Deep Learning Methods for Detecting Side Effects of Cancer Chemotherapies Reported in a Remote Monitoring Web Application.

The objective of our work was to develop deep learning methods for extracting and normalizing patient-reported free-text side effects in a cancer chemotherapy side effect remote monitoring web application. The F-measure was 0.79 for the medical concept extraction model and 0.85 for the negation extraction model (Bi-LSTM-CRF). The next step was the normalization. Of the 1040 unique concepts in the dataset, 62, 3% scored 1 (corresponding to a perfect match with an UMLS CUI). These methods need to be improved to allow their integration into home telemonitoring devices for automatic notification of the hospital oncologists.

Designing and describing an electronic referral system to facilitate direct hospital admissions.

BACKGROUND: In France, the progressive use of emergency departments (EDs) by primary care providers (PCPs) as a point of access to hospitalization for nonurgent patients is one of the many causes of their overcrowding. To increase the proportion of direct hospital admissions, it is necessary to improve coordination between PCPs and hospital specialists. The objective of our work was to describe the design and implementation of an electronic referral system aimed at facilitating direct hospital admissions. METHODS: This initiative was conducted in a French area (Hauts-de-Seine Sud) through a partnership between the Antoine-Béclère University Hospital, the Paris-Saclay University Department of General Medicine and the local health care network. The implementation was carried out in 3 stages, namely, conducting a survey of PCPs in the territory about their communication methods with the hospital, designing and implementing a web-based application called "SIPILINK" (Système d'Information de la Plateforme d'Intermédiation Link) and an innovative organization for hospital management of the requests, and analysing through descriptive statistics the platform use 9 months after launch. RESULTS: The e-referral platform was launched in November 2019. First, a PCP filled out an electronic form describing the reason for his or her request. Then, a hospital specialist worked to respond within 72 h. Nine months after the launch, 132 PCPs had registered for the SIPILINK platform, which represented 36.6% of PCPs in this area. Of the 124 requests made, 46.8% corresponded to a hospitalization request (conventional or day hospitalization). The most requested specialty was internal medicine (48.4% of requests). The median time to first response was 43 min, and 43.5% of these requests resulted in direct admission (conventional or day hospitalization). CONCLUSIONS: This type of system responds to a need for coordination in the primary-secondary care direction, which is less often addressed than in the secondary-primary care direction. The first results show the potential of the system to facilitate direct admissions within a short time frame. To make the system sustainable, the next step is to extend its use to other hospitals in the territory.

Glycemic response, satiety, gastric secretions and emptying after bread consumption with water, tea or lemon juice: a randomized crossover intervention using MRI.

PURPOSE: Numerous studies, including our previous work with lemon juice, have reported that low-pH meals reduce the glycemic response to starchy foods. However, the underlying mechanism is not yet understood. Tea, for its polyphenol content, has also been investigated. The main objective of this research was to concurrently study gastric emptying, appetite perceptions and glycemic responses to bread consumed with water, tea, or lemon juice. METHODS: In this randomized, crossover intervention, ten participants consumed equal portions of bread (100 g) with 250 mL of water, water-diluted lemon juice, or black tea at breakfast. Gastric volumes, blood glucose concentrations and appetite perceptions were alternately assessed over 180 min using magnetic resonance imaging, the finger-prick method and visual analogue scales, respectively. RESULTS: Compared to water, lemon juice led to a 1.5 fold increase of the volume of gastric contents, 30 min after the meal (454.0 ± 18.6 vs. 298.4 ± 19.5 mL, [Formula: see text] ± SEM P < 0.00001). Gastric emptying was also 1.5 times faster (P < 0.01). Conversely, lemon juice elicited a lower glycemic response than water (blood glucose concentrations at t = 55 min were 35% lower, P = 0.039). Tea had no effect. Changes in appetite perceptions and gastric volumes correlated well, but with no significant differences between the meals. CONCLUSIONS: Lemon juice lowered the glycemic response and increased both gastric secretions and emptying rate. The results are compatible with the hypothesis that the reduction of the glycemic response is mainly due to the interruption of starch hydrolysis via the acid-inhibition of salivary α-amylase. TRIAL REGISTRATION NUMBER: NCT03265392, August 29, 2017.

