Axl as a potential therapeutic target for adamantinomatous craniopharyngiomas: Based on single nucleus RNA-seq and spatial transcriptome profiling.

Craniopharyngiomas (CPs), particularly Adamantinomatous Craniopharyngiomas (ACPs), often exhibit a heightened risk of postoperative recurrence and severe complications of the endocrine and hypothalamic function. The primary objective of this study is to investigate potential novel targeted therapies within the microenvironment of ACP tumors. Cancer-Associated Fibroblasts (CAFs) were identified in the craniopharyngioma microenvironment, notably in regions characterized by cholesterol clefts, wet keratin, ghost cells, and fibrous stroma in ACPs. CAFs, alongside ghost cells, basaloid-like epithelium cells and calcifications, were found to secrete PROS1 and GAS6, which can activate AXL receptors on the surface of tumor epithelium cells, promoting immune suppression and tumor progression in ACPs. Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.

Posterior intra-articular distraction technique to treat pediatric atlantoaxial instability.

PURPOSE: Surgical treatment for atlantoaxial instability in pediatric patients is challenging. We report our experience with posterior intra-articular distraction technique in treating this disorder. METHODS: This is a retrospective descriptive study which included 15 patients of atlantoaxial instability whose age was less than 16 years at the time of clinical presentation. All patients underwent anterior soft tissue released through a posterior-only approach, followed by intra-facet cage implantation, cantilever correction, and instrumentation. Clinical results were measured using the Japanese Orthopedic Association (JOA) scale and radiographic measurements including the atlantodental interval (ADI), posterior atlantodental interval (pADI), the distance of odontoid tip above Chamberlain's line, clivuscanal angle (CCA), and triangular area (TA) of craniovertebral junction. RESULTS: The follow-up period ranged from 18 to 72 months, with an average of 41.2 ± 15.2 months. The JOA score increased from 13.6 ± 2.3 to 16.6 ± 0.8. ADI decreased from 4.31 ± 2.37 to 1.85 ± 1.09 mm, and TA decreased from 261.96 ± 107.99 to 197.12 ± 72.37 mm2. pADI increased from 12.89 ± 3.52 to 18.25 ± 3.89 mm, and CCA improved from 132.19 ± 16.34 to 144.35 ± 13.91°. All changes in measurements showed statistically significant. There were no evidence of surgery-related complications or iatrogenic secondary cervical deformity during follow-up. Radiological evaluation showed satisfactory corrections and bony fusions of C1-2 facet joint in all cases. CONCLUSION: Posterior intra-articular distraction followed by cage implantation and cantilever correction can be one of the safe and effective ways to solve atlantoaxial instability in pediatric patients.

Surgical timing and long-term outcomes in patients with severe haemorrhagic spinal cord cavernous malformations.

BACKGROUND: Surgical resection of the lesions remains the main treatment method for most symptomatic spinal cord cavernous malformations (SCCMs) to eliminate the occupation and associated subsequent lifelong haemorrhagic risk. However, the timing of surgical intervention remains controversial, especially for patients in the acute stage after severe haemorrhage. METHODS: Patients diagnosed with SCCMs who were surgically treated between January 2002 and December 2021 were selected and retrospectively reviewed. The Modified McCormick Scale (MMS) was used to evaluate neurological and disability status. All medical information was reviewed, and all patients were followed up for at least 6 months. RESULTS: A total of 279 patients were ultimately included. With regard to long-term outcomes, 110 (39.4%) patients improved, 159 (57.0%) remained unchanged and 10 (3.6%) worsened. For patients with an MMS score of 2-5 on admission, in univariate and multivariate analyses, a ≤6 weeks period between onset and surgery (adjusted OR 3.211, 95% CI 1.504 to 6.856, p=0.003) was a significant predictor of improved MMS. Among 69 patients who first presented with severe haemorrhage, undergoing surgery within 6 weeks of the onset of severe haemorrhage (adjusted OR 4.901, 95% CI 1.126 to 21.325, p=0.034) was significantly associated with improvement of MMS score. CONCLUSION: Surgical timing can influence the long-term outcome of SCCMs. For patients with symptomatic SCCMs, especially those with severe haemorrhage, early surgical intervention within 6 weeks can provide more benefit.

