Factors limiting complete tumor ablation by radiofrequency ablation

The purpose of this study was to determine radiological or physical factors to predict the risk of residual mass or local recurrence of primary and secondary hepatic tumors treated by radiofrequency ablation (RFA). Eighty-two patients, with 146 lesions (80 hepatocellular carcinomas, 66 metastases), were treated by RFA. Morphological parameters of the lesions included size, location, number, ultrasound echogenicity, computed tomography density, and magnetic resonance signal intensity were obtained before and after treatment. Parameters of the generator were recorded during radiofrequency application. The recurrence-free group was statistically compared to the recurrence and residual mass groups on all these parameters. Twenty residual masses were detected. Twenty-nine lesions recurred after a mean follow-up of 18 months. Size was a predictive parameter. Patients\u27 sex and age and the echogenicity and density of lesions were significantly different for the recurrence and residual mass groups compared to the recurrence-free group (p < 0.05). The presence of an enhanced ring on the magnetic resonance control was more frequent in the recurrence and residual mass groups. In the group of patients with residual lesions, analysis of physical parameters showed a significant increase (p < 0.05) in the time necessary for the temperature to rise. In conclusion, this study confirms risk factors of recurrence such as the size of the tumor and emphasizes other factors such as a posttreatment enhanced ring and an increase in the time necessary for the rise in temperature. These factors should be taken into consideration when performing RFA and during follow-up

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study

Background Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Methods Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1−6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1−6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. Results Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. Conclusions Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II stud

Wernicke's region--where is it

In this subject, the first question both logically and chronologically was and is: Can a lesion (focal damage) of the cerebrum cause a loss of language without causing a loss of intelligence? That is the original question, still debated hotly by many people. Much of the heat is attributable to the way in which the question is phrased. Suppose we phrase it relatively, as follows: Can a lesion of the cerebrum produce a deficit in language that is far in excess of the concomitant deficit in intelligence? Asked in this way, almost everyone would answer yes. There are worthy persons who are still arguing that anyone who has a loss of language from a cerebral lesion must have some accompanying loss of intelligence. Similarly, there are equally worthy persons recurrently showing us that intelligence can be preserved in spite of severe aphasia. Both parties are undoubtedly correct. But the force of either argument is largely dissipated when the question is rephrased in the relative way. Of course, how much intelligence is lost (or retained) depends upon how one goes about measuring intelligence; but with almost any measures, except those strictly linguistic, the answer will be yes. Indeed, if the answer were not yes, there would not be such a thing a

Hydrogenation of ZnFe2O4 Flat Films: Effects of the Pre-Annealing Temperature on the Photoanodes Efficiency for Water Oxidation

The effects induced by post-synthesis hydrogenation on ZnFe2O4 flat films in terms of photoelectrochemical (PEC) performance of photoanodes for water oxidation have been deeply investigated as a function of the pre-annealing temperature of the materials. The structure and morphology of the films greatly affect the efficacy of the post synthesis treatment. In fact, highly compact films are obtained upon pre-annealing at high temperatures, and this limits the exposure of the material bulk to the reductive H2 atmosphere, making the treatment largely ineffective. On the other hand, a mild hydrogen treatment greatly enhances the separation of photoproduced charges in films pre-annealed at lower temperatures, as a result of the introduction of oxygen vacancies with n-type character. A comparison between present results and those obtained with ZnFe2O4 nanorods clearly demonstrates that specific structural and/or surface properties, together with the initial film morphology, differently affect the overall contribution of post-synthesis hydrogenation on the efficiency of zinc ferrite-based photoanodes

Automated database-guided expert-supervised orientation for immunophenotypic diagnosis and classification of acute leukemia

Precise classification of acute leukemia (AL) is crucial for adequate treatment. EuroFlow has previously designed an AL orientation tube (ALOT) to guide towards the relevant classification panel (T-cell acute lymphoblastic leukemia (T-ALL), B-cell precursor (BCP)-ALL and/or acute myeloid leukemia (AML)) and final diagnosis. Now we built a reference database with 656 typical AL samples (145 T-ALL, 377 BCP-ALL, 134 AML), processed and analyzed via standardized protocols. Using principal component analysis (PCA)-based plots and automated classification algorithms for direct comparison of single-cells from individual patients against the database, another 783 cases were subsequently evaluated. Depending on the database-guided results, patients were categorized as: (i) typical T, B or Myeloid without or; (ii) with a transitional component to another lineage; (iii) atypical; or (iv) mixed-lineage. Using this automated algorithm, in 781/783 cases (99.7%) the right panel was selected, and data comparable to the final WHO-diagnosis was already provided in >93% of cases (85% T-ALL, 97% BCP-ALL, 95% AML and 87% mixed-phenotype AL patients), even without data on the full-characterization panels. Our results show that database-guided analysis facilitates standardized interpretation of ALOT results and allows accurate selection of the relevant classification panels, hence providing a solid basis for designing future WHO AL classifications

Unveiling spatial variability within the Dotson Melt Channel through high-resolution basal melt rates from the Reference Elevation Model of Antarctica

