Reconstruction of cranial vault defect with polyetheretherketone implants

OBJECT: Reconstruction of a cranial vault defect is a frequent challenge in neurosurgery. Polyetheretherketone (PEEK) is used in many types of prostheses and has been employed for 10 years in our institution (University Hospital of Toulouse, France). The objectives of this study are to describe the benefits and drawbacks of reconstructing the cranial vault defect with a PEEK prosthesis. METHODS: Clinical data of the 37 patients who received a reconstruction with a custom-made PEEK prosthesis from 2007-2015 were retrospectively analysed. Operative technique, postoperative complications, and patient's satisfaction with the aesthetic result-on a scale ranging from 1 (very dissatisfied) to 5 (very satisfied)-were studied. RESULTS: Average follow-up was 4.3 years (from 2 months-9 years). The placement of the prosthesis was performed 195 days on average (from 0-1051 days, standard deviation 258 days) after the initial bone flap removal. One infection (2.7%), which required the removal of the prosthesis, was described. Six patients (16%) were reoperated by the maxillofacial surgery team to treat a lack of temporal projection related to muscle atrophy, using a fat cell autograft taken from the abdominal region. Overall, 30 patients (81%) answered the question about their aesthetic satisfaction, with good results on the satisfaction scale (average 4.5; from 3-5). CONCLUSION: The use of a PEEK prosthesis in cranial vault defect reconstruction is a reliable technique with a high patient satisfaction rate and few complications. Corrections of the temporal muscle atrophy by fat grafting may be performed in addition, without increasing the rate of complications

Lipid Nanocapsules Loaded with Rhenium-188 Reduce Tumor Progression in a Rat Hepatocellular Carcinoma Model

International audienceBACKGROUND: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. METHODOLOGY/PRINCIPAL FINDINGS: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. CONCLUSIONS/SIGNIFICANCE: Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment

AGuIX® from bench to bedside-Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine

International audienceAGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.Peer reviewe

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Functional architecture of the somatosensory homunculus detected by electrostimulation

International audienceIn this prospective electrostimulation study, based on 50 operated patients with no sensory deficit and no brain lesion in the postcentral gyrus, we acquired coordinates in the standard MNI space of the functional areas of the somatosensory homunculus. The 3D brain volume of each patient was normalized to that space to obtain the MNI coordinates of the stimulation site locations. For 647 sites stimulated on Brodmann Area 1 (and 1025 in gyri nearby), 258 positive points for somatosensory response (40%) were found in the postcentral gyrus. In the contralateral BA1, the hand representation displayed not only medial‐to‐lateral and little‐finger‐to‐thumb somatotopy, but also rostral‐to‐caudal discrete somatotopy, with the tip of each finger located more caudally than the proximal phalanx. We detected a medial‐to‐lateral, tip‐to‐base tongue organization but no rostral‐to‐caudal functional organization. The analysis of the MNI body coordinates showed rare inter‐individual variations in the medial‐to‐lateral somatotopic organization in these patients with intact somatosensory cortex. Positive stimulations were detected through the ‘on/off’ outbreak effect and discriminative touch sensations were the sensations reported almost exclusively by all patients during stimulation. Mean hand (2.39 mA) and tongue (2.60 mA) positive intensity thresholds were lower (P < 0.05) than the intensities required to elicit sensations in the other parts of the body. Unlike the previous, seminal works of Penfield and colleagues, we detected no sensations such as sense of movement or desire to move, no somatosensory responses outside the postcentral gyrus, and no bilateral responses for face/tongue stimulations. We propose a rationalization of the standard drawing of the somatosensory homunculus according to MNI space

Who Actually Read Exner? Returning to the Source of the Frontal "Writing Centre" Hypothesis

International audienceWe have translated the most famous text of Sigmund Exner (1846-1926), the one relating to the existence of a localised "writing centre" in the brain. We discuss its relevance to the modern study and understanding of writing and agraphia. In Exner's most famous text, he hypothesised about the eponymous "Exner's Area", a discrete area within the brain that was located in the left middle frontal gyrus, which was dedicated to the function of writing. This text in German, included in a book published in 1881 "Untersuchungen über die Lokalisation der Functionen in der Grosshirnrinde des Menschen" (Studies on the localization of functions in the cerebral cortex of humans), lent itself to passionate debates during the following decades on the possibility of finding a specific writing centre in left middle frontal gyrus. Modern authors still refer back to the evidence cited in this seminal text. However, over the 281 pages of Exner's book, only a few chapters dealt with agraphia. Only four of the 167 case reports in the book explicitly mention agraphia. Although Exner describes the anatomical details of these lesions (from autopsies), none of them had pure agraphia, and only one case had an isolated lesion of the posterior part of the middle frontal gyrus. The small number of patients, the absence of pure agraphia symptoms, and the variation in the anatomy of these lesions are the main reasons why Exner's hypothesis of a writing centre in left middle frontal gyrus has been continually debated until now. More than the seminal publication of Sigmund Exner on agraphia, the diffusion of his theory was partly due to the influence that Exner and his family had within the scientific community at the turn of the 20th century

Awake Craniotomy and Memory Induction Through Electrical Stimulation: Why Are Penfield's Findings Not Replicated in the Modern Era?

International audienc

Intraoperative electrostimulation for awake brain mapping: how many positive interference responses are required for reliability?

International audienceThe purpose of this study was to characterize the reproducibility of language trials within and between brain mapping sessions

The neural basis for writing from dictation in the temporoparietal cortex

Cortical electrical stimulation mapping was used to study neural substrates of the function of writing in the temporoparietal cortex. We identified the sites involved in oral language (sentence reading and naming) and writing from dictation, in order to spare these areas during removal of brain tumours in 30 patients (23 in the left, and 7 in the right hemisphere). Electrostimulation of the cortex impaired writing ability in 62 restricted cortical areas (.25 cm2). These were found in left temporoparietal lobes and were mostly located along the superior temporal gyrus (Brodmann's areas 22 and 42). Stimulation of right temporoparietal lobes in right-handed patients produced no writing impairments. However there was a high variability of location between individuals. Stimulation resulted in combined symptoms (affecting oral language and writing) in fourteen patients, whereas in eight other patients, stimulation-induced pure agraphia symptoms with no oral language disturbance in twelve of the identified areas. Each detected area affected writing in a different way. We detected the various different stages of the auditory-to-motor pathway of writing from dictation: either through comprehension of the dictated sentences (word deafness areas), lexico-semantic retrieval, or phonologic processing. In group analysis, barycentres of all different types of writing interferences reveal a hierarchical functional organization along the superior temporal gyrus from initial word recognition to lexico-semantic and phonologic processes along the ventral and the dorsal comprehension pathways, supporting the previously described auditory-to-motor process. The left posterior Sylvian region supports different aspects of writing function that are extremely specialized and localized, sometimes being segregated in a way that could account for the occurrence of pure agraphia that has long-been described in cases of damage to this region