (P=0.027). The high DTT score of corticospinal tracts and the lesion diameter more than 2 cm were considered as factors negatively correlated with the patient's neurological function.
The application of DTT in the surgical resection of brain stem cavernous malformation could be helpful for the surgeon's choice of surgical approach, preventing intraoperative injury of fiber tract and improving the patient's clinical outcome.
To explore the role of stereotactic approach combined with surgical plan made by preoperative three-dimensional computed tomographic (3D CT) reconstruction in treatment of trigeminal neuralgia by percutaneous radiofrequency thermocoagulation of Gasserian Ganglion.
A retrospective analysis was conducted on 30 patients of trigeminal neuralgia who underwent percutaneous radiofrequency thermocoagulation of Gasserian Ganglion at Department of Neurosurgery, China-Japan Union Hospital of Jilin University, from May 2012 to March 2016. Stereotactic frame was installed and 3D CT reconstruction image was made prior to surgery. Image processing software (Vitrea fX, Version 6.6.2) was used to analyze difficult factors and make surgical plan.
Foramen ovale puncture was successfully performed in all 30 patients. In the 11 cases with less than 2 difficult factors, an average of (1.4±0.7, range: 1-3) punctures were performed. In the remaining 19 cases with at least 2 difficult factors, an average of (2.6±0.9, range: 1-5) punctures were performed. All cases without bended puncture needles intraoperatively confirmed by fluoroscopy required only 1 puncture. No severe surgical complication occurred. The short-term and 1-year effective rates were 100% and 96.7% (29/30), respectively. Four cases reported recurrence at 2-year follow-up with the recurrence rate of 14.3% (4/28), and the 2-year effective rate was 85.7% (24/28).
Percutaneous radiofrequency thermocoagulation of Gasserian Ganglion using surgical plan made by stereotactic approach combined with preoperative three-dimensional computed tomographic (3D CT) reconstruction could provide accurate localization, which seems to be safe and effective, particularly for cases with difficult-to-puncture foramen ovale.
Glioblastoma multiforme, referred to as glioblastoma for short, is the most common malignant tumor of the nervous system. The occurrence probability of glioblastoma is not the same in different parts, and it is most likely to occur in the white matter near the posterior horn of the lateral ventricle[
With the development of endovascular therapy techniques and embolization materials, endovascular therapy has become the first choice for intracranial aneurysm. However, postoperative recurrence is still a difficult problem to be solved in endovascular treatment of aneurysms. Uniform and dense packing of coils can effectively reduce recurrence, but for complex intracranial aneurysms, especially irregular aneurysms, it is still difficult to achieve uniform and dense embolization and reduce postoperative recurrence. From October 2011 to October 2016, 33 cases of irregular ruptured intracranial aneurysms were treated by double microcatheter combined with staggered basket embolization in the Department of Neurosurgery of the Provincial Hospital affiliated to Anhui Medical University, with satisfactory results. The retrospective report is as follows.
Cranioplasty is a common procedure in neurosurgery. Studies have shown that early cranioplasty can improve the blood perfusion of brain tissue at the skull defect, thus improving the quality of life of patients[
Craniopharyngioma often adheres closely to important structures such as pituitary stem, internal carotid artery, optic nerve, optic chiasma, endplate and hypothalamus, which makes surgery difficult. Different surgical approaches have different degrees of tumor exposure, vascular neuroprotection and hydrocephalus remission[
During the treatment of patients with severe cerebral hemorrhage, adequate fluid rehydration can increase the effective circulating blood volume, but also easily lead to increased intracranial pressure and neurogenic pulmonary edema (NPE). Therefore, fluid rehydration should be limited in clinical treatment. However, restriction of fluid rehydration and insufficient fluid intake may lead to cerebral infarction. Therefore, fluid management in patients with severe cerebral hemorrhage is an important link in the treatment. In the past, the traditional method of fluid management was central venous pressure (CVP) monitoring, but there were many drawbacks. pulse index continuous cardiac output (PICCO) monitoring is a new technology for fluid management in recent years. Previous studies have confirmed that PICCO monitoring can effectively manage fluids and improve the treatment rate of patients with severe cerebral hemorrhage[
Surgical clipping or endovascular therapy are the main methods of intracranial ruptured aneurysms at present, and the question of "optimal surgical timing" has been controversial both at home and abroad[
To analyze the expression of podoplanin (PDPN) in gliomas, and to investigate its relationship to clinical features and prognosis of gliomas.