Potential of unilateral combined bypass surgery to accelerate contralateral radiological progression in pediatric moyamoya disease.

Background: Surgical cerebral revascularization is recommended for treating pediatric moyamoya disease (MMD). However, whether unilateral combined bypass surgery can cause disease progression on the contralateral side is uncertain. The study aimed to investigate the vascular architecture and regional cerebral blood flow (rCBF) status of patients with pediatric MMD after successful unilateral combined bypass surgery and to identify the possible risk factors. Methods: Pediatric patients diagnosed with MMD and admitted to Xuanwu Hospital who underwent combined bypass surgery between 2019 and 2021 were enrolled. Digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) with arterial spin labeling (ASL) were performed to investigate the vascular architecture and rCBF during surgery and at short-term follow-up. Suzuki's angiographic staging and moyamoya vessel grading system were both used. Progression was defined as an increase in either Suzuki stage or moyamoya vessel grade detected after unilateral surgery. All analyses were performed with conventional statistic methods. Results: A total of 27 successive patients with a median age of 8 [interquartile range (IQR), 5-14] years old were identified. On the non-operated (non-OP) side, 11 (40.7%) patients demonstrated progression, all of whom showed an increase in the moyamoya vessel grade, and 5 also displayed Suzuki stage progression during the median 4.7 (IQR, 3.7-5.7) months follow-up. However, rCBF barely changed on the non-OP side compared to preoperation [preoperation: median, 49.6, (IQR, 42.9-61.1) mL/100 g/min; postoperation: median, 50.2, (IQR, 43.5-59.3) mL/100 g/min; P=0.445]. Conclusions: Combined bypass surgery might accelerate the radiological progression on the contralateral side, which occurs before the decline of rCBF. Those with earlier Suzuki stage MMD of the non-OP side are prone to rapid progression after unilateral combined revascularization.

Vascular Malformations of the Spinal Cord in Children.

Vascular malformation of the spinal cord in children is a rare and complicated disease spectrum. We will start from the basic spinal cord vascular anatomy and the controversial classification of this kind of disease. Then, we will elaborate the clinical manifestations, diagnostic imaging and treatment of pediatric spinal vascular malformations based on the practical experience of our center and from literature.

Effectiveness of pedometer- and accelerometer-based interventions in improving physical activity and health-related outcomes among college students: A systematic review and meta-analysis.

Background: Although the pedometer- and accelerometer-based interventions (PABI) have demonstrated efficacy in improving physical activity (PA) and health-related outcomes, the dearth of empirical evidence in college students warrants further investigation. Objective: This systematic review and meta-analysis aim to examine the effects of PABI on improving PA and health-related outcomes among college students. Methods: PubMed, Web of Science, Embase, Cochrane Library, and PsycINFO were searched for relevant literature from inception to 20 February 2022. Randomized controlled trials (RCTs) conducted among college students with PABI to increase objectively measured PA as the primary outcome were included in this study. Results: A total of nine RCTs with 527 participants were included in this study. The combined results showed that PABI significantly improved PA (standardized mean difference = 0.41, 95% confidence interval (CI): 0.08, 0.74, P = 0.016) and significantly contributed to weight loss (mean differences (MD) = -1.56 kg, 95% CI: -2.40 kg, -0.73 kg, P < 0.01), and lower body mass index (MD = -0.33 kg/m2, 95% CI: -0.66 kg/m2, 0.00 kg/m2, P = 0.05) compared to the control group, but no significant effects were observed on improvements of body fat (%) and exercise self-efficacy. Interventions in the group of step, general students, pedometer-based intervention, theory, and developed region were significantly more effective in subgroup analyses. Conclusions: PABI was found to be effective in promoting PA and weight loss among college students. Future research is needed to further explore the long-term effects of PABI and the characteristics of multiple intervention models.

In reply to the letter to editor regarding "Fourth ventricle stent placement for treatment of type I Chiari malformation in children".

