Emergency Cranial Surgeries Without the Support of a Neurosurgeon: Experience of the French Military Surgeons.

INTRODUCTION: Unlike orthopedic or visceral surgeons, French military neurosurgeons are not permanently deployed on the conflict zone. Thus, craniocerebral war casualties are often managed by general surgeons in the mobile field surgical team. The objective of the study was to provide the feedback of French military surgeons who operated on craniocerebral injuries during their deployment in a role 2 surgical hospital without a neurosurgeon. MATERIALS AND METHODS: A cross-sectional survey was conducted by phone in March 2020, involving every military surgeon currently working in the French Military Training Hospitals, with an experience of cranial surgery without the support of a neurosurgeon during deployment. We strived to obtain contextual, clinical, radiological, and surgical data. RESULTS: A total of 33 cranial procedures involving 64 surgeons were reported from 1993 to 2018. A preoperative CT scan was not available in 18 patients (55%). Half of the procedures consisted in debridement of craniocerebral wounds (52%, n = 17), followed by decompressive craniectomies (30%, n = 10), craniotomy with hematoma evacuation (15%, n = 5), and finally one (3%) surgery with exploratory burr holes were performed. The 30-day survival rate was 52% (n = 17) and 50% (n = 10/20) among the patients who sustained severe traumatic brain injury. CONCLUSIONS: This survey demonstrates the feasibility and the plus-value of a neurosurgical damage control procedure performed on the field by a surgeon nonspecialized in cranial surgery. The stereotyped neurosurgical techniques used by the in-theater surgeon were learned during a specific predeployment training course. However, the use of a live telemedicine neurosurgical support seems indispensable and could benefit the general surgeon in strained resources setting.

Severe Trauma Patients Requiring Undelayable Combined Cranial and Extra-Cranial Surgery: A Proof-of-Concept Monocentric Study.

INTRODUCTION: To date, there is no evidence concerning the emergency surgical management of severe trauma patients (STP) with severe traumatic brain injury (STBI) presenting a life-threatening intracranial hematoma and a concomitant extra-cranial noncompressible active bleeding. Current guidelines recommend stopping the extra-cranial bleeding first. Nevertheless, the long-term outcome of STP with STBI mainly depends from intracranial lesions. Thus, we propose a combined damage-control surgical strategy aiming to reduce the time spent with intracranial hypertension and to hasten the admission in the intensive care unit. The main objective of the study is to evaluate the benefits of combined cranial and extra-cranial surgery of STP on the long-term outcome. MATERIALS AND METHODS: We retrospectively searched through the database of STBI of a level 1 trauma center facility (Sainte-Anne Military Teaching Hospital, Toulon, France) from 2007 until 2021 looking for patients who benefited from combined cranial and extra-cranial surgery in an acute setting. RESULTS: The research yielded 8 patients. The mean age was 35 years old (±14) and the male to female sex ratio was 1.7/1. The trauma mechanism was a fall in 50% of the cases and a traffic accident in 50% of the cases. The median Glasgow coma scale score was 8 (IQR 4) before intubation. The median Injury Severity Score was 41 (IQR 16). Seven patients (88%) presented hypovolemic shock upon admission. Six patients (75%) benefited from damage-control laparotomy among, whom 4 (67%) underwent hemostatic splenectomy. One patient benefited from drainage of tension pneumothorax, and one patient benefited from external fixator of multiple limb fractures. Seven patients (88%) benefited from decompressive craniectomy for acute subdural hematoma (5 patients) or major brain contusion (2 patients). One patient (12%) benefited from craniotomy for epidural hematoma. Three patients presented intraoperative profound hypovolemic shock. Six patients (75%) presented a favorable neurologic outcome with minor complications from extra-cranial surgeries and 2 patients died (25%). CONCLUSION: Performing combined life-saving cranial and extra-cranial surgery is feasible and safe as long as the trauma teams are trained according to the principles of damage control. It may be beneficial for the neurologic prognostic of STP with STBI requiring cranial and extra-cranial surgery.

Chronic subdural hematoma under local anesthesia with manual burr hole.

