Le rôle du lactate et du N-acétylcystéine intra-tympanique dans la prévention de l’ototoxicité secondaire au cisplatin

Objectifs Aucun agent n’a été approuvé pour prévenir l’ototoxicité secondaire au cisplatin. Nos objectifs consistaient à évaluer la protection auditive offerte par le lactate et le N-acétylcystéine (NAC) intra-tympaniques après injection de cisplatin, ainsi que l’absorption systémique du NAC intra-tympanique. Méthodes Seize cochons d’inde formaient 2 groupes ayant reçu une solution de lactate et de NAC à 20% dans l’oreille testée. L’oreille contro-latérale a reçu une solution saline contrôle. Après 30 minutes, une injection intrapéritonéale de 3 mg/kg de cisplatin a été effectuée et répétée une fois par semaine jusqu’à une dose finale de 24 mg/kg. Les potentiels évoqués auditifs du tronc cérébral (PEATC) ont été mesurés avant les injections, après 9 mg/kg et 24 mg/kg de cisplatin. Les cochlées ont été analysées au microscope électronique à balayage. La diffusion systémique du NAC a été évaluée par chromatographie en phase liquide. Résultats Pour les oreilles contrôles, les seuils auditifs des PEATC ont augmenté uniformément sur toutes les fréquences (28,4 dB en moyenne). Le groupe lactate montrait une augmentation moins importante (17,0 dB). Les basses fréquences étaient nettement moins affectées. Le groupe NAC a subi une augmentation des seuils de 89 dB. La microscopie électronique a démontré une préservation partielle des cellules ciliées externes des cochlées traitées au lactate et une destruction complète de celles traitées au NAC. La chromatographie n’a démontré aucune diffusion de NAC. Conclusions Le lactate offre une protection partielle significative contre l’ototoxicité induite par le cisplatin. Les injections de NAC n’offrent pas de protection lorsque administrées en concentrations élevée. Le NAC intra-tympanique ne se diffuse pas systémiquement.Objectives There is no approved agent to prevent cisplatin-induced ototoxicity. Our objectives are to identify and compare the protective effect of intratympanic injections of lactate or N-acetylcysteine (NAC) in the prevention of cisplatin-induced ototoxicity and to study systemic diffusion of intratympanic NAC. Methods Sixteen guinea pigs, forming two groups, received respectively intratympanic lactate and 20% NAC in one ear. The contra-lateral ears received a control saline solution. After 30 minutes, an intra-peritoneal cisplatin injection of 3 mg/kg was performed and repeated once a week to achieve a final dose of 24mg/kg. Auditory brainstem responses (ABR) were recorded before any injection, after 9mg/kg and after 24mg/kg of cisplatin for the frequencies 2, 4, 6 and 8kHz. Cochleas were analyzed under scanning electron microscope. Systemic diffusion of NAC was studied using high performance liquid chromatography. Results For the control ears, ABR thresholds increased uniformly by an average of 28.4dB. The lactate group showed a lower threshold increase by an average of 17.0dB. The NAC showed an important threshold increase of 89.0dB. Lactate showed a significant hearing protection at 2000Hz (p<0.01). Electron microscopy revealed partial preservation of cochlear outer hair cells stereocilia for the ears treated with lactate and severe disruption for NAC group. No systemic diffusion of NAC was observed with chromatography. Conclusion Lactate offers significant partial protection against cisplatin-induced ototoxicity. NAC does not offer any protection when administered in high concentrations. Intratympanic NAC does not diffuse systemically

Extracellular Vesicles in Sickle Cell Disease: Plasma Concentration, Blood Cell Types Origin Distribution and Biological Properties