We made a reply to the letter to editor regarding "Fourth ventricle stent placement for treatment of type I Chiari malformation in children" by Prof. Afshari. He gave some comments on the primary cause of low-lying cerebellar tonsils and the risk of the fourth ventricle stent (FVS). We make further explanation of our opinion on Chiari malformation and the value of FVS.

Pediatric spinal cord diffuse midline glioma with H3 K27M-alteration with leptomeningeal dissemination: a rare case with intracranial hypertension onset and no spinal cord-related symptom.

PURPOSE: Spinal cord diffuse midline glioma (DMG) with H3 K27-alteration is a group of spinal cord high-grade glioma with poor outcome. We present a case with rare onset symptom pattern of pediatric spinal DMG, contributing to the understanding of the clinical presentations and natural history of pediatric spinal cord DMG. METHODS AND RESULTS: A 7-year-old boy was admitted due to symptoms of intracranial hypertension without obvious spinal cord-related symptoms. Head radiological examinations, blood and cerebral spinal fluid tests did not support intracranial lesion, infection, or autoimmune diseases. Spinal magnetic resonance imaging revealed intraspinal occupying lesion with leptomeningeal dissemination. Pathology of the lesion verified DMG with H3 K27M-alteration. CONCLUSION: Pediatric DMG with leptomeningeal dissemination could present with initial symptoms of intracranial hypertension without obvious spinal cord-related symptoms. Spinal cord examinations in cases of intracranial hypertension with negative head radiological examination results could be valuable in finding the etiology.

De novo cerebral cavernous malformations with PIK3CA somatic mutation and EPHB4 germline mutation in a child with multiple developmental venous anomalies and cutaneous vascular malformations.

Cavernous malformations (CM) that arise in the central nervous system have long been considered congenital, while there are many reports of de novo non-familial-type CM adjacent to developmental venous anomalies (DVA) or after radiation. The mechanisms that cause de novo formations of sporadic cavernous malformation (CM) still remain unknown and purely speculative. We report a case of de novo cerebral CM in a child with multiple developmental venous anomalies and cutaneous vascular malformations. Histological examination and whole-exome sequencing (WES) was performed on a fresh-frozen tissue sample of the CM. WES revealed 2 missense non-synonymous variants in two genes, EPHB4 and PIK3CA. The mutant allele of EPHB4 (NM_004444.4: c.1840 T > C, p.Y614H) appeared in 248/469 WES reads (allele frequency, 52.88%), which suggested the mutation a germline one. PIK3CA (NM_006218.2) somatic mutations were found in exon 9: c.1624G > A (p.Glu542Lys) with variant frequency of 2.2% (2/89 WES reads). We did not find any non-synonymous mutations of the three CCM genes (KRIT1, CCM2, and PDCD10) in this patient. Our findings suggested that the combination of gain of function in PIK3CA and loss of function in EPHB4 may play an important role in the pathogenesis of CM, which can develop in acquired form like tumorigenesis.

Meningioma originating from the oculomotor nerve without dural attachment in a child.

Meningioma originating from the oculomotor nerve without dural attachment in children has been rarely reported. A 6-year-old patient presented ptosis of the right eye for 5 years. MRI indicated an occupying lesion in the right cavernous sinus. A tumor originating from the oculomotor nerve without dural attachment was found during subsequent surgery and confirmed as meningioma by pathology. Subsequently, the tumor was removed completely, and the oculomotor nerve was reconstructed using the sural nerve. The patient's symptoms were relieved partially after 3 months. The findings of this case suggested that the mechanisms underlying meningioma involve ectopic arachnoid cap cells within the nerve sheath. Thus, the tumor should be removed completely; also, nerve reconstruction is suggested.

Fourth ventricle stent placement for treatment of type I Chiari malformation in children.

