Traumatismes oculaires, principale cause de cécité unilatérale. Les impératifs de cette chirurgie sont analgésie, normotonie,stabilité du patient. But de l’étude : évaluer l’efficacité et sécurité de ...l’anesthésie locorégionale.
Étude prospective,descriptive,colligeant 186 patients opérés sous ALR sur 2ans (2012–2013). Population étudiée définie par sexe, âge, ASA, type de traumatisme, modalité d’anesthésie sont exclus âge<18ans et monophtalme. Modalité d’anesthésie : péribulbaire (injection lente, faible volume, sans compression), bloc facial, topique. Facteurs évalués et critères de jugement. Efficacité : analgésie (score ENA 0–10), Akinésie (score 0–4), variation PIO (hypertonie.normotonie) satisfaction chirurgiens et patients (note 0/10). Sécurité : incidents locaux par élévation de PIO (Hémorragie choroïdienne expulsive, Issue du vitré). Incidents généraux (Décompensation de pathologies associées, réflexes à point de départ oculaire, instabilité psychologique). Résultats exprimés en moyenne,pourcentage.
Âge moyen 39ans. Sex-ratio 4,38. ASA I 46 %, ASA (III+IV) 26 %. Durée opératoire 60 mn. Plaie du globe 80 %, canaliculaire 11 %, paupière 9 % .Peribulbaire 72 %,Topique 16 %, Bloc facial 12 %. Efficacité : volume moyen 6 cc. Analgésie adéquate ENA<3 (93 % à la ponction, 97 % peropératoire, 81 % postopératoire). Akinésie satisfaisante>3/4 chez 86 % des patients. Normotonie 93 %. note de satisfaction>7/10(93 % chirurgiens,88 % patients). Sécurité : absence de complication locales,équilibre satisfaisant des pathologies associées. Stabilité hémodynamique, respiratoire et psychologique,baisse NVPO.
Traumatisme oculaire représente 20 % des urgences ophtalmique 1. Concerne la population masculine jeune. Chirurgie précoce souhaitable vu le risque infectieux et pronostic visuel>6h. Anesthésie en urgence,met en balance le bénéfice chirurgical (préserver la vision)et risque anesthésique (âge, jeun comorbidité) 2. Le choix est réfléchit entre AG et ALR. Anesthésie générale5. Avantages :Immobilité du patient, control de la PIO, couvre la durée opératoire. Inconvénients : recours aux explorations (cause de report d’intervention), incidents hémodynamique et respiratoir, risque allergique, élévation PIO à intubation, NVPO, douleur postopératoire. Anesthésie locorégionale 5 Avantages : limite les explorations, écourte le délai opératoire, stabilité hémodynamique,sécurité respiratoire 4, réduit NVPO analgésie postopératoire, simple, économique, mobilise peu de personnel. Inconvénients : coopération du patient, risque de complication spécifique (perforation du globe), apprentissage particulier indications classiques de l’anesthésie pour urgences ophtalmiques 3. Topique : lésion superficielle), anesthésie locorégionale : plaie de cornée simple localisée anesthésie générale : plaie du globe oculaire, voies lacrymales, paupières. Conclusion : ALR pratiquée par un anesthésisté expérimenté répond aux impératifs de la chirurgie traumatique de l’oeil. C’est une technique simple,sécurisante économique,appelée à se développer dans cette indication.
As the first FDA-approved tyrosine kinase inhibitor for treatment of patients with myelofibrosis (MF), ruxolitinib improves clinical symptoms but does not lead to eradication of the disease or ...significant reduction of the mutated allele burden. The resistance of MF clones against the suppressive action of ruxolitinib may be due to intrinsic or extrinsic mechanisms leading to activity of additional pro-survival genes or signalling pathways that function independently of JAK2/STAT5. To identify alternative therapeutic targets, we applied a pooled-shRNA library targeting ~5000 genes to a JAK2V617F-positive cell line under a variety of conditions, including absence or presence of ruxolitinib and in the presence of a bone marrow microenvironment-like culture medium. We identified several proteasomal gene family members as essential to HEL cell survival. The importance of these genes was validated in MF cells using the proteasomal inhibitor carfilzomib, which also enhanced lethality in combination with ruxolitinib. We also showed that proteasome gene expression is reduced by ruxolitinib in MF CD34+ cells and that additional targeting of proteasomal activity by carfilzomib enhances the inhibitory action of ruxolitinib in vitro. Hence, this study suggests a potential role for proteasome inhibitors in combination with ruxolitinib for management of MF patients.
Molecular failure in NPM1-mutated acute myeloid leukemia (AML) inevitably progresses to frank relapse if untreated. Recently published small case series show that venetoclax combined with low-dose ...cytarabine or azacitidine can reduce or eliminate measurable residual disease (MRD). Here, we report on an international multicenter cohort of 79 patients treated for molecular failure with venetoclax combinations and report an overall molecular response (≥1-log reduction in MRD) in 66 patients (84%) and MRD negativity in 56 (71%). Eighteen of 79 patients (23%) required hospitalization, and no deaths were reported during treatment. Forty-one patients were bridged to allogeneic transplant with no further therapy, and 25 of 41 were MRD negative assessed by reverse transcription quantitative polymerase chain reaction before transplant. Overall survival (OS) for the whole cohort at 2 years was 67%, event-free survival (EFS) was 45%, and in responding patients, there was no difference in survival in those who received a transplant using time-dependent analysis. Presence of FLT3-ITD mutation was associated with a lower response rate (64 vs 91%; P < .01), worse OS (hazard ratio HR, 2.50; 95% confidence interval CI, 1.06-5.86; P = .036), and EFS (HR, 1.87; 95% CI, 1.06-3.28; P = .03). Eighteen of 35 patients who did not undergo transplant became MRD negative and stopped treatment after a median of 10 months, with 2-year molecular relapse free survival of 62% from the end of treatment. Venetoclax-based low intensive chemotherapy is a potentially effective treatment for molecular relapse in NPM1-mutated AML, either as a bridge to transplant or as definitive therapy.
Conditions and thresholds applied for evidence weighting of within-codon concordance (PM5) for pathogenicity vary widely between laboratories and expert groups. Because of the sparseness of available ...clinical classifications, there is little evidence for variation in practice.
We used as a truthset 7541 dichotomous functional classifications of BRCA1 and MSH2, spanning 311 codons of BRCA1 and 918 codons of MSH2, generated from large-scale functional assays that have been shown to correlate excellently with clinical classifications. We assessed PM5 at 5 stringencies with incorporation of 8 in silico tools. For each analysis, we quantified a positive likelihood ratio (pLR, true positive rate/false positive rate), the predictive value of PM5-lookup in ClinVar compared with the functional truthset.
pLR was 16.3 (10.6-24.9) for variants for which there was exactly 1 additional colocated deleterious variant on ClinVar, and the variant under examination was equally or more damaging when analyzed using BLOSUM62. pLR was 71.5 (37.8-135.3) for variants for which there were 2 or more colocated deleterious ClinVar variants, and the variant under examination was equally or more damaging than at least 1 colocated variant when analyzed using BLOSUM62.
These analyses support the graded use of PM5, with potential to use it at higher evidence weighting where more stringent criteria are met.
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