Lemon juice, but not tea, reduces the glycemic response to bread in healthy volunteers: a randomized crossover trial.

PURPOSE: The inhibition of enzymes that hydrolyze starch during digestion could constitute an opportunity to slow down the release, and ultimately the uptake, of starch-derived glucose. Simple dietary approaches consisting in pairing starch-rich foods with beverages that have the capacity to inhibit such enzymes could be an effective and easily implementable strategy. The objective of this work was to test the impact of black tea and lemon juice on the glycemic response to bread and subsequent energy intake in healthy adults. METHODS: A randomized crossover study was conducted with equal portions of bread (100 g) and 250 ml of water, black tea or lemon juice. Capillary blood glucose concentrations were monitored during 180 min using the finger-prick method. Ad libitum energy intake was assessed 3 h later. RESULTS: Tea had no effect on the glycemic response. Lemon juice significantly lowered the mean blood glucose concentration peak by 30% (p < 0.01) and delayed it more than 35 min (78 vs. 41 min with water, p < 0.0001). None of the tested beverages had an effect on ad libitum energy intake. CONCLUSION: These results are in agreement with previous in vitro studies showing that lowering the pH of a meal can slow down starch digestion through premature inhibition of salivary α-amylase. Furthermore, the effect of lemon juice was similar to what has been repeatedly observed with vinegar and other acidic foods. Including acidic beverages or foods in starchy meals thus appears to be a simple and effective strategy to reduce their glycemic impact.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Self-Induced Crystallization in Charged Gold Nanoparticle-Semiflexible Biopolyelectrolyte Complexes.

Mixing negatively charged polyelectrolyte (PEL) with positively charged gold nanoparticles (Au NPs) in aqueous solution results in electrostatics complexes of different shapes and compactness. Here, when complexing with a semirigid PEL hyaluronic acid (HA), we obtain crystals made of nanoparticles in a new region of the phase diagram, as evidenced by small-angle X-ray scattering (SAXS). The Au NPs were initially well dispersed in solution; their size distribution is well controlled but does not need to be extremely narrow. The bacterial hyaluronic acid, polydispersed, is commercially available. Such rather simple materials and mixing preparation produce a highly ordered crystalline phase of electrostatic complexes. The details of the interactions between spherical nanoparticles and linear polymer chains remain to be investigated. In practice, it opens a completely new and unexpected method of complexation. It has high potential, in particular because one can take advantage of the versatility of Au NPs associated with the specificity of biopolymers, varied due to natural biodiversity.

In situ BCL2 expression is an independent prognostic factor in HIV-associated DLBCL, a LYMPHOVIR cohort study.

The prognostic value of cell of origin (COO) classification and BCL2 expression is not well established in diffuse large B-cell lymphoma (DLBCL) patients with human immunodeficiency virus (HIV) infection in the recent era. Phenotypic patterns were determined by immunohistochemistry (IHC) of pathological samples from patients with HIV-associated DLBCL prospectively enrolled in the French AIDS and Viral Hepatitis CO16 Lymphovir cohort between 2008 and 2015. Molecular subgroup classification into germinal centre B-cell (GCB) and non-GCB subtypes was determined using the Hans algorithm. Among 52 samples of systemic DLBCL subjected to centralized pathological analysis, 25 of the 42 tested for BCL2 expression were positive. Samples were further classified into GCB (n = 19) and non-GCB (n = 16) subtypes and 17 remained unclassified. In multivariable analysis, BCL2 expression was an independent pejorative prognostic biomarker [4-year progression-free survival (PFS): 52% for BCL2+ vs. 88% for BCL2- , P = 0·02] and tended to reduce 4-year overall survival (OS) (63% for BCL2+ vs. 88% for BCL2- , P = 0·06). The difference between CGB and non-GCB subtypes on PFS and OS did not reach significance (4-year PFS: 79% for GCB vs. 53% for non-GCB, P = 0·24 and 4-year OS: 78% for GCB vs. 69% for non-GCB, P = 0·34). BCL2 expression determined by IHC is an independent pejorative prognostic biomarker in HIV-associated DLBCL in the recent era. This supports the investigation of new therapeutic strategies in patients with BCL2 expression.

Hepatitis C virus or hepatitis B virus coinfection and lymphoma risk in people living with HIV.

