Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy

Perfusion Imaging to select patients with large ischemic core for mechanical thrombectomy

International audienceBackground and purpose: Patients with acute ischemic stroke, proximal vessel occlusion and a large ischemic core at presentation are commonly not considered for mechanical thrombectomy (MT). We tested the hypothesis that in patients with baseline large infarct cores, identification of remaining penumbral tissue using perfusion imaging would translate to better outcomes after MT.Methods: This was a multicenter, retrospective, core lab adjudicated, cohort study of adult patients with proximal vessel occlusion, a large ischemic core volume (diffusion weighted imaging volume ≥70 mL), with pre-treatment magnetic resonance imaging perfusion, treated with MT (2015 to 2018) or medical care alone (controls; before 2015). Primary outcome measure was 3-month favorable outcome (defined as a modified Rankin Scale of 0-3). Core perfusion mismatch ratio (CPMR) was defined as the volume of critically hypo-perfused tissue (Tmax >6 seconds) divided by the core volume. Multivariable logistic regression models were used to determine factors that were independently associated with clinical outcomes. Outputs are displayed as adjusted odds ratio (aOR) and 95% confidence interval (CI).Results: A total of 172 patients were included (MT n=130; Control n=42; mean age 69.0±15.4 years; 36% females). Mean core-volume and CPMR were 102.3±36.7 and 1.8±0.7 mL, respectively. As hypothesized, receiving MT was associated with increased probability of favorable outcome and functional independence, as CPMR increased, a difference becoming statistically significant above a mismatch-ratio of 1.72. Similarly, receiving MT was also associated with favorable outcome in the subgroup of 74 patients with CPMR >1.7 (aOR, 8.12; 95% CI, 1.24 to 53.11; P=0.028). Overall (prior to stratification by CPMR) 73 (42.4%) patients had a favorable outcome at 3 months, with no difference amongst groups.Conclusion: s In patients currently deemed ineligible for MT due to large infarct ischemic cores at baseline, CPMR identifies a subgroup strongly benefiting from MT. Prospective studies are warranted

High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia

<p>Abstract</p> <p>Background</p> <p>The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia.</p> <p>Methods</p> <p>Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm.</p> <p>Results</p> <p>Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm³and the median viral load was 4.7 Log₁₀. Second-line regimens prescribed were ddI/3TC/LPV_/r(65.7%), ddI/TDF/LPV_/r(10.0%), ddI/AZT/LPV_/r(8.6%) and TDF/3TC/LPV_/r(7.1%). The median CD4 T cell gain was +258 cells/mm³at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis.</p> <p>Conclusions</p> <p>These data suggest that a LPV_/r-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.</p

Efficacité et morbi-mortalité de la radio-chirurgie dans le traitement des MAVs cérébrales non rompues ≤ 5cc éligibles selon ARUBA : étude d'une cohorte de 249 patients

Thèse présentée sous la forme d'une "Thèse Article"Objectif : selon ARUBA, le traitement conservateur des malformations artério-veineuses cérébrales (MAV) non rompues serait supérieur à tout type d’intervention. Notre objectif est d'évaluer l’efficacité et les effets secondaire de la radiochirurgie stéréotaxique (RCS) chez les patients porteurs de MAV répondant aux critères d’inclusion selon ARUBA.Matériels et méthodes : nous avons évalué la morbi-mortalité à moyen terme des MAV cérébrales naïves non rompues avec un volume ⩽ 5 cc et éligibles selon l’étude ARUBA après traitement par Gamma-Knife (GKRS) et avec un suivi minimum de 3 ans.Résultats : de 1992 à 2014, 249 patients répondaient à nos critères d'inclusion. L'âge médian était de 36 ans (18-78). Le volume médian du nidus traité était de 1,3 cm3 (0,4-5) et 63% des MAV étaient situés dans des zones éloquentes (n=157). Pour la plupart des MAV, le RBAS était entre 1-1,8 (76%) (n=190), le grade de Spetzler-Martin entre II-III (73%) (n=180), le VBAS était évalué ≤1 point pour 75% des patients (n=187).Le taux global d'oblitération des MAV était de 77,1% après au moins 3 GKRS. Après 1 GKRS, le taux d'oblitération était de 67% et 73,5% après 2 GKRS. La dose moyenne à la marge était de 24 Gy (15-25) et le suivi moyen de 45,04 mois (36-205,28). Le taux de saignement jusqu’au dernier suivi était de 3.2% (n=8) correspondant à un taux annuel de 1.03%. Le taux de changements induits par les radiations (CIR) symptomatiques permanents était de 2% (n=5), parmi lesquels 4 patients ont présenté une majoration de la manifestation épileptique initiale et 1 patient a présenté une apparition de déficit neurologique (2.1%). Aucun patient ne présentait de radionécrose ni de kyste radio-induit lors du dernier suivi.Conclusion : nos résultats ne confirment pas les conclusions d’ARUBA. L’association du taux très faible de toxicité associé au taux d'occlusion élevé orienterait en faveur d’une stratégie initiale par GKRS pour les petites MAV non rompues

