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Extracellular vesicles (EVs) are mediators of intercellular communication in the tumor microenvironment. Tumor EVs are commonly associated with metastasis, immunosuppression or drug resistance. Viral infections usually increase EV secretion, but little is known about the effect of oncolytic viruses (OVs) on tumor EVs. Here, we investigated the impact of oncolytic vesicular stomatitis virus (VSV) and vaccinia virus on EVs secreted by human melanoma and thoracic cancer cells. We found that OV infection increases the production of EVs by tumor cells. These EVs contain proteins of viral origin, such as VSV-G, thus creating a continuum of particles sharing markers of both canonical EVs and viruses. As such, the presence of VSV-G on EVs improves the transfer of their protein content to cell types commonly found in the tumor microenvironment. A proteomic analysis also revealed that EVs-OV secreted during VSV infection are enriched in immunity-related proteins. Finally, CD8 + T cells incubated with EVs-OV from infected cells display slightly enhanced cytotoxic functions. Taken together, these data suggest that OVs enhance the communication mediated by tumor EVs, which could participate in the therapeutic efficacy of OVs. These results also provide rationale for engineering OVs to exploit EVs and disseminate therapeutic proteins within the tumor microenvironment., Competing Interests: P.E. is an employee of Transgene SA. Transgene SA is a member of the Institut Mérieux Group, a publicly traded French biopharmaceutical company., (© 2024 The Author(s).)

Introduction: The French mobile neurosurgical unit (MNSU) is used to provide specific support to remote military medicosurgical units deployed in foreign theatres. If a neurosurgical casualty is present, the Role 2 team may request the MNSU to be deployed directly from France. The deployed neurosurgeon can then perform surgery in Role 2 or decide to evacuate the casualty and perform surgery in Role 4 in France. We provide an epidemiological analysis of MNSU missions between 2001 and 2023 and investigate the value of the MNSU for the French Armed Forces., Methods: We conducted a retrospective case series that included patients managed by the MNSU from 1 January 2001 to 31 January 2023. We collected epidemiological data (eg, age, military or civilian status, delay between transmission and takeoff, origin of the injury and mission location), clinical records (aetiologies of the injury and disease), data on surgical intervention (operator nature and type of surgery) and data on postoperative outcomes recorded at the time of discharge from hospital., Results: 51 patients were managed by the MNSU. 36 (70.5%) and 3 (5.8%) patients underwent surgery on Role 2 and Role 4, respectively. 39 (76.9%) interventions were due to traumatic injury, 4 (7.8%) due to hydrocephalus, 4 (7.8%) due to vascular causes, 3 (5.9%) due to tumour and 1 (2%) due to spine degeneration. In 30 (76.9%) of these cases, the first operator was a neurosurgeon from the MNSU, whereas in the remaining 9 (23.1%) cases, procedures were initially performed by a non-neurosurgeon., Conclusion: The MNSU contribution to D1 casualties' strategic evacuation (STRATEVAC) is important. The MNSU provides additional support for STRATEVAC during the reorganisation of French Armed Forces engaged in several fronts. With the return of high-intensity wars, the French MNSU must develop and adjust for the management of massive influxes of casualties., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Combat penetrating brain injury (PBI) differs significantly from PBI in civilian environments. Differences include technical factors such as the weapons involved, strained resource environments, and limited medical materials and human resources available. Ethical issues regarding the management of PBI in military settings may occur. This case study examines the case of a 20-year-old member of the French Armed Forces that suffered a penetrating brain injury in a combat situation. The four-quadrant method along with the four principles of medical ethics (respect for autonomy, beneficence, nonmaleficence, and justice) was used to analyze this case and to apply ethics to the practice of military medicine. Nowadays, we possess the medical and surgical resources as well as the aeromedical evacuation capability to save the life of a soldier with a penetrating craniocerebral wound. Nonetheless, the functional outcome of this type of wound places military doctors in an ethical dilemma. The line of conduct and clinical protocol established by the French Medical Health Service is to manage all PBIs when the patient's life can be saved and to provide all available financial and social support for the rehabilitation of patients and their family., (© Crown copyright 2023.)