INTRODUCTION: Type I Chiari malformation (CM-I) is a common congenital malformation, often accompanied by syringomyelia. Obstruction of CSF circulation in the foramen magnum is the reason for the formation of the syringomyelia. Fourth ventricle stenting (FVS) could ensure the CSF flow from the fourth ventricle, which might represent an effective approach to achieve syringomyelia relief. METHODS: We have reviewed four cases of CM-I children who received FVS implantation from November 2021 to July 2022. Each of the patients underwent FMD. The ventricular catheter of an Ommaya reservoir (Medtronic, Inc.) was used as a stent. Duraplasty was performed with autologous fascia. Cervical MRI rechecks were routinely done 3 months later, and the clinical symptoms were followed up. RESULTS: Four children received FVS, including one boy and three girls, aged from 12 months to 10 years, with a mean age of 6.8 years. No major complication occurred. The syringomyelia or hydrocephalus in each patient were all attenuated, as observed on the reexamination MRI images. During the follow-up time with a mean of 10.8 months, no patient had new symptoms. CONCLUSION: FVS is an effective and safe method for operation of CM-1 in children. The indications of FVS include redo-FMD, difficulties to ensure post-FMD CSF circulation patency at the foramen magnum and with obstructive hydrocephalus. A long-term follow-up duration is necessary.

Delineation of molecular characteristics in pediatric PFA ependymoma involving rare osseous and pulmonary metastases: A case report and literature review.

Ependymoma is the third most common pediatric primary brain tumor, with its most aggressive subtype being posterior fossa group A (PFA). Extraneural metastasis of pediatric PFA ependymoma is rare. Herein, we present a case of a 9-year-old girl with PFA ependymoma characterized by a lack of trimethylation of histone H3 at lysine 27 and elevated chromosome X open reading frame 67 expression. Despite multiple surgeries and radiotherapies, the patient had a rapid recurrence and developed osseous and pulmonary metastases, which may be attributed to the homozygous deletion of cyclin-dependent kinase (CDK) inhibitor 2A/B and CDK12 mutation. Importantly, the CDK12 mutation observed in the patient may be indicative of the need for further work-up to consider chemotherapy rather than administering poly (adenosine diphosphate-ribose) polymerase inhibitors. Taken together, this is the first report of pediatric PFA ependymoma with extraneural metastases, wherein we clarified the diagnostic procedures of this newly identified PFA ependymoma and provided new cues to study the invasiveness of this disease and treatment selection for such patients.

Phenotypes and Prognostic Factors of Syringomyelia in Single-Center Patients With Chiari I Malformation: Moniliform Type as a Special Configuration.

OBJECTIVE: The specific association between morphometric characteristics of the syrinx and the prognosis of Chiari malformation type I (CM-I) with syringomyelia following surgical procedure seems to have not been fully elaborated. This study focused on the preoperative clinical and radiologic parameters in CM-I patients with syringomyelia to find out the relationship between the patients' clinical status and the phenotypes of the syrinx with surgical outcome. METHODS: A continuous series of pediatric and adult patients with CM-I and syringomyelia from a prospectively maintained database in a single center were included, and we explored the related factors affecting the prognosis following decompression surgery through retrospective analysis of clinical presentations, imaging characteristics, and the morphological features of syringomyelia, to provide a clinical reference for the treatment of syringomyelia. RESULTS: There were 28 pediatric patients (13.8%), and 174 adults (86.2%) included in our study. The average Chicago Chiari Outcome Scale score was 14.56 ± 1.78. The overall prognosis after surgery was good in our series, among them 152 cases (75.25%) with a favorable prognosis, and syrinx was resolved effectively in 172 cases (85.15%). According to the univariate and multivariate analyses, the preoperative symptom duration, observation time, and with/without moniliform type were independent factors affecting the prognosis in adults. The most obvious difference between moniliform type and nonmoniliform type lies in the preoperative symptom duration, ventral subarachnoid space at the foramen magnum, and with/without straightened cervical physio-curve. CONCLUSION: Timely decompression surgery could achieve a better outcome in CM-I patients with syringomyelia. Moniliform syringomyelia may suggest a relatively better prognosis.

Analysis of the risk factors of post-operative seizure in pediatric patients with hydrocephalus undergoing endoscopic third ventriculostomy.