OBJECTIVE: Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are associated with increased risks of lymphomas in the non-HIV setting. Their impacts on HIV-associated lymphomas deserved further studies in the modern combined antiretroviral therapy (cART) era. DESIGN: We evaluated the associations between HCV, HBV and HIV-related lymphomas in the Lymphovir-ANRS-CO16 cohort. METHODS: Prevalence of HCV seropositivity and chronic HBV infections were compared with those observed in the French Hospital Database on HIV (FHDH-ANRS-CO4). RESULTS: Between 2008 and 2015, 179 patients with HIV-related lymphomas from 32 French hospitals were enrolled, 69 had Hodgkin's lymphoma (39%), and 110 non-Hodgkin's lymphoma (NHL) (61%). The prevalence of HCV infection was higher in patients with NHL than in the FHDH-ANRS-CO4 [26 versus 14%, odd ratio (OR): 2.15; 95% confidence interval (1.35-3.32)] whereas there was no association between Hodgkin's lymphoma and chronic HCV infection. Chronic HBV infection was not associated with NHL in our cohort with a prevalence of 5 versus 7% in FHDH-ANRS-CO4 but tended to be associated with Hodgkin's lymphoma [prevalence of 14%, OR: 2.16 (0.98-4.27)]. Chronic HCV infection tended to pejoratively impact 2-year overall survival in patients with NHL: 72% [57%, 91%] versus 82% [74%, 91%], hazard ratio: 2.14 [0.95-4.84]. In contrast, chronic HBV infection did not correlate with outcome. CONCLUSION: In the modern cART era, chronic HCV infection is associated with an increased risk of NHL in PLWHIV and tends to pejoratively impact overall survival. HBV infection is not associated with the risk of NHL but with a borderline increase of Hodgkin's lymphoma risk.

Tuning the Structure of Galacturonate Hydrogels: External Gelation by Ca, Zn, or Fe Cationic Cross-Linkers.

We show here how the nature of various divalent cations M2+ (Ca2+, Zn2+, or Fe2+) influences the structure and mechanical properties of ionotropic polygalacturonate (polyGal) hydrogels designed by the diffusion of cations along one direction (external gelation). All hydrogels exhibit strong gradients of polyGal and cation concentrations, which are similar for all studied cations with a constant ratio R = [M2+]/[Gal] equal to 0.25, showing that every M2+ cation interacts with four galacturonate (Gal) units all along the gels. The regions of the hydrogels formed in the early stages of the gelation process are also similar for all cations and are homogeneous, with the same characteristic mesh size (75 ± 5 Å, as measured by small angle neutron scattering (SANS)) and the same storage modulus G' (∼5 × 104 Pa). Conversely, in the regions of the gels formed in later stages of the process there exist differences in mechanical properties, turbidity, and local structure from one cation to another. Zn(II)-polyGal and Fe(II)-polyGal hydrogels display mesoscopic heterogeneities, more marked in case of Fe than for Zn, that are not present in Ca(II)-polyGal hydrogels. This comes from the mode and the strength of association between the cation and the Gal unit (bidentate for Ca2+ and monodentate "egg-box" for Zn2+ and Fe2+). Cross-links formed by Zn2+ and Fe2+ have a higher stability (lower ability to untie and reform) that induces the formation of local heterogeneities in the early stages of the gelation process whose size progressively increases during the gel growth, a mechanism that does not occur for cross-links made by Ca2+ that are less stable and enable possible reorganizations between polyGal chains.

Respective roles of migration and social deprivation for virological non-suppression in HIV-infected adults on antiretroviral therapy in France.

