Facteurs de risque lors de la conduite d'un projet de mise en place d'un dispositif de veille anticipative dans plusieurs organismes du secteur public

Le présent article s'intéresse aux facteurs de risque susceptibles d'advenir lors de la conduite de projets de mise en place d'un dispositif de veille anticipative stratégique. Sur la base d'une recherche action/intervention au sein de plusieurs organismes du secteur public, les chercheurs ont confronté, plusieurs des facteurs déjà identifiés dans des études antérieures concernant les risques des projets de SI et de veille à ceux rencontrés lors de leur intervention. L'objectif de cette confrontation est d'une part l'identification de facteurs de risques des projets de veille identiques à ceux des projets de SI et d'autre part, l'identification de facteurs de risques spécifiques aux projets de veille. L'intérêt de l'article d'un point de vu théorique est d'avoir fait émerger quatre hypothèses de nouveaux facteurs de risque qui sont autant de pistes de recherche. Il s'agit du mode de communication en face à face, du soutien du " middle management ", du choix du moment de mise en place du projet et du choix du chef de projet. D'un point de vu managérial, cette recherche permet de construire un début de connaissances actionnables permettant de faire de recommandations fondées à un chef de projet de veille démarrant sa tâche dans un tel contexte.Projet de SI, Veille anticipative stratégique, facteur de risque, secteur public, recherche action/intervention

Ocular lesions in hereditary hemorrhagic telangiectasia: genetics and clinical characteristics

Background: The aim of our study is to study the association between eye lesions in Hereditary Hemorrhagic Telangiectasia (HHT) and other signs of the disease, as well as to characterize its genetics. Methods: A cross-sectional study was conducted of a cohort of 206 patients studied in the HHT Unit of Hospital de Sierrallana, a reference centre for Spanish patients with HHT. Odds ratios for several symptoms or characteristics of HHT and ocular lesions were estimated using logistic regression adjusting for age and sex. Results: The ocular involvement was associated with being a carrier of a mutation for the ENG gene, that is, suffering from a type 1 HHT involvement (OR = 2.09; 95% CI [1.17–3.72]). p = 0.012). In contrast, patients with ocular lesions have less frequently mutated ACVRL1/ALK1 gene (OR = 0.52; 95% CI [0.30–3.88], p = 0.022). Conclusions: In conclusion, half of the patients with HHT in our study have ocular involvement. These eye lesions are associated with mutations in the ENG gene and ACVRL1/ALK1 gene. Thus, the ENG gene increases the risk of ocular lesions, while being a carrier of the mutated ACVRL1/ALK1 gene decreases said risk

Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies are a heterogeneous group of early-onset epilepsy syndromes dramatically impairing neurodevelopment. Modern genomic technologies have revealed a number of monogenic origins and opened the door to therapeutic hopes. Here we describe a new syndromic developmental and epileptic encephalopathy caused by bi-allelic loss-of-function variants in GAD1, as presented by 11 patients from six independent consanguineous families. Seizure onset occurred in the first 2 months of life in all patients. All 10 patients, from whom early disease history was available, presented with seizure onset in the first month of life, mainly consisting of epileptic spasms or myoclonic seizures. Early EEG showed suppression-burst or pattern of burst attenuation or hypsarrhythmia if only recorded in the post-neonatal period. Eight patients had joint contractures and/or pes equinovarus. Seven patients presented a cleft palate and two also had an omphalocele, reproducing the phenotype of the knockout Gad1-/- mouse model. Four patients died before 4 years of age. GAD1 encodes the glutamate decarboxylase enzyme GAD67, a critical actor of the γ-aminobutyric acid (GABA) metabolism as it catalyses the decarboxylation of glutamic acid to form GABA. Our findings evoke a novel syndrome related to GAD67 deficiency, characterized by the unique association of developmental and epileptic encephalopathies, cleft palate, joint contractures and/or omphalocele

Predictive value of baseline [18f]fdg pet/ct for response to systemic therapy in patients with advanced melanoma

