AIM: To evaluate the antiviral potency of a new antihepatitis C virus(HCV) antiviral agent targeting the cellular autophagy machinery. METHODS: Non-infected liver slices, obtained from human liver ...resection and cut in 350 μm-thick slices(2.7 × 106 cells per slice) were infected with cell culture-grown HCV Con1b/C3 supernatant(multiplicity of infection = 0.1) cultivated for up to ten days. HCV infected slices were treated at day 4 post-infection with GNS-396 for 6 d at different concentrations. HCV replication was evaluated by strand-specific real-time quantitative reverse transcription- polymerase chain reaction. The infectivity titers of supernatants were evaluated by foci formation upon inoculation into naive Huh-7.5.1 cells. The cytotoxic effect of the drugs was evaluated by lactate dehydrogenase leakage assays. RESULTS: The antiviral efficacy of a new antiviral drug, GNS-396, an autophagy inhibitor, on HCV infection of adult human liver slices was evidenced in a dosedependent manner. At day 6 post-treatment, GNS-396 EC50 was 158 nmol/L without cytotoxic effect(compared to hydroxychloroquine EC50 = 1.17 μmol/L).CONCLUSION: Our results demonstrated that our ex vivo model is efficient for evaluation the potency of autophagy inhibitors, in particular a new quinoline derivative GNS-396 as antiviral could inhibit HCV infection in a dosedependent manner without cytotoxic effect.
Les gliomes de haut grade IDH-mutés prennent souvent le contraste. Cependant la fréquence et la valeur pronostique de la prise de contraste (PC) au sein de ces tumeurs restent à déterminer.
Décrire ...la fréquence et la valeur pronostique de la PC au sein des gliomes de haut grade IDH-mutés diagnostiqués (classification OMS 2021).
Étude rétrospective au sein des gliomes de haut grade IDH-mutés inclus dans le réseau POLA dans une série de référence (IRM relues, n=108) et au sein d’une série de validation (n=684, annotation disponible dans l’e-crf).
Dans la série de référence et la série de validation, une PC était plus fréquente dans les oligodendrogliomes de grade 3 (O3) et les astrocytomes de grade 4 (A4) que dans les astrocytomes de grade 3 (A3), 75 %, 63 % vs 46 % (p<0,001) et 70 %, 78 % vs 53 % (p<0,001). Dans les 2 séries, la présence d’une PC était associée à un moins bon pronostic au sein des O3 (p=0,08 et p=0,006), indépendamment de l’âge, de l’index de Karnofsky et du type de traitement initial (p=0,001).
La fréquence et la valeur pronostique de la PC varient au sein des gliomes de haut grade IDH-mutés.
Face à une suspicion clinicoradiologique de gliome IDH-muté, l’absence de PC ne permet pas d’écarter le diagnostic de gliome de haut grade. Au sein des oligodendrogliomes, l’existence d’une PC est associée à un moins bon pronostic.
We combine Dark Energy Survey Year 1 clustering and weak lensing data with baryon acoustic oscillations and Big Bang nucleosynthesis experiments to constrain the Hubble constant. Assuming a flat ΛCDM ...model with minimal neutrino mass (∑m_ν = 0.06 eV), we find |$H_0=67.4^{+1.1}_{-1.2}\ \rm {km\,\rm s^{-1}\,\rm Mpc^{-1}}$| (68 per cent CL). This result is completely independent of Hubble constant measurements based on the distance ladder, cosmic microwave background anisotropies (both temperature and polarization), and strong lensing constraints. There are now five data sets that: (a) have no shared observational systematics; and (b) each constrains the Hubble constant with fractional uncertainty at the few-per cent level. We compare these five independent estimates, and find that, as a set, the differences between them are significant at the 2.5σ level (χ^2/dof = 24/11, probability to exceed = 1.1 per cent). Having set the threshold for consistency at 3σ, we combine all five data sets to arrive at |$H_0=69.3^{+0.4}_{-0.6}\ \rm {km\,\mathrm{ s}^{-1}\,\mathrm{ Mpc}^{-1}}$|.
A new curative embolization technique with Onyx for selected small and medium-sized superficially located brain AVMs was developed, which consists of obliteration of the nidus, including incremental ...occlusion of the draining veins. We report our first clinical results.
Between June 2008 and July 2011, 24 patients (7 women, 17 men; mean age, 41 years; range, 6-74 years) with AVMs were selected for curative embolization with Onyx. Presentation was hemorrhage in 14 and seizures in 10 patients. AVM location was frontal in 11, occipital in 6, parietal in 4, and temporal in 3. AVM size was a mean of 2.2 cm (median, 2; range, 1-3 cm).
Complete angiographic obliteration of the AVM with Onyx in a single session was achieved in all 24 patients. There were no hemorrhagic or ischemic complications (0%; 95% CI, 0%-16.3%), and no new deficits induced by the treatment. Of 14 patients with ruptured AVMs, 1 patient who presented with a large frontal hematoma died shortly after surgical evacuation of the hematoma following complete embolization of a micro-AVM. Follow-up angiography at 3 months in 23 patients demonstrated a small AVM remnant in 1 that was treated with gamma knife radiosurgery. The other 22 AVMs remained completely occluded.
In selected patients with small and medium-sized superficial brain AVMs, as defined in our study, injection of Onyx by using a curative embolization technique in a single session seems to provide a safe and effective alternative to radiosurgery or surgery.
Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a ...kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.
The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update ...of the 2018 guideline from KDIGO.
The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence.
The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.
PDF