Background: Middle meningeal artery (MMA) embolization has been proposed as a treatment of chronic subdural hematoma (CSDH). The benefit of the procedure has yet to be demonstrated in a randomized controlled trial. We aim to assess the efficacy of MMA embolization in reducing the risk of CSDH recurrence 6 months after burr-hole surgery compared with standard medical treatment in patients at high risk of postoperative recurrence., Methods: The EMPROTECT trial is a multicenter open label randomized controlled trial (RCT) involving 12 French centers. Adult patients (≥18 years) operated for CSDH recurrence or for a first episode with a predefined recurrence risk factor are randomized 1:1 to receive either MMA embolization within 7 days of the burr-hole surgery (experimental group) or standard medical care (control group). The number of patients to be included is 342., Results: The primary outcome is the rate of CSDH recurrence at 6 months. Secondary outcomes include the rate of repeated surgery for a homolateral CSDH recurrence during the 6-month follow-up period, the rate of disability and dependency at 1 and 6 months, defined by a modified Rankin Scale (mRS) score ≥4, mortality at 1 and 6 months, total cumulative duration of hospital stay during the 6-month follow-up period, directly or indirectly related to the CSDH and embolization procedure-related complication rates., Conclusions: The EMPROTECT trial is the first RCT evaluating the benefit of MMA embolization as a surgical adjunct for the prevention of CSDH recurrence. If positive, this trial will have a significant impact on patient care., Trial Registration Number: NCT04372147., Competing Interests: Competing interests: Dr Sourour reports a conflict of interest with Medtronic, Balt Extrusion, Microvention (consultant). Prof Clarençon reports a conflict of interest with Medtronic, Balt Extrusion (consultant), ClinSearch (core lab), Penumbra, Stryker (payment for reading) and Artedrone (Board). The other authors report no conflicts of interest., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The origins of military neurosurgery are closely linked to those of neurosurgery in France and more particularly in Paris. The history of the field starts with its origins by 2 men, Thierry de Martel and Clovis Vincent. The first note about the creation of military neurosurgery was in 1942, when Marcel David was reassigned from the Sainte Anne Hospital to practice at the Val-de-Grâce Military Hospital. David trained the first military neurosurgeon. The field of military neurosurgery was subsequently developed at the Val-de-Grâce Military Hospital, at Sainte Anne Military Teaching Hospital in Toulon in 1990 and then at Percy Military Teaching Hospital in 1996. Over 29 military neurosurgeons were trained in these institutions. Since 2000, French military neurosurgeons have been deployed from France in the Mobile Neurosurgical Unit. This Mobile Neurosurgical Unit represents 12% of all medical evacuation of casualties categorized as the high dependency level. Neurosurgeons were able to adapt to asymmetrical wars, such as in the Afghanistan campaign where they were deployed in the Role 3 medical treatment facility, and more recently in sub-Saharan conflicts where they were deployed in forward surgical roles. To manage the increasing craniocerebral war casualties in the forward surgical team, the French Military Health Service Academy established a training course referred to as the "Advanced Course for Deployment Surgery" providing neurosurgical damage control skills to general surgeons. Finally, military neurosurgery is reinventing itself to adapt to future conflicts through the enhancement of surgical practices via the addition of head, face, and neck surgeons., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Mating-type switching in the budding yeast Saccharomyces cerevisiae relies on the Sir protein complex to silence HML and HMR, the two loci containing copies of the alleles of the mating type locus, MAT. Sir-based transcriptional silencing has been considered locus-specific, but the recent discovery of rare and transient escapes from silencing at HMLα2 with a sensitive assay called to question if these events extend to the whole locus. Adapting the same assay, we measured that transient silencing failures at HML were more frequent for the α2 gene than α1, similarly to their expression level in unsilenced cells. By coupling a mating assay, at HML we found that one of the two genes at that locus can be transiently expressed while the other gene is maintained silent. Thus, transient silencing loss can be a property of the gene rather