Background/Aim: To evaluate the association between baseline [18F]FDG-PET/CT tumor burden parameters and disease progression rate after first-line target therapy or immunotherapy in advanced melanoma patients. Materials and Methods: Forty four melanoma patients, who underwent [18F]FDG-PET/CT before first-line target therapy (28/44) or immunotherapy (16/44), were retrospectively analyzed. Whole-body and per-district metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. Therapy response was assessed according to RECIST 1.1 on CT scan at 3 (early) and 12 (late) months. PET parameters were compared using the Mann–Whitney test. Optimal cut-offs for predicting progression were defined using the ROC curve. PFS and OS were studied using Kaplan–Meier analysis. Results: Median (IQR) MTVwb and TLGwb were 13.1 mL and 72.4, respectively. Non-responder patients were 38/44, 26/28 and 12/16 at early evaluation, and 33/44, 21/28 and 12/16 at late evaluation in the whole-cohort, target, and immunotherapy subgroup, respectively. At late evaluation, MTVbone and TLGbone were higher in non-responders compared to responder patients (all p < 0.037) in the whole-cohort and target subgroup and MTVwb and TLGwb (all p < 0.022) in target subgroup. No significant differences were found for the immunotherapy subgroup. No metabolic parameters were able to predict PFS. Controversially, MTVlfn, TLGlfn, MTVsoft + lfn, TLGsoft + lfn, MTVwb and TLGwb were significantly associated (all p < 0.05) with OS in both the whole-cohort and target therapy subgroup. Conclusions: Higher values of whole-body and bone metabolic parameters were correlated with poorer outcome, while higher values of whole-body, lymph node and soft tissue metabolic parameters were correlated with OS

Mutation analysis of "Endoglin" and "Activin receptor-like kinase" genes in German patients with hereditary hemorrhagic telangiectasia and the value of rapid genotyping using an allele-specific PCR-technique

<p>Abstract</p> <p>Background</p> <p>Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is an autosomal dominant disorder which is clinically characterised by recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations. Genetic linkage studies identified two genes primarily related to HHT: endoglin (<it>ENG</it>) on chromosome 9q33-34 and activin receptor-like kinase1 (<it>ACVRL1</it>) on chromosome 12q13. We have screened a total of 41 unselected German patients with the suspected diagnosis of HHT. Mutation analysis for the <it>ENG </it>and <it>ACVRL1 </it>genes in all patients was performed by PCR amplification. Sequences were then compared to the HHT database <url>http://www.hhtmutation.org</url> sequences of the <it>ENG </it>mRNA (accession no. BC014271.2) and the <it>ACVRL1 </it>mRNA (accession no. NM000020.1).</p> <p>Results</p> <p>We identified 15 different mutations in 18 cases by direct sequencing. Among these mutations, one novel <it>ENG </it>mutation could be detected which has not yet been described in the literature before. The genotype-phenotype correlation was consistent with a higher frequency of pulmonary arteriovenous malformations in patients with <it>ENG </it>mutations than in patients with <it>ACVRL1 </it>mutations in our collective.</p> <p>Conclusion</p> <p>For rapid genotyping of mutations and SNPs (single nucleotide polymorphisms) in <it>ENG </it>and <it>ACVRL1</it>, allele-specific PCR methods with sequence-specific primers (PCR-SSP) were established and their value analysed.</p

Concurrent chemoradiation in anal cancer patients delivered with bone marrow-sparing imrt: Final results of a prospective phase ii trial

We investigated the role of the selective avoidance of haematopoietically active pelvic bone marrow (BM), with a targeted intensity-modulated radiotherapy (IMRT) approach, to reduce acute hematologic toxicity (HT) in anal cancer patients undergoing concurrent chemo-radiation. We designed a one-armed two-stage Simon’s design study to test the hypothesis that BM-sparing IMRT would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05; β = 0.20). A minimum of 21/39 (54%) with G0–G2 toxicity represented the threshold for the fulfilment of the criteria to define this approach as ‘promising’. We employed18 FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. From December 2017 to October 2020, we enrolled 39 patients. Maximum observed acute HT comprised 20% rate of ≥G3 leukopenia and 11% rate of ≥G3 thrombocytopenia. Overall, 11 out of 39 treated patients (28%) experienced ≥G3 acute HT. Conversely, in 28 patients (72%) G0–G2 HT events were observed, above the threshold set. Hence,18 FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in this clinical setting

Progressive Myoclonus Epilepsy Caused by a Homozygous Splicing Variant of SLC7A6OS

Exome sequencing was performed in 2 unrelated families with progressive myoclonus epilepsy. Affected individuals from both families shared a rare, homozygous c.191A > G variant affecting a splice site in SLC7A6OS. Analysis of cDNA from lymphoblastoid cells demonstrated partial splice site abolition and the creation of an abnormal isoform. Quantitative reverse transcriptase polymerase chain reaction and Western blot showed a marked reduction of protein expression. Haplotype analysis identified a similar to 0.85cM shared genomic region on chromosome 16q encompassing the c.191A > G variant, consistent with a distant ancestor common to both families. Our results suggest that biallelic loss-of-function variants in SLC7A6OS are a novel genetic cause of progressive myoclonus epilepsy. ANN NEUROL 2020Peer reviewe