OBJECTIVE: The cause and mechanism of epilepsy after endoscopic third ventriculostomy (ETV) have still remained elusive. This single-center study aimed to explore and analyze the risk factors of post-operative seizure in pediatric patients with hydrocephalus undergoing ETV. METHODS: Data of pediatric patients with hydrocephalus who were treated with ETV from October 1, 2015, to November 31, 2021, were retrospectively analyzed. Basic demographic characteristics, etiology of hydrocephalus, surgical details, and laboratory measurements were collected. An early postoperative seizure was defined as the occurrence of at least one clinical seizure within 24 h of ETV. RESULTS: A total of 50 participants were included in the study, of whom 5 (10.00%) cases were in postoperative epilepsy group and 45 (90.00%) cases were in non-epilepsy group. Epilepsy patients were younger than those without epilepsy, while no statistically significant difference was found (P = 0.0836). In the age subgroup, children with epilepsy were younger than 2 years old. All patients with epilepsy received Ringer's solution intraoperatively. The mean postoperative serum calcium and potassium concentrations were significantly lower in patients with epilepsy than in those without epilepsy (Pcalcium = 0.0429; Ppotassium = 0.0250). Moreover, a faster decrease of serum potassium and calcium levels was found in children with epilepsy compared with those without epilepsy after ETV. CONCLUSION: The decrease of serum calcium and potassium levels, younger age, and using Ringer's solution as irrigation fluid were risk factors for epilepsy after ETV.

Pediatric Cerebral Meningioma: A Single-Center Study with 10 Children Not Associated with Neurofibromatosis Type 2 and Literature Review.

INTRODUCTION: Pediatric meningiomas (PMs) are rare tumors; they differ from their adult counterparts by their atypicality of location, higher rates of malignant change, male preponderance, recurrence, and sometimes, their association with neurofibromatosis. This case series analyzes the clinical behavior, pathological presentation, location, and its association with neurofibromatosis type 2 (NF2). METHODS: This case series consists of pediatric patients between the ages of 4 and 16 years who were hospitalized in the neurosurgical department of our hospital from 2012 to 2021 with different neurological symptoms and a literature review using the PubMed/MEDLINE database. RESULTS: Sixty percent of the patients were males, while 40% were females. The most common neurological manifestations were signs of increased intracranial pressure. NF2 was absent in all patients. The predominant histopathology subtypes are atypical and WHO grade II, representing 30% and 40%, respectively. CONCLUSION: This study supports the relationship between NF2 and pediatric cerebral meningioma but at a lower concomitant rate from 0 to 13%, taking into consideration our original data and the literature review, contrasting some reported cases, which suggest rates as high as 33%, 50%, and 100% in a very small number of patients. Gross total resection without postoperative radiation therapy for nonmalignant and non-NF2-associated PM proved to be a sufficient and a good treatment option.

Treatment of spontaneous spinal epidural hematoma in children: analysis of 25 cases.

INTRODUCTION: Spontaneous spinal epidural hematoma (SSEH) is a rare neurosurgical emergency, presenting as sudden onset of back pain and weakness of lower extremities. Many patients have no definite cause. Some cases of SSEH caused by vascular malformation have been reported. The treatment strategy remains controversial. This study aimed to analyze the causes of SSEH and proposed a treatment strategy according to clinical outcomes of patients at a single institution. METHODS: A total of 25 cases of SSEH under 18 years of age treated between March 2004 and July 2021 were retrospectively analyzed. RESULTS: The mean age of the first SSEH onset was 7.1 years. The most common location was cervicothorax. Nine patients suffered from multiple episodes. Twenty-three patients underwent spinal digital subtraction angiography (DSA), of which seven (30.4%) patients had positive findings: three cases had epidural artery venous fistula (AVF), two cases had epidural artery venous malformation (AVM), and two cases had abnormal concentration of contrast agent. Seventeen patients received surgery. Eleven patients (44%) were diagnosed as vascular malformation by either DSA or pathology. The follow-up rate was 80%, with 20 patients (80%) achieving satisfactory clinical outcome. Risk factors for poor clinical outcome included multiple episodes (p = 0.028) and higher Aminoff-Logue score (p = 0.005). CONCLUSION: Spinal epidural vascular malformation is a significant cause of SSEH. Spinal DSA is necessary. Surgery should be recommended for patients with multiple episodes, positive findings on DSA, or severe neurological deficits. Conservation therapy can be considered for other patients, but long-time follow-up is necessary.

