Type I Interferon in Children with Viral or Bacterial Infections.

BACKGROUND: Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. METHODS: Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P 0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). CONCLUSIONS: IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT03163628)

Microcontact printing of polyelectrolyte multilayer thin films : glass-viscous flow transition based effects and hydratation methods

International audienceMicro and nano-patterned surfaces are important for many applications ranging from antibiofouling over tissue engineering to electronics. Often the incorporation of functional entities is of interest. Polymer coatings especially polyelectrolyte multilayer (PEM) films and patterns are materials offering a large variety of tuning and engineering. The PEM pattern printing quality bases not only on the surface force balance but also in the way the PEM is softened, which can be done by printing the PEM in water, using an ultrasound humidifier or by exposing the film to (hot) water vapor. In this publication it is shown, that cold water vapor from an ultrasound humidifier or direct printing in water is superior to steam evaporation onto PEM thin films as humidification method. In addition the capillary pressure of the patterns within the stamp and the glass–viscous flow transition point of the PEM thin film are the significant parameters for PEM printing. This is because the PEM can surpass the glass–viscous flow transition point due to the shear forces and be sucked into the stamp microwells (or holes) preventing a structure replication. Under high temperatures and in aqueous conditions, the PEM can be expelled from the microwells due to the osmotic pressure produced by the counter ions of PEM in glass–viscous flow state and dissolving polyelectrolyte if a PEM with counter ion based charge balance is used

Microcontact printing of polyelectrolyte multilayer thin films : glass-viscous flow transition based effects and hydratation methods

International audienceMicro and nano-patterned surfaces are important for many applications ranging from antibiofouling over tissue engineering to electronics. Often the incorporation of functional entities is of interest. Polymer coatings especially polyelectrolyte multilayer (PEM) films and patterns are materials offering a large variety of tuning and engineering. The PEM pattern printing quality bases not only on the surface force balance but also in the way the PEM is softened, which can be done by printing the PEM in water, using an ultrasound humidifier or by exposing the film to (hot) water vapor. In this publication it is shown, that cold water vapor from an ultrasound humidifier or direct printing in water is superior to steam evaporation onto PEM thin films as humidification method. In addition the capillary pressure of the patterns within the stamp and the glass–viscous flow transition point of the PEM thin film are the significant parameters for PEM printing. This is because the PEM can surpass the glass–viscous flow transition point due to the shear forces and be sucked into the stamp microwells (or holes) preventing a structure replication. Under high temperatures and in aqueous conditions, the PEM can be expelled from the microwells due to the osmotic pressure produced by the counter ions of PEM in glass–viscous flow state and dissolving polyelectrolyte if a PEM with counter ion based charge balance is used

Carrier-inside-carrier: polyelectrolyte microcapsules as reservoir for drug-loaded liposomes

International audienceConventional liposomes have a short life-time in blood, unless they are protected by a polymer envelope, most often polyethylene glycol. However, these stabilizing polymers frequently interfere with cellular uptake, impede liposome-membrane fusion and inhibit escape of liposome content from endosomes. To overcome such drawbacks, polymer-based systems as carriers for liposomes are currently developed. Conforming to this approach, we propose a new and convenient method for embedding small size liposomes, 30–100 nm, inside porous calcium carbonate microparticles. These microparticles served as templates for deposition of various polyelectrolytes to form a protective shell. The carbonate particles were then dissolved to yield hollow polyelectrolyte microcapsules. The main advantage of using this method for liposome encapsulation is that carbonate particles can serve as a sacrificial template for deposition of virtually any polyelectrolyte. By carefully choosing the shell composition, bioavailability of the liposomes and of the encapsulated drug can be modulated to respond to biological requirements and to improve drug delivery to the cytoplasm and avoid endosomal escape

Prognostic value of lesion dissemination in doxorubicin, bleomycin, vinblastine, and dacarbazine-treated, interimPET-negative classical Hodgkin Lymphoma patients: A radio-genomic study

We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. We included patients diagnosed with cHL from 2007 to 2020, initially treated with ABVD, with available baseline PET for review, and with at least two FDG avid lesions. Patients with available RNA from diagnostic biopsy were eligible for gene expression analysis. Dmax was deduced from the three-dimensional coordinates of the baseline metabolic tumor volume (MTV) and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR = 2.70, 95% CI 1.1–6.63, pValue = 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET-). Among patients with iPET-low Dmax was associated with a 4-year PFS of 90% (95% CI 82.0–98.9) significantly better compared to high Dmax (4-year PFS 72.4%, 95% CI 61.9–84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. In conclusion our results support tumor dissemination measured through Dmax as novel prognostic factor for cHL patients treated with ABVD

Treatment of intracranial hypertension and aspects on lumbar dural puncture in severe bacterial meningitis - Reply

BACKGROUND: Brain stem herniation due to raised intracranial pressure (ICP) is a common cause of mortality in severe bacterial meningitis, but continuous measurements of ICP and the effects of ICP-reducing therapy in these patients have, to our knowledge, not been described. METHODS: During a four-year period, an ICP-monitoring device was implanted in patients admitted to our hospital with severe bacterial meningitis and suspected intracranial hypertension. ICP above 20 mmHg was treated using the Lund Concept, which includes antihypertensive therapy (beta1-antagonist,alpha2-agonist), normalization of the plasma colloid osmotic pressure and the blood volume, and antistress therapy. RESULTS: ICP above 20 mmHg was found in all 12 patients studied. It was effectively reduced in all but two patients, who died. Both patients had a low cerebral perfusion pressure (<10 mmHg), dilated pupils at start of therapy and were beyond recovery. Radiological signs of brain swelling were present in only five patients. Seven patients recovered fully, while mild audiological impairment was observed in two and minor neurological sequelae in one patient. Eight patients showed signs suggesting imminent brain stem herniation before start of ICP-reducing treatment, seven of whom had been subjected to diagnostic lumbar dural puncture shortly before development of the brain stem symptoms. These symptoms gradually regressed after initiation of therapy, and in one patient reversal of brain stem herniation was documented by MRI. CONCLUSIONS: Severe bacterial meningitis can be associated with increased ICP, which can be reduced using the Lund Concept. The high survival rate, the low frequency of sequelae and the reversal of signs of imminent brain stem herniation in these high-risk patients indicated beneficial effects of the intervention. The study confirms earlier observations that lumbar dural puncture is potentially hazardous in patients with intracranial hypertension, because it may trigger brain stem herniation. A normal CT brain scan does not rule out intracranial hypertension