The TcdE holin drives toxin secretion and virulence in Clostridioides difficile.

Clostridioides difficile is the leading cause of healthcare associated infections. The Pathogenicity Locus (PaLoc) toxins TcdA and TcdB promote host disease. These toxins lack canonical N-terminal signal sequences for translocation across the bacterial membrane, suggesting alternate mechanisms of release, which have included targeted secretion and passive release from cell lysis. While the holin TcdE has been implicated in TcdA and TcdB release, its role in vivo remains unknown. Here, we show profound reductions in toxin secretion in ΔtcdE mutants in the highly virulent strains UK1 (epidemic ribotype 027, Clade 3) and VPI10463 (ribotype 087, Clade 1). Notably, tcdE deletion in either strain rescued highly susceptible gnotobiotic mice from lethal infection by reducing acute extracellular toxin to undetectable levels, limiting mucosal damage, and enabling long-term survival, in spite of continued toxin gene expression in ΔtcdE mutants. Our findings confirm TcdE's critical functions in vivo for toxin secretion and C. difficile virulence.

Security and reliability of CUSTOMBONE cranioplasties: A prospective multicentric study.

BACKGROUND: Repairing bone defects generated by craniectomy is a major therapeutic challenge in terms of bone consolidation as well as functional and cognitive recovery. Furthermore, these surgical procedures are often grafted with complications such as infections, breaches, displacements and rejections leading to failure and thus explantation of the prosthesis. OBJECTIVE: To evaluate cumulative explantation and infection rates following the implantation of a tailored cranioplasty CUSTOMBONE prosthesis made of porous hydroxyapatite. One hundred and ten consecutive patients requiring cranial reconstruction for a bone defect were prospectively included in a multicenter study constituted of 21 centres between December 2012 and July 2014. Follow-up lasted 2 years. RESULTS: Mean age of patients included in the study was 42±15 years old (y.o), composed mainly by men (57.27%). Explantations of the CUSTOMBONE prosthesis were performed in 13/110 (11.8%) patients, significantly due to infections: 9/13 (69.2%) (p<0.0001), with 2 (15.4%) implant fracture, 1 (7.7%) skin defect and 1 (7.7%) following the mobilization of the implant. Cumulative explantation rates were successively 4.6% (SD 2.0), 7.4% (SD 2.5), 9.4% (SD 2.8) and 11.8% (SD 2.9%) at 2, 6, 12 and 24 months. Infections were identified in 16/110 (14.5%): 8/16 (50%) superficial and 8/16 (50%) deep. None of the following elements, whether demographic characteristics, indications, size, location of the implant, redo surgery, co-morbidities or medical history, were statistically identified as risk factors for prosthesis explantation or infection. CONCLUSION: Our study provides relevant clinical evidence on the performance and safety of CUSTOMBONE prosthesis in cranial procedures. Complications that are difficulty incompressible mainly occur during the first 6 months, but can appear at a later stage (>1 year). Thus assiduous, regular and long-term surveillances are necessary.

[Brain abscess and Osler-Weber-Rendu syndrome: Do not forget to look for pulmonary arteriovenous malformations]. / Abcès cérébral et maladie de Rendu-Osler-Weber : pensez à rechercher des malformations artério-veineuses pulmonaires.

INTRODUCTION: Osler-Rendu-Weber syndrome or hereditary hemorrhagic telangiectasia affects between 1/5000 and 1/8000 people. It is characterized by presence of recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations. It is a genetic disease with autosomal dominant transmission inducing an endothelial cells hyper-proliferation. CASE REPORT: A 68-year-old women with Osler-Rendu-Weber syndrome was referred for management of general impairment with confusional syndrome and hyperthermia. Various examinations have allowed us to conclude at diagnosis of brain abscess with ventriculitis probably favored by right-left shunt secondary to pulmonary arteriovenous malformations. Evolution was favorable after antibiotic treatment and endovascular embolization. CONCLUSION: In case of brain abscess without obvious promoting factor, don't forget to looking for a right-left shunt providing septic or aseptic emboli. Furthermore, diagnosis of Rendu-Osler-Weber syndrome should be considered presence of telangiectasias and/or epistaxis.