International audiencePrototype of monogenic disorder, sickle cell disease (SCD) is caused by a unique single mutation in the β-globin gene, leading to the production of the abnormal hemoglobin S (HbS). HbS polymerization in deoxygenated condition induces the sickling of red blood cells (RBCs), which become less deformable and more fragile, and thus prone to lysis. In addition to anemia, SCD patients may exhibit a plethora of clinical manifestations ranging from acute complications such as the frequent and debilitating painful vaso-occlusive crisis to chronic end organ damages. Several interrelated pathophysiological processes have been described, including impaired blood rheology, increased blood cell adhesion, coagulation, inflammation and enhanced oxidative stress among others. During the last two decades, it has been shown that extracellular vesicles (EVs), defined as cell-derived anucleated particles delimited by a lipid bilayer, and comprising small EVs (sEVs) and medium/large EVs (m/lEVs); are not only biomarkers but also subcellular actors in SCD pathophysiology. Plasma concentration of m/lEVs, originated mainly from RBCs and platelets (PLTs) but also from the other blood cell types, is higher in SCD patients than in healthy controls. The concentration and the density of externalized phosphatidylserine of those released from RBCs may vary according to clinical status (crisis vs. steady state) and treatment (hydroxyurea). Besides their procoagulant properties initially described, RBC-m/lEVs may promote inflammation through their effects on monocytes/macrophages and endothelial cells. Although less intensely studied, sEVs plasma concentration is increased in SCD and these EVs may cause endothelial damages. In addition, sEVs released from activated PLTs trigger PLT-neutrophil aggregation involved in lung vaso-occlusion in sickle mice. Altogether, these data clearly indicate that EVs are both biomarkers and bio-effectors in SCD, which deserve further studies

Extracellular Vesicles in Sickle Cell Disease: A Promising Tool

International audienceSickle cell disease (SCD) is the most common hemoglobinopathy worldwide. It is characterized by an impairment of shear stress-mediated vasodilation, a pro-coagulant, and a pro-adhesive state orchestrated among others by the depletion of the vasodilator nitric oxide, by the increased phosphatidylserine exposure and tissue factor expression, and by the increased interactions of erythrocytes with endothelial cells that mediate the overexpression of adhesion molecules such as VCAM-1, respectively. Extracellular vesicles (EVs) have been shown to be novel actors involved in SCD pathophysiological processes. Medium-sized EVs, also called microparticles, which exhibit increased plasma levels in this pathology, were shown to induce the activation of endothelial cells, thereby increasing neutrophil adhesion, a key process potentially leading to the main complication associated with SCD, vaso-occlusive crises (VOCs). Small-sized EVs, also named exosomes, which have also been reported to be overrepresented in SCD, were shown to potentiate interactions between erythrocytes and platelets, and to trigger endothelial monolayer disruption, two processes also known to favor the occurrence of VOCs. In this review we provide an overview of the current knowledge about EVs concentration and role in SCD

Cranial approaches to sellar and parasellar tumors

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Delayed facial nerve decompression for severe refractory cases of Bell’s palsy: a 25-year experience

Abstract Background This study aims to assess the effectiveness of delayed facial nerve decompression for Bell’s palsy (BP). Methods We performed a retrospective case review of all patients having undergone facial nerve decompression for severe refractory BP between 1984 and 2009 at our tertiary referral center. Demographics, timing between onset of symptoms and surgical decompression, degree of facial nerve dysfunction pre- and post-operatively, follow-up length after surgery and postoperative complications were recorded. Facial nerve dysfunction was assessed using the House-Brackmann (HB) scale. Electroneuronography, electromyography and imaging results were assessed when available. Results Eighteen patients had surgery between 21 and 60 days after onset of BP (group I), and 18 patients had surgery more than 60 days after onset of symptoms (group II). In group II, 11 patients had surgery between 61 and 89 days and 7 patients after 90 days. Groups I and II showed similar functional gain and rates of improvement to HB 3 or better (11/18 vs. 11/18, p > 0.05). In group II, patients operated 60 to 89 days after onset of BP showed a significantly higher rate of improvement to HB 3 or better (9/11 vs. 2/6, p = 0.049) with higher functional gain compared to those operated after 90 days (p = 0.0293). Conclusions When indicated, facial nerve decompression for BP is usually recommended within the first 2 weeks of onset of facial paralysis. Nonetheless, our results suggest that patients with severe BP could benefit from decompression surgery within 90 days after onset of symptoms in the absence of an opportunity to proceed earlier to surgery. Further investigation is still required to confirm our findings. Trial registration Retrospective registered. IRB# 2016–6154, CE 15.154 – C