CONTEXT: Burr hole evacuation (BHE) of symptomatic chronic subdural hematoma (CSH) carries significant morbidity and mortality in the elderly because they are a fragile population. As military neurosurgeons, we perform a simplified technique under local anesthesia using a manual craniotome. METHODS: We present the case of an 85-year-old woman suffering from a right-sided CSH causing confusion and severe left-sided hemiparesis. CONCLUSION: After the procedure, the patient presented immediate neurological improvement. Performing manual BHE of symptomatic CSH under local anesthesia is safe, and it is of great interest for very old patients or in case of strained resources, thus we think that this technique should be taught to every young neurosurgery resident.

Neurosurgery for intracranial meningioma in patients aged more than 80 years: benefits and rationale.

BACKGROUND: Elderly patients with symptomatic benign intracranial tumours such as meningioma pose particular problems in decision making. We report on the outcome, morbidity and mortality in patients aged over 80 years after undergoing cranial surgery for meningiomas. METHODS: In this retrospective study, 37 patients aged more than 80 years underwent surgery at our neurosurgery department. The Karnofsky Performance Scale (KPS) was used to assess functional status. The American Society of Anesthesiologists (ASA) classification system, the Geriatric Scoring System, the Clinical-Radiological Grading System and the Sex, Karnofsky, ASA, Location and Edema score were used to define clinical status and tumour characteristics. The Charlson Comorbidity Index and Clavien-Dindo classification scores reflected therapeutic morbidity. RESULTS: Preoperative KPS scores were generally higher than 60 (n = 32). Of the 37 patients, 24 (64.8%) were in ASA class I or II, and 27 (73.0%) had one or more comorbidities. The median length of follow-up was 80.0 months (range: 1-96 months). The 1-year mortality rate was 2.7% (n = 1). Tumour control was achieved in 33 patients. At discharge, KPS scores were improved in 21 patients (with an average gain of +18.1 ± 8.7), stable in 10 patients and poorer in 6 patients. KPS scores improved or were stable in patients with shorter lengths of hospital stay (15.5 ± 17.9 days vs 51.4 ± 25.4 days; p < 0.01), those with Clavien-Dindo scores lower than 2 (p < 0.01) and those with less favourable preoperative KPS scores (69.4 ± 10.9 vs 82.0 ± 11.0; p = 0.04). CONCLUSION: Historically, surgery for intracranial meningiomas in patients aged >80 years has been feasible; this series demonstrated decreasing rates of postoperative mortality. Functional benefit should be the main goal of surgery. Perioperative morbidity should be better assessed and predicted because it significantly influences functional outcomes.

Brain metastases in endometrial cancer: A systematic review of the surgical prognostic factors.

CONTEXT: Although endometrial cancer is the fourth most common malignancy in women, dissemination to the brain is an exceptional event in the course of the disease. The aim of this review is to determine the important surgical prognostic factors for patients with endometrial cancer metastatic to the brain. MATERIALS AND METHODS: Report of two cases. Medline database was used to conduct a systematic literature review from inception to December 2020 looking for English-language articles focused on brain metastases from endometrial cancer. RESULTS: The research yielded 108 articles, among which 23 articles were retained for a total of 87 patients. Mean age was 60 years-old ±11 at the time of diagnosis of endometrial cancer, and most of the tumors were aggressive (grade 3) with an advanced-stage disease (FIGO III-IV). At the time of diagnosis of cerebral disease, a single brain metastasis (p < 0.0001) and no extra-cerebral metastatic site (p = 0.0011) were significant good prognostic factors for the median overall survival. Surgical excision of brain metastasis followed by radiotherapy provided the longest median overall survival compared to radiotherapy and/or chemotherapy, and surgery alone (respectively 32, 5.4 and 4.8 months, p < 0.0001). An age of 60-year-old or less was not associated with a better prognosis. CONCLUSION: This review confirms that surgical excision followed by radiotherapy is a reliable option in patients with a single brain metastasis from endometrial cancer and no extra-cerebral metastatic site. This work could help to adapt the Graded Prognostic Assessment for brain metastases in endometrial cancer.

