Evaluation of procalcitonin and CRP as sepsis markers in 74 consecutive patients admitted with prolonged febrile neutropenia

International audienceFever is a major event in critically ill patients. Its causes are difficult to identify and among them, bacterial infections must be rapidly identified and treated before sepsis reach a life threatening stage. CRP is a very sensitive marker of inflammation of whatever causes including sepsis. This is particularly crucial in immunocompromised patients. On the other hand, PCT has been extensively shown to be strongly and rapidly produced in bacterial infections only. Furthermore, PCT decreases very soon after bacterial resolution, and is thus a very useful in monitoring adequacy and efficiency of antibiotics. The utility of this marker in sever sepsis is now widely admitted

Compared to wildfire, management practices reduced old-growth forest diversity and functionality in primary boreal landscapes of Eastern Canada

Large primary forest residuals can still be found in boreal landscapes. Their areas are however shrinking rapidly due to anthropogenic activities, in particular industrial-scale forestry. The impacts of logging activities on primary boreal forests may also strongly differ from those of wildfires, the dominant stand-replacing natural disturbance in these forests. Since industrial-scale forestry is driven by economic motives, there is a risk that stands of higher economic value will be primarily harvested, thus threatening habitats, and functions related to these forests. Hence, the objective of this study was to identify the main attributes differentiating burned and logged stands prior to disturbance in boreal forests. The study territory lies in the coniferous and closed-canopy boreal forest in Québec, Canada, where industrial-scale logging and wildfire are the two main stand-replacing disturbances. Based on Québec government inventories of primary forests, we identified 427 transects containing about 5.5 circular field plots/transect that were burned or logged shortly after being surveyed, between 1985 and 2016. Comparative analysis of the main structural and environmental attributes of these transects highlighted the strong divergence in the impact of fire and harvesting on primary boreal forests. Overall, logging activities mainly harvested forests with the highest economic value, while most burned stands were low to moderately productive or recently disturbed. These results raise concerns about the resistance and resilience of remnant primary forests within managed areas, particularly in a context of disturbance amplification due to climate change. Moreover, the majority of the stands studied were old-growth forests, characterized by a high ecological value but also highly threatened by anthropogenic disturbances. A loss in the diversity and functionality of primary forests, and particularly the old-growth forests, therefore adds to the current issues related to these ecosystems. Since 2013, the study area is under ecosystem-based management, which implies that there have been marked changes in forestry practices. Complementary research will be necessary to assess the capacity of ecosystem-based management to address the challenges identified in our study

Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir

<p>Abstract</p> <p>Background</p> <p>Human Immunodeficiency Virus type 2 is naturally resistant to some antiretroviral drugs, restricting therapeutic options for patients infected with HIV-2. Regimens including integrase inhibitors (INI) seem to be effective, but little data on HIV-2 integrase (IN) polymorphisms and resistance pathways are available.</p> <p>Materials and methods</p> <p>The <it>integrase </it>coding sequence from 45 HIV-2-infected, INI-naïve, patients was sequenced and aligned against the ROD (group A) or EHO (group B) reference strains and polymorphic or conserved positions were analyzed.</p> <p>To select for raltegravir (RAL)-resistant variants <it>in vitro</it>, the ROD strain was cultured under increasing sub-optimal RAL concentrations for successive rounds. The phenotype of the selected variants was assessed using an MTT assay.</p> <p>Results</p> <p>We describe <it>integrase </it>gene polymorphisms in HIV-2 clinical isolates from 45 patients. Sixty-seven percent of the integrase residues were conserved. The HHCC Zinc coordination motif, the catalytic triad DDE motif, and AA involved in IN-DNA binding and correct positioning were highly conserved and unchanged with respect to HIV-1 whereas the connecting residues of the N-terminal domain, the dimer interface and C-terminal LEDGF binding domain were highly conserved but differed from HIV-1. The N155 H INI resistance-associated mutation (RAM) was detected in the virus population from one ARV-treated, INI-naïve patient, and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively. No other known INI RAM was detected.</p> <p>Under RAL selective pressure <it>in vitro</it>, a ROD variant carrying the Q91R+I175M mutations was selected. The Q91R and I175M mutations emerged simultaneously and conferred phenotypic resistance (13-fold increase in IC₅₀). The Q91R+I175M combination was absent from all clinical isolates. Three-dimensional modeling indicated that residue 91 lies on the enzyme surface, at the entry of a pocket containing the DDE catalytic triad and that adding a positive charge (Gln to Arg) might compromise IN-RAL affinity.</p> <p>Conclusions</p> <p>HIV-2 polymorphisms from 45 INI-naïve patients are described. Conserved regions as well as frequencies of HIV-2 IN polymorphisms were comparable to HIV-1. Two new mutations (Q91R and I175M) that conferred high resistance to RAL were selected <it>in vitro</it>, which might affect therapeutic outcome.</p

Defective NKT cell development in mice and humans lacking the adapter SAP, the X-linked lymphoproliferative syndrome gene product

SAP is an adaptor protein expressed in T cells and natural killer cells. It plays a critical role in immunity, as it is mutated in humans with X-linked lymphoproliferative syndrome (XLP), a fatal immunodeficiency characterized by an abnormal response to Epstein-Barr virus (EBV) infection. SAP interacts with the SLAM family receptors and promotes transduction signal events by these receptors through its capacity to recruit and activate the Src kinase FynT. Because it has been previously established that FynT is selectively required for the development of NKT cells, we examined NKT cells in SAP-deficient mice and in humans with XLP. In the absence of SAP, the development of NKT cells is severely impaired both in mice and in humans. These results imply that SAP is a potent regulator of NKT cell development. They also identify for the first time a defect in NKT cells associated with a human primary immunodeficiency, revealing a potential role of NKT cells in the immune response to EBV

Toxicity report of once weekly radiation therapy for low-risk prostate adenocarcinoma: preliminary results of a phase I/II trial

<p>Abstract</p> <p>Background</p> <p>Increasing clinical data supports a low α/β ratio for prostate adenocarcinoma, potentially lower than that of surrounding normal tissues. A hypofractionated, weekly radiation therapy (RT) schedule should result in improved tumour control, reduced acute toxicity, and similar or decreased late effects. We report the toxicity profile of such treatment.</p> <p>Materials and Methods</p> <p>We conducted a multi-institution phase I/II trial of three-dimensional conformal radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason ≤ 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once weekly. Primary end-points were feasibility and late gastrointestinal (GI) toxicity (RTOG scale), while secondary end-points included acute GI toxicity, acute and late genitourinary (GU) toxicity, biochemical control, and survival.</p> <p>Results</p> <p>Between 2006 and 2008, 80 patients were treated. No treatment interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2 occurred in 14% (no grade 3 or 4). Crude late grade ≥ 3 toxicity rates at 31 months were 2% for both GU and GI toxicity. Cumulative late grade ≥ 3 GI toxicity at 3 years was 11%. Two patients had PSA failure according to the Phoenix definition. The three-year actuarial biochemical control rate is 97%.</p> <p>Conclusions</p> <p>Weekly RT with 45 Gy in 9 fractions is feasible and results in comparable toxicity. Long term tumour control and survival remain to be assessed.</p

Le Forum, Vol. 44 #3

https://digitalcommons.library.umaine.edu/francoamericain_forum/1105/thumbnail.jp

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay &gt;=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission