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Author(s): Cristian Fidanzi (corresponding author) [1]; Flavia Manzo Margiotta [1]; Matteo Bevilacqua [1]; Valerio Ortenzi [2]; Valerio Rocchi [3]; Giammarco Granieri [1]; Marco Romanelli [1]; Elisabetta Manni [1] Case Presentation [...]

Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch signaling, populate tumors regardless of local vascularity and selectively utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis and resistance to hypoxia. These findings demonstrate a novel role for Notch signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity ensures metabolic adaptations to support tumor growth in diverse tumor microenvironments.

Dysplastic nevi represent one of the least agreed-upon entities in dermatopathology despite the existence of established criteria. This study explores preferentially expressed antigen in melanoma (PRAME) in dysplastic nevi, an uncharted area. We examined 22 common melanocytic nevi (CMN), 20 cutaneous melanomas (CM), 48 low-grade dysplastic nevi (LG-DN), and 40 high-grade dysplastic nevi (HG-DN). PRAME was immunohistochemically assessed using a five-tiered system (0 to 4 +). Among CMN, 59% scored 0, 32% scored 1 + , and 9% scored 2 +. CM had score 2 + and 4 + in 11% and 89% of cases, respectively. Among LG-DN, 38% presented score 0, 31% score 1 + , 17% score 2 + , 8% score 3 + , and 6% score 4 +. Thirty per cent of HG-DN demonstrated a score 0, 30% with score 1 + , 15% score 2 + , 10% score 3 + , and 15% score 4 +. Compared to CMN and CM, LG-DN and HG-DN showed heterogeneous expression profiles of PRAME. PRAME positivity effectively distinguished HG-DN from CM with 85% specificity and 80% sensitivity (p < 0.0001). Predictive values were 87% (negative) and 76% (positive). Furthermore, a trend of increased PRAME expression from LG-DN to HG-DN was observed. However, the applicability of PRAME in the differential diagnosis of dysplastic lesions remains unclear as can yield conflicting results with morphology, which remains the primary diagnostic tool for melanocytic lesions. [ABSTRACT FROM AUTHOR]

Teleoperation allows workers to safely control powerful construction machines; however, its primary reliance on visual feedback limits the operator's efficiency in situations with stiff contact or poor visibility, hindering its use for assembly of pre-fabricated building components. Reliable, economical, and easy-to-implement haptic feedback could fill this perception gap and facilitate the broader use of robots in construction and other application areas. Thus, we adapted widely available commercial audio equipment to create AiroTouch, a naturalistic haptic feedback system that measures the vibration experienced by each robot tool and enables the operator to feel a scaled version of this vibration in real time. Accurate haptic transmission was achieved by optimizing the positions of the system's off-the-shelf accelerometers and voice-coil actuators. A study was conducted to evaluate how adding this naturalistic type of vibrotactile feedback affects the operator during telerobotic assembly. Thirty participants used a bimanual dexterous teleoperation system (Intuitive da Vinci Si) to build a small rigid structure under three randomly ordered haptic feedback conditions: no vibrations, one-axis vibrations, and summed three-axis vibrations. The results show that users took advantage of both tested versions of the naturalistic haptic feedback after gaining some experience with the task, causing significantly lower vibrations and forces in the second trial. Subjective responses indicate that haptic feedback increased the realism of the interaction and reduced the perceived task duration, task difficulty, and fatigue. As hypothesized, higher haptic feedback gains were chosen by users with larger hands and for the smaller sensed vibrations in the one-axis condition. These results elucidate important details for effective implementation of naturalistic vibrotactile feedback and demonstrate that our accessible audio-based approach could enhance user performance and experience during telerobotic assembly in construction and other application domains. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter 2 inhibitors have proven strong efficacy in reducing end-stage renal disease in patients with type 2 diabetes. We are presenting here the case of a 40-year-old woman with acquired partial lipodystrophy, type 2 diabetes and essential hypertension complicated by chronic kidney disease and proteinuria in the nephrotic range. She first came to our attention in 2012; estimated glomerular filtration rate (eGFR) was 41.5 ml/ min/1.73 m2 and total proteinuria was 375 mg/24h; she was treated with dual renin angiotensin system blocking. Proteinuria significantly increased during the following years, reaching a nephrotic range (>5 g/day). A kidney biopsy revealed a tubule-interstitial involvement compatible with type 2 diabetes. Leptin replacement therapy, started in 2018, improved glycaemic control and lipid profile, also determining a reduction in insulin total daily dose. In 2019, after the publication of the CREDENCE study, canagliflozin was started on top of losartan and ramipril. After an initial, expected eGFR drop, kidney function stabilized, and albuminuria significantly reduced (from 4120 to 984 mg/24h), while serum potassium showed only minimal increase. At last follow-up (2022) total proteinuria was still reducing (510 mg/24h), while kidney function was substantially unchanged (eGFR 40 ml/min/1.73 m2). This case report suggests that, despite not recommended in international guidelines, the use of SGLT2i in combination with dual renin angiotensin system blockade should be considered in specific conditions and under close clinical monitoring. [ABSTRACT FROM AUTHOR]

Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (p < 0.0001 and p = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (rs = 0.417—p = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, p = 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, p = 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, p = 0.006). Adjuvant treatment, methylguanine methyltransferase (MGMT) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM. [ABSTRACT FROM AUTHOR]

Background: Tanycytic ependymoma is a rare variant of ependymoma that commonly affects the cervical and thoracic spinal cord. It usually arises as intramedullary lesions and extramedullary cases are extremely rare. Case Description: We present a 77-year-old woman with the complaints of a 2-year history of progressive paraparesis and sensory loss in her lower extremities. Magnetic resonance imaging revealed a stretched and fusiform intradural extramedullary lesion at T5-T10 level. Gross total removal of the tumor was achieved and a definitive diagnosis of tanycytic ependymoma was established. Conclusion: This case thus represents a rare case of thoracic intradural extramedullary tanycytic ependymoma and, to the best of our knowledge, it represents the longest intradural extramedullary tanycytic ependymoma in craniocaudal direction ever reported in the literature. [ABSTRACT FROM AUTHOR]

This article surveys the literature on human–robot object handovers. A handover is a collaborative joint action, where an agent, the giver, gives an object to another agent, the receiver. The physical exchange starts when the receiver first contacts the object held by the giver and ends when the giver fully releases the object to the receiver. However, important cognitive and physical processes begin before the physical exchange, including initiating implicit agreement with respect to the location and timing of the exchange. From this perspective, we structure our review into the two main phases delimited by the aforementioned events: a prehandover phase and the physical exchange. We focus our analysis on the two actors (giver and receiver) and report the state of the art of robotic givers (robot-to-human handovers) and the robotic receivers (human-to-robot handovers). We report a comprehensive list of qualitative and quantitative metrics commonly used to assess the interaction. While focusing our review on the cognitive level (e.g., prediction, perception, motion planning, and learning) and the physical level (e.g., motion, grasping, and grip release) of the handover, we also discuss safety. We compare the behaviors displayed during human-to-human handovers to the state of the art of robotic assistants and identify the major areas of improvement for robotic assistants to reach performance comparable to human interactions. Finally, we propose a minimal set of metrics that should be used in order to enable a fair comparison among the approaches. [ABSTRACT FROM AUTHOR]

We address the problem of shaping deformable plastic materials using non-prehensile actions. Shaping plastic objects is challenging, because they are difficult to model and to track visually. We study this problem, by using kinetic sand, a plastic toy material that mimics the physical properties of wet sand. Inspired by a pilot study where humans shape kinetic sand, we define two types of actions: pushing the material from the sides and tapping from above. The chosen actions are executed with a robotic arm using image-based visual servoing. From the current and desired view of the material, we define states based on visual features such as the outer contour shape and the pixel luminosity values. These are mapped to actions, which are repeated iteratively to reduce the image error until convergence is reached. For pushing, we propose three methods for mapping the visual state to an action. These include heuristic methods and a neural network, trained from human actions. We show that it is possible to obtain simple shapes with the kinetic sand, without explicitly modeling the material. Our approach is limited in the types of shapes it can achieve. A richer set of action types and multi-step reasoning is needed to achieve more sophisticated shapes. [ABSTRACT FROM AUTHOR]