than the locus. Cells lacking the SIR1 gene experience epigenetic bistability at HML and HMR. Our previous result led us to ask if HML could allow for two independent epigenetic states within the locus in a sir1Δ mutant. A simple construct using a double fluorescent reporter at HMLα1 and HMLα2 ruled out this possibility. Each HML locus displayed a single epigenetic state. We revisited the question of the correlation between the states of two HML loci in diploid cells, and showed they were independent. Finally, we determined the relative strength of gene repression achieved by Sir-based silencing with that achieved by the a1-α2 repressor., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: As a complement to the clinical development of new anticancer molecules, innovations in therapeutic vectorization aim at solving issues related to tumor specificity and associated toxicities. Nanomedicine is a rapidly evolving field that offers various solutions to increase clinical efficacy and safety. MAIN: Here are presented the recent advances for different types of nanovectors of chemical and biological nature, to identify the best suited for translational research projects. These nanovectors include different types of chemically engineered nanoparticles that now come in many different flavors of 'smart' drug delivery systems. Alternatives with enhanced biocompatibility and a better adaptability to new types of therapeutic molecules are the cell-derived extracellular vesicles and micro-organism-derived oncolytic viruses, virus-like particles and bacterial minicells. In the first part of the review, we describe their main physical, chemical and biological properties and their potential for personalized modifications. The second part focuses on presenting the recent literature on the use of the different families of nanovectors to deliver anticancer molecules for chemotherapy, radiotherapy, nucleic acid-based therapy, modulation of the tumor microenvironment and immunotherapy., Conclusion: This review will help the readers to better appreciate the complexity of available nanovectors and to identify the most fitting "type" for efficient and specific delivery of diverse anticancer therapies.

This article aims to describe the French concept regarding combat casualty neurosurgical care from the theater of operations to a homeland hospital. French military neurosurgeons are not routinely deployed to all combat zones. As a consequence, general surgeons initially treat neurosurgical wounds. The principle of this medical support is based on damage control. It is aimed at controlling intracranial hypertension spikes when neuromonitoring is lacking in resource-limited settings. Neurosurgical damage control permits a medevac that is as safe as can be expected from a conflict zone to a homeland medical treatment facility. French military neurosurgeons can occasionally be deployed within an airborne team to treat a military casualty or to complete a neurosurgical procedure performed by a general surgeon in theaters of operation. All surgeons regardless of their specialty must know neurosurgical damage control. General surgeons must undergo the required training in order for them to perform this neurosurgical technique.

Introduction: France deployed to Afghanistan from 2001 to 2014 within the International Security and Assistance Force. A French role 3 hospital was built in 2009 in the vicinity of Kabul International Airport (KaIA). The objectives of this study were to describe the epidemiology, management, and outcome of war-related craniocerebral injuries during the Afghan campaign in a French role 3 hospital., Methods: From March 1, 2010 to September 30, 2012, we conducted a retrospective descriptive study in Kabul, Afghanistan. All patients presenting with a ballistic craniocerebral injury to the KaIA role 3 hospital were included., Results: We analyzed 48 records. Mean age was 21.9 years (1-46 years) with a 37:11 (male:female) sex ratio and a majority Afghan population (n = 41). Civilians represented 64.6% (n = 31) of casualties. On the battlefield, mean Glasgow Coma Scale score was 9.4 [3-15]. On arrival at the KaIA field hospital, 20 of the 48 patients were hemodynamically unstable. All patients underwent a full-body computed tomography scan. The majority of our casualties had associated injuries. Neurosurgery was indicated for 42 (87.5%) patients. The surgery consisted of wound debridement plane by plane associated with decompressive craniectomy (n = 11), debridement craniectomy (n = 19), and craniotomy (n = 12). A total of 32.4% wounded died at the point of injury, 8.4% at the emergency