[Three-Dimensional Nonlinear Finite Element Modeling and Analysis of Concomitant Atlanto-Occipital Fusion and Atlantoaxial Joint Dislocation].

OBJECTIVE: To establish, with finite element technology, a three-dimensional nonlinear finite element model of the normal occipital bone, atlas and axis and a three-dimensional nonlinear finite element model of concomitant atlanto-occipital fusion and atlantoaxial dislocation, providing a biomechanical method for clinical research on the upper cervical spine. METHODS: Finite element analysis was conducted with the CT data of a 27-year-old male volunteer, and a three-dimensional nonlinear finite element model, i.e., the normal model, of the normal occipital bone, atlas and axis was established accordingly. Finite element analysis was conducted with the CT data of a 35-year-old male patient with concomitant atlanto-occipital fusion and atlantoaxial dislocation. Then, the ideal state of a simple ligament rupture under high load was generated by computer simulation, and a three-dimensional nonlinear finite element model of concomitant atlanto-occipital fusion and atlantoaxial dislocation was established, i.e., the atlanto-occipital fusion with atlantoaxial dislocation model. For both models, a vertical upward torque of 1.5 N·m was applied on the upper surface of the occipital bone. Through comparative analysis of the two models under stress, the data of the range of motion (ROM) for flexion, extension, lateral bending, and rotation were examined. In addition, stress and deformation analysis with 1.5 N·m torque load was conducted to validate the effectiveness of the two three-dimensional nonlinear finite element models established in the study. RESULTS: When the normal model established in the study was under 1.5 N·m torque load, it exhibited a maximum ROM for each unit of flexion, extension, and the ROM approximated the experimental measurement results of human mechanics, confirming the validity of the simulation. The stress and deformation results of the model were consistent with the basic principles of mechanics. The moment-angular displacement of the model showed obvious nonlinear characteristics. Compared with the normal model, the atlanto-occipital fusion with atlantoaxial dislocation model showed reduced ROM of the atlanto-occipital joint under a torque of 1.5 N·m, while the ROM of the C1-C2 joint for the four conditions of flexion, posterior extention, lateral bending, and rotation under load, with the exception of rotating motion, was greatly increased compared with that of the normal model, which was in line with the actual clinical performance of the patient. CONCLUSION: The atlanto-occipital fusion with atlantoaxial dislocation model and the three-dimensional nonlinear finite element model of the normal occipital bone, atlas and axis were successfully established by finite element technology. The models had valid simulation and reliable kinematic characteristics, and could be used as a reliable tool to simulate clinical diseases.

Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis.

Lipotoxicity is a recognized pathological trigger and accelerator of nonalcoholic steatohepatitis (NASH). However, the molecular basis of lipotoxicity-induced NASH remains elusive. Here, we systematically mapped the changes in hepatic transcriptomic landscapes in response to lipotoxic insults across multiple species. Conserved and robust activation of the arachidonic acid pathway, in particular the arachidonate 12-lipoxygenase (ALOX12) gene, was closely correlated with NASH severity in humans, macaques with spontaneously developed NASH, as well as swine and mouse dietary NASH models. Using gain- and loss-of-function studies, we found that ALOX12 markedly exacerbated NASH in both mice and Bama pig models. ALOX12 was shown to induce NASH by directly targeting acetyl-CoA carboxylase 1 (ACC1) via a lysosomal degradation mechanism. Overall, our findings reveal a key molecular driver of NASH pathogenesis and suggest that ALOX12-ACC1 interaction may be a therapeutic target in NASH.

A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques.

Nonalcoholic steatohepatitis (NASH) is a progressive liver disease and has become a leading indication for liver transplantation in the United States. The development of effective therapies for NASH is a major unmet need. Here, we identified a small molecule, IMA-1, that can treat NASH by interrupting the arachidonate 12-lipoxygenase (ALOX12)­acetyl-CoA carboxylase 1 (ACC1) interaction. IMA-1 markedly blocked diet-induced NASH progression in both male mice and Cynomolgus macaque therapeutic models. The anti-NASH efficacy of IMA-1 was comparable to ACC inhibitor in both species. Protein docking simulations and following functional experiments suggested that the anti-NASH effects of IMA-1 were largely dependent on its direct binding to a pocket in ALOX12 proximal to its ACC1-interacting surface instead of inhibiting ALOX12 lipoxygenase activity. IMA-1 treatment did not elicit hyperlipidemia, a known side effect of direct inhibition of ACC enzymatic activity, in both mice and macaques. These findings provide proof of concept across multiple species for the use of small molecule­based therapies for NASH.

Cerebral Microbleed Burden in Ischemic Stroke Patients on Aspirin: Prospective Cohort of Intracranial Hemorrhage.

Objective: This investigation aimed at studying the prevalence of cerebral microbleeds (CMBs), including risk factors and the correlation of CMBs to ischemic stroke (IS) patient end results. Methods: Four hundred and fifty-nine acute IS cases were recruited between April 2014 and December 2016. Cerebral microbleeds were analyzed using susceptibility-weighted imaging (SWI) brain MRI scan. The enrolled patients with acute IS were followed up for 12-24 months, with a median follow-up time of 19 months. The follow-up endpoint events including recurrent ischemic stroke (RIS), intracranial hemorrhage (ICH), transient ischemic attack (TIA), mortality, and cardiovascular events. The associations between vascular risk factors and CMBs in IS patients were analyzed using univariate and multivariate logistic regression analysis. Cox regression model was employed for evaluating CMB impact on clinical outcome. Results: Among 459 enrolled patients, 187 (40.7%) had CMBs and 272 (59.2%) had no CMB. In comparison with patients with no CMBs, age was higher and hypertension was more frequent in patients with CMBs. Multivariate logistic regression analyses revealed age and hypertension were independently associated with the presence of CMBs. Among the patient cohort, 450 cases completed the follow-up. During the follow-up period, 22 (4.9%) of patients developed ICH, 12 (2.7%) developed TIA, 68 (15.1%) developed RIS, cardiovascular events occurred in 20 (4.44%), and 13 (2.89%) cases were mortalities. Compared with patients without CMBs, IS patients with CMBs have an increased prevalence of ICH (p < 0.05). However, no statistically valid variations regarding other outcome incidences between both groups was identified (p > 0.05). The incidence of ICH was elevated in tandem with elevations in number of CMBs. Following adjusting for age, multivariate Cox proportional-hazards regression analysis revealed that CMBs ≥10 were independent predictors of ICH in acute IS patients. Conclusion: Age and hypertension are independently associated with the presence of CMBs. Intracranial hemorrhage incidence rate was increased with the number of CMBs, and the number of CMBs ≥10 were independent predictors of ICH in acute stroke patients.

Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species.

Myocardial ischemia-reperfusion (MIR) injury is a major cause of adverse outcomes of revascularization after myocardial infarction. To identify the fundamental regulator of reperfusion injury, we performed metabolomics profiling in plasma of individuals before and after revascularization and identified a marked accumulation of arachidonate 12-lipoxygenase (ALOX12)-dependent 12-HETE following revascularization. The potent induction of 12-HETE proceeded by reperfusion was conserved in post-MIR in mice, pigs, and monkeys. While genetic inhibition of Alox12 protected mouse hearts from reperfusion injury and remodeling, Alox12 overexpression exacerbated MIR injury. Remarkably, pharmacological inhibition of ALOX12 significantly reduced cardiac injury in mice, pigs, and monkeys. Unexpectedly, ALOX12 promotes cardiomyocyte injury beyond its enzymatic activity and production of 12-HETE but also by its suppression of AMPK activity via a direct interaction with its upstream kinase TAK1. Taken together, our study demonstrates that ALOX12 is a novel AMPK upstream regulator in the post-MIR heart and that it represents a conserved therapeutic target for the treatment of myocardial reperfusion injury.

Skin-Inspired Pressure Sensor with MXene/P(VDF-TrFE-CFE) as Active Layer for Wearable Electronics.