Clinical data and mRNA microarray data of 301 glioma samples from Chinese Glioma Genome Atlas (CGGA) database were collected, and the expression of PDPN was analyzed. GSE16011 mRNA microarray datasets, TCGA RNA sequencing database and REMBRANDT mRNA microarray datasets were used as validation sets. Kaplan-Meier survival and Cox regression analysis were used to estimate the role of PDPN in the prognosis of patients. In addition, Gene ontology (GO) analysis was performed to study the function of genes positively related to expression of PDPN.
In CGGA, the expression of PDPN protein was the highest in grade IV gliomas (0.62±0.07, all P<0.05), while was the lowest in grade II gliomas (-0.59±0.06, allP<0.05); the expression of PDPN protein in IDH1 wild-type patients was higher than that in mutant patients (0.48±0.07 and -0.58±0.07 respectively,P<0.05). The cumulative survival rate of patients with high expression of PDPN protein was significantly lower than that of low expression group (P<0.05). The above characteristics of PDPN protein obtained similar results in the other three databases. Multivariate analysis showed that age, pathological grade, the expression of PDPN protein and radiotherapy were independent factors affecting the survival of glioma patients (allP<0.05), which could be used for prognosis. PDPN was found related to the immune response, extracellular matrix regulation, cell adhesion and migration and other biological processes of glioma.
PDPN could promote the development of gliomas and thus be used as a prognostic biomarker and potential therapeutic target.
To investigate the mechanism of development and rupture of intracranial aneurysm (IA) on the protein level and to search for target protein.
Specimens were collected from 3 cases of IA undergoing microsurgical clipping and STA (superficial temporal artery) in 3 cases as controls undergoing craniotomy through pterional approach from October 2015 to May 2016 at Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University. All those samples were analyzed by bioinformatics and proteomics. The GO (gene ontology) analysis was performed for study of biological process, cell component and molecular function. PPI (protein-protein interaction) and KEGG (Kyoto Encyclopedia of Genes and Genomes) were used to analyze pathway and differentially expressed proteins.
Compared between the IA and STA groups, there were 106 differentially expressed proteins identified. Among them, 20 were significantly dysregulated including 6 down-regulated proteins and 14 up-regulated ones. The GO analysis showed that differentially expressed proteins in IA group were mainly related to cellular biosynthetic process, and membrane-bounded organelles represented the most significant cellular structural difference between the IA and STA groups. Further analysis through PPI and KEGG pathway showed that the most significantly up-regulated protein was THBS4, which played a key role in extracellular matrix interaction; and the most significantly down-regulated protein was PTGS1, which was important for platelet activation.
Label-free quantitative mass spectrometry and bioinformatics could be effective ways to analyze the proteins in IA tissues. THBS could be a key protein in IA progression and a potential target for intervention.
During lateral ventricular drainage, drainage tube blockage often occurs. The anti-blockage lateral ventricular drainage system (patent number: ZL2016 2 1006553,9) designed by the Department of Neurosurgery of Longhai (Brain Department) Hospital in Kaifeng City has the advantages of repeated flushing and aspiration of the lateral ventricular drainage system without opening the drainage system, which solves the blockage problem of most drainage tubes, and has achieved good clinical efficacy. It is now introduced as follows.
Sellar tumors are mainly pituitary adenomas in adults, only about 10% are tumors of other nature, and primary undifferentiated sarcoma of the sellar region is even more rare[
Neuromuscular maltumor, also known as benign salamander tumor, is a rare clinical disease. It is caused by ectopic growth of normal embryonic tissue, and mostly involves peripheral nerves such as sciatic nerve and brachial plexus[
PatientFemale, 24 years old, 27 weeks pregnant, refugee from South Sudan. On 18 April 2014, he was flown by United Nations helicopter to the 12th batch of peacekeeping medical teams in South Sudan from Jinan Military Region because he was "unconscious for 30 hours after being hit in the head by a bullet". Physical examination of the patient at admission: normal basic vital signs, light coma, Glasgow Coma Scale (GCS) 8, no abnormalities in bilateral pupils. A tangential injury of 7 cm ×3 cm was seen on the left temporal roof of the skull (
Hemangioblastoma is a rare benign tumor of the central nervous system. It originates from the embryonic residual tissue of mesodermal cells. It is a vascular-rich and localized tumor, which occurs in the cerebellum, spinal cord and brainstem. The onset of most hemangioblastomas is sporadic, but about 25% of them belong to a clinical manifestation of von Hippel-Lindau (VHL) disease with a familial predisposition. brainstem hemangioblastomas (BSHs) account for about 2% to 10% of brainstem tumors[
intracerebral hemorrhage (ICH) is a serious neurological disease, and its mortality and disability rate are higher than those of ischemic stroke[
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