A case of Erdheim-Chester disease with spinal cord compression and sphenoid sinus involvement.

Erdheim-Chester disease is a rare form of non-Langerhans cell histiocytosis. It is an inflammatory disorder associated with BRAF V600E mutation in 50% of cases. This multisystem disease is rarely associated with spinal involvement. Neurological involvement is an independent predictive factor of poor prognosis. The diagnosis is histopathological based on CD68-positive and CD1A-negative histiocytes. Treatment with interferon-alpha is an independent predictor of survival in Erdheim-Chester disease and vemurafenib has also been shown to be effective for BRAF V600E mutation. We report a clinical case of a 51-year-old patient with multiple and rare locations of Erdheim-Chester disease, particularly at the sphenoid sinus.

Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11.

Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle endocytosis during high-frequency stimulation, suggesting it should play key roles in neurotransmission during periods of intense neuronal activity. However, efforts in elucidating the physiological role of ADBE have been hampered by the lack of identified molecules which are unique to this endocytosis mode. To address this, we performed proteomic analysis on purified bulk endosomes, which are a key organelle in ADBE. Bulk endosomes were enriched via two independent approaches, a classical subcellular fractionation method and isolation via magnetic nanoparticles. There was a 77% overlap in proteins identified via the two protocols, and these molecules formed the ADBE core proteome. Bioinformatic analysis revealed a strong enrichment in cell adhesion and cytoskeletal and signaling molecules, in addition to expected synaptic and trafficking proteins. Network analysis identified Rab GTPases as a central hub within the ADBE proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11 both facilitated ADBE and accelerated clathrin-mediated endocytosis. These findings suggest that the ADBE proteome will provide a rich resource for the future study of presynaptic function, and identify Rab11 as a regulator of presynaptic function.

Perfusion magnetic resonance imaging in pediatric brain tumors.

PURPOSE: The use of DSC-MR imaging in pediatric neuroradiology is gradually growing. However, the number of studies listed in the literature remains limited. We propose to assess the perfusion and permeability parameters in pediatric brain tumor grading. METHODS: Thirty children with a brain tumor having benefited from a DSC-MR perfusion sequence have been retrospectively explored. Relative CBF and CBV were computed on the ROI with the largest lesion coverage. Assessment of the lesion's permeability was also performed through the semi-quantitative PSR parameter and the K2 model-based parameter on the whole-lesion ROI and a reduced ROI drawn on the permeability maps. A statistical comparison of high- and low-grade groups (HG, LG) as well as a ROC analysis was performed on the histogram-based parameters. RESULTS: Our results showed a statistically significant difference between LG and HG groups for mean rCBV (p < 10-3), rCBF (p < 10-3), and for PSR (p = 0.03) but not for the K2 factor (p = 0.5). However, the ratio K2/PSR was shown to be a strong discriminating factor between the two groups of lesions (p < 10-3). For rCBV and rCBF indicators, high values of ROC AUC were obtained (> 0.9) and mean value thresholds were observed at 1.07 and 1.03, respectively. For K2/PSR in the reduced area, AUC was also superior to 0.9. CONCLUSIONS: The implementation of a dynamic T2* perfusion sequence provided reliable results using an objective whole-lesion ROI. Perfusion parameters as well as a new permeability indicator could efficiently discriminate high-grade from low-grade lesions in the pediatric population.

[Management of postoperative complications in cases of Gorham's disease with cervical spine involvement: A case report]. / Gestion des complications postopératoires dans le cas de la maladie de Gorham de localisation cervicale : cas clinique.

