Surgical management of medial tentorial meningioma: falcotentorial and torcular

Falcotentorial meningiomas (FTM) stand out for their rarity, inconsistent definition, and surgical complexity. It is appropriate to deal with them in the context of medial tentorial meningiomas (MTM)

Metastatic Group 3 Medulloblastoma in a Patient With Tuberous Sclerosis Complex: Case Description and Molecular Characterization of the Tumor

Medulloblastoma is the most common pediatric brain tumor. We describe a child with tuberous sclerosis complex that developed a Group 3, myc overexpressed, metastatic medulloblastoma (MB). Considering the high risk of treatment-induced malignancies, a tailored therapy, omitting radiation, was given. Based on the evidence of mammalian target of rapamycin mTORC, mTOR Complex; RAS, Rat sarcoma; RAF, rapidly accelerated fibrosarcoma (mTOR) pathway activation in the tumor, targeted therapy was applied resulting in complete remission of disease. Although the PI3K/AKT/mTOR signaling pathway plays a role in MB, we did not find TSC1/TSC2 (TSC, tuberous sclerosis complex) mutation in our patient. We speculate that a different pathway resulting in mTOR activation is the basis of both TSC and MB in this child; H&E, haematoxilin and eosin; Gd, gadolinium

Weekend mortality in an Italian hospital: immediate versus delayed bedside critical care treatment

Background: a number of studies highlighted increased mortality associated with hospital admissions during weekends and holidays, the so-call "weekend effect". In this retrospective study of mortality in an acute care public hospital in Italy between 2009 and 2015, we compared inpatient mortality before and after a major organizational change in 2012. The new model (Model 2) implied that the intensivist was available on call from outside the hospital during nighttime, weekends, and holidays. The previous model (Model 1) ensured the presence of the intensivist coordinating a Medical Emergency Team (MET) inside the hospital 24 h a day, 7 days a week. Methods: life status at discharge after 9298 and 8223 hospital admissions that occurred during two consecutive periods of 1185 days each (organizational Model 1 and 2), respectively, were classified into "discharged alive", "deceased during nighttime-weekends-holidays" and "deceased during daytime-weekdays". We estimated Relative Risk Ratios (RRR) for the associations between the organizational model and life status at discharge using multinomial logistic regression models adjusted for demographic and case-mix indicators, and timing of admission (nighttime-weekends-holidays vs. daytime-weekdays). Results: there were 802 and 840 deaths under Models 1 and 2, respectively. Total mortality was higher for hospital admissions under Model 2 compared to Model 1. Model 2 was associated with a significantly higher risk of death during nighttime-weekends-holidays (IRR: 1.38, 95% CI 1.20-1.59) compared to daytime-weekdays (RRR: 1.12, 95% CI 0.97-1.31) (p = 0.04). Respiratory diagnoses, in particular, acute and chronic respiratory failure (ICD 9 codes 510-519) were the leading causes of the mortality excess under Model 2. Conclusions: our data suggest that the immediate availability of an intensivist coordinating a MET 24 h, 7 days a week can result in a better prognosis of in-hospital emergencies compared to delayed consultation

MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors

MRE11 is a component of the MRE11/RAD50/NBS1 (MRN) complex, whose activity is essential to control faithful DNA replication and to prevent accumulation of deleterious DNA double-strand breaks. In humans, hypomorphic mutations in these genes lead to DNA damage response (DDR)-defective and cancer-prone syndromes. Moreover, MRN complex dysfunction dramatically affects the nervous system, where MRE11 is required to restrain MYCN-dependent replication stress, during the rapid expansion of progenitor cells. MYCN activation, often due to genetic amplification, represents the driving oncogenic event for a number of human tumors, conferring bad prognosis and predicting very poor responses even to the most aggressive therapeutic protocols. This is prototypically exemplified by neuroblastoma, where MYCN amplification occurs in about 25% of the cases. Intriguingly, MRE11 is highly expressed and predicts bad prognosis in MYCN-amplified neuroblastoma. Due to the lack of direct means to target MYCN, we explored the possibility to trigger intolerable levels of replication stress-dependent DNA damage, by inhibiting MRE11 in MYCN-amplified preclinical models. Indeed, either MRE11 knockdown or its pharmacological inhibitor mirin induce accumulation of replication stress and DNA damage biomarkers in MYCN-amplified cells. The consequent DDR recruits p53 and promotes a p53-dependent cell death, as indicated by p53 loss- and gain-of-function experiments. Encapsulation of mirin in nanoparticles allowed its use on MYCN-amplified neuroblastoma xenografts in vivo, which resulted in a sharp impairment of tumor growth, associated with DDR activation, p53 accumulation, and cell death. Therefore, we propose that MRE11 inhibition might be an effective strategy to treat MYCN-amplified and p53 wild-type neuroblastoma, and suggest that targeting replication stress with appropriate tools should be further exploited to tackle MYCN-driven tumors

