Embolization of the middle meningeal artery for the prevention of chronic subdural hematoma recurrence in high-risk patients: a randomized controlled trial-the EMPROTECT study protocol.

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.

Pituitary apoplexy score, toward standardized decision-making: a descriptive study.

Pituitary apoplexy (PA), a rare and life-threatening complication of pituitary adenomas, prompts urgent glucocorticoid administration. The optimal surgical approach is debated, and the Pituitary Apoplexy Score (PAS) aids decision-making. Our retrospective study (2003-2022) assesses variables in PA patient groups (surgical vs. non-surgical), applying PAS to establish a significant threshold for surgical decisions. Additionally, we aim to compare the rates of ophthalmological and endocrine deficit between both groups and identify any associated variables. PAS discrepancies were observed, with averages of 1.7 ± 1.7 (p < 0.0001) for conservative and 3.9 ± 1.7 (p < 0.0001) for surgical groups, confirmed by multivariate analysis (p = 0.009). A PAS threshold of 5, showing over 80% positive predictive value, was established. Patients with low prolactin levels (< 5 ng/ml) had higher corticotropic deficiency prevalence at 3-month and 1-year follow-ups (p = 0.017 and 0.027). Our study supports PAS as a valuable PA management tool, suggesting potential variable adjustments. Multicenter studies are crucial due to PA's low incidence.

Comparative analysis of histopathological parameters, genome-wide copy number alterations, and variants in genes involved in cell cycle regulation in chordomas of the skull base and sacrum.

Chordomas are rare tumors of the axial skeleton that are refractory to conventional therapy. Few studies have compared the morphological and molecular characteristics of chordomas according to the skull base and sacral locations. Histopathological data and changes revealed by array comparative genomic hybridization (CGH) and next-generation sequencing (NGS) of cell cycle regulation genes were analyzed for 28 skull base (SBCs) and 15 sacral (SC) chordomas. All cases were conventional chordomas. SBCs were significantly more frequent in patients aged <40 years and SCs predominated in patients aged >60 years. Mitotic indices ≥2 mitoses/10 high-power fields were correlated with high degrees of nuclear atypia and Ki67 labeling indices ≥6%. We identified 321 genomic positions, and copy number variation losses were more frequent than gain. Moreover, we report a panel of 85 genetic variants of cell cycle genes and the presence of molecular clusters for chordoma as well in CGH as in NGS. These new data strengthen the view that the chordoma should not be considered as a single molecular entity.

Extended endoscopic transsphenoidal approach for suprasellar craniopharyngiomas.

BACKGROUND: Craniopharyngiomas are benign sellar lesions. Surgical excision of craniopharyngiomas is difficult because of the surrounding important neurovascular structures. The choice of surgery depends on the histological type, location, hormonal status, and size of the craniopharyngioma, surrounding neurovascular structures, and invasion of the brain parenchyma. METHODS: We describe the resection of an adamantinomatous craniopharyngioma using an extended endoscopic endonasal approach and discuss the relevant surgical anatomy, indications, limitations, and possible complications. CONCLUSIONS: The extended endoscopic endonasal approach allows successful removal of the craniopharyngioma and poses little risk to surrounding neurovascular structures.

Treatment of congenital thrombocytopenia and decreased collagen reactivity in G6b-B-deficient mice.

Mice lacking the immunoreceptor tyrosine-based inhibition motif-containing co-inhibitory receptor G6b-B (Mpig6b, G6b knockout, KO) are born with a complex megakaryocyte (MK) per platelet phenotype, characterized by severe macrothrombocytopenia, expansion of the MK population, and focal myelofibrosis in the bone marrow and spleen. Platelets are almost completely devoid of the glycoprotein VI (GPVI)-FcRγ-chain collagen receptor complex, have reduced collagen integrin α2ß1, elevated Syk tyrosine kinase activity, and a subset has increased surface immunoglobulins. A similar phenotype was recently reported in patients with null and loss-of-function mutations in MPIG6B. To better understand the cause and treatment of this pathology, we used pharmacological- and genetic-based approaches to rescue platelet counts and function in G6b KO mice. Intravenous immunoglobulin resulted in a transient partial recovery of platelet counts, whereas immune deficiency did not affect platelet counts or receptor expression in G6b KO mice. Syk loss-of-function (R41A) rescued macrothrombocytopenia, GPVI and α2ß1 expression in G6b KO mice, whereas treatment with the Syk kinase inhibitor BI1002494 partially rescued platelet count but had no effect on GPVI and α2ß1 expression or bleeding. The Src family kinase inhibitor dasatinib was not beneficial in G6b KO mice. In contrast, treatment with the thrombopoietin mimetic romiplostim rescued thrombocytopenia, GPVI expression, and platelet reactivity to collagen, suggesting that it may be a promising therapeutic option for patients lacking functional G6b-B. Intriguingly, GPVI and α2ß1 expression were significantly downregulated in romiplostim-treated wild-type mice, whereas GPVI was upregulated in romiplostim-treated G6b KO mice, suggesting a cell intrinsic feedback mechanism that autoregulates platelet reactivity depending on physiological needs.