Crystalline defects in bulk metallic glasses: consequences on fracture toughness determination and ductility.

Dating back to the late 1980s, bulk metallic glasses (BMGs) are relatively new materials that exhibit exceptional mechanical properties (strength, hardness, fracture toughness, stored elastic energy ...), compared to those of most crystalline metallic alloys. Their apparent brittleness under uniaxial loading, however, is still a major obstacle to their industrialization. Moreover, BMGs often contain crystalline defects developed, intentionally or not, during their complex and delicate elaboration. These flaws are known to affect their fracture toughness and their plastic behaviour. This paper reviews twenty years of works about this subject on Zr-based bulk metallic glasses that may contain a low volume fraction of crystalline defects of different natures, e.g. dendrites or spherulites, depending on the synthesis method. Dedicated experimental set-ups, mainly bending tests on notched beams, were developed to create in the specimen a proper pre-crack by fatigue and then load it monotonically up to fracture. The measured fracture toughness and the fractographic observations allow to conclude that these crystalline defects facilitate pre-cracking, but result in an embrittlement that is more or less significant depending on their type. The loading mode of the crack -- mode I, II or mixed -- as well as the temperature were shown to play a key role in crack initiation and propagation, whether steadily or catastrophically, in the BMG. By means of finite element computations analyses, explanations on how the crystalline flaws presence can affect fracture toughness and perturbate crack growth, under mode I and mode II, were proposed.Finally, the relevance of these experimental techniques as well as the link between crystalline defects, fracture toughness and their consequences on the ductility of a structural component are discussed.

Two fatty acid-binding proteins expressed in the intestine interact differently with endocannabinoids.

Two different members of the fatty acid-binding protein (FABP) family are found in enterocyte cells of the gastrointestinal system, namely liver-type and intestinal fatty acid-binding proteins (LFABP and IFABP, also called FABP1 and FABP2, respectively). Striking phenotypic differences have been observed in knockout mice for either protein, for example, high fat-fed IFABP-null mice remained lean, whereas LFABP-null mice were obese, correlating with differences in food intake. This finding prompted us to investigate the role each protein plays in directing the specificity of binding to ligands involved in appetite regulation, such as fatty acid ethanolamides and related endocannabinoids. We determined the binding affinities for nine structurally related ligands using a fluorescence competition assay, revealing tighter binding to IFABP than LFABP for all ligands tested. We found that the head group of the ligand had more impact on binding affinity than the alkyl chain, with the strongest binding observed for the carboxyl group, followed by the amide, and then the glycerol ester. These trends were confirmed using two-dimensional 1 H-15 N nuclear magnetic resonance (NMR) to monitor chemical shift perturbation of the protein backbone resonances upon titration with ligand. Interestingly, the NMR data revealed that different residues of IFABP were involved in the coordination of endocannabinoids than those implicated for fatty acids, whereas the same residues of LFABP were involved for both classes of ligand. In addition, we identified residues that are uniquely affected by binding of all types of ligand to IFABP, suggesting a rationale for its tighter binding affinity compared with LFABP.

A summer wave of vertebral fractures: the "deck-slap" injury.

BACKGROUND: Every summer, several patients who suffer from vertebral fractures are hospitalized at the Sainte-Anne Military Hospital after going on a boat trip around the French Riviera. The uniqueness of these fractures lies in their mechanism of injury, called the "deck-slap" injury. The aim of this study is to describe the characteristics of the "deck-slap" injury. METHODS: The data of 26 vertebral fractures that occurred during boat trips between January 2010 and September 2017 were collected and analyzed. RESULTS: The mechanism of injury observed was similar for every patient. Patients sitting on the front of the boat, or bow, (77% of cases, n = 20); patients being on a rigid-inflatable boat (65% of cases, n = 17); and when the sea state was calm (62% of cases, n = 16). The patients were bounced up in the air because of a strong wave and landed in a sitting position. The affected population was young (mean age of 42.5 years) and women were the main victims (sex ratio of 0.3). The lesion topography was found near the thoracolumbar junction in each case. It was always a vertebral body compression. Twenty-three percent of them (n = 6) suffered from neurologic complications. CONCLUSION: This type of fractures, frequently encountered during the summer, has not previously been described in the literature, yet is a relevant cause of hospital admissions to the emergency departments of the south of France. A better knowledge of this mechanism would provide a more efficient approach to prevention measures that should be imposed to potential boat passengers.

