Destructuration of Canola Protein Gels during In Situ Gastrointestinal Digestion Studied by X-ray Scattering.

We are studying the destructuration of canola protein gels, as a solid food model, during in situ gastrointestinal digestion using synchrotron small-angle X-ray scattering (SAXS). Digestion of two gels, prepared by heating pH 8 and pH 11 solutions, was carried out by diffusion of enzymatic juices into the gel from the top of the capillary and monitored for several tens of hours. Very similar time evolutions of SAXS curves occur at different positions of the gel in the capillary, with a delay determined by the distance from the surface initially in contact with the digestive juice. The main phenomena observed are (i) at the scale of the protein conformation (1-5 nm). The scattering curve is a power law, the exponent of which measures the compactness (related to the degree of unfolding). It can be plotted as a function of the characteristic size of proteins/and interprotein distances and as a function of the scattering intensity. Such diagrams clearly show successive digestion processes. For the pH 11 gel, in which proteins are initially hardly unfolded, the digestive processes are unfolding (1st step), recompaction-aggregation phenomena (2nd step) due to gastrointestinal pH conditions and enzymatic cleavage, further unfolding-disaggregation (3rd step), and final protein cleavage (4th step) down to small peptides. For the pH 8 gel, proteins are initially unfolded, and only the last three steps are observed, showing the influence of easier access for the enzymes. (ii) At the scale of large aggregates (10-50 nm), we observe for both gels a decrease in the size and/or number of these aggregates during digestion and alteration of their interfaces. (iii) At the scale of the secondary protein structure, wide-angle X-ray scattering is very useful for detecting the degradation of the secondary protein structure at different steps of digestion.

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.

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.

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.

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.

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.

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.

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.

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.

Interplay between polymer chain conformation and nanoparticle assembly in model industrial silica/rubber nanocomposites.

The question of the influence of nanoparticles (NPs) on chain dimensions in polymer nanocomposites (PNCs) has been treated mainly through the fundamental way using theoretical or simulation tools and experiments on well-defined model PNCs. Here we present the first experimental study on the influence of NPs on the polymer chain conformation for PNCs designed to be as close as possible to industrial systems employed in the tire industry. PNCs are silica nanoparticles dispersed in a styrene-butadiene-rubber (SBR) matrix whose NP dispersion can be managed by NP loading with interfacial coatings or coupling additives usually employed in the manufacturing mixing process. We associated specific chain (d) labeling, and the so-called zero average contrast (ZAC) method, with SANS, in situ SANS and SAXS/TEM experiments to extract the polymer chain scattering signal at rest for non-cross linked and under stretching for cross-linked PNCs. NP loading, individual clusters or connected networks, as well as the influence of the type, the quantity of interfacial agent and the influence of the elongation rate have been evaluated on the chain conformation and on its related deformation. We clearly distinguish the situations where the silica is perfectly matched from those with unperfected matching by direct comparison of SANS and SAXS structure factors. Whatever the silica matching situation, the additive type and quantity and the filler content, there is no significant change in the polymer dimension for NP loading up to 15% v/v within a range of 5%. One can see an extra scattering contribution at low Q, as often encountered, enhanced for non-perfect silica matching but also visible for perfect filler matching. This contribution can be qualitatively attributed to specific h or d chain adsorption on the NP surface inside the NP cluster that modifies the average scattering neutron contrast of the silica cluster. Under elongation, NPs act as additional cross-linking junctions preventing chain relaxation and giving a deformation of the chain with the NP closer to a theoretical phantom network prediction than a pure matrix.

High Risk Features Contrast With Favorable Outcomes in HIV-associated Hodgkin Lymphoma in the Modern cART Era, ANRS CO16 LYMPHOVIR Cohort.