Treatment of A3.2 and A2 traumatic thoracolumbar spine compression fractures using vertebral body stenting: a 63-patient series.

BACKGROUND: Percutaneous treatments for spinal injury are underused by neuroradiologists and spine surgeons, mainly owing to a lack of data on indications. OBJECTIVE: To assess the safety and efficacy of vertebral body stenting (VBS) for post-traumatic A3.2 and A2 fractures (Magerl classification) and determine the factors that influence the improvements. METHODS: We retrospectively reviewed patients who underwent VBS to treat a single traumatic thoracolumbar fracture from 2010 to 2019. Kyphosis, loss of vertebral body height (VBH), and clinical and functional outcomes (including the Visual Analog Scale pain score and Oswestry Disability Index) were assessed. We examined the overall effects of VBH in all patients by constructing a linear statistical model and evaluated whether the efficacy was dependent on the characteristics of the patients or fractures. RESULTS: We included 63 patients comprising 44 A3.2 and 19 A2 fractures. No patient had worsening neurological symptoms or wound infection. The average rates of change were 67.1% (95% CI 59.1% to 75%) for kyphosis and 88.5% (95% CI 85.6% to 91.3%) for VBH (both p<0.0001). After 1 year, the VBS treatment was more effective for kyphosis in younger patients and at the L1 level, and for VBH in younger patients and cases of Magerl A3.2 fracture. CONCLUSIONS: This large reported series on VBS validates this surgical treatment. All patients had improved kyphosis and restored VBH. We recommend using VBS rather than open surgery for A3.2 and A2 fractures at the thoracolumbar junction and in young patients.

Leukodepletion Filters-Derived CD34+ Cells As a Cell Source to Study Megakaryocyte Differentiation and Platelet Formation.

The in vitro expansion and differentiation of human hematopoietic progenitors into megakaryocytes capable of elongating proplatelets and releasing platelets allows an in-depth study of the mechanisms underlying platelet biogenesis. Available culture protocols are mostly based on hematopoietic progenitors derived from bone marrow or cord blood raising a number of ethical, technical, and economic concerns. If there are already available protocols for obtaining CD34 cells from peripheral blood, this manuscript proposes a straightforward and optimized protocol for obtaining CD34+ cells from leukodepletion filters readily available in blood centers. These cells are isolated from leukodepletion filters used in the preparation of blood transfusion products, corresponding to eight blood donations. These filters are meant to be discarded. A detailed procedure to collect hematopoietic progenitors identified as CD34+ cells from these filters is described. The method to obtain mature megakaryocytes extending proplatelets while discussing their phenotypic evolution is also detailed. Finally, the protocol present a calibrated pipetting method, to efficiently release platelets that are morphologically and functionally similar to native ones. This protocol can serve as a basis for evaluating pharmacological compounds acting at various steps of the process to dissect the underlying mechanisms and approach the in vivo platelet yields.

Treating traumatic thoracolumbar spine fractures using minimally invasive percutaneous stabilization plus balloon kyphoplasty: a 102-patient series.

