Abstract Objectives Our main aim was to describe and explore a multidisciplinary approach to the management of elderly patients with cancer, who constitute a heterogeneous population. Materials and ...Methods This descriptive study was performed between October 2009 and September 2010. Patients with cancer ≥ 70 years of age were included. Some underwent a simplified multidimensional geriatric assessment with a Charlson score administered by an oncologist, and the evaluation was submitted to a geriatrician who decided whether or not a complete a comprehensive geriatric assessment (CGA) (n = 54) should be done. Another group of patients directly underwent a CGA (n = 49), and a few patients included in a specific trial underwent a geriatric assessment (n = 8). Each patient was classified as fit, vulnerable, or frail by a multidisciplinary team. Results 111 patients were included (median age: 81 years range: 65–96; 60 males). The most frequent types of cancer were lung (n = 29), gastrointestinal (n = 20) and head and neck (n = 14). Median Charlson score was 2.1 range: 0–9. Standard therapy was given to 37/41 (90%) fit, 19/41 (42%) vulnerable, and 6/29 (21%) frail patients. Thirteen frail patients received best supportive care. A social worker was mobilized for 2/41 (5%) fit, 14/41 (34%) vulnerable, and 11/29 (38%) frail patients. Conclusions Our study outlines the possibilities of cooperation between geriatricians and oncologists in a general hospital. This collaboration could modify therapeutic schedules especially in frail and vulnerable patients.
The replicative potential of HIV-1 strains in a well-characterized group of eight HIV controllers was investigated. Replication-competent viruses were detected in CD4 T-cell co-culture supernatants ...from all HIV controllers. The phylogenetic analysis of C2V4 suggested viral evolution or co-infection or superinfection in two out of the four patients analysed. The vif and vpr genes were normal. Infection with HIV-1 variants with attenuated replicative capacity cannot be a general factor accounting for undetectable viraemia in HIV controllers.
Minority resistant variants of human immunodeficiency virus type 1 (HIV-1) could influence the virological response to treatment based on nonnucleoside reverse transcriptase inhibitors (NNRTIs). Data ...on minority rilpivirine-resistant variants are scarce. This study used next-generation sequencing (NGS) to identify patients harboring minority resistant variants to nucleos(t)ide reverse transcriptase inhibitors and NNRTIs and to assess their influence on the virological response (VR).
All the subjects, 541 HIV-1-infected patients started a first-line regimen containing rilpivirine. VR was defined as a HIV-1 RNA load <50 copies/mL at month 6 with continued suppression at month 12. NGS was performed at baseline (retrospectively) on the 454 GS-FLX platform (Roche).
NGS revealed resistance-associated mutations accounting for 1% to <5% of variants in 17.2% of samples, for 5%-20% in 5.7% of samples, and for >20% in 29% of samples. We identified 43 (8.8%) and 36 (7.4%) patients who harbored rilpivirine-resistant variants with a 1% sensitivity threshold according to the French National Agency for Research on AIDS and Viral Hepatitis and Stanford algorithms, respectively. The VR was 96.9% at month 12. Detection of minority rilpivirine resistant variants was not associated with virological failure (VF). Multivariate analysis indicated that VF at month 12 was associated with a CD4 count <250 cells/µL at baseline, a slower decrease in viral load at month 3, and rilpivirine resistance at baseline using the Stanford algorithm with a 20% threshold.
Minority resistant variants had no impact on the VR of treatment-naive patients to a rilpivirine-based regimen.
PI susceptibility results from a complex interplay between protease and Gag proteins, with Gag showing wide variation across HIV-1 subtypes. We explored the impact of pre-treatment susceptibility on ...the outcome of lopinavir/ritonavir monotherapy.
Treatment-naive individuals who experienced lopinavir/ritonavir monotherapy failure from the MONARK study were matched (by subtype, viral load and baseline CD4 count) with those who achieved virological response ('successes'). Successes were defined by viral load <400 copies/mL after week 24 and <50 copies/mL from week 48 to week 96. Full-length Gag-protease was amplified from patient samples for in vitro phenotypic susceptibility testing, with susceptibility expressed as fold change (FC) relative to a subtype B reference strain.