Acute neurosurgical management of traumatic brain injury and spinal cord injury in French armed forces during deployment.

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.

Fatal acute disseminated encephalomyelitis (ADEM) after third ventricle colloid cyst resection with ultrasonic aspirator during neuroendoscopic procedure.

We present the case of a patient who died of a fatal meningoencephalitis after removal of a third ventricle colloid cyst. Postoperative clinical and iconographic evolution let us think about an acute disseminated encephalomyelitis probably due to cerebrospinal fluid contamination by inflammatory proteins contained in the colloid cyst. This case raises the question of a possibility of colloid cyst content spraying while using an ultrasonic aspiration device.

Spontaneous Cervical Spinal Epidural Hematoma Associated with Dabigatran.

BACKGROUND: While spontaneous spinal epidural hematomas are rare, 1 of the identified risk factors is vitamin K antagonist therapy. CASE DESCRIPTION: We present a case of a spontaneous spinal epidural hematoma occurring in a patient under treatment with dabigatran, a non-vitamin K oral anticoagulant. The initial hemiparesis symptom was misleading and was retrospectively identified as Brown-Séquard syndrome. Immediate dabigatran antagonism with idarucizumab followed by posterior cervical laminectomy permitted a complete neurologic recovery at day 4. CONCLUSIONS: This is the first description of a spontaneous spinal epidural hematoma under non-vitamin K antagonist oral anticoagulant therapy that has been successfully antagonized and emphasizes the importance of specific antidote development.

Protocols and pitfalls in obtaining fatty acid-binding proteins for biophysical studies of ligand-protein and protein-protein interactions.

Adipocyte fatty acid-binding protein (AFABP: FABP4) is a member of the intracellular lipid-binding protein family that is thought to target long-chain fatty acids to nuclear receptors such as peroxisome proliferator-activated receptor gamma (PPARγ), which in turn plays roles in insulin resistance and obesity. A molecular understanding of AFABP function requires robust isolation of the protein in liganded and free forms as well as characterization of its oligomerization state(s) under physiological conditions. We report development of a protocol to optimize the production of members of this protein family in pure form, including removal of their bound lipids by mixing with hydrophobically functionalized hydroxypropyl dextran beads and validation by two-dimensional NMR spectroscopy. The formation of self-associated or covalently bonded protein dimers was evaluated critically using gel filtration chromatography, revealing conditions that promote or prevent formation of disulfide-linked homodimers. The resulting scheme provides a solid foundation for future investigations of AFABP interactions with key ligand and protein partners involved in lipid metabolism.

Post cardiac surgery vasoplegia is associated with high preoperative copeptin plasma concentration.

INTRODUCTION: Post cardiac surgery vasodilatation (PCSV) is possibly related to a vasopressin deficiency that could relate to chronic stimulation of adeno-hypophysis. To assess vasopressin system activation, a perioperative course of copeptin and vasopressin plasma concentrations were studied in consecutive patients operated on for cardiac surgery. METHODS: Sixty-four consecutive patients scheduled for elective cardiac surgery with cardiopulmonary bypass were studied. Hemodynamic, laboratory and clinical data were recorded before and during cardiopulmonary bypass, and at the eighth postoperative hour (H8). At the same time, blood was withdrawn to determine plasma concentrations of arginine vasopressin (AVP, radioimmunoassay) and copeptin (immunoluminometric assay). PCSV was defined as mean arterial blood pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m², and was treated with norepinephrine to restore mean blood pressure > 60 mmHg. Patients with PCSV were compared with the other patients (controls). Student's t test, Fisher's exact test, or nonparametric tests (Mann-Whitney, Wilcoxon) were used when appropriate. Correlation between AVP and copeptin was evaluated and receiver-operator characteristic analysis assessed the utility of preoperative copeptin to distinguish between controls and PCSV patients. RESULTS: Patients who experienced PCSV had significantly higher copeptin plasma concentration before cardiopulmonary bypass (P < 0.001) but lower AVP concentrations at H8 (P < 0.01) than controls. PCSV patients had preoperative hyponatremia and decreased left ventricle ejection fraction, and experienced more complex surgery (redo). The area under the receiver-operator characteristic curve of preoperative copeptin concentration was 0.86 ± 0.04 (95% confidence interval = 0.78 to 0.94; P < 0.001). The best predictive value for preoperative copeptin plasma concentration was 9.43 pmol/l with a sensitivity of 90% and a specificity of 77%. CONCLUSIONS: High preoperative copeptin plasma concentration is predictive of PSCV and suggests an activation of the AVP system before surgery that may facilitate depletion of endogenous AVP stores and a relative AVP deficit after surgery.

The assembly mode of the pseudopilus: a hallmark to distinguish a novel secretion system subtype.

In gram-negative bacteria, type II secretion systems assemble a piston-like structure, called pseudopilus, which expels exoproteins out of the cell. The pseudopilus is constituted by a major pseudopilin that when overproduced multimerizes into a long cell surface structure named hyper-pseudopilus. Pseudomonas aeruginosa possesses two type II secretion systems, Xcp and Hxc. Although major pseudopilins are exchangeable among type II secretion systems, we show that XcpT and HxcT are not. We demonstrate that HxcT does not form a hyper-pseudopilus and is different in amino acid sequence and multimerization properties. Using structure-based mutagenesis, we observe that five mutations are sufficient to revert HxcT into a functional XcpT-like protein, which also becomes capable of forming a hyper-pseudopilus. Phylogenetic and experimental analysis showed that the whole Hxc system was acquired by P. aeruginosa PAO1 and other Pseudomonas species through horizontal gene transfer. We thus identified a new type II secretion subfamily, of which the P. aeruginosa Hxc system is the archetype. This finding demonstrates how similar bacterial machineries evolve toward distinct mechanisms that may contribute specific functions.

A nuclear magnetic resonance-based structural rationale for contrasting stoichiometry and ligand binding site(s) in fatty acid-binding proteins.

Liver fatty acid-binding protein (LFABP) is a 14 kDa cytosolic polypeptide, differing from other family members in the number of ligand binding sites, the diversity of bound ligands, and the transfer of fatty acid(s) to membranes primarily via aqueous diffusion rather than direct collisional interactions. Distinct two-dimensional (1)H-(15)N nuclear magnetic resonance (NMR) signals indicative of slowly exchanging LFABP assemblies formed during stepwise ligand titration were exploited, without determining the protein-ligand complex structures, to yield the stoichiometries for the bound ligands, their locations within the protein binding cavity, the sequence of ligand occupation, and the corresponding protein structural accommodations. Chemical shifts were monitored for wild-type LFABP and an R122L/S124A mutant in which electrostatic interactions viewed as being essential to fatty acid binding were removed. For wild-type LFABP, the results compared favorably with the data for previous tertiary structures of oleate-bound wild-type LFABP in crystals and in solution: there are two oleates, one U-shaped ligand that positions the long hydrophobic chain deep within the cavity and another extended structure with the hydrophobic chain facing the cavity and the carboxylate group lying close to the protein surface. The NMR titration validated a prior hypothesis that the first oleate to enter the cavity occupies the internal protein site. In contrast, (1)H and (15)N chemical shift changes supported only one liganded oleate for R122L/S124A LFABP, at an intermediate location within the protein cavity. A rationale based on protein sequence and electrostatics was developed to explain the stoichiometry and binding site trends for LFABPs and to put these findings into context within the larger protein family.

Solution structure of the C-terminal X domain of the measles virus phosphoprotein and interaction with the intrinsically disordered C-terminal domain of the nucleoprotein.

In this report, the solution structure of the nucleocapsid-binding domain of the measles virus phosphoprotein (XD, aa 459-507) is described. A dynamic description of the interaction between XD and the disordered C-terminal domain of the nucleocapsid protein, (N(TAIL), aa 401-525), is also presented. XD is an all alpha protein consisting of a three-helix bundle with an up-down-up arrangement of the helices. The solution structure of XD is very similar to the crystal structures of both the free and bound form of XD. One exception is the presence of a highly dynamic loop encompassing XD residues 489-491, which is involved in the embedding of the alpha-helical XD-binding region of N(TAIL). Secondary chemical shift values for full-length N(TAIL) were used to define the precise boundaries of a transient helical segment that coincides with the XD-binding domain, thus shedding light on the pre-recognition state of N(TAIL). Titration experiments with unlabeled XD showed that the transient alpha-helical conformation of N(TAIL) is stabilized upon binding. Lineshape analysis of NMR resonances revealed that residues 483-506 of N(TAIL) are in intermediate exchange with XD, while the 475-482 and 507-525 regions are in fast exchange. The N(TAIL) resonance behavior in the titration experiments is consistent with a complex binding model with more than two states.

Structure of the Pseudomonas aeruginosa XcpT pseudopilin, a major component of the type II secretion system.

The bacterial type II protein secretion (T2S) and type IV piliation (T4P) systems share several common features. In particular, it is well established that the T2S system requires the function of a pilus-like structure, called pseudopilus, which is built upon assembly of pilin-like subunits, called pseudopilins. Pilins and pseudopilins have a hydrophobic N-terminal region, which precedes an extended hydrophilic C-terminal region. In the case of pilins, it was shown that oligomerisation and formation of helical fibers, takes place through interaction between the hydrophobic domains. XcpT, is the most abundant protein of the Pseudomonas aeruginosa T2S, and was proposed to be the main component in the pseudopilus. In this study we present the high-resolution NMR structure of the hydrophilic domain of XcpT (XcpTp). XcpTp is lacking the C-terminal disulfide bridged "D" domain found in type IV pilins and likely involved in receptor binding. This is in agreement with the idea that the XcpT-containing pseudopilus is required for protein secretion and not for bacterial attachment. Interestingly, by solving the 3D structure of XcpTp we revealed that the previously called alphabeta-loop pilin region is in fact highly conserved among major type II pseudopilins and constitutes a specific consensus motif for identifying major pseudopilins, which belong to this family.

The XcpV/GspI pseudopilin has a central role in the assembly of a quaternary complex within the T2SS pseudopilus.

Gram-negative bacteria use the sophisticated type II secretion system (T2SS) to secrete a large number of exoproteins into the extracellular environment. Five proteins of the T2SS, the pseudopilins GspG-H-I-J-K, are proposed to assemble into a pseudopilus involved in the extrusion of the substrate through the outer membrane channel. Recent structural data have suggested that the three pseudopilins GspI-J-K are organized in a trimeric complex located at the tip of the GspG-containing pseudopilus. In the present work we combined two biochemical techniques to investigate the protein-protein interaction network between the five Pseudomonas aeruginosa Xcp pseudopilins. The soluble domains of XcpT-U-V-W-X (respectively homologous to GspG-H-I-J-K) were purified, and the interactions were tested by surface plasmon resonance and affinity co-purification in all possible combinations. We found an XcpV(I)-W(J)-X(K) complex, which demonstrates that the crystallized trimeric complex also exists in the P. aeruginosa T2SS. Interestingly, our systematic approach revealed an additional and yet uncharacterized interaction between XcpU(H) and XcpW(J). This observation suggested the existence of a quaternary, rather than ternary, complex (XcpU(H)-V(I)-W(J)-X(K)) at the tip of the pseudopilus. The assembly of this quaternary complex was further demonstrated by co-purification using affinity chromatography. Moreover, by testing various combinations of pseudopilins by surface plasmon resonance and affinity chromatography, we were able to dissect the different possible successive steps occurring during the formation of the quaternary complex. We propose a model in which XcpV(I) is the nucleator that first binds XcpX(K) and XcpW(J) at different sites. Then the ternary complex recruits XcpU(H) through a direct interaction with XcpW(J).