Gorham's disease is a rare osteolytic bone disease, caused by pathological vascular tissue, which may spread to adjacent organs. It is a disease of unknown etiology, primarily involving the axial skeleton and whose treatment is not codified. Cervical spine involvement is unusual. Stabilization of the cervical spine is a real surgical challenge. We report the case of a young adult treated in our neurosurgery department for a cervical spine localization of Gorham's disease.

Cortical and subcortical functional neuroanatomy for low-grade glioma surgery.

Knowledge of the encephalon anatomy is crucial for neurosurgical practice, especially the main cortical functional structures and their connections. General organisation of the encephalon is presented with frontal, parietal, occipital, temporal, limbic and insular lobes and their Brodmann correspondence. Secondly, subcortical anatomy will be presented with main white matter fasciculi in three separated categories: association, commissural and projection fibers. Main association fibers are inferior occipitofrontal fasciculus, superior longitudinal fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, uncinate fasciculus, and cingulum. Commissural fibers include anterior commissure, corpus callosum and fornix. Projection fibers are internal capsule and optic radiations.

Microsurgical anatomy of branches of musculocutaneous nerve: clinical relevance for spastic elbow surgery.

PURPOSE: The neurotomy of musculocutaneous nerve is a treatment for patients who suffer from spastic elbow flexion when medical and reeducative treatments have failed. It consists in sectioning motor branches of musculocutaneous nerve which are destined to the biceps brachii and brachialis muscles, both being the main elbow flexor muscles. The aim of this study was to analyse the distance, where each motor branch arises from the musculocutaneous nerve to both biceps brachii and brachialis muscles, to establish precisely the localisation and length of the necessary incision to reach its branches for surgery. MATERIALS AND METHODS: Eighteen musculocutaneous nerves from ten cadavers were dissected. None of them reported with a previous pathology. The cadavers were laid on the back with 30-35° of abduction, a complete extension, and supination of the upper limb. RESULTS: The localization of motor branches was to be found in the middle third of the upper arm, with an average from the base of the humeral major tubercle of 11.46, 12.40, and 12.87 cm for the biceps brachii and 16.36, 19.10, and 16.88 cm for the brachialis muscle. CONCLUSION: The incision needed to reach the motor branches of the musculocutaneous nerve should be localised between 10 and 20 cm from the major humeral tubercle and may be shorter than usual.

[Surgical anatomy of spinal cord tumors]. / Anatomie chirurgicale des tumeurs de moelle épinière.

In this article, we respectively describe the morphology of the spinal cord, spinal meningeal layers, main fiber tracts, and both arterial and venous distribution in order to explain signs of spinal cord compression. We will then describe a surgical technique for spinal cord tumor removal.

Evaluation of the ROSA™ Spine robot for minimally invasive surgical procedures.

The ROSA® robot (Medtech, Montpellier, France) is a new medical device designed to assist the surgeon during minimally invasive spine procedures. The device comprises a patient-side cart (bearing the robotic arm and a workstation) and an optical navigation camera. The ROSA® Spine robot enables accurate pedicle screw placement. Thanks to its robotic arm and navigation abilities, the robot monitors movements of the spine throughout the entire surgical procedure and thus enables accurate, safe arthrodesis for the treatment of degenerative lumbar disc diseases, exactly as planned by the surgeon. Development perspectives include (i) assistance at all levels of the spine, (ii) improved planning abilities (virtualization of the entire surgical procedure) and (iii) use for almost any percutaneous spinal procedures not limited in screw positioning such as percutaneous endoscopic lumbar discectomy, intracorporeal implant positioning, over te top laminectomy or radiofrequency ablation.

Accuracy of thoracolumbar transpedicular and vertebral body percutaneous screw placement: coupling the Rosa® Spine robot with intraoperative flat-panel CT guidance--a cadaver study.