Multi-functional electronic skin is of paramount significance for wearable electronics in health monitoring, medical analysis, and human-machine interfacing systems. In order to achieve the function of natural skin, mechanical sensing with high sensitivity is an important feature of electronic skin. Inspired by the spinosum structure under the skin, herein, we fabricate a new capacitive pressure sensor with two-dimensional transition-metal carbides and nitrides (MXene) and ferroelectric polymer (P(VDF-TrFE-CFE)) as an active layer and micropatterned Cr-Au deposited on polydimethylsiloxane as flexible electrodes. Such a method is facile, effective, easily operated, and low-cost. The device design provides great capacitive change as a consequence of large deformation under pressure. Benefiting from the randomly distributed microstructure and high dielectric constant of the active layer, the device demonstrates high sensitivity with great linearity (16.0 kPa-1 for less than 10 kPa), that is, a low detection limit of 8.9 Pa, and quick response. A series of dynamic physiological signals, including typing, knuckle motion, and voice recognition can be facilely detected, making it a competitive candidate in the field of wearable electronics.

The clinical, radiological, and immunohistochemical characteristics and outcomes of primary intracranial gliosarcoma: a retrospective single-centre study.

Primary intracranial gliosarcoma is a rare malignant brain tumour, and the most effective treatment for gliosarcoma remains unclear. This study aimed to identify risk factors for progression-free survival (PFS) and overall survival (OS) in these cases. This retrospective single-centre study evaluated 103 patients (median age, 51 years; 67 men [65%]) with primary intracranial gliosarcoma between 2006 and 2017. Treatments included surgery (GTR, 63 patients; STR, 39 patients; biopsy, 1 patient), radiotherapy (adjuvant, 76 patients; exclusive treatment, 1 patient), and chemotherapy (adjuvant temozolomide, 52 patients; adjuvant nimustine/teniposide, 19 patients; adjuvant bevacizumab, 1 patient; exclusive nimustine/teniposide treatment, 1 patient). The median OS was 13.3 months, and the median PFS was 9.1 months. In the multivariate analyses, the poor prognostic factors were ependymal lining enhancement of the lateral ventricle (PFS, HR 2.406, p = 0.005; OS, HR 2.946, p = 0.009) and enhancement in the motor functional cortex (PFS, HR 2.892, p = 0.002; OS, HR 2.639, p = 0.009). Good OS was predicted by adjuvant radiotherapy alone (HR 0.071, p < 0.001), adjuvant temozolomide-based chemotherapy alone (HR 0.063, p = 0.005), adjuvant temozolomide-based chemotherapy with concurrent radiotherapy (HR 0.056, p < 0.001), and salvage surgery at recurrence (HR 0.449, p = 0.031). The present study revealed that, in patients with primary intracranial gliosarcoma, enhancement in the functional motor cortex and ependymal lining enhancement of the lateral ventricle were both poor prognostic factors. Survival was optimized in cases treated using maximal safe resection followed by adjuvant temozolomide-based chemotherapy with concurrent radiotherapy. Furthermore, salvage surgery provided meaningful therapeutic benefits for recurrent gliosarcoma.

Surgical management and long-term outcomes of primary intracranial leiomyosarcoma: a case series and review of literature.

Primary intracranial leiomyosarcomas (PILMSs) are extremely rare neoplasms, and their management remains unclear. The authors aimed to enunciate the radiological features and design a treatment protocol based on previously published cases combined with our series. Clinical data from all 12 cases of PILMS treated at their institute between 2008 and 2018 were reviewed. Meanwhile, they searched the Ovid MEDLINE, Embase, PubMed, Web of Science and Cochrane databases using the keywords "leiomyosarcoma" and "intracranial," "central nervous system," "cerebral," or "brain" Previously published data were processed and used according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The authors' cohort included 4 males (33.3%) and 8 females (66.7%) ranging in age from 13 to 67 years with a mean of 44.1 ± 5.0 years. Gross total resection (GTR), subtotal resection, and partial resection were achieved in 8 (66.7%), 3 (25%), and 1 (8.3%) patient, respectively, and only four patients (33.3%) received adjuvant therapy after surgery. After a mean follow-up of 30.5 ± 7.6 months, 6 patients (50%) experienced recurrences, and all of them died at the final. Twenty-seven patients (15 were male and 12 were female), in the literature cases, were identified between January 1980 and November 2019, presenting with PILMS. GTR and non-GTR were achieved in 21 (77.8%) and 6 (22.2%) patients, respectively. Postoperative radiotherapy was administrated in 17 patients (63.0%), and postoperative chemotherapy was administrated in 9 patients (33.3%), After a mean follow-up of 22.2 ± 4.1 months, recurrence and death occurred in 8 (36.4%) and 4 (14.8%) cases, respectively. In the pooled cases, the univariate analysis model revealed that only GTR was a significantly favorable factor for increased progression-free survival (hazard ratio 0.270, 95% confidence interval = 0.093-0.787, p = 0.016) and overall survival (hazard ratio 0.255, 95% confidence interval = 0.073-0.890, p = 0.032). GTR was recommended as an optimal treatment; meanwhile, postoperative radiation was also a choice to help increase the survival of patients of PILMS.

Adverse Factors of Treatment Response and Overall Survival in Pediatric and Adult Patients with Pineoblastoma.

OBJECTIVE: Intracranial pineoblastomas are rare neoplasms with poor prognosis. The aim of this study was to describe the independent prognostic factors and treatment strategies for overall survival in pediatric and adult patients. METHODS: Sixty-four patients were surgically treated between January 2012 and December 2018. RESULTS: The series included 37 (57.8%) males and 27 (42.2%) females. Gross total resection was achieved in 41 (64.1%) cases, and the 1-, 3-, and 5-year rates of overall survival were 86.3, 52.3, and 36.6%, respectively. In the pediatric group (n=42), 28 patients (66.7%) were male, with the median, and the mean age was 4 and 6.2±4.7 years, respectively. After a median follow-up of 25.0 months, twenty-six patients (61.9%) died, and the 1-, 3-, and 5-year rates of overall survival were 84.9, 46.4, and 26.7%, respectively. Postoperative radiotherapy (p=0.058) and postoperative chemotherapy (p=0.183) had a positive influence on the increased overall survival. Meanwhile, postoperative radiotherapy combined with chemotherapy following surgery had a positive impact on overall survival (p=0.174, Log rank). In the adult group, the mean overall survival was 67.3±9.3 months (range, 0.8-95.3 months), and the 1-, 3-, and 5-year rates of overall survival were 89.5, 64.4, and 64.4%, respectively. In this group, no statistical association was observed between clinical factors and outcomes. However, patients who received postoperative radiotherapy (60.7 vs 57.6 month, mean survival; p=0.510, Log rank) or chemotherapy (63.0 vs 59.9 month, mean survival; p=0.404, Log rank) had better survival rates compared with those who declined. CONCLUSION: In the pediatric group, surgery with postoperative radiotherapy and chemotherapy was a favorable factor for overall survival. In the adult group, a positive trend in overall survival was found when patients received radiation and/or chemotherapy following surgery.

Natural history of brainstem cavernous malformations: prospective hemorrhage rate and adverse factors in a consecutive prospective cohort.