Barriers to achieve sustained HIV virological suppression on antiretroviral therapy (ART) jeopardize the success of the 90:90:90 UNAIDS initiative which aims to end the HIV/AIDS epidemic. In France, where access to ART is free and universally available, we analyze the way in which social determinants of health (i.e. cultural, environmental) and economic factors might influence virological outcomes. A cross-sectional study was performed in two hospitals located in Paris area. All consecutive people living with HIV (PLHIV) on ART for at least 6 months attending the outpatient clinics between 01/05/2013 and 31/10/2014 answered an individual score of deprivation, EPICES, retrieving information on health insurance status, economic status, family support and leisure activity. This score varies from 0 to 100 with deprivation state defined above 30.17. Factors associated with HIV viral load >50 copies/ml were assessed by logistic regression modeling with a backward stepwise selection to select the final multivariable model. Sensitivity analyses were performed using two other thresholds for virological non-suppression (100 or 200 copies/ml). Overall, 475 PLHIV were included (53% male, median age 47 years, 66% not born in France mainly in a sub-Saharan African country). Half of French natives and 85% of migrants were classified as deprived. Median duration on ART was 9.7 years with virological suppression in 95.2% of non-deprived participants and in 83.5% of deprived ones (p = 0.001). The final multivariable model retained ART tiredness, younger age, a previous AIDS event and social deprivation (adjusted Odds Ratio, 2.9; 95%CI, 1.2-7.0) as determinants of virological non-suppression but not migration in itself. When using separate components of EPICES score, reporting economic difficulties and non-homeownership were associated with virological non-suppression. In addition to interventions focusing on cultural aspects of migration, social interventions are needed to help people with social vulnerability to obtain sustained responses on ART.

Factors associated with DAA virological treatment failure and resistance-associated substitutions description in HIV/HCV coinfected patients.

AIM: To describe factors associated with treatment failure and frequency of resistance-associated substitutions (RAS). METHODS: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients starting a first direct-acting antiviral (DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligible. Failure was defined as: (1) non-response [HCV-RNA remained detectable during treatment, at end of treatment (EOT)]; and (2) relapse (HCV-RNA suppressed at EOT but detectable thereafter). Sequencing analysis was performed to describe prevalence of drug class-specific RAS. Factors associated with failure were determined using logistic regression models. RESULTS: Among 559 patients, 77% had suppressed plasma HIV-RNA < 50 copies/mL at DAA treatment initiation, 41% were cirrhotic, and 68% were HCV treatment-experienced. Virological treatment failures occurred in 22 patients and were mainly relapses (17, 77%) then undefined failures (3, 14%) and non-responses (2, 9%). Mean treatment duration was 16 wk overall. Post-treatment NS3, NS5A or NS5B RAS were detected in 10/14 patients with samples available for sequencing analysis. After adjustment for age, sex, ribavirin use, HCV genotype and treatment duration, low platelet count was the only factor significantly associated with a higher risk of failure (OR: 6.5; 95%CI: 1.8-22.6). CONCLUSION: Only 3.9% HIV-HCV coinfected patients failed DAA regimens and RAS were found in 70% of those failing. Low platelet count was independently associated with virological failure.

Exploring the breakdown of dairy protein gels during in vitro gastric digestion using time-lapse synchrotron deep-UV fluorescence microscopy.

A novel time-lapse synchrotron deep-UV microscopy methodology was developed that made use of the natural tryptophan fluorescence of proteins. It enabled the monitoring in situ of the microstructural changes of protein gels during simulated gastric digestion. Two dairy gels with an identical composition, but differing by the coagulation mode, were submitted to static in vitro gastric digestion. The kinetics of gel particle breakdown were quantified by image analysis and physico-chemical analyses of digesta. The results confirm the tendency of rennet gels, but not acid gels, to form compact protein aggregates under acidic conditions of the stomach. Consequently, the kinetics of proteolysis were much slower for the rennet gel, confirming the hypothesis of a reduced pepsin accessibility to its substrate. The particle shapes remained unchanged and the disintegration kinetics followed an exponential trend, suggesting that erosion was the predominant mechanism of the enzymatic breakdown of dairy gels in these experimental conditions.

Outcomes for HIV-associated diffuse large B-cell lymphoma in the modern combined antiretroviral therapy era.