Recurrent atypical meningiomas: combining surgery and radiosurgery in one effective multimodal treatment

OBJECTIVE: Owing to their rarity and proteiform pathologic features, the clinical behavior of atypical meningiomas is not yet well characterized. Though the extent of resection is believed to be a key determinant of prognosis, limited data exist regarding optimal management of patients with recurrent disease. METHODS: In this 20-year retrospective case series, we reviewed the medical records of 46 patients with recurrent atypical meningiomas (185 lesions, 89 of which were local, 78 marginal, and 18 distant recurrences); treatment was radiosurgery (n = 60), surgery (n = 56), or both (n = 8). The median follow-up period was 53 months. Outcome measures were length of overall survival and disease-free intervals and prognostic factors for survival. RESULTS: Overall, the median progression-free survival was 26 months at the first recurrence and 100 months thereafter (the sum of the later intervals). Multivariate analysis showed that no treatment-related factors influenced prognosis, whereas recurrence at the skull base was a significant tumor-related factor limiting further treatment. Irrespective of treatment type, the recurrence-free interval was increasingly shorter during the clinical course, with a higher occurrence of marginal and distant lesions migrating to the midline and to the skull base. In sporadic cases, disease-free intervals were longer after wide craniotomy, tumor and dural resection with tumor-free margin. CONCLUSIONS: The disease-free interval was substantially similar after surgery and radiosurgery for treating recurrent disease in patients with atypical meningiomas. Surgery is the mainstay for prolonging survival, while radiosurgery can be an adjuvant strategy to gain time for clinical observation and planning aggressive surgical treatment

A HST study of the environment of the Herbig Ae/Be star LkHa 233 and its bipolar jet

We present the results of HST/STIS and WFPC2 observations of LkHa 233 and its environment. LkHa233 is a Herbig Ae/Be star with a collimated bipolar jet. We investigate optical forbidden lines along the LkHa 233 jet to determine physical parameters of this jet (electron density n_e, hydrogen ionisation fraction x_e, electron temperature T_e, and mass density n_H). The knowledge of these parameters allows us a direct comparison of a jet from a Herbig star with those from T Tauri stars. The WFPC2 images in broad-band filters clearly show a dark lane caused either by a circumstellar disk or a dust torus. In the blueshifted lobe, n_e is close to or above the critical density for [SII] lines (2.5x10^4 cm^-3) in the first arcsecond and decreases with distance from the source. The ionisation x_e~0.2-0.6 gently rises for the first 500 AU of the flow and shows two re-ionisation events further away from the origin. The T_e varies along the flow between 10^4 K and 3x10^4 K. The (radial) outflow velocities are ~ 80-160 km s^(-1), and they appear to increase with distance from the source. In the redshifted lobe, T_e, n_e, x_e, and n_H are all lower than in the blueshifted lobe, but have the same order of magnitude. All these derived parameters are just beyond or at the upper limits of those observed for classical T Tauri star jets. This may indicate that the flows from the higher mass Herbig stars are indeed scaled-up examples of the same phenomenon as in T Tauri stars.Comment: 21 pages, 5 figures, accepted for publication in the Astronomy and Astrophysic

Anomalous vascularization in a Wnt medulloblastoma: A case report

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. To date only few cases of medulloblastoma with hemorrhages have been reported in the literature. Although some studies speculate on the pathogenesis of this anomalous increased vascularization in medulloblastoma, the specific mechanism is still far from clearly understood. A correlation between molecular medulloblastoma subgroups and hemorrhagic features has not been reported, although recent preliminary studies described that WNT-subtype tumors display increased vascularization and hemorrhaging. CASE PRESENTATION: Herein, we describe a child with a Wnt-medulloblastoma presenting as cerebellar-vermian hemorrhagic lesion. Brain magnetic resonance imaging (MRI) showed the presence of a midline posterior fossa mass with a cystic hemorrhagic component. The differential diagnosis based on imaging included cavernous hemangioma, arteriovenous malformation and traumatic lesion. At surgery, the tumor appeared richly vascularized as documented by the preoperative angiography. CONCLUSIONS: The case we present showed that Wnt medulloblastoma may be associated with anomalous vascularization. Further studies are needed to elucidate if there is a link between the hypervascularization and the Wnt/β-catenin signaling activation and if this abnormal vasculature might influence drug penetration contributing to good prognosis of this medulloblastoma subgroup

Ductal invasive carcinoma arising within atypical microglandular adenosis in a patient with BRCA-1 mutation: A case report

Abstract Microglandular adenosis (MGA) of the breast is a benign lesion that may mimic invasive carcinoma and which has been proposed to be a potential precursor of a well defined subset of triple-negative and basal-like breast carcinomas, characterized by specific expression of both basal and luminal markers (positive for EGFr and luminal cytokeratins such as CK 8/18, negative for high molecular weight cytokeratins such as CK 5/6), with a crucial role played by p53 mutation as "driver mutation" in the multistep model of cancerization. When an invasive carcinoma arises in a background of MGA, it is possible to identify a clear multistep transition from conventional MGA to atypical MGA (AMGA), Ductal Carcinoma In Situ (DCIS) arising within AMGA and invasive carcinoma. This is the first histological case report of an invasive carcinoma arising within MGA and AMGA in a patient carrying a germline BRCA-1 mutation, recognized as one of the most important genetic alterations correlated with the development of triple-negative carcinoma

Complex dynamics in simplified neuronal models: reproducing Golgi cell electroresponsiveness

Brain neurons exhibit complex electroresponsive properties – including intrinsic subthreshold oscillations and pacemaking, resonance and phase-reset – which are thought to play a critical role in controlling neural network dynamics. Although these properties emerge from detailed representations of molecular-level mechanisms in “realistic” models, they cannot usually be generated by simplified neuronal models (although these may show spike-frequency adaptation and bursting). We report here that this whole set of properties can be generated by the extended generalized leaky integrate-and-fire (E-GLIF) neuron model. E-GLIF derives from the GLIF model family and is therefore mono-compartmental, keeps the limited computational load typical of a linear low-dimensional system, admits analytical solutions and can be tuned through gradient-descent algorithms. Importantly, E-GLIF is designed to maintain a correspondence between model parameters and neuronal membrane mechanisms through a minimum set of equations. In order to test its potential, E-GLIF was used to model a specific neuron showing rich and complex electroresponsiveness, the cerebellar Golgi cell, and was validated against experimental electrophysiological data recorded from Golgi cells in acute cerebellar slices. During simulations, E-GLIF was activated by stimulus patterns, including current steps and synaptic inputs, identical to those used for the experiments. The results demonstrate that E-GLIF can reproduce the whole set of complex neuronal dynamics typical of these neurons – including intensity-frequency curves, spike-frequency adaptation, post-inhibitory rebound bursting, spontaneous subthreshold oscillations, resonance, and phase-reset – providing a new effective tool to investigate brain dynamics in large-scale simulations

Pnictogens Allotropy and Phase Transformation during van der Waals Growth

Pnictogens have multiple allotropic forms resulting from their ns2 np3 valence electronic configuration, making them the only elemental materials to crystallize in layered van der Waals (vdW) and quasi-vdW structures throughout the group. Light group VA elements are found in the layered orthorhombic A17 phase such as black phosphorus, and can transition to the layered rhombohedral A7 phase at high pressure. On the other hand, bulk heavier elements are only stable in the A7 phase. Herein, we demonstrate that these two phases not only co-exist during the vdW growth of antimony on weakly interacting surfaces, but also undertake a spontaneous transformation from the A17 phase to the thermodynamically stable A7 phase. This metastability of the A17 phase is revealed by real-time studies unraveling its thickness-driven transition to the A7 phase and the concomitant evolution of its electronic properties. At a critical thickness of ~4 nm, A17 antimony undergoes a diffusionless shuffle transition from AB to AA stacked alpha-antimonene followed by a gradual relaxation to the A7 bulk-like phase. Furthermore, the electronic structure of this intermediate phase is found to be determined by surface self-passivation and the associated competition between A7- and A17-like bonding in the bulk. These results highlight the critical role of the atomic structure and interfacial interactions in shaping the stability and electronic characteristics of vdW layered materials, thus enabling a new degree of freedom to engineer their properties using scalable processes