OBJECTIVE: Given the paucity of data on the natural history of brainstem cavernous malformations (CMs), the authors aimed to evaluate the annual hemorrhage rate and hemorrhagic risk of brainstem CMs. METHODS: Nine hundred seventy-nine patients diagnosed with brainstem CMs were referred to Beijing Tiantan Hospital from 2006 to 2015; 224 patients were excluded according to exclusion criteria, and 47 patients were lost to follow-up. Thus, this prospective observational cohort included 708 cases (324 females). All patients were registered, clinical data were recorded, and follow-up was completed. RESULTS: Six hundred ninety (97.5%) of the 708 patients had a prior hemorrhage, 514 (72.6%) had hemorrhagic presentation, and developmental venous anomaly (DVA) was observed in 241 cases (34.0%). Two hundred thirty-seven prospective hemorrhages occurred in 175 patients (24.7%) during 3400.2 total patient-years, yielding a prospective annual hemorrhage rate of 7.0% (95% CI 6.2%-7.9%), which decreased to 4.7% after the 1st year. Multivariate Cox regression analysis after adjusting for sex and age identified hemorrhagic presentation (HR 1.574, p = 0.022), DVA (HR 1.678, p = 0.001), mRS score ≥ 2 on admission (HR 1.379, p = 0.044), lesion size > 1.5 cm (HR 1.458, p = 0.026), crossing the axial midpoint (HR 1.446, p = 0.029), and superficially seated location (HR 1.307, p = 0.025) as independent adverse factors for prospective hemorrhage, but history of prior hemorrhage was not significant. The annual hemorrhage rates were 8.3% and 4.3% in patients with and without hemorrhagic presentation, respectively; the rate was 9.9%, 6.0%, and 1.0% in patients with ≥ 2, only 1, and 0 prior hemorrhages, respectively; and the rate was 9.2% in patients with both hemorrhagic presentation and focal neurological deficit on admission. CONCLUSIONS: The study reported an annual hemorrhage rate of 7.0% exclusively for brainstem CMs, which significantly increased if patients presented with both hemorrhagic presentation and focal neurological deficit (9.2%), or any other risk factor. Patients with a risk factor for hemorrhage needed close follow-up regardless of the number of prior hemorrhages. It should be noted that the referral bias in this study could have overestimated the annual hemorrhage rate. This study improved the understanding of the natural history of brainstem CMs, and the results are important for helping patients and physicians choose a suitable treatment option based on the risk factors and stratified annual rates.Clinical trial registration no.: ChiCTR-POC-17011575 (http://www.chictr.org.cn/).

Natural Growth Dynamics of Untreated Skull Base Chordomas In Vivo.

OBJECTIVE: To study the natural growth dynamics of skull base chordomas. METHODS: A retrospective study of skull base chordomas was performed. Patients with ≥2 preoperative magnetic resonance (MR) images and with pathologically confirmed chordomas were enrolled. All clinical data and MR images were studied. RESULTS: Twenty-one patients with pathologically confirmed skull base chordomas were enrolled. The mean volume of the tumors at diagnosis was 19.9 ± 17.0 cm3, with a mean interval examination period of 22.4 ± 26.1 (range, 3-113) months. The mean tumor volume change was approximately 15.4 ± 16.3 cm3. The mean specific growth rate was 8% ± 9% per month, and the mean specific growth volume was 0.8 ± 0.7 cm3 per month. The tumor MR signal index grade, female gender, no dura mater breakthrough, endophytic type, small tumors, and soft tumor texture were related to a higher tumor growth rate (P < 0.05), and small tumors showed the greatest growth rate compared with the middle-sized and large tumors. Curve estimation was performed using a power function (R2 = 0.545). CONCLUSIONS: The skull base chordoma is a slow-growing tumor. The cases involving characteristics of female gender, endophytic type, small tumor size, and MR grade 3 showed a higher growth rate.

Hepatocyte TNF Receptor-Associated Factor 6 Aggravates Hepatic Inflammation and Fibrosis by Promoting Lysine 6-Linked Polyubiquitination of Apoptosis Signal-Regulating Kinase 1.

Activation of apoptosis signal-regulating kinase 1 (ASK1) is a key driving force of the progression of nonalcoholic steatohepatitis (NASH) and represents an attractive therapeutic target for NASH treatment. However, the molecular and cellular mechanisms underlying ASK1 activation in the pathogenesis of NASH remain incompletely understood. In this study, our data unequivocally indicated that hyperactivated ASK1 in hepatocytes is a potent inducer of hepatic stellate cell (HSC) activation by promoting the production of hepatocyte-derived factors. Our previous serial studies have shown that the ubiquitination system plays a key role in regulating ASK1 activity during NASH progression. Here, we further demonstrated that tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes lysine 6 (Lys6)-linked polyubiquitination and subsequent activation of ASK1 to trigger the release of robust proinflammatory and profibrotic factors in hepatocytes, which, in turn, drive HSC activation and hepatic fibrosis. Consistent with the in vitro findings, diet-induced liver inflammation and fibrosis were substantially attenuated in Traf6+/- mice, whereas hepatic TRAF6 overexpression exacerbated these abnormalities. Mechanistically, Lys6-linked ubiquitination of ASK1 by TRAF6 facilitates the dissociation of thioredoxin from ASK1 and N-terminal dimerization of ASK1, resulting in the boosted activation of ASK1-c-Jun N-terminal kinase 1/2 (JNK1/2)-mitogen-activated protein kinase 14(p38) signaling cascade in hepatocytes. Conclusion: These results suggest that Lys6-linked polyubiquitination of ASK1 by TRAF6 represents a mechanism underlying ASK1 activation in hepatocytes and a key driving force of proinflammatory and profibrogenic responses in NASH. Thus, inhibiting Lys6-linked polyubiquitination of ASK1 may serve as a potential therapeutic target for NASH treatment.