The primary objective of the present study was to evaluate the accuracy of a new robotic device when coupled with intraoperative flat-panel CT guidance. Screws (D8-S1) were implanted during two separate cadaver sessions by coupling the Rosa(®) Spine robot with the flat-panel CT device. Of 38 implanted screws, 37 (97.4 %) were fully contained within the pedicle. One screw breached the lateral cortical of one pedicle by <1 mm. The mean ± SD accuracy (relative to pre-operative planning) was 2.05 ± 1.2 mm for the screw head, 1.65 ± 1.11 for the middle of the pedicle and 1.57 ± 1.01 for the screw tip. When coupled with intraoperative flat-panel CT guidance, the Rosa(®) Spine robot appears to be accurate in placing pedicle screws within both pedicles and the vertebral body. Large clinical studies are mandatory to confirm this preliminary cadaveric report.

[Oculomotor nerve schwannoma in a child: Case report and literature review]. / Schwannome du nerf oculomoteur chez l'enfant: cas clinique et revue de la littérature.

An isolated schwannoma of the oculomotor nerve is rare in children without an associated neurofibromatosis. A 13-year-old girl, with a previous medical history of migraine, was admitted for disabling ophthalmic migraine with oblique diplopia. The clinical examination showed a right incomplete ophthalmoplegia with reduced ipsilateral visual acuity (8/10). There was no particular skin reaction. The MRI revealed a right (isosignal-T1 and isosignal-T2) nodular schwannoma located within the cisternal segment of the oculomotor nerve. The angio-CT performed later confirmed the absence of any vascular malformation. The treatment consisted of analgesics and corticotherapy, with complete regression of symptoms three weeks later and a normal MRI follow-up. Therefore, radiosurgery was not performed.

Caspofungin irrigation through percutaneous calicostomy catheter combined with oral flucytosine to treat fluconazole-resistant symptomatic candiduria.

Candiduria may be a marker of serious fungal infections such as pyelonephritis. With the exception of fluconazole and flucytosine, antifungals drugs are not excreted into the urine as active drugs, making the management of infection due to fluconazole-resistant Candida difficult. We report a case of recurrent Candida parapsilosis candiduria in a kidney transplant recipient suffering from chronic ureteral obstruction requiring permanent ureteral catheterization (double-J stent). Attempts to remove the stent led to pyelonephritis episodes during which only Candida was isolated from the urine. Following several courses of azole-based therapy, the causative agent became resistant to fluconazole. Clinical and mycological cure were obtained combining irrigations of caspofungin through a percutaneous calicostomy catheter and oral flucytosine. This strategy may represent an interesting therapeutic alternative in case of fluconazole-resistant symptomatic candiduria.

[Persistent Müllerian ducts syndrome: one case of late hypofertility]. / Syndrome de persistance des canaux de Müller de type féminin : un cas de diagnostic tardif dans le cadre d'une infertilité

We report the case of a 35-year-old patient with a syndrome of persistent Müllerian ducts (PMDS) of the female type (group A). The diagnosis was made in adulthood during an infertility workup. Clinical examination revealed an empty scrotum, a normal penis and bilateral inguinal cystic masses. The spermogram found azoospermia. Imaging using MRI and tomotensidometry found the presence of an uterus, two fallopian tubes and two inguinal positions of polycystic testes. A surgical management was performed for surgical testicular biopsy. Histological examination then found a cystic formation of multi-celled mesothelial origin, with atrophic testis Sertoli cell involution and without sperm. PMDS is a rare form of pseudo-internal hermaphroditism characterized by the presence in a man of the uterus, fallopian tubes and upper vagina with external male genitalia and virilized characters. About 200 cases are reported in the literature. The diagnosis is often made in children intraoperatively during a cure of testicular ectopia. The karyotype is 46 XY type. The pathogenesis is related to a deficiency of anti-Müllerian hormone (AMH) or tissue resistance to its action by receptor abnormalities. The regression of the Müllerian duct derivatives can give three types of PMDS : masculine type, feminine type and a transverse type. Surgical treatment is difficult but necessary because of the risk of infertility and ectopic testicular degeneration.