department, and 16.9% after surgery., Conclusions: War casualties with ballistic head injuries were predominantly multitraumatized patients with hemodynamic compromise requiring neurosurgical damage control management and multidisciplinary care. The neurosurgeon has thus an essential role to play., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To describe the evolution of the use and reporting of propensity score (PS) analysis in observational studies assessing a surgical procedure., Background: Assessing surgery in randomized controlled trials raises several challenges. Observational studies with PS analysis are a robust alternative for comparative effectiveness research., Methods: In this methodological systematic review, we identified all PubMed reports of observational studies with PS analysis that evaluated a surgical procedure and described the evolution of their use over time. Then, we selected a sample of articles published from August 2013 to July 2014 and systematically appraised the quality of reporting and potential bias of the PS analysis used., Results: We selected 652 reports of observational studies with PS analysis. The publications increased over time, from 1 report in 1987 to 198 in 2013. Among the 129 reports assessed, 20% (n = 24) did not detail the covariates included in the PS and 77% (n = 100) did not report a justification for including these covariates in the PS. The rate of missing data for potential covariates was reported in 9% of articles. When a crossover by conversion was possible, only 14% of reports (n = 12) mentioned this issue. For matched analysis, 10% of articles reported all 4 key elements that allow for reproducibility of a PS-matched analysis (matching ratio, method to choose the nearest neighbors, replacement and method for statistical analysis)., Conclusions: Observational studies with PS analysis in surgery are increasing in frequency, but specific methodological issues and weaknesses in reporting exist.

Background: In 2009, during the war in Afghanistan, the increasing number of head injuries led to the deployment of a military neurosurgeon at the Kabul International Airport (KaIA) medical treatment facility, in March 2010. The main goal of this study was to depict the neurosurgical activity in this centre and to analyse its different aspects., Method: A retrospective study of all the neurosurgical patients treated in KaIA from March 2010 to June 2013., Results: Three hundred and seventy-three interventions performed by the neurosurgeon deployed were reported for 373 surgeries, in 335 patients, representing 10.6 % of the overall surgical activity of the centre. Among the 69 interventions performed on soldiers, 57 surgeries were undertaken in emergency (82.6 %), while 12 were elective procedures (17.4 %). On the other hand, 289 surgeries were performed in civilian Afghans, with 126 emergency procedures in (43.6 %), against 163 elective interventions (56.4 %). Among the 44.5 % (n = 149) of the traumatic casualties, cerebral lesions represented 28.7 % (n = 96) and spinal lesions 12.4 % (n = 42). Ninety patients had multiple injuries. Additionally, patients without trauma accounted for 55.5 % (n = 186) of the overall population. Thus, 49 % (n = 164) were operated on for non-traumatic lesion of the spine. These were mostly civilian Afghans treated under medical aid to the population (90.2 %, n = 148/164)., Conclusions: The military neurosurgeon had two roles in KaIA: both to support the armed forces and to manage medical aid to the civilian population. This study gives food for thought on the neurosurgical needs in modern warfare, and on the skills required for the military neurosurgeon.

Periodic arrays of micro- or nanopillars constitute solid-state matrices with excellent properties for DNA size separation. Nanofabrication technologies offer many solutions to tailor the geometry of obstacle arrays, yet most studies have been conducted with cylinders arranged in hexagonal lattices. In this report, we investigate the dynamics of single DNA collision with elliptical nanoposts using hydrodynamic actuation. Our data show that the asymmetry of the obstacles has minor effect on unhooking dynamics, and thus confirm recent predictions obtained by Brownian dynamics simulations. In addition, we show that the disengagement dynamics are correctly predicted by models of electrophoresis, and propose that this consistency is associated to the confinement in slit-like channels. We finally conclude that elliptical posts are expected to marginally improve the performances of separation devices., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)