Laser capture microdissection (LCM) coupled with RNA-seq is a powerful tool to identify genes that are differentially expressed in specific histological tumor subtypes. To better understand the role of single tumor cell populations in the complex heterogeneity of glioblastoma, we paired microdissection and NGS technology to study intra-tumoral differences into specific histological regions and cells of human GBM FFPE tumors. We here isolated astrocytes, neurons and endothelial cells in 6 different histological contexts: tumor core astrocytes, pseudopalisading astrocytes, perineuronal astrocytes in satellitosis, neurons with satellitosis, tumor blood vessels, and normal blood vessels. A customized protocol was developed for RNA amplification, library construction, and whole transcriptome analysis of each single portion. We first validated our protocol comparing the obtained RNA expression pattern with the gene expression levels of RNA-seq raw data experiments from the BioProject NCBI database, using Spearman's correlation coefficients calculation. We found a good concordance for pseudopalisading and tumor core astrocytes compartments (0.5 Spearman correlation) and a high concordance for perineuronal astrocytes, neurons, normal, and tumor endothelial cells compartments (0.7 Spearman correlation). Then, Principal Component Analysis and differential expression analysis were employed to find differences between tumor compartments and control tissue and between same cell types into distinct tumor contexts. Data consistent with the literature emerged, in which multiple therapeutic targets significant for glioblastoma (such as Integrins, Extracellular Matrix, transmembrane transport, and metabolic processes) play a fundamental role in the disease progression. Moreover, specific cellular processes have been associated with certain cellular subtypes within the tumor. Our results are promising and suggest a compelling method for studying glioblastoma heterogeneity in FFPE samples and its application in both prospective and retrospective studies. [ABSTRACT FROM AUTHOR]

Background: Bladder cancer (BC) is the 9th most common cancer diagnosis worldwide. Low grade (LG) represents 70% of all BCs, characterized by recurrence and rare ability (10–15%) to progress to high grade (HG) and invade. The remaining 30% is high grade (HG), fast invasive BC, which is resistant to therapy. Identifying biomarkers for predicting those tumors able to progress is a key goal for patient outcome improvement. This study focuses on the most promising prognostic markers. Materials and methods: TP53 and FGFR3 mutational status, Survivin, CK19, CK20, E-cadherin and CD44 gene expression analysis were performed on 66 BCs. Results: Survivin was found associated to tumor grade (p<0.05). Moreover, Survivin correlated with CD44 in TP53 wild type (p = 0.0242) and FGFR3 wild type (p = 0.0036) tumors. In particular the Survivin-CD44 correlation was associated to HG FGFR3 wild type BCs (p = 0.0045). Unsupervised hierarchical clustering based on gene expression data identified four distinct molecular groups reflecting the patient histology (p = 0.038). Conclusion: We suggest Survivin, both as a biomarker associated to G3 BCs but negatively related to TP53 mutational status, and as a potential novel therapeutic target. [ABSTRACT FROM AUTHOR]

This paper addresses the problem of estimating the configuration of robots with no proprioceptive sensors and with kinematic constraints while performing tasks. Our work is motivated by the use of unsensored (industrial) manipulators, currently teleoperated in rudimentary ways, in hazardous environments, such as nuclear decommissioning. For such robots, basic proprioceptive sensors are often unavailable. Even if radiation-hardened sensors could be retrofitted, such manipulators are typically deployed on a mobile base, while equipped with powerful end-effector tools for forceful contact tasks, which significantly perturb the robot base. This work contributes a step towards enabling advanced control and increased autonomy in nuclear applications, but could also be applied to mechanically compliant, under-actuated arms and hands, and soft manipulators. Our proposed framework: estimates the robot configuration by casting it as an optimization problem using visually tracked information; detects contacts during task execution; triggers an exploration task for detected kinematic constraints, which are then modelled by comparing observed versus commanded velocity vectors. Unlike previous literature, no additional sensors are required. We demonstrate our method on a KUKA iiwa 14 R820, reliably estimating and controlling robot motions and checking our estimates against ground truth values, and accurately reconstructing kinematic constraints. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate if swab sampling was trustable and comparable to bone specimen in multidrug resistant (MDR) diabetic foot (DF) osteomyelitis (OM). Method: We prospectively evaluated all the consecutive patients undergoing to bone resection in operatory room for OM between July and December 2021 in our Department. From all patients deep swab sampling was collected immediately before the surgery according to guidelines procedures (SS) and intraoperative bone specimens were collected for microbiological analysis (BS). Results were compared, searching for the prevalence of Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA) and Enterobacteriae (EB), sorting out Methicillin-Resistant SA (MRSA), PA resistant to Ciprofloxacin (CiproRPA) and Carbapenem (CRPA), EB resistant to Ciprofloxacin (CiproRE) or Extended Spectrum Beta Lactamase producers (ESBL). Results / Discussion: We derived data from 46 patients underwent to surgical procedures: SA was detected in 29 patients in SS (63.0%) and 31 in BS (67.4% - p=ns), PA in 21 patients in SS (45.6%) and 22 in BS (47.8%, p=ns) and EB in 25 patients in SS (54.3% and 26 in BS (56.5% - p=ns). No difference was detected also in microbial susceptibility comparing swab and bone specimens particularly regarding: MRSA (55.1% vs 54.8%, p=ns), CiproRPA (47.6% vs 45.4%, p=ns), CRPA (28.5% vs 31.8%, p=ns), CiproRE (44.0% vs 42.3%, p=ns), and ESBL (56.0% vs 53.8%, p=ns). Conclusion: When correctly performed, swab sampling is able to detect bacterial strains and susceptibility with results superimposable to intraoperative bone specimens. [ABSTRACT FROM AUTHOR]

Aim: We aimed to evaluate if a proactive multidisciplinary diagnostic program could improve outcomes in the management of multidrug resistant (MDR) diabetic foot (DF) osteomyelitis (OM). Method: We evaluated all the consecutive patients undergoing to minor amputation for OM July-December 2021 in our department (Group A). Intraoperative bone specimens were collected for microbiological and histological analysis on whose results antibacterial therapy was decided. Controls were patients admitted January-June 2021 with same indications (Group B) but with no systematic intraoperative bone sampling. Clinical and demographic characteristics, procedures, healing rate (HR) and healing time (HT), were compared between the groups. Results / Discussion: We derived data from 89 patients: 46 in Group A [51.7%; age 68.8±13.5 yrs; diabetes duration (DD) 19.6±11.6 yrs Hba1c 8.7±4.8%;] and 43 in Group B (48.3%; age 70.4±12.9 yrs; DD 18.8±12.1 yrs; Hba1c 8.4±5.1%). No differences in demographic and clinical features, i.e. renal failure (39.1% vs 37.2%, p=ns), ischemic cardiac disease (41.3% vs 39.5%, p=ns), peripheral arterial disease (65.2% vs 67.4%, p=ns) and peripheral revascularizations (56.5% vs 53.4%, p=ns). Group A had a higher healing rate (80.4% vs 60.4%, p=0.0021) and a shorter healing time (67±41 days vs 134±92 days, p=0.020) compared to Group B. Conclusion: Systematic intraoperative bone sampling for culture and histology, and consequent antibiotic adaptation, increases healing rates and reduces healing times in DF patients submitted to minor amputations for OM. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) is the most aggressive type of primary brain tumor. Despite the progress in recent years regarding the diagnosis and treatment of GB, the recurrence rate remains high, due to the infiltrative and dispersive nature of the tumor, which typically results in poor patient prognosis. In the present study, 19 formalin-fixed, paraffin-embedded GB samples were selected from patients with GB tumors. The samples were classified into a short or long recurrence-free survival (RFS) group, based on the time of first recurrence of the disease in the patients. The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. Then, the expression of 84 genes involved in cell-cell and cell-matrix interactions, and that of 84 microRNAs (miRNAs) associated with brain cancer, was profiled. In addition, a copy number variation analysis of 23 genes reported to undergo frequent genomic alterations in human glioma was also performed. Differences in the expression levels of a number of genes were detected across the short and long RFS groups. Among these genes, 5 in particular were selected, and a 5-genes combination approach was developed, which was able to differentiate between patients with short and long RFS outcome. The high levels of sensitivity and precision displayed by this 5-genes combination approach, which were confirmed with a cross-validation method, provide a strong foundation for further validation of the involvement of the aforementioned genes in GB in a larger patient population. In conclusion, the present study has demonstrated how the expression pattern of miRNAs and mRNAs in patients with GB defines a particular molecular hallmark that may increase or reduce the aggressive behavior of GB tumors, thus influencing the survival rates of patients with GB, their response to therapy and their tendency to suffer a relapse. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common and aggressive primary brain malignancy in adults. In addition to extensive inter-patient heterogeneity, glioblastoma shows intra-tumor extensive cellular and molecular heterogeneity, both spatially and temporally. This heterogeneity is one of the main reasons for the poor prognosis and overall survival. Moreover, it raises the important question of whether the molecular characterization of a single biopsy sample, as performed in standard diagnostics, actually represents the entire lesion. In this study, we sequenced the whole exome of nine spatially different cancer regions of three primary glioblastomas. We characterized their mutational profiles and copy number alterations, with implications for our understanding of tumor biology in relation to clonal architecture and evolutionary dynamics, as well as therapeutically relevant alterations. Glioblastoma is one of the most common and lethal primary neoplasms of the brain. Patient survival has not improved significantly over the past three decades and the patient median survival is just over one year. Tumor heterogeneity is thought to be a major determinant of therapeutic failure and a major reason for poor overall survival. This work aims to comprehensively define intra- and inter-tumor heterogeneity by mapping the genomic and mutational landscape of multiple areas of three primary IDH wild-type (IDH-WT) glioblastomas. Using whole exome sequencing, we explored how copy number variation, chromosomal and single loci amplifications/deletions, and mutational burden are spatially distributed across nine different tumor regions. The results show that all tumors exhibit a different signature despite the same diagnosis. Above all, a high inter-tumor heterogeneity emerges. The evolutionary dynamics of all identified mutations within each region underline the questionable value of a single biopsy and thus the therapeutic approach for the patient. Multiregional collection and subsequent sequencing are essential to try to address the clinical challenge of precision medicine. Especially in glioblastoma, this approach could provide powerful support to pathologists and oncologists in evaluating the diagnosis and defining the best treatment option. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. Despite the combination of novel therapeutical approaches, it remains a deadly malignancy with an abysmal prognosis. GBM is a polymorphic tumour from both molecular and histological points of view. It consists of different malignant cells and various stromal cells, contributing to tumour initiation, progression, and treatment response. GBM's microenvironment is multifaceted and is made up of soluble factors, extracellular matrix components, tissue-resident cell types (e.g., neurons, astrocytes, endothelial cells, pericytes, and fibroblasts) together with resident (e.g., microglia) or recruited (e.g., bone marrow-derived macrophages) immune cells. These latter constitute the so-called immune microenvironment, accounting for a substantial GBM's tumour volume. Despite the abundance of immune cells, an intense state of tumour immunosuppression is promoted and developed; this represents the significant challenge for cancer cells' immune-mediated destruction. Though literature data suggest that distinct GBM's subtypes harbour differences in their microenvironment, its role in treatment response remains obscure. However, an in-depth investigation of GBM's microenvironment may lead to novel therapeutic opportunities to improve patients' outcomes. This review will elucidate the GBM's microenvironment composition, highlighting the current state of the art in immunotherapy approaches. We will focus on novel strategies of active and passive immunotherapies, including vaccination, gene therapy, checkpoint blockade, and adoptive T-cell therapies. [ABSTRACT FROM AUTHOR]

Purpose. Is it possible a correlation between some periprosthetic femoral fractures and atypical fractures? Case. We present a case of a 77-year-old woman with atypical periprosthetic femoral fracture. The patient had a history of long-term bisphosphonate use. We performed an open reduction, a synthesis of the fracture and a histological exam. The patient stopped the bisphosphonate (BF) therapy. Three months later, before starting the teriparatide treatment, the patient had a re-fracture so we did a second osteosynthesis and began a teriparatide therapy. After six months, the radiography showed a bone healing at the fracture site. Result. The histological examination confirmed the diagnosis of atypical femoral fracture. Conclusion. At first, the fracture showed a delayed union which led to a new surgery, as often happens in BF-related atypical fractures. Appropriate treatment (BF suspension and teriparatide beginning) permitted fracture healing. The atypical characteristic of the fracture was confirmed by histological exam. Some periprosthetic femoral fractures in patients treated with BF, especially in long time therapies, should be suspected as atypical fractures and a specific medical treatment should be performed, as well as a correct surgical treatment. [ABSTRACT FROM AUTHOR]

Task-aware robotic grasping is critical if robots are to successfully cooperate with humans. The choice of a grasp is multi-faceted; however, the task to perform primes this choice in terms of hand shaping and placement on the object. This grasping strategy is particularly important for a robot companion, as it can potentially hinder the success of the collaboration with humans. In this work, we investigate how different grasping strategies of a robot passer influence the performance and the perceptions of the interaction of a human receiver. Our findings suggest that a grasping strategy that accounts for the subsequent task of the receiver improves substantially the performance of the human receiver in executing the subsequent task. The time to complete the task is reduced by eliminating the need of a post-handover re-adjustment of the object. Furthermore, the human perceptions of the interaction improve when a task-oriented grasping strategy is adopted. The influence of the robotic grasp strategy increases as the constraints induced by the object's affordances become more restrictive. The results of this work can benefit the wider robotics community, with application ranging from industrial to household human-robot interaction for cooperative and collaborative object manipulation., (Copyright © 2020 Ortenzi, Cini, Pardi, Marturi, Stolkin, Corke and Controzzi.)

Solitary fibrous tumors (SFTs) are uncommon mesenchymal lesions originally described as pleura-based neoplasms. Intradural juxtamedullary SFTs are rare, hard, and scarcely vascularized and generally present a conspicuous extramedullary exophytic component without dural attachment and nerve root involvement. Gross-total resection is the mainstay of treatment, although the absence of an arachnoidal plane and the firm adherence to the spinal cord make resection challenging.  We describe the case of a 74-yr-old female patient presenting with a history of progressive spastic tetraparesis due to a cervical juxtamedullary SFT. The patient was not able to walk and magnetic resonance imaging (MRI) of the cervical spine demonstrated a possible intramedullary lesion at C2-C3 with homogeneous enhancement after gadolinium injection. Given the progressive nature of symptoms, the patient elected to have surgical resection of the tumor. The patient underwent C2-C3 laminoplasty and tumor resection under neurophysiologic monitoring. The tumor presented extremely hard without dural attachment or nerve root involvement and was progressively debulked using microsurgical techniques and ultrasonic aspirator. The identification of a plane between the mass and the spinal cord white matter allowed for a gross total resection. Permanent pathological analysis eventually demonstrated SFT. The patient's neurological condition was unchanged postoperatively. MRI performed 2 mo after the operation demonstrated gross total resection of the lesion. At the 6-mo follow-up visit, the patient was able to walk with assistance.  The patient signed the Institutional Consent Form to undergo the surgical procedure and to allow the use of her images and videos for any type of medical publications., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Glioblastoma is a devastating disease that despite all the information gathered so far, its optimal management remains elusive due to the absence of validated targets from clinical studies. A better clarification of the molecular mechanisms is needed. In this study, having access to IDH1 wild-type glioblastoma of patients with exceptionally long recurrence free survival (RFS), we decided to compare their mutational and gene expression profile to groups of IDH1 wild-type glioblastoma of patients with shorter RFS, by using NGS technology. The exome analysis revealed that Long-RFS tumors have a lower mutational rate compared to the other groups. A total of 158 genes were found differentially expressed among the groups, 112 of which distinguished the two RFS extreme groups. Overall, the exome data suggests that shorter RFS tumors could be, chronologically, in a more advanced state in the muli-step tumor process of sequential accumulation of mutations. New players in this kind of cancer emerge from the analysis, confirmed at the RNA/DNA level, identifying, therefore, possible oncodrivers or tumor suppressor genes., Competing Interests: CONFLICTS OF INTEREST There is no conflicts of interest in this study.

In this paper we report on a successful management of multiple bone metastases from differentiated thyroid cancer. In 2007, a 75-year-old female patient, previously referred for thyroidectomy for multinodular goiter, underwent surgical removal of a lumbar mass with histological findings of metastasis from well differentiated thyroid cancer. After surgery, serum thyroglobulin (sTg) was 204.4 ng/mL. A diagnostic/dosimetric (123)I WBS was performed, following stimulation by rTSH. Serial WBSs were acquired, along with SPECT/CT and bone scan for localization of lesions. sTg raised to 3.810 ng/mL, and (123)I WBS showed thyroid remnants and numerous areas with high iodine-uptake corresponding to skeletal sites, the two largest loading on the skull, with osteolytic pattern. Calculated radiation absorbed dose for skull lesions, determined by mean of MIRD methodology, was 63.5 mGy/MBq. The patient underwent surgical removal of the two major skull lesions. Successively, 100 mCi (131)I was administered after stimulation by rTSH, with stimulated sTg 297 ng/mL. After 8 months, diagnostic WBS was negative both for remnants and metastases and rTSH-stimulated Tg was 0.6 ng/mL. To date, the patient has maintained sTg values <1 ng/mL during L-T4 suppressive therapy and after rTSH stimulations. In this unusual case of extensive bone cancerous involvement with high iodine avidity, a multidisciplinary approach based on surgery and dosimetry-guided radiometabolic therapy allowed to accurately assess the patient, execute a small number of treatments and achieve a complete remission of the disease in a very short time, with no additive morbidity., (Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.)

High-grade gliomas (glioblastomas) are the most common and deadly brain tumors in adults, currently with no satisfactory treatment available. Apart from de novo glioblastoma, it is currently accepted that these malignancies mainly progress from lower grade glial tumors. However, the molecular entities governing the progression of gliomas are poorly understood. Extracellular and membrane proteins are key biomolecules found at the cell-to-cell communication interface and hence are a promising proteome subpopulation that could help understand the development of glioma. Accordingly, the current study aims at identifying new protein markers of human glioma progression. For this purpose, we used glial tumors generated orthotopically with T98G and U373 human glioma cells in nude mice. This setup allowed also to discriminate the protein origin, namely, human (tumor) or mouse (host). Extracellular and membrane proteins were selectively purified using biotinylation followed by streptavidin affinity chromatography. Isolated proteins were digested and then identified and quantified employing 2D-nano-HPLC-MS/MS analysis. A total of 23 and 27 up-regulated extracellular and membrane proteins were identified in the T98G and U373 models, respectively. Approximately two-thirds of these were predominantly produced by the tumor, whereas the remaining proteins appeared to be mainly overexpressed by the host tissue. Following extensive validation, we have focused our attention on sparc-like protein 1. This protein was further investigated using immunohistochemistry in a large collection of human glioma samples of different grades. The results showed that sparc-like protein 1 expression correlates with glioma grade, suggesting the possible role for this protein in the progression of this malignancy.