[A Case Report of Ectopic Sweat Duct Ectasia of Conus Medullaris].

A healthy 52-year-old woman presented with 10-days history of back pain. Neurologic testing failed to detect any functional deficits in the upper and lower extremities, and the patient had a full range of cervical spine motion without associated pain. Spinal CT and MRI revealed a well-circumscribed intradural mass located at conus medullaris. The operation of L1 hemilaminectomy was performed, and pathological examination discovered dilatation of sweat ducts and suggested the diagnosis of ectopic sweat duct ectasia. IHC staining in epithelia immunophenotype showed: pan-cytokeratin (PCK)(+), epithelia membrane antigen (EMA)(+), P63(+), cytokeratin 5/6 (CK5/6)(+), gross cystic disease fluid protein 15 (GCDFP15)(-). Intraspinal ectopic sweat duct ectasia is extremely rare, which has not been reported in the literature to date.

Primary Intracranial Angioleiomyomas as Rare, Nonmalignant, and Distinct Neoplastic Entities: A Series of 8 Cases and a Literature Review.

OBJECTIVE: Primary intracranial angioleiomyoma is a rare and distinct neoplasm. Only 29 cases have been reported previously, and we aimed to investigate the clinical and radiopathologic features of these lesions. METHODS: Medical records and radiographs of 8 patients (7 male and 1 female; mean age: 48.7 years) at our institution were reviewed retrospectively. Patient follow-up and a literature review were performed. RESULTS: The most common preoperative symptom was a visual defect (n = 2), followed by diplopia (n = 1) and abducens paralysis (n = 1). Three patients were asymptomatic. The parasellar area (particularly the cavernous sinus) was the predilection site (n = 4; 50.0%). Radiographically, all lesions were solid without cystic degeneration. All lesions appeared with T1 hypointensity and T2 hyperintensity, and they were gradually heterogeneously enhanced after the administration of gadolinium. Complete resection was achieved in 7 patients (87.5%) without recurrence after 26.8 months of follow-up. Mitosis was rarely observed, and the Ki-67 labeling index was less than 1%; pathologically, the cavernous type was the most common. CONCLUSIONS: Primary intracranial angioleiomyomas were prevalent in middle-aged men, and they usually involved the cavernous sinus and were frequently pathologically identified as the cavernous type. Preoperative symptoms varied depending on lesion location. The preoperative diagnosis of primary intracranial angioleiomyomas is difficult without pathology. Digital subtraction angiography and preoperative embolization are useful for differential diagnosis and surgery. Given the indolent biology of these tumors, a favorable outcome can be achieved using total resection without recurrence. A larger sample size with long-term follow-up is needed to verify our findings.

Intradural Extramedullary Bronchogenic Cyst: Clinical and Radiologic Characteristics, Surgical Outcomes, and Literature Review.