Abscess of the cavernous sinus in a child: a case report.

BACKGROUND: The cavernous sinus, which has several important structures, can be affected by various lesions, including tumor, vascular, infection, and inflammation. CASE REPORT: We reported a rare case of abscess of the cavernous sinus in a child presenting with headache and abducens paralysis. Exploratory surgery was performed via the Dolenc approach, and the patient recovered from abducens paralysis 3 months later. CONCLUSION: Abscess of the cavernous sinus is rare.  Inspection of cavernous sinus can confirm the characteristics of the lesion and decompress the cavernous sinus, which may be beneficial for nerve function recovery.

Impact of the COVID-19 Pandemic on ST-Elevation Myocardial Infarction Management in Hunan Province, China: A Multi-Center Observational Study.

Background: This study aimed to investigate the impact of the COVID-19 pandemic on ST-segment elevation myocardial infarction (STEMI) care in China. Methods: We conducted a multicenter, retrospective cohort study in Hunan province (adjacent to the epidemic center), China. Consecutive patients presenting with STEMI within 12 h of symptom onset and receiving primary percutaneous coronary intervention, pharmaco-invasive strategy and only thrombolytic treatment, were enrolled from January 23, 2020 to April 8, 2020 (COVID-19 era group). The same data were also collected for the equivalent period of 2019 (pre-COVID-19 era group). Results: A total of 610 patients with STEMI (COVID-19 era group n = 286, pre-COVID-19 era group n = 324) were included. There was a decline in the number of STEMI admissions by 10.5% and STEMI-related PCI procedures by 12.7% in 2020 compared with the equivalent period of 2019. The key time intervals including time from symptom onset to first medical contact, symptom onset to door, door-to-balloon, symptom onset to balloon and symptom onset to thrombolysis showed no significant difference between these two groups. There were no significant differences for in-hospital death and major adverse cardiovascular events between these two groups. Conclusion: During the COVID-19 pandemic outbreak in China, we observed a decline in the number of STEMI admissions and STEMI-related PCI procedures. However, the key quality indicators of STEMI care were not significantly affected. Restructuring health services during the COVID-19 pandemic has not significantly adversely influenced the in-hospital outcomes.

Adapalene Inhibits Prostate Cancer Cell Proliferation In Vitro and In Vivo by Inducing DNA Damage, S-phase Cell Cycle Arrest, and Apoptosis.

Aims: Prostate cancer is a well-known aggressive malignant tumor in men with a high metastasis rate and poor prognosis. Adapalene (ADA) is a third-generation synthetic retinoid with anticancer properties. We investigated the anti-tumor activity and molecular mechanisms of ADA in the RM-1 prostate cancer cell line in vivo and in vitro. Methods: The effects of ADA on cell proliferation were estimated using the CCK-8 and colony formation assays. The wound-healing assay and the Transwell assay were employed to examine the migratory capacity and invasiveness of the cells. Flow cytometry was utilized to evaluate the cell cycle and apoptosis, and Western blotting analysis was used to assess the expression of the associated proteins. Micro-CT, histomorphological, and immunohistochemical staining were used to assess the effects of ADA on bone tissue structure and tumor growth in a mouse model of prostate cancer bone metastasis. Result: ADA dramatically inhibited cell proliferation, migration, invasiveness, and induced S-phase arrest and apoptosis. ADA also regulated the expression of S-phase associated proteins and elevated the levels of DNA damage markers, p53, and p21 after ADA treatment, suggesting that the anti-tumor effect of ADA manifests through the DNA damage/p53 pathway. Furthermore, we observed that ADA could effectively inhibited tumor growth and bone destruction in mice. Conclusion: ADA inhibited prostate cancer cell proliferation, elicited apoptosis, and arrested the cell cycle in the S-phase. ADA also slowed the rate of tumor growth and bone destruction in vitro. Overall, our results suggest that ADA may be a potential treatment against prostate cancer.