Akkermansia muciniphila upregulates genes involved in maintaining the intestinal barrier function via ADP-heptose-dependent activation of the ALPK1/TIFA pathway.

The commensal bacteria that make up the gut microbiota impact the health of their host on multiple levels. In particular, the interactions taking place between the microbe-associated molecule patterns (MAMPs) and pattern recognition receptors (PRRs), expressed by intestinal epithelial cells (IECs), are crucial for maintaining intestinal homeostasis. While numerous studies showed that TLRs and NLRs are involved in the control of gut homeostasis by commensal bacteria, the role of additional innate immune receptors remains unclear. Here, we seek for novel MAMP-PRR interactions involved in the beneficial effect of the commensal bacterium Akkermansia muciniphila on intestinal homeostasis. We show that A. muciniphila strongly activates NF-κB in IECs by releasing one or more potent activating metabolites into the microenvironment. By using drugs, chemical and gene-editing tools, we found that the released metabolite(s) enter(s) epithelial cells and activate(s) NF-κB via an ALPK1, TIFA and TRAF6-dependent pathway. Furthermore, we show that the released molecule has the biological characteristics of the ALPK1 ligand ADP-heptose. Finally, we show that A. muciniphila induces the expression of the MUC2, BIRC3 and TNFAIP3 genes involved in the maintenance of the intestinal barrier function and that this process is dependent on TIFA. Altogether, our data strongly suggest that the commensal A. muciniphila promotes intestinal homeostasis by activating the ALPK1/TIFA/TRAF6 axis, an innate immune pathway exclusively described so far in the context of Gram-negative bacterial infections.

Chiari malformation type I surgery in children: French multicenter 10-year cohort.

OBJECTIVE: Chiari malformation type I (CM-I) is frequent in children and remains a surgical challenge. Several techniques have been described for posterior fossa decompression. No decision algorithm has been validated, and strategies are highly variable between institutions. The goal of this study was to define therapeutic guidelines that take into consideration patient specificities. METHODS: The authors retrospectively collected data from patients who were < 18 years of age, were diagnosed with CM-I, and were treated surgically between 2008 and 2018 in 8 French pediatric neurosurgical centers. Data on clinical features, morphological parameters, and surgical techniques were collected. Clinical outcomes at 3 and 12 months after surgery were assessed by the Chicago Chiari Outcome Scale. The authors used a hierarchical clustering method to define clusters of patients by considering their anatomical similarities, and then compared outcomes between surgical strategies in each of these clusters. RESULTS: Data from 255 patients were collected. The mean age at surgery was 9.6 ± 5.0 years, syringomyelia was reported in 60.2% of patients, the dura mater was opened in 65.0% of patients, and 17.3% of patients underwent a redo surgery for additional treatment. The mean Chicago Chiari Outcome Scale score was 14.4 ± 1.5 at 3 months (n = 211) and 14.6 ± 1.9 at 12 months (n = 157). The hierarchical clustering method identified three subgroups with potentially distinct mechanisms underlying tonsillar herniation: bony compression, basilar invagination, and foramen magnum obstruction. Each cluster matched with specific outcomes. CONCLUSIONS: This French multicenter retrospective cohort study enabled the identification of three subgroups among pediatric patients who underwent surgery for CM-I, each of which was associated with specific outcomes. This morphological classification of patients might help in understanding the underlying mechanisms and providing personalized treatment.

A case series of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

In this study, we report three paediatric cases of Diffuse Glioneuronal Tumours with Oligodendroglioma-like features and Nuclear Clusters (DGONC).

Decompressive Craniectomy in Children with Severe Traumatic Brain Injury: A Multicenter Retrospective Study and Literature Review.

BACKGROUND: Severe traumatic brain injury (TBI) is the most common cause of disability in children. Refractory increased intracranial pressure can be a therapeutic challenge. Decompressive craniectomy can be proposed when medical management is insufficient, but its place is not clearly defined in guidelines. The aim of this study was to identify prognostic factors in children with TBI. METHODS: We performed a retrospective, multicenter study to analyze long-term outcomes of 150 children with severe TBI treated by decompressive craniectomy and to identify prognostic factors. RESULTS: A satisfactory neurologic evolution (represented by a King's Outcome Scale for Childhood Head Injury score >3) was observed in 62% of children with a mean follow-up of 3.5 years. Mortality rate was 17%. Prognostic factors associated with outcome were age, initial Glasgow Coma Scale score, presence of mydriasis, neuromonitoring values (maximal intracranial pressure >30 mm Hg), and radiologic findings (Rotterdam score ≥4). CONCLUSIONS: This study in a large population confirms that children with severe TBI treated by decompressive craniectomy can achieve a good neurologic outcome. Further studies are needed to clarify the use of this surgery in the management of children with severe TBI.

Awake Surgery for Gliomas within the Right Inferior Parietal Lobule: New Insights into the Functional Connectivity Gained from Stimulation Mapping and Surgical Implications.

OBJECTIVE: Little is known about the functional role of the white matter connections running within and around the right inferior parietal lobule (IPL). We used direct electrostimulation during awake surgery to investigate this connectivity and to avoid permanent deficit after resection for right IPL gliomas. METHODS: We reviewed patients who underwent awake mapping for a glioma involving the right IPL. Resection was achieved up to functional corticosubcortical boundaries detected by electrostimulation. Results of the intraoperative mapping were confronted to preoperative and postoperative magnetic resonance imaging to perform anatomofunctional correlations. RESULTS: Fourteen consecutive patients were enrolled (9 men; mean age, 44 years). Cortically, the resection was limited anteriorly by the retrocentral somatosensory area (11 patients) or by the precentral motor cortex (3 patients). Subcortically, the thalamocortical pathways were identified anteriorly in all patients. Articulatory disturbances were elicited anteriorly and laterally (6 patients) corresponding to the superior longitudinal fasciculus part III. Deeper and superiorly, stimulating the superior longitudinal fasciculus part II or the arcuate fasciculus induced spatial disorders (6 patients). More laterally and posteriorly, disrupting the inferior fronto-occipital fasciculus induced nonverbal semantic disorders (7 patients). Six patients had visual deficits while the optic radiations were stimulated. A total or subtotal resection was achieved in all patients but one. There were no permanent impairments, except an expected left superior quadrantanopia in 4 patients. CONCLUSIONS: This is the first surgical series focusing on right IPL gliomas. The complex functional connectivity detected within and around this region fully supports the use of intraoperative multimodal functional mapping for optimizing outcomes.