OBJECTIVE: Non-Hodgkin's lymphoma (NHL) remains among the most frequent malignancies in persons living with HIV (PLWHIV). Survival among patients with HIV-associated diffuse large B-cell lymphoma (DLBCL), the most frequent NHL subtype, has improved markedly in recent years. We aimed to analyze characteristics and outcomes of DLBCL in HIV-infected patients in the era of modern combined antiretroviral therapy (cART). DESIGN: PLWHIV with lymphoma were prospectively enrolled in the French ANRS-CO16 Lymphovir cohort between 2008 and 2015. We compared the patients treated with R-CHOP) (rituximab, cyclophosphamide, daunorubicin, vin-cristine, prednisolone) with HIV-negative DLBCL patients enrolled simultaneously in the R-CHOP arms of Lymphoma Study Association trials. RESULTS: Among 110 PLWHIV with NHL, 52 (47%) had systemic DLBCL. These 52 cases had frequent extranodal disease (81%), poor performance status (35%) and advanced age-adjusted international prognostic index (aaIPI) (58%), and were mainly treated with R-CHOP (n = 44, 85%). Their median CD4 T-cell count was 233 cells/µl, and 79% of patients were on cART. The 2-year overall and progression-free survival rates were both 75% (95% confidence interval: 64%, 88%). Factors associated with progression or death in univariate analysis were poor performance status [hazard ratio: 3.3 (1.2, 8.9)], more than one extranodal site [hazard ratio: 3.4 (1.1, 10.5)] and an advanced aaIPI [hazard ratio: 3.7 (1.0, 13.1)]. Progression-free survival after R-CHOP therapy did not differ from that of the HIV-negative counterparts (P = 0.11). CONCLUSION: In the recent cART era, despite frequent high-risk features, the 2-year overall survival of HIV-DLBCL patients reaches 75%. Outcomes after R-CHOP therapy are similar to those of HIV-negative patients with similar aaIPI.

Probing foam with neutrons.

Foams are multiscale materials that have an enormous number of uses. As the relevant structural length-scales span from a few nanometres up to millimetres a number of characterisation methods need to be combined to obtain the full material structure. In this review we explain how foams can be explored using Small Angle Neutron Scattering (SANS). We remind the reader of the basics of SANS and contrast variation before we describe the different types of experiments that have been carried out on foams emphasising the specific role of neutrons in learning about the systems. To date SANS has been used to measure different foam structural parameters, such as the film thickness and the bubble size. Several studies have also been carried out to elucidate the organisation of the stabilising objects in the bulk solution. Finally we show how SANS measurements can be used to measure foam composition. Some of the accessible information is unique to SANS experiments, but as the method is still not very widely used on foams the review is also aimed to act as an introduction on how to carry out such measurements on foams.

Significant reductions in alcohol use after hepatitis C treatment: results from the ANRS CO13-HEPAVIH cohort.

BACKGROUND AND AIMS: Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving pegylated interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. DESIGN: A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioural characteristics were collected by yearly self-administered questionnaires. SETTING: Data were collected across 17 hospitals in France. PARTICIPANTS: All HIV-HCV co-infected patients who initiated HCV treatment during follow-up and answered items regarding substance use in at least one yearly questionnaire (258 patients, 671 visits). INTERVENTION: HCV treatment consisted of Peg-IFN-based regimens. MEASUREMENTS: Four time-varying outcomes: hazardous alcohol use (Alcohol Use Disorders Identification Test-C > 3/4 for women/men), number of alcohol units/month, binge drinking, cannabis and tobacco use. Mixed models assessed the effect of HCV treatment status (not yet treated, treated and HCV-cleared, treated and HCV-chronic) on each outcome. FINDINGS: A significant decrease (more than 60% reduction) in both hazardous alcohol use and binge drinking and a reduction of 10 alcohol units/month was observed after HCV treatment (irrespective of HCV clearance). No significant effect of HCV treatment status was found on tobacco use and regular cannabis use, but HCV 'clearers' reported less non-regular use of cannabis. CONCLUSIONS: Hepatitis C virus (HCV) treatment appears to help HIV-HCV co-infected patients reduce alcohol use.

Efficacy and safety of direct-acting antiviral regimens in HIV/HCV-co-infected patients - French ANRS CO13 HEPAVIH cohort.