Clostridium difficile infection secondary to ileostomy closure

Protective ileostomy may be a risk factor for the development of Clostridium difficile (CD) infection (CDI). In the postoperative period signs of CDI may be particularly difficult to differentiate from intra-abdominal sepsis. Presented here are 2 cases that developed CDI after ileostomy reversal. Two patients who underwent low anterior resections after neoadjuvant chemoradiation with protective ileostomy developed fever, leukocytosis and elevated serum C-reactive protein (CRP) levels. The first patient also had negative CD stool toxins and his signs were so severe that he underwent a negative diagnostic laparoscopy and re-creation of ileostomy. The second patient who presented in a similar fashion was more fortunate in that her CD stool toxin was positive and she was treated successfully with oral vancomycin. CDI after ileostomy reversal after low anterior resection can be difficult to diagnose. In the first patient, the situation was so misleading that diagnostic laparoscopy was required. Outcome was eventually favorable in both cases. CDI must be high on the list of differential diagnoses for febrile patients with a leukocytosis and elevated CRP level even in the setting of negative CD stool toxins. Prophylactic intravenous metronidazole and/or vancomycin enemas should be considered prior to colorectal surgery when a protective ileostomy is likely

Does endurance training improve red blood cell aging and hemorheology in moderate-trained healthy individuals?

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Primary Pineal Melanoma With Leptomeningeal Carcinomatosis

Pineal region tumors commonly present with features of increased intracranial pressure such as headache, nausea, and vomiting due to obstructive hydrocephalus. Parinaud syndrome is also common

Proliferative retinopathy and maculopathy are two independent conditions in sickle cell disease: Is there a role of blood rheology?1

International audienceOur study investigated the prevalence of retinopathy and maculopathy in sickle cell patients and tested the association between these two conditions. In addition, we tested whether hematological and hemorheological parameters, as well as genotype, were involved in the development of these two conditions

Biological scoring system for early prediction of acute bowel ischemia after cardiac surgery: the PALM score

Abstract Background Bowel ischemia is a life-threatening emergency defined as an inadequate vascular perfusion leading to bowel inflammation resulting from impaired colonic/small bowel blood supply. Main issue for physicians regarding bowel ischemia diagnosis lies in the absence of informative and specific clinical or biological signs leading to delayed management, resulting in a poorer prognosis, especially after cardiac surgery. The aim of the present series was to propose a simple scoring system based on biological data for the diagnosis of bowel ischemia. Methods In a retrospective monocentric study, patients admitted in cardiac ICU, after cardiovascular surgery, were screened for inclusion. According to a 1:2 ratio (case–control), matching between two groups was based on sex, type of cardiovascular surgery, and the operative period (per month). Patients were divided into two groups: “ischemic group” which corresponds to patients with confirmed bowel ischemia and “non-ischemic group” which corresponds to patients without bowel ischemia. Primary objective was the conception of a scoring system for the diagnosis of bowel ischemia. Secondary objectives were to detail the postoperative morbidity and the diagnostic features for the distinction between acute mesenteric ischemia and ischemic colitis. Results Forty-eight patients (1.3%) had confirmed bowel ischemia (“ischemic group”). According to the 2:1 matching, 96 patients were included in the “non-ischemic group.” Aspartate aminotransferase > 449 UI/L, lactate > 4 mmol/L, procalcitonin > 4.7 μg/L, and myoglobin > 1882 μg/L were found to be independently associated with bowel ischemia. Based on their respective odds ratios, points were assigned to each item ranging from 4 to 8. AUROCC [95% confidence interval] of the scoring system to diagnose bowel ischemia was 0.93 [0.91–0.95], p < 0.001. The optimal threshold after bootstrapping was ≥ 14 points; this yielded a sensitivity of 85.4%, a specificity of 94.8%, a positive likelihood ratio of 16.42, a negative likelihood ratio of 0.15, a Youden’s index of 0.802, and a diagnostic odds ratio of 106.62. Conclusions A biological scoring system based on PCT, ASAT, lactate, and myoglobin measurement allows the diagnosis of bowel ischemia after cardiac surgery with high accuracy. This score could help clinician to propose an early diagnosis and an early treatment in this high mortality disease