Pediatric haemorrhagic stroke : etiological, diagnostic and prognostic radiological assessment

La maladie hémorragique intracrânienne chez l’enfant (hors traumatisme) reste encore une entité trop méconnue avec des conséquences médicales et psychosociales dramatiques. Son épidémiologie relativement rare, est à l'origine d’une absence de littérature avec un niveau de preuve robuste et d'une absence de recommandations internationales spécifiques. Les déterminants clinique et radiologique guidant la pratique actuelle sont actuellement basés sur l'expérience plutôt que sur des données issues de grandes populations. Les AVC hémorragiques chez l’enfant sont majoritairement expliqués par une cause macrovasculaire, avec une prédominance de rupture de malformations artérioveineuses (MAV). L’évaluation étiologique d’un AVC hémorragique à la phase aigüe revêt alors une place importante car les prises en charge diagnostique, thérapeutique, pronostique et de suivi sont adaptées à l’étiologie sous-jacente. En nous basant sur une cohorte inédite de plus de 250 enfants victimes d'hémorragie cérébrale, nous avons évalué l’apport d’une séquence IRM innovante non invasive tant sur le diagnostic étiologique à la phase aigüe que sur le suivi à long-terme. De plus, devant le caractère dynamique des MAV avec une tendance au recrutement d’artères nourricières dysplasiques, nous avons évalué le devenir des MAV considérées «guéries» à travers l’évaluation de leur taux de récurrence dans une revue systématique de la littérature avec méta-analyse. Dans une perspective de développement de modalités diagnostiques et d’élaboration d’agents thérapeutiques innovants, nous avons validé et comparé deux modèles pré-cliniques de MAV à travers l’utilisation d’un marqueur métabolique innovant.Pediatric intracranial hemorrhage (pICH) disease in children (excluding trauma) is still a poorly understood entity with dramatic medical and psychosocial consequences. Its relatively rare epidemiology is explaining the lack of literature with a good level of evidence and lack of specific international guidelines. Clinical and radiological determinants guiding current practice are currently based on experience rather than on data from large cohort. PICH is predominantly explained by a macrovascular cause, with a predominance of arteriovenous malformation (AVM) rupture. The etiological workup of a pICH in the acute phase is therefore important, as the diagnostic, therapeutic, prognostic and follow-up management will be adapted to the underlying etiology. Based on a cohort of more than two hundred and fifty children with pICH treated between 2000 and 2020 at the Necker Hospital (Paris, France), we evaluated the contribution of an innovative non-invasive advanced MRI technique for the etiological diagnosis in the acute phase as well as in the long-term follow-up. Moreover, since AVMs are dynamic in nature, we evaluated the fate of "cured" AVMs by assessing their recurrence rate in a systematic review of the literature with meta-analysis. While various therapeutic management modalities in ruptured AVMs have been widely developed, the pathology was first modeled only 44 years ago without any validation other than immunohistochemical. In a perspective of developing innovative diagnostic imaging and therapeutic agents, we have validated and compared two preclinical models of AVM using an innovative metabolic marker