BACKGROUND: Human immunodeficiency virus (HIV) infection is associated with a high risk of classical Hodgkin's lymphoma (cHL) in the combined antiretroviral therapy (cART) era. METHODS: We analyzed the characteristics and outcome of HIV-associated cHL diagnosed in the modern cART era. The French ANRS-CO16 Lymphovir cohort enrolled 159 HIV-positive patients with lymphoma, including 68 (43%) with cHL. HIV-HL patients were compared with a series of non-HV-infected patients consecutively diagnosed with HL. RESULTS: Most patients (76%) had Ann-Arbor stages III-IV and 96% of patients were treated with ABVD. At diagnosis, median CD4 T-cell count was 387/µL and 94% of patients were treated with cART. All patients received cART after diagnosis. Five patients died from early progression (n = 2), sepsis (1) or after relapse (2). Two additional patients relapsed during follow-up. Two-year overall and progression free survivals (PFS) were 94% [95% CI, 89%, 100%] and 89% [82%, 97%], respectively. The only factor associated with progression or death was age with a relative risk of 8.1 [1.0; 67.0] above 45 years. The PFS of Lymphovir patients appeared similar to PFS of HIV-negative patients, 86% [82%, 90%], but patients with HIV infection displayed higher risk features than HIV-negative patients. CONCLUSIONS: Although high-risk features still predominate in HIV-HL, the prognosis of these patients, treated with cART and mainly ABVD, has markedly improved in the modern cART era and is now similar to non-HIV-infected patients.

Treatment factors affecting outcomes in HIV-associated non-Hodgkin lymphomas: a pooled analysis of 1546 patients.

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.

Shape-tailored colloidal molecules obtained by self-assembly of model gold nanoparticles with flexible polyelectrolyte.

We study for the first time the structure of stable finite size clusters (i.e., colloidal molecules) obtained by self-assembly of cationic gold nanoparticles (i.e., atoms) mediated by a flexible polyanion. We reveal with nondenaturizing techniques a striking structural transition from 1D small chains of 12 gold nanoparticles (AuNPs) with a self-avoiding conformation to 3D fractal clusters of 130 AuNPs with short-range ordering around the charge inversion threshold. Interestingly, these well-defined structures are obtained by simple mixing in water without anisotropic functionalization or external forces. As a preliminary step, we introduce a new synthesis pathway leading to well-defined cationic AuNPs of controllable size that can be dispersed in H2O or D2O without aggregation and ligands' self-assemblies. On this occasion, we point for the first time that usual procedures do not enable to eliminate cationic ligands' self-assemblies that could play an undesired role in AuNPs' self-assembly through electrostatic interactions.

Structure investigation of nanohybrid PDMA/silica hydrogels at rest and under uniaxial deformation.

Nano-hybrid hydrogels were prepared by cross-linking polymerization of N,N-dimethylacrylamide (DMA) within a dispersion of silica nano-particles. Working at constant polymer/water ratio, the mechanical properties of hydrogels can be finely tuned by changing either the level of covalent cross-linker and/or the amount of particles that act as physical cross-linkers through specific adsorption of PDMA chains. Whatever is the cross-linking ratio (from 0 to 1 mol%), the introduction of silica nano-particles dramatically improves the mechanical behavior of hydrogels with a concomitant increase of stiffness and nominal strain at failure. The physical interactions being reversible in nature, the dynamics of the adsorption/desorption process of PDMA chains directly controls the time-dependence of the mechanical properties. Small angle neutron scattering experiments, performed in contrast matching conditions, show that silica particles, which repel themselves at short range, remain randomly dispersed during the formation of the PDMA network. Although PDMA chains readily interact with silica particles, no significant variation of the polymer concentration was observed in the vicinity of silica surfaces. Together with the time dependence of physical interactions pointed out by mechanical analyses, this result is attributed to the moderate adsorption energy of PDMA chains with silica surfaces at pH 9. From 2D SANS experiments, it was shown that strain rapidly gives rise to a non affine deformation of the hybrid network with shearing due to the transverse compression of the particles. After loading at intermediate deformation, the particles recover their initial distribution due to the covalent network that is not damaged in these conditions. That is no longer true at high deformation where residual anisotropy is observed.