[The occipital sinus: a radioanatomic study]. / Étude radioanatomique du sinus occipital.

INTRODUCTION: The aim of this study was to assess the presence of an occipital sinus in both children and adults, and to detail its main associated anatomical characteristics. METHODS: One hundred of patients' MRI (3D T1 EG) between 0 and 86 years old were studied, in sagittal and axial sections, with the software DxMM. Occipital sinus length, perimeter, and cerebellar falx length measurements were performed with the software's tools. RESULTS: Forty-three percent of patients had an occipital sinus (average perimeter was 3.02 mm, average length was 19.85 mm), and 23.26% of these patients had a cerebellar falx, 30.23% of these patients had one vein or more draining into the occipital sinus. Sixty-two percent of children had an occipital sinus (average perimeter was 2.87 mm, average length was 21.63 mm), and 29.03% of them had a cerebellar falx. Twenty-four percent of adults had an occipital sinus (average perimeter was 3.4mm, average length was 15.28 mm), and 8.33% of them had a cerebellar falx. CONCLUSION: This work highlights a link between the age and the occipital sinus existence. The perimeter of this sinus seems to be superior for adults, but its length seems to be superior for children. A cerebellar falx with the occipital sinus was found more frequently for children.

[Microsurgical anatomy of perforating branches of anterior communicating artery]. / Anatomie microchirurgicale des branches perforantes de l'artère communicante antérieure.

INTRODUCTION: The anterior communicating artery (ACoA) gives perforating branches to the optic chiasma, the hypothalamus and the corpus callosum. Perforating branches are variable (number, direction). Nevertheless, their knowledge is crucial during surgery of this area to spare injuries leading to ischemic post-operative complications. OBJECTIVE: The objective was to update the anatomical knowledge about perforating branches of the ACoA. METHODS: The study was led on a series of seven brains taken from human cadavers. An injection of latex neoprene was performed for every case. The region of interest was observed under operating microscope. Were examined: the length of the ACoA, its diameter, its orientation, its configuration and perforating branches (number and areas). RESULTS: Three cases on five presented with an anatomical variation at the level of the ACoA. The average length of AcoA was 2.1 millimeters (min: 2, max: 2.2). The average diameter of the ACoA was 1.67 mm (min: 1.1, max: 2.1). The average number of perforating branches was 4.2 (min: 2, max: 6). The presence of a median artery of the corpus callosum seemed to correlated with a low number of perforating branches. Branches supplying the optic chiasma seemed to be more numerous.

[Warfarin-related nephropathy: a case report]. / Néphropathie aux anti-vitamine K : à propos d'une observation.

INTRODUCTION: Warfarin-related nephropathy (WRN) is a newly recognized entity, which is characterized by the occlusion of renal tubules by red blood cells following glomerular hemorrhage in a patient overexposed to warfarin (international normalized ratio>3). CASE REPORT: We report a 70-year-old man with no previous renal condition who developed WRN when his INR was>12. He did not fully recover his previous renal function. CONCLUSION: The diagnosis of WRN should be considered whenever INR exceeds 3 in patients exposed to warfarin, particularly in the presence of hematuria. Vitamin K is the only therapeutic option.

Unusual course of the aberrant right hepatic artery running through the pancreatic parenchyma during modified Frey's procedure.

We report a variation of an aberrant right hepatic artery arising from the superior mesenteric artery and crossing into pancreatic head without other hepatic artery substitution. The variant was discovered during radiological examinations in a patient with symptomatic chronic pancreatitis requiring Frey's procedure with reinsertion of the common bile duct into the pancreatic head. An aberrant right hepatic artery arising from the superior mesenteric artery is present in 10 to 20% of case and its course is usually retro-pancreatic. The course of this artery into the pancreatic head is uncommon and can be present up to 10% in case of ARHA. Knowledge of an aberrant right hepatic artery crossing into the pancreatic head is important before pancreatic surgery in order to avoid surgical complications, especially for liver necrosis.