OBJECTIVE: An intradural extramedullary bronchogenic cyst (IEBC) is a congenital malformation and an extremely rare type of endodermal cyst. This study aims to report the clinical and radiologic characteristics and surgical outcomes of IEBCs and to review the available literature. METHODS: The medical records of 6 patients (3 female) with pathologically confirmed bronchogenic cysts involving the spinal cord between 2009 and 2016 were retrospectively reviewed, and follow-up evaluations were performed. RESULTS: Of the 6 symptomatic lesions, 4 were located in the cervical vertebra, 1 at the lumbar vertebra, and the remaining 1 at the craniocervical junction. Radiographs showed signals similar to cerebral spinal fluid on all magnetic resonance imaging sequences without contrast enhancement. Total resection was achieved in 3 patients. Histopathology revealed simple and pseudostratified respiratory epithelium with benign subepithelial mucous glands and fat components neighboring the cyst. After a mean follow-up duration of 49.2 months, 2 asymptomatic residual lesions regrew after nontotal resection. In previous literature including 19 cases, most IEBCs (84.2%) tended to be homogeneous and well demarcated on radiologic images, and 85.7% were not contrast enhancing. Cervical or upper thoracic segments were predilection sites with intradural extramedullary localization. The majority of IEBCs had similar benign histological features. The recurrence rate was 15.4% after nontotal resection but nil after total resection. CONCLUSIONS: IEBCs displayed an indolent course, and the most effective management with positive outcomes was total resection. Nontotal resection, cystic fenestration, and biopsy, which were associated with recurrence, should be avoided.

Surgical Management and Outcomes of Intracranial Chondromas: a Single-Center Case Series of 66 Patients.

OBJECTIVE: Management of intracranial chondromas (ICDs) is difficult. This study aims to propose a tailored management strategy based on our management of ICDs. METHODS: A retrospective review was performed in 66 patients who received surgical operations at our institute. Clinical charts and radiographs were reviewed, follow-up was performed, and adverse factors for progression-free survival (PFS) and overall survival were evaluated. RESULTS: The preoperative and postoperative Karnofsky performance status was 81.8 and 72.3, respectively. The mean tumor size was 3.5 cm. Gross total resection was achieved in 15 patients (22.7%). Six patients (10.3%) received postoperative radiation. After a mean follow-up duration of 85.5 months, recurrence occurred to 15 patients (28.8%) with surgery alone, and no recurrence was observed in patients receiving postoperative radiotherapy. Six patients (10.3%) died due to tumor progression. The risk factors affecting the PFS included age <33 years (hazard rate [HR] 6.876; 95% confidence interval [CI] 1.599-29.560; P = 0.010), tumor size ≥3.1 cm (HR 6.138; 95% CI 1.259-29.926; P = 0.025), tumor with evident atypia/mitotic activity (HR 4.672; 95% CI 1.352-16.152; P = 0.015), and partial resection (HR 12.841; 95% CI 3.004-54.896; P = 0.001). In all patients, the PFS rate was 75% at 5 years and 64% at 10 years; in addition, the overall survival rate was 93% at 5 years and 83% at 10 years. CONCLUSIONS: The therapeutic strategy for ICDs should be individualized and should consider preoperative variables. Gross total resection was attempted if the tumors were resectable; otherwise, subtotal resection was an alternative. In patients with partial resection and evident atypia/mitotic activity, consultation with an oncologist for radiotherapy was recommended.

Curative effect of transcatheter arterial chemoembolization combined with radiofrequency ablation in treating hepatic cell carcinoma and its effect on serum markers.

BACKGROUND: Hepatic cell carcinoma (HCC) is more common in clinical practice, and has high malignant degree. OBJECTIVE: This study aims to analyze the curative effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in treating hepatic cell carcinoma (HCC) and its effect on serum markers. METHODS: A total of 106 cases of patients with hepatic cell carcinoma treated in our hospital were randomly divided into two groups: observation group and control group. Patients in the observation group (53 cases) received transcatheter arterial chemoembolization combined with radiofrequency ablation therapy, while subjects in the control group (53 cases) received transcatheter arterial chemoembolization therapy. Differences in the overall effect, indicators of inflammation and oxidative stress, tumor activity-related indicators and tumor recurrence-related indicators between these two groups were compared. RESULTS: At one and two weeks after treatment, the number of cases of CR and PR in the observation group was higher than that in the control group, the number of cases of SD was not different from that in the control group, and the number of cases of PD was lower than that in the control group. At two weeks after treatment, differences in serum MDA, SOD, GSH, CRP, TNF-α and ESR between the two groups were significant. However, serum EC, VEGF, MMP, AFP, CA199 and GGT content was significantly lower in the observation group than that in the control group. CONCLUTIONS: Transcatheter arterial chemoembolization combined with radiofrequency ablation therapy can effectively control the growth of liver cancer lesions, reduce the levels of tumor-related serum markers, and inhibit the activity of tumor cells.

