L'Afrique

A. Volvey (dir.

NOS knockout or inhibition but not disrupting PSD-95-NOS interaction protect against ischemic brain damage

Promising results have been reported in preclinical stroke target validation for pharmacological principles that disrupt the N-methyl-D-aspartate receptor-post-synaptic density protein-95-neuronal nitric oxide synthase complex. However, post-synaptic density protein-95 is also coupled to potentially neuroprotective mechanisms. As post-synaptic density protein-95 inhibitors may interfere with potentially neuroprotective mechanisms and sufficient validation has often been an issue in translating basic stroke research, we wanted to close that gap by comparing post-synaptic density protein-95 inhibitors with NOS1(-/-) mice and a NOS inhibitor. We confirm the deleterious role of NOS1 in stroke both invivo and invitro, but find three pharmacological post-synaptic density protein-95 inhibitors to be therapeutically ineffective

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created. This consortium is composed of the various national cooperative groups and their respective member institutions. The strategic value of this project is based on the Europe-wide data collection concerning the treatment of VRTs. These data are provided to experts and constitute the basis for new clinical practice guidelines for use by ERN (European Reference Network) and non-ERN institutions. The proposed tasks and milestones will increase collaboration in the field of pediatric oncology among member states and will also facilitate the inclusion of low health expenditure average rate (LHEAR) countries in this process. In addition, this project creates a platform for VRTs that may represent a model on how to elaborate a comprehensive approach (case registration, international case consultation and treatment recommendations, and website to provide information for parents/patients) for rare diseases

Adrenocortical Tumors in Children and Adolescents: The European PARTN-ER Project for Consensus Guidelines Development.

Background and Aims: Adrenocortical carcinomas (ACC) are rare diseases. Several collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis andmanagement of pediatric ACC are still unavailable. Methods: We present European consensus guidelines developed by the Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) according to the ESMO scale, based on the evidence collected from published series, case reports and personal expertise. Results: ACT should be removed without rupture [Level V; Grade B]. Preferred option is open approach through a lateral transverse abdominal incision or a midline laparotomy in case of huge masses [Level IV; Grade B]. Mini-invasive surgery should be discouraged when volume exceeds 200cm3, suspicious regional nodal involvement and/or signs of local invasion are present [Level IV; Grade B]. All enlarged lymph nodes detected at radiology or intra-operatively should be removed [Level III; Grade A]. A systematic biopsy of the regional nodes should be performed, though they are not found suspicious pre- or intraoperatively [Level IV; Grade C]. Adjuvant therapy should be considered in advanced-stage ACT or in case of incomplete tumor resection [Level IV; Grade B]. First-line recommended regimen is CED (cisplatinum-etoposide-doxorubicin) plus mitotane [Level IV; Grade B]. For COG stage II tumors, mitotane is considered if several risk factors are associated: unfavorable histology (5-item score or Wieneke score >3), older age, hormonal secretion [Level IV; Grade C]. For unresectable tumors, gross/macroscopic residual disease, retroperitoneal lymph nodes involvement, CED with mitotane are considered [Level III; Grade B]. No data exist about the optimal duration of therapy. CED is usually scheduled in 6 to 8 cycles. Mitotane is continued for 1 to 2 years depending on patient\u2019s tolerance and compliance [Level IV; Grade C]. Conclusions: This European PARTN-ER project leads to a consensus strategy regarding the treatment of children and adolescents with ACC

Inspiration-promoting vagal reflex under NMDA receptor blockade in anaesthetized rabbits

This study describes a novel vagal respiratory reflex in anaesthetized rabbits. In contrast to the well-known inspiratory (I) off-switching by vagal afferent excitation, this vagal reflex initiates and maintains the central I activity of phrenic nerve discharges in rabbits pre-treated with antagonists of N-methyl-D-aspartate-type excitatory amino acid receptors (NMDA-Rs).Under NMDA-R blockade with either dizocilpine (0·025-0·3 mg kg−1), D-2-amino-5-phosphonopentanoic acid (AP5, 0·5-1 mg, i.c.v.) or ketamine (10 mg kg−1), vagal stimulation at low frequencies (5-40 Hz) during the I phase prevented or markedly delayed the spontaneous I termination. In contrast, stimulation of the same vagal afferent at the same intensity but at a higher frequency (100-160 Hz) during the I phase immediately terminated the I phase.In non-vagotomized rabbits, maintaining the tidal volume at end-expiratory levels during the I phase prevented spontaneous I termination and maintained apneusis after NMDA-R blockade with dizocilpine.Brief stimulation of vagal afferents at low frequency (5-40 Hz) during the expiratory (E) phase constantly initiated phrenic I discharge after NMDA-R block.We conclude that low-frequency discharge of vagal pulmonary stretch receptor afferents, as when lung volume is near functional residual capacity, promotes central I activity under NMDA-R blockade

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations

Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT). Main recommendations include induction chemotherapy with cisplatin and 5-flurouracil, concomitant chemoradiotherapy in advanced disease, and to consider maintenance treatment with interferon beta (IFN-\u3b2) for selected high-risk patients. Dose adjustments of radiotherapy based on response to induction chemotherapy may decrease the rates of long-term treatment-related complications that affect most of the survivors