The intrusion of Circumpolar Deep Water in the Amundsen and Bellingshausen Sea embayments of Antarctica causes ice shelves in the region to melt from below, potentially putting their stability at risk. Earlier studies have shown how digital elevation models can be used to obtain ice shelf basal melt rates at a high spatial resolution. However, there has been limited availability of high-resolution elevation data, a gap the Reference Elevation Model of Antarctica (REMA) has filled. In this study we use a novel combination of REMA and CryoSat-2 elevation data to obtain high-resolution basal melt rates of the Dotson Ice Shelf in a Lagrangian framework, at a 50 m spatial posting on a 3-yearly temporal resolution. We present a novel method: Basal melt rates Using REMA and Google Earth Engine (BURGEE). The high resolution of BURGEE is supported through a sensitivity study of the Lagrangian displacement. The high-resolution basal melt rates show a good agreement with an earlier basal melt product based on CryoSat-2. Both products show a wide melt channel extending from the grounding line to the ice front, but our high-resolution product indicates that the pathway and spatial variability of this channel is influenced by a pinning point on the ice shelf. This result emphasizes the importance of high-resolution basal melt rates to expand our understanding of channel formation and melt patterns. BURGEE can be expanded to a pan-Antarctic study of high-resolution basal melt rates. This will provide a better picture of the (in)stability of Antarctic ice shelves.</p

Bioavailable Trace Metals in Neurological Diseases

Medical treatment in Wilson’s disease includes chelators (d-penicillamine and trientine) or zinc salts that have to be maintain all the lifelong. This pharmacological treatment is categorised into two phases; the first being a de-coppering phase and the second a maintenance one. The best therapeutic approach remains controversial, as only a few non-controlled trials have compared these treatments. During the initial phase, progressive increase of chelators’ doses adjusted to exchangeable copper and urinary copper might help to avoid neurological deterioration. Liver transplantation is indicated in acute fulminant liver failure and decompensated cirrhosis; in cases of neurologic deterioration, it must be individually discussed. During the maintenance phase, the most important challenge is to obtain a good adherence to lifelong medical therapy. Neurodegenerative diseases that lead to a mislocalisation of iron can be caused by a culmination of localised overload (pro-oxidant siderosis) and localised deficiency (metabolic distress). A new therapeutic concept with conservative iron chelation rescues iron-overloaded neurons by scavenging labile iron and, by delivering this chelated metal to endogenous apo-transferrin, allows iron redistribution to avoid systemic loss of iron

Observations of Buried Lake Drainage on the Antarctic Ice Sheet.

Between 1992 and 2017, the Antarctic Ice Sheet (AIS) lost ice equivalent to 7.6 ± 3.9 mm of sea level rise. AIS mass loss is mitigated by ice shelves that provide a buttress by regulating ice flow from tributary glaciers. However, ice-shelf stability is threatened by meltwater ponding, which may initiate, or reactivate preexisting, fractures, currently poorly understood processes. Here, through ground penetrating radar (GPR) analysis over a buried lake in the grounding zone of an East Antarctic ice shelf, we present the first field observations of a lake drainage event in Antarctica via vertical fractures. Concurrent with the lake drainage event, we observe a decrease in surface elevation and an increase in Sentinel-1 backscatter. Finally, we suggest that fractures that are initiated or reactivated by lake drainage events in a grounding zone will propagate with ice flow onto the ice shelf itself, where they may have implications for its stability

Neonatal Oral Imitation in Patients with Severe Brain Damage

Background: Neonates reproduce facial movements in response to an adult model just after birth. This neonatal oral imitation usually disappears at about 2- to 3-months of age following the development of cortical control. There is controversy relating to the nature and neural basis of such neonatal imitation. To address this issue, we studied the relationship between oral imitation, primitive reflexes, and residual voluntary movement in patients with severe brain damage. Methods: Six male and six female patients with cerebral palsy, from 4 to 39 years, were included in this study. Oral imitation was examined when they were awake and looked at the experimenter. Patients were evaluated as performing oral imitation when they opened their mouth repeatedly without visual feedback regarding their own behavior in response to the experimenter’s oral movement. Tongue or lip protrusion was not examined because none of patients were able to do those behaviors due to their physical disability. Rooting and sucking reflexes were also investigated as representatives of primitive reflexes. Results: Six patients (50%) performed oral imitation. Mouth opening was not observed repeatedly in response to other facial expression without opening the mouth such as surprise or smile, excluding the possibility of nonspecific oral reaction. They exhibited little voluntary movement of their extremities. Half of them also manifested at least one primitive reflex. N

Hypoxic Environment and Paired Hierarchical 3D and 2D Models of Pediatric H3.3-Mutated Gliomas Recreate the Patient Tumor Complexity.

BACKGROUND:Pediatric high-grade gliomas (pHGGs) are facing a very dismal prognosis and representative pre-clinical models are needed for new treatment strategies. Here, we examined the relevance of collecting functional, genomic, and metabolomics data to validate patient-derived models in a hypoxic microenvironment. METHODS:From our biobank of pediatric brain tumor-derived models, we selected 11 pHGGs driven by the histone H3.3K28M mutation. We compared the features of four patient tumors to their paired cell lines and mouse xenografts using NGS (next generation sequencing), aCGH (array comparative genomic hybridization), RNA sequencing, WES (whole exome sequencing), immunocytochemistry, and HRMAS (high resolution magic angle spinning) spectroscopy. We developed a multicellular in vitro model of cell migration to mimic the brain hypoxic microenvironment. The live cell technology Incucyte© was used to assess drug responsiveness in variable oxygen conditions. RESULTS:The concurrent 2D and 3D cultures generated from the same tumor sample exhibited divergent but complementary features, recreating the patient intra-tumor complexity. Genomic and metabolomic data described the metabolic changes during pHGG progression and supported hypoxia as an important key to preserve the tumor metabolism in vitro and cell dissemination present in patients. The neurosphere features preserved tumor development and sensitivity to treatment. CONCLUSION:We proposed a novel multistep work for the development and validation of patient-derived models, considering the immature and differentiated content and the tumor microenvironment of pHGGs