Comparison of efficacy between TACE combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma: A single-center randomized controlled trial.

OBJECTIVE: This study was designed to compare the clinical efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with apatinib and TACE alone in the treatment of intermediate and advanced hepatocellular carcinoma (HCC). METHODS: From March 2015 to August 2015, a total of 44 patients with moderate and advanced HCC, who were admitted in the Navy General Hospital of China, were included into this study. These patients were randomly divided into 2 groups: group A and group B. Patients in group A underwent TACE alone, while patients in group B underwent the combined treatment of TACE with apatinib. Differences in preoperative general data between these 2 groups were not statistically significant (P > 0.05). All patients were followed up for 12-18 months. Changes in α-fetal protein (AFP) at 3 months after treatment and the objective response rate (ORR) at 3, 6, 9 and 12 months after treatment were compared between these 2 groups. Furthermore, progression-free survival (PFS) and the incidence of adverse reactions were also compared between these 2 groups. RESULTS: AFP levels in groups A and B significantly decreased after 3 months of treatment, compared with the levels before treatment, and the differences were statistically significant (P < 0.05). However, at 3 months after treatment, the difference between these 2 groups was not statistically significant (P > 0.05). ORR at 3, 6, 9 and 12 months after treatment was 36.36%, 27.27%, 13.64% and 9.09%, respectively, in group A; and 60%, 50%, 45% and 35%, respectively, in group B. At 3 and 6 months after treatment, the differences between these 2 groups were not statistically significant (P > 0.05); while at 9 and 12 months after treatment, the differences between these 2 groups were statistically significant (P < 0.05). The median PFS was 6.0 months in group A and 12.5 months in group B, and the difference was statistically significant (P < 0.05). The incidences of complications were related to oral apatinib, such as hypertension, hand-foot syndrome and proteinuria, were higher in group B than in group A, and the differences were statistically significant (P < 0.05). These symptoms all alleviated after symptomatic treatments. CONCLUSIONS: For intermediate and advanced HCC, the long-term curative effect of TACE combined with apatinib is better than that of TACE alone. The former can obviously prolong the PFS of patients and has a confirmed safety.

Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes.

OBJECTIVE The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs. METHODS This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed. RESULTS A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (χ2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336-5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275-4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic pres entation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272-9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815-6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023-15.855, p < 0.001) had a greater chance of worsened neurological status. CONCLUSIONS This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

Proposal and Validation of a Basic Progression Scoring System for Patients with Skull Base Chordoma.

OBJECTIVE: To propose and further validate a basic progression scoring system for patients with skull base chordoma. METHODS: All patients (n = 170) undergoing operation for skull base chordoma were classified randomly into a training (n = 113) or validation set (n = 57). In the training set, adverse factors for progression were analyzed by univariate and multivariate analyses. Significant independent factors were included into the scoring system. Scores for each risk category were allocated 1 point and each protection category 0 point. Three prognostic groups were formed on the basis of total score. The same scoring and grouping dispositions were made in the validation set. Analyses of the differences among the 3 groups in individual sets with regard to recurrence and the comparisons between the corresponding prognostic groups of both sets were all carried out by the Kaplan-Meier method. RESULTS: In the training set, age, treatment history, preoperative Karnofsky performance scale, pathology, and features on magnetic resonance imaging were all significant independent factors and were included into the scoring system. According to the total score, 3 prognostic groups were formed, group A (0-1 points), group B (2-3 points), and group C (3-4 points), respectively. The pairwise comparisons between every 2 of 3 groups in the training set showed significance with P < 0.001, whereas in validation set, a log-rank test showed significance, P ≤ 0.001 (log-rank test). The comparisons between the corresponding prognostic groups of both sets did not show significance. CONCLUSIONS: The basic progression scoring system for patients with skull base chordoma is valid and reproducible.