BACKGROUND & AIMS: There is little data available on the use of new oral direct-acting antiviral (DAA) regimens to treat human immunodeficiency virus and hepatitis C virus (HIV/HCV) co-infected patients in real-life settings. Here, the efficacy and safety of all-oral DAA-based regimens in HIV/HCV-co-infected patients enrolled in the French nationwide ANRS CO13 HEPAVIH observational cohort are reported. METHODS: HIV/HCV-co-infected patients enrolled in the ANRS CO13 HEPAVIH observational cohort were included if they began an all-oral DAA-based regimen before 1st May 2015 (12-week regimens) or 1st February 2015 (24-week regimens). Treatment success (SVR12) was defined by undetectable HCV-RNA 12weeks after treatment cessation. Exact logistic regression analysis was used to identify factors associated with SVR12. RESULTS: A total of 323 patients (74% men) with a median age of 53years were included, 99% of whom were on combination antiretroviral therapy (cART). HIV RNA load was <50 copies/ml in 88% of patients; median CD4 cell count was 540/mm3; 60% of patients were cirrhotic; 68% had previously received unsuccessful anti-HCV treatment. cART was protease inhibitor (PI)-based in 23%, non-nucleoside reverse transcriptase inhibitor (NNRTI)-based in 15%, and integrase inhibitor (II)-based in 38%, while 24% of patients received other regimens. The SVR12 rate was 93.5% overall (95% confidence interval [CI]: 90.2-95.9), 93.3% (88.8-96.4) in patients with cirrhosis and 93.8% (88.1-97.3) in patients without cirrhosis. The SVR12 rates were 93.1% (84.5-97.7), 91.8% (80.4-97.7) and 95.8% (90.5-98.6) respectively, in patients receiving PI-based, NNRTI-based and II-based cART. In adjusted analysis, SVR12 was not associated with HIV RNA load, the cART regimen, cirrhosis, prior anti-HCV treatment, the duration of anti-HCV therapy, or ribavirin use. The most common adverse effects were fatigue and digestive disorders. CONCLUSIONS: New all-oral DAA regimens were well-tolerated and yielded high SVR12 rates in HIV/HCV-co-infected patients. LAY SUMMARY: We evaluated efficacy and safety of all-oral DAA regimens in a large French nationwide observational cohort study of HIV/HCV co-infected patients. Sustained virological response 12weeks after treatment cessation was 93.5% overall. The all-oral DAA regimens were well-tolerated and most common adverse effects were fatigue and digestive disorders.

How does the size of gold nanoparticles depend on citrate to gold ratio in Turkevich synthesis? Final answer to a debated question.

The dependence between the size of gold nanoparticle (AuNP) and the citrate to gold molar ratio (X) is still a matter of debate 65years after the seminal work by Turkevich et al. for high X values. We assume that this dispersion of results is due to the variation of certain parameters that are often not mentioned in the protocols, and to the use of a single characterization technique (dynamic light scattering (DLS) or transmission electron microscopy (TEM)). To adress definitely the question of this dependence, we have synthesized AuNPs with very precise protocols ensuring that the only parameters to be modified are X and the sequence of reagent addition. We have then studied, for the first time, the dependence of the size with X quantitatively with a multimodal approach (UV-Visible spectroscopy, DLS and TEM) for 2 synthetic routes differing only by the sequence of reagent addition. We show unambiguously that AuNPs' size decay monotonically, with X whatever the order of reagent addition. It allows us to exclude the occurrence of a measurable discontinuity for a peculiar value of X that prompted some authors to postulate the existence of two different reaction pathways when the citrate to gold molar ratio is around this value. In contrast, our result is in line with one reaction pathway, likely a "seed-mediated" growth mechanism, which should leads to monotonic size decrease. Also, we note that our result agrees with the sole available theoretical prediction (Kumar et al., 2007) on the whole range of X. Despite this apparent agreement, we point some contradictions between recent experimental results and basal hypothesis of this model.

Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial.

Lenalidomide, an oral immunomodulating agent, has shown promising activity in HIV-infected individuals with Kaposi's sarcoma (KS). This single-arm, multicenter, open-label, Gehan's two-stage phase II trial evaluated the efficacy and safety of lenalidomide in HIV-infected patients with progressive KS despite previous chemotherapy (NCT01282047, ANRS 154 Lenakap trial). The primary endpoint was the rate of partial response (PR) or complete response (CR) at week 24, evaluated by both the study investigators and the patients using the Physical Global Assessment (PGA). AIDS Clinical Trials Group (ACTG) criteria for KS treatment evaluation were used as a secondary endpoint. The data and safety monitoring board recommended that enrollments be halted on April 24, 2013, because of lack of responses. We enrolled 12 antiretroviral-treated HIV-infected men with progressive KS despite previous chemotherapy. Their HIV plasma viral load was <50 copies/ml and their median CD4 cell count 444/mm3. One patient stopped taking lenalidomide because of hives at week 1 and a second patient died at week 7. The remaining 10 patients were assessable at week 24, when none had PGA-defined CR or PR and one had ACTG-defined PR. There were no additional PGA responses at week 48, but an additional three patients had ACTG responses, for a total of four patients with ACTG PR at week 48 (40%; 95% confidence interval: 12.2-73.8). Fourteen grade 3-4 adverse events were considered at least possibly related to lenalidomide during a total of 101 cycles. Lenalidomide was well tolerated in antiretroviral experienced patients with progressive KS previously treated with chemotherapy. The ACTG-defined response rate at week 48 was 40%, while it was 0% using PGA criteria.

Role of the ratio of biopolyelectrolyte persistence length to nanoparticle size in the structural tuning of electrostatic complexes.

Aggregation of nanoparticles of given size R induced by addition of a polymer strongly depends on its degree of rigidity. This is shown here on a large variety of silica nanoparticle self-assemblies obtained by electrostatic complexation with carefully selected oppositely charged biopolyelectrolytes of different rigidity. The effective rigidity is quantified by the total persistence length L_{T} representing the sum of the intrinsic (L_{p}) and electrostatic (L_{e}) polyelectrolyte persistence length, which depends on the screening, i.e., on ionic strength due to counterions and external salt concentrations. We experimentally show that the ratio L_{T}/R is the main tuning parameter that controls the fractal dimension D_{f} of the nanoparticles' self-assemblies, which is determined using small-angle neutron scattering: (i) For L_{T}/R<0.3 (obtained with flexible poly-l-lysine in the presence of an excess of salt), chain flexibility promotes easy wrapping around nanoparticles in excess, hence ramified structures with D_{f}∼2. (ii) For 0.31,L_{e} is strongly increased due to the absence of salt and repulsions between nanoparticles cannot be compensated for by the polyelectrolyte wrapping, which allows a spacing between nanoparticles and the formation of one-dimensional pearl necklace complexes. (iv) Finally, electrostatic screening, i.e., ionic strength, turned out to be a reliable way of controlling D_{f} and the phase diagram behavior. It finely tunes the short-range interparticle potential, resulting in larger fractal dimensions at higher ionic strength.

All-oral Direct-acting Antiviral Regimens in HIV/Hepatitis C Virus-coinfected Patients With Cirrhosis Are Efficient and Safe: Real-life Results From the Prospective ANRS CO13-HEPAVIH Cohort.

BACKGROUND: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients with cirrhosis have long been considered to be difficult to treat, and real-life efficacy and tolerance data with all-oral direct-acting antiviral (DAA) combinations in these patients are scarce. METHODS: Cirrhotic HIV/HCV-coinfected patients enrolled in the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) CO13 HEPAVIH cohort initiating an all-oral DAA regimen were consecutively included. A negative HCV RNA result at 12 weeks of follow-up or thereafter was assumed as a sustained virologic response (SVR12). Adjusted exact logistic regression was used to study factors associated with treatment outcome. RESULTS: We included 189 patients who initiated an all-oral DAA regimen with the following characteristics: median age 53.2 years; 74.6% male; Centers for Disease Control and Prevention classification A/B/C: 37%/31%/32%; Child-Pugh class A/B/C: 91%/8%/1%; 87% with HIV RNA <50 copies/mL; 99% on antiretrovirals; median CD4 count: 489 cells/µL; HCV treatment naive 29%; HCV genotype 1/2/3/4: 58%/4%/17%/21%. Sofosbuvir (SOF) + daclatasvir ± ribavirin (RBV) was used in 123 patients, SOF + RBV in 30, SOF + simeprevir in 11, and SOF + ledipasvir in 23. An SVR12 was reported in 93.1% of the patients (95% confidence interval, 88.5%-96.3%). In adjusted analyses, no difference was found between 12 or 24 weeks of treatment, in patients receiving RBV or not, and in treatment-naive vs experienced patients. Premature stop of DAA was reported for 8 patients. One patient died during treatment (unknown cause), and 12 other patients developed liver-related events. CONCLUSIONS: In this prospective real-life cohort, all-oral DAA regimens were well tolerated and associated with a high virologic efficacy in cirrhotic HIV/HCV-coinfected patients. This should not alleviate the surveillance for liver-related events in these patients.