Complete remission of Schnitzler syndrome and Waldenström macroglobulinemia under rituximab-cyclophosphamide-dexamethasone.

In Schnitzler syndrome, which is mostly diagnosed with a low and asymptomatic monoclonal peak, anakinra has always exhibited a complete but only transient control of the auto-inflammatory signs, which are induced by interleukin (IL)-1 auto-activation. We focused on the treatment of a case of Schnitzler syndrome with moderate macroglobulinemia peak. Anakinra failed to improve the severe inflammatory anaemia and the dysglobulinemia, but rituximab-dexamethasone-cyclophosphamide chemotherapy alone allowed a complete response. The correlation between the clinical, pro-inflammatory cytokines and dysglobulinemia complete controls with chemotherapy proves the following: (1) the dual action of this treatment in both the auto-inflammatory and dysglobulinemia components of the syndrome and (2) a different but entangled cytokine network in the pathogenesis of the auto-inflammatory and dysglobulinemia components of the syndrome.

A new prognostic score for AIDS-related lymphomas in the rituximab-era.

While the International Prognostic Index is commonly used to predict outcomes in immunocompetent patients with aggressive B-cell non-Hodgkin lymphomas, HIV-infection is an important competing risk for death in patients with AIDS-related lymphomas. We investigated whether a newly created prognostic score (AIDS-related lymphoma International Prognostic Index) could better assess risk of death in patients with AIDS-related lymphomas. We randomly divided a dataset of 487 patients newly diagnosed with AIDS-related lymphomas and treated with rituximab-containing chemoimmunotherapy into a training (n=244) and validation (n=243) set. We examined the association of HIV-related and other known risk factors with overall survival in both sets independently. We defined a new score (AIDS-related lymphoma International Prognostic Index) by assigning weights to each significant predictor [age-adjusted International Prognostic Index, extranodal sites, HIV-score (composed of CD4 count, viral load, and prior history of AIDS)] with three risk categories similar to the age-adjusted International Prognostic Index (low, intermediate and high risk). We compared the prognostic value for overall survival between AIDS-related lymphoma International Prognostic Index and age-adjusted International Prognostic Index in the validation set and found that the AIDS-related lymphoma International Prognostic Index performed significantly better in predicting risk of death than the age-adjusted International Prognostic Index (P=0.004) and better discriminated risk of death between each risk category (P=0.015 vs. P=0.13). Twenty-eight percent of patients were defined as low risk by the ARL-IPI and had an estimated 5-year overall survival (OS) of 78% (52% intermediate risk, 5-year OS 60%; 20% high risk, 5-year OS 50%).

HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy: incidence and evolution of CD4⁺ T-cell lymphocytes.

The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/µL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/µL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P < .0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.

Conformational control of hydrogen-bonded aromatic bis-ureas.

The phenylurea moiety is a ubiquitous synthon in supramolecular chemistry because it contains strong complementary hydrogen bonding groups and is synthetically very accessible. Here we investigate the possibility to strengthen self-association by conformational preorganization of the phenylurea moiety. In fact, we show that it is possible to strongly enhance intermolecular interactions between hydrogen bonded aromatic bis-ureas by substitution at the ortho positions of the phenylurea groups. Ortho substituents enforce a noncoplanar conformation of the urea and phenyl moieties better suited for hydrogen bonding. Substitution by methyl groups is more efficient than with larger groups, probably because of reduced steric hindrance. These effects have been demonstrated in the case of two different supramolecular architectures, which points to the probable generality of the phenomenon. In addition, this study has led to the discovery of a new bis-urea able to form very stable self-assembled nanotubes in toluene up to high temperatures (boiling point) or low concentrations (10(-7) M) and in chloroform down to 3 × 10(-4) M.

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.

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.