Baseline lopinavir susceptibility was lower in viral failures compared with viral successes, but the differences were not statistically significant (median lopinavir susceptibility: 4.4 versus 8.5, respectively, P = 0.17). Among CRF02_AG/G patients, there was a significant difference in lopinavir susceptibility between the two groups (7.1 versus 10.4, P = 0.047), while in subtype B the difference was not significant (2.7 versus 3.4, P = 0.13). Subtype CRF02_AG/G viruses had a median lopinavir FC of 8.7 compared with 3.1 for subtype B (P = 0.001).
We report an association between reduced PI susceptibility (using full-length Gag-protease sequences) at baseline and subsequent virological failure on lopinavir/ritonavir monotherapy in antiretroviral-naive patients harbouring subtype CRF02_AG/G viruses. We speculate that this may be important in the context of suboptimal adherence in determining viral failure.
Experimental evidence on high-Tc cuprates reveals ubiquitous charge density wave (CDW) modulations, which coexist with superconductivity. Although the CDW had been predicted by theory, important ...questions remain about the extent to which the CDW influences lattice and charge degrees of freedom and its characteristics as functions of doping and temperature. These questions are intimately connected to the origin of the CDW and its relation to the mysterious cuprate pseudogap. Here, we use ultrahigh resolution resonant inelastic x-ray scattering (RIXS) to reveal new CDW character in underdoped Bi2Sr2CaCu2O8+{\delta} (Bi2212). At low temperature, we observe dispersive excitations from an incommensurate CDW that induces anomalously enhanced phonon intensity, unseen using other techniques. Near the pseudogap temperature T*, the CDW persists, but the associated excitations significantly weaken and the CDW wavevector shifts, becoming nearly commensurate with a periodicity of four lattice constants. The dispersive CDW excitations, phonon anomaly, and temperature dependent commensuration provide a comprehensive momentum space picture of complex CDW behavior and point to a closer relationship with the pseudogap state.
We investigated the high energy spin excitations in electron-doped La2−xCexCuO4 (LCCO), a cuprate superconductor, by resonant inelastic x-ray scattering (RIXS) measurements. Efforts were paid to ...disentangle the paramagnon signal from non-spin-flip spectral weight mixing in the RIXS spectrum at Q∥ = (0.6π,0) and (0.9π,0) along the (1 0) direction. Our results show that, for doping level x from 0.07 to 0.185, the variation of the paramagnon excitation energy is marginal. We discuss the implication of our results in connection with the evolution of the electron correlation strength in this system.
Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or ...associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients.
A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin.
The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy.
There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.
Characterization of the early establishment of the viral reservoir in patients acquiring resistant strains at primary HIV-1 infection (PHI), and longitudinal analysis of resistance mutations in ...circulating virions and intracellular HIV strains.
Drug-resistance was compared between HIV RNA and peripheral blood mononuclear cell (PBMC)-HIV DNA at the time of PHI in 44 patients enrolled in the Primo Cohort and harbouring plasma HIV-1 resistant to at least one antiretroviral drug. Longitudinal monitoring of viral load and resistance genotype was performed in plasma-HIV RNA and PBMC HIV DNA for at least 24 months in a subset of 10 patients. Phylogenetic analysis of HIV DNA protease gene clones was used to explore the diversity of quasi-species at baseline.
Baseline resistance profile was identical in paired HIV RNA and PBMC HIV DNA for all 44 patients. All resistance-associated mutations persisted in plasma and PBMC over 2 years in the five untreated patients. Of the five patients started on empirical HAART, two achieved undetectable HIV RNA at month 6, with long-term persistence of archived drug-resistance mutations in PBMC HIV DNA. Virological failure was observed in the other three patients, resulting in the accumulation of additional drug-resistance mutations in HIV RNA and HIV DNA for two of them. Phylogenetic analysis of HIV DNA clones showed highly homogenous and exclusively resistant quasi-species in the cellular reservoir at baseline.
HIV resistant strains acquired at the time of PHI massively fuel the cellular reservoir, and their prolonged persistence is supported by the early expansion of a dominant homogenous and resistant viral population. Results in treated patients showed that classical empirical triple-combination may be suboptimal.
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