Hypocalcemia-induced seizure with Fahr’s syndrome

International audienceIntroduction Fahr's syndrome is a rare but severe brain complication of hypoparathyroidism and its consequences. Case Presentation A 72-year-old female patient was hospitalized in intensive care unit after two generalized seizures along with a severe hypocalcemia, due to hypoparathyroidism following a thyroidectomy for benign nodules and poor compliance with calcium treatment with treatment due to cognitive disorders. Brain CT showed cortical atrophy and extensive bilateral symmetrical calcifications of the cerebellum, thalami and basal ganglia, typical of Fahr's syndrome. Conclusion Nephrologists should be aware Fahr's syndrome in patients with hypoparathyroidism, it is associated with an increased risk of seizures. Thus, the control of calcemia in hypoparathyroidism is important, especially in patients with brain calcifications

Kidney disease and stroke: epidemiology and potential mechanisms of susceptibility

ABSTRACT Patients with chronic kidney disease (CKD) have an increased risk of both ischaemic and haemorrhagic stroke compared with the general population. Both acute and chronic kidney impairment are independently associated with poor outcome after the onset of a stroke, after adjustment for confounders. End-stage kidney disease (ESKD) is associated with a 7- and 9-fold increased incidence of both ischaemic and haemorrhagic strokes, respectively, poorer neurological outcome and a 3-fold higher mortality. Acute kidney injury (AKI) occurs in 12% of patients with stroke and is associated with a 4-fold increased mortality and unfavourable functional outcome. CKD patients seem to have less access to revascularisation techniques like thrombolysis and thrombectomy despite their poorer prognosis. Even if CKD patients could benefit from these specific treatments in acute ischaemic stroke, their prognosis remains poor. After thrombolysis, CKD is associated with a 40% increased risk of intracerebral haemorrhage (ICH), a 20% increase in mortality and poorer functional neurological outcomes. After thrombectomy, CKD is not associated with ICH but is still associated with increased mortality, and AKI with unfavourable outcome and mortality. The beneficial impact of gliflozins on the prevention of stroke is still uncertain. Non-traditional risk factors of stroke, like uraemic toxins, can lead to chronic cerebrovascular disease predisposing to stroke in CKD, notably through an increase in the blood–brain barrier permeability and impaired coagulation and thrombosis mechanisms. Preclinical and clinical studies are needed to specifically assess the impact of these non-traditional risk factors on stroke incidence and outcomes, aiming to optimize and identify potential therapeutic targets

Key parameters influencing metallic element mobility associated with sediments in a daily-managed reservoir

International audienceIn a hydroelectric reservoir, sediments are subject to remobilization events, water-level fluctuations and physicochemical changes. Depending on their associated metallic content, surficial oxic to suboxic sediments could constitute a major source of metals. To identify the key parameters that control metallic elements in terms of their mobility and sensitivity to reservoir management, sediments were subject to resuspension and drying/wetting cycle experiments over a wide range of pH values, solid/liquid ratios (S/L) and redox (Eh) conditions. During these tests, special attention was also paid to the influence of pretreatments on samples, i.e., drying, aeration and the leachate composition (ultrapure water vs. natural water); on the preservation of the sediment characteristics; and especially on metallic element release. The results of this study show that the pH, S/L ratio and Eh parameters are key variables in metal solubilization; the pH influences metal mobility primarily through sorption-desorption phenomena as well as the dissolution of metallic-bearing phases, the S/L ratio modifies the sorption-desorption equilibria, and the Eh primarily affects the reducible sensitive phases and associated metallic elements through dissolution-precipitation processes. Under environmental conditions, evolution of these parameters can lead to a > 20% solubilization of the most mobile elements, i.e., As and Cd. These results are influenced by the sample pretreatment and experimental conditions. In fact, even if the solubilization patterns show no significant differences between dry and wet sediment depending on the physicochemical conditions, the magnitude of their release is significantly affected. Drying pretreatment induces changes in metal speciation, notably altering the distribution of the most weakly bound elements; there is almost half the amount of metallic elements associated with the exchangeable fraction in dry compared to wet sediments. The solubilization percentages were higher in the ultrapure phase than in reservoir water primarily due to the low pH, which influenced the sorption equilibria