BACKGROUND: There is no consensus on the treatment for spinal injuries resulting in thoracolumbar fractures without neurological impairment. Many trauma centers are opting for open surgery rather than a neurointerventional approach combining posterior percutaneous short fixation (PPSF) plus balloon kyphoplasty (BK). OBJECTIVE: To assess the safety and efficacy of PPSF+BK and to estimate the expected improvement by clarifying the factors that influence improvement. METHODS: We retrospectively reviewed patients who underwent PPSF+BK for the treatment of single traumatic thoracolumbar fractures from 2007 to 2019. Kyphosis, loss of vertebral body height (VBH), clinical and functional outcomes including visual analog scale and Oswestry disability index were assessed. We examined the overall effects in all patients by constructing a linear statistical model, and then examined whether efficacy was dependent on the characteristics of the patients or the fractures. RESULTS: A total of 102 patients were included. No patient experienced neurological worsening or wound infections. The average rates of change were 74.4% (95% CI 72.6% to 76.1%) for kyphosis and 85.5% (95% CI 84.4% to 86.6%) for VBH (both p<0.0001). The kyphosis treatment was more effective on Magerl A3 and B2 fractures than on those classified as A2.3, as well as for fractures with slight posterior wall protrusion on the spinal canal. A higher postoperative visual analog scale score was predictive of poorer outcome at 1 year. CONCLUSIONS: This is the largest series reported to date and confirms and validates this surgical treatment. All patients exhibited improved kyphosis and restoration of VBH. We advise opting for this technique rather than open surgery.

Surgical Site Infections after glioblastoma surgery: results of a multicentric retrospective study.

BACKGROUND: The effects of surgical site infections (SSI) after glioblastoma surgery on patient outcomes are understudied. The aim of this retrospective multicenter study was to evaluate the impact of SSI on the survival of glioblastoma patients. METHODS: Data from SSI cases after glioblastoma surgeries between 2009 and 2016 were collected from 14 French neurosurgical centers. Collected data included patient demographics, previous medical history, risk factors, details of the surgical procedure, radiotherapy/chemotherapy, infection characteristics, and infection management. Similar data were collected from gender- and age-paired control individuals. RESULTS: We used the medical records of 77 SSI patients and 58 control individuals. 13 were excluded. Our analyses included data from 64 SSI cases and 58 non-infected glioblastoma patients. Infections occurred after surgery for primary tumors in 38 cases (group I) and after surgery for a recurrent tumor in 26 cases (group II). Median survival was 381, 633, and 547 days in patients of group I, group II, and the control group, respectively. Patients in group I had significantly shorter survival compared to the other two groups (p < 0.05). The one-year survival rate of patients who developed infections after surgery for primary tumors was 50%. Additionally, we found that SSIs led to postoperative treatment discontinuation in 30% of the patients. DISCUSSION: Our findings highlighted the severity of SSIs after glioblastoma surgery, as they significantly affect patient survival. The establishment of preventive measures, as well as guidelines for the management of SSIs, is of high clinical importance.

Systematic review of patient reported outcomes (PROs) and quality of life measures after pressurized intraperitoneal aerosol chemotherapy (PIPAC).

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) constitutes a recently described surgical technique to administer chemotherapy directly to the peritoneum, under pressure, for patients with peritoneal metastasis (PM). The purpose of an oncological treatment is to improve survival but without altering the patient's quality of life. The aim of this review was to evaluate patient-reported outcomes (PRO) after PIPAC for patients with PM. This systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Between January 1, 2013, and January 1, 2020, studies were selected according to the following criteria: "pressurized intraperitoneal aerosol chemotherapy" OR "PIPAC" AND "patient-reported outcomes" OR "PRO" OR "Quality of life". In this review, 959 PIPAC and five PITAC (Pressurized IntraThoracic Aerosol Chemotherapy) were performed in 425 patients. We highlight the prominent application of generic EORTC QLQ-C30 followed by SF-36 in this review. The PROs according to the EORTC-QLQ-C30 global health score and based on symptom and function scores were stable across most studies. Moreover, PIPAC has improved the PRO of altered patients in two studies. Among 425 patients, the mortality rate was 0.7% and adverse events of Common Terminology Criteria of Adverse Events grade 3 and grade 4 were 9.6% and 1.6%, respectively. We synthesised current research on PROs among patients with PM. This review increases our understanding of the PIPAC strategy from the patient perspective. The implementation of PROs can be complex but will be essential in delivering quality care.

Immunotherapy in Corticotroph and Lactotroph Aggressive Tumors and Carcinomas: Two Case Reports and a Review of the Literature.

Once temozolomide has failed, no other treatment is recommended for pituitary carcinomas and aggressive pituitary tumors. Recently, the use of immune checkpoint inhibitors (ICIs) has raised hope, but so far, only one corticotroph carcinoma and one aggressive corticotroph tumor treated with immunotherapies have been reported in the literature. Here, we present two cases, one corticotroph carcinoma and one aggressive prolactinoma (the first one reported in the literature) treated with ipilimumab (1 mg/kg) and nivolumab (3 mg/kg) every three weeks, followed by maintenance treatment with nivolumab (3 mg/kg every 2 weeks) in the case of the corticotroph carcinoma, and we compare them with the two previously reported cases. Patient #1 presented a biochemical partial response (plasma ACTH decreased from 13,813 to 841 pg/mL) and dissociated radiological response to the combined ipilimumab and nivolumab-the pituitary mass decreased from 37 × 32 × 41 to 29 × 23 × 42 mm, and the pre-existing liver metastases decreased in size (the largest one from 45 to 14 mm) or disappeared, while a new 11-mm liver metastasis appeared. The maintenance nivolumab (21 cycles) resulted in a stable disease for the initial liver metastases, and in progressive disease for the newly appeared metastasis (effectively treated with radiofrequency ablation) and the pituitary mass. Patient #2 presented radiological and biochemical progressive disease after two cycles of ICIs-the pituitary mass increased from 38 × 42 × 26 to 53 × 57 × 44 mm, and the prolactin levels increased from 4410 to 9840 ng/mL. In conclusion, ICIs represent a promising therapeutic option for aggressive pituitary tumors and carcinomas. The identification of subgroups of responders will be key.

Megakaryocytes use in vivo podosome-like structures working collectively to penetrate the endothelial barrier of bone marrow sinusoids.

BACKGROUND: Blood platelets are anucleate cell fragments that prevent bleeding and minimize blood vessel injury. They are formed from the cytoplasm of megakaryocytes located in the bone marrow. For successful platelet production, megakaryocyte fragments must pass through the sinusoid endothelial barrier by a cell biology process unique to these giant cells as compared with erythrocytes and leukocytes. Currently, the mechanisms by which megakaryocytes interact and progress through the endothelial cells are not understood, resulting in a significant gap in our knowledge of platelet production. OBJECTIVE: The aim of this study was to investigate how megakaryocytes interact and progress through the endothelial cells of mouse bone marrow sinusoids. METHODS: We used a combination of fluorescence, electron, and three-dimensional microscopy to characterize the cellular events between megakaryocytes and endothelial cells. RESULTS: We identified protrusive, F-actin-based podosome-like structures, called in vivo-MK podosomes, which initiate the formation of pores through endothelial cells. These structures present a collective and spatial organization through their interconnection via a contractile network of actomyosin, essential to regulate the endothelial openings. This ensures proper passage of megakaryocyte-derived processes into the blood circulation to promote thrombopoiesis. CONCLUSION: This study provides novel insight into the in vivo function of podosomes of megakaryocytes with critical importance to platelet production.

[High fidelity simulation training for medical oncology announcement consultation]. / Simulation haute-fidélité à la consultation d'annonce en oncologie médicale.

INTRODUCTION: Medical oncology bad news consultation is a particularly stressful situation for both the patient and the physician. High-fidelity simulation is a learning option that has never been evaluated in France in this field. MATERIALS AND METHODS: This is a feedback from simulated announcement consultations carried out from January 2018 to May 2019. Residents from the medical oncology and radiotherapy departments performed high-fidelity simulations at the announcement consultation with an announcement nurse, a psychologist, a certified coach and an oncologist. A competency assessment was completed in pre-test, immediate post-test and after 5 months. RESULTS: Fourteen of the 16 eligible interns participated. The pre-test competency assessment showed that interns over 5 semesters reported being more comfortable at the consultation (P=0.04) and thought they were clearly explaining the disease (P=0.03). However, all residents, regardless of the semester, felt stressed before a consultation. The evolution of parameters skills after the simulation was positive for all criteria, particularly for adaptation to patient reactions, use of appropriate vocabulary and reduction of stress (P<0.05). This evolution was independent of the gender, curriculum, semester, or previous completion of a medical oncology internship. More than 80% of the students were ready to repeat this type of training. CONCLUSION: This training demonstrates the value of simulation training for medical oncology advertising consultation.