Incidence of nosocomial pneumonia and risk of recurrence after antimicrobial therapy in critically ill lung and heart–lung transplant patients

Little is known about the resolution of symptoms of nosocomial pneumonia (NosoP) after lung and heart–lung transplantation. The aim of this study was to describe the clinical response to antimicrobial therapy in (ICU) patients with NosoP after lung or heart–lung transplantation. Between January 2008 and August 2010, 79 lung or heart–lung transplantations patients were prospectively studied. NosoPwas confirmed by quantitative cultures of bronchoalveolar lavage or endotracheal aspirates. Clinical variables, sequential organ failure assessment (SOFA) score, and radiologic score were recorded from start of therapy until day 9. Thirty‐five patients (44%) experienced 64 episodes of NosoP in ICU. Fourteen patients (40%) had NosoP recurrence. Most frequently isolated organisms were Enterobacteriaceae (30%), Pseudomonas aeruginosa (25%), and Staphylococcus aureus (20%). Sequential organ failure assessment (SOFA) score improved significantly at day 6 and C‐reactive protein level at day 9. SOFA and radiologic scores differed significantly between patients with and without NosoP recurrence at day 3 and 9. The ICU mortality rate did not differ between patients with and without NosoP recurrence, and free of NosoP (14.3%, 9.5%, 11.4%, respectively) (p = 0.91). Severities of illness and lung injury were the two major risk factors for NosoP recurrence. Occurrence of NosoP has no impact on ICU mortality.     

Virological response after short-term CCR5 antagonist exposure in HIV-infected patients: frequency of subjects with virological response and associated factors

The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log₁₀ HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients'' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4⁺ T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4⁺ T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains.     

Association Between Ageing and Short-Term Survival Outcomes in Patients Undergoing Surgery for Primary Retroperitoneal Sarcoma

Annals of Surgical Oncology - As the population ages, more elderly patients are receiving surgery for retroperitoneal sarcoma (RPS). However, high-quality data investigating associations between...     

Thermosensitive and Mucoadhesive Pluronic-Hydroxypropylmethylcellulose Hydrogel Containing the Mini-CD4 M48U1 Is a Promising Efficient Barrier against HIV Diffusion through Macaque Cervicovaginal Mucus

To be efficient, vaginal microbicide hydrogels should form a barrier against viral infections and prevent virus spreading through mucus. Multiple particle tracking was used to quantify the mobility of 170-nm fluorescently labeled COOH-modified polystyrene particles (COOH-PS) into thermosensitive hydrogels composed of amphiphilic triblock copolymers with block compositions EO_n-PO_m-EO_n (where EO refers to ethylene oxide and PO to propylene oxide) containing mucoadhesive hydroxypropylmethylcellulose (HPMC). COOH-PS were used to mimic the size and the surface charge of HIV-1. Analysis of COOH-PS trajectories showed that particle mobility was decreased by Pluronic hydrogels in comparison with cynomolgus macaque cervicovaginal mucus and hydroxyethylcellulose hydrogel (HEC; 1.5% by weight [wt%]) used as negative controls. Formulation of the peptide mini-CD4 M48U1 used as an anti-HIV-1 molecule into a mixture of Pluronic F127 (20 wt%) and HPMC (1 wt%) did not affect its anti-HIV-1 activity in comparison with HEC hydrogel. The 50% inhibitory concentration (IC₅₀) was 0.53 μg/ml (0.17 μM) for M48U1-HEC and 0.58 μg/ml (0.19 μM) for M48U1-F127-HPMC. The present work suggests that hydrogels composed of F127-HPMC (20/1 wt%, respectively) can be used to create an efficient barrier against particle diffusion in comparison to conventional HEC hydrogels.     

Topical photodynamic therapy using transfersomal aluminum phthalocyanine tetrasulfonate: in vitro and in vivo study

The efficacy of transfersomes (flexible liposomes) as a novel technique for topical delivery of the hydrophilic tetra-anionic photodynamic sensitizer aluminum (III) phthalocyanine tetrasulfonate (AlPcS4) was investigated, on mammalian fibroblasts and on Balb/c mice dorsal skin. AlPcS4 was loaded in transfersomes composed of phosphatidylcholine/sodium deoxycholate (5:1, 10:1, and 15:1?w/w, ratios), resulting in 110-, 160-, and 200-nm mean size vesicles with encapsulation efficiencies of 16, 25, and 30 %, respectively. In vitro studies on baby hamster kidney-21 fibroblasts revealed twofold enhancement of the photocytotoxicity of AlPcS4 loaded in transfersomes (Trans-AlPcS4), compared to free AlPcS4 dissolved in culture medium. The photocytotoxicity of Trans-AlPcS4 was less dependent on the incubation time with cells, compared to free AlPcS4. Topical application on the dorsal skin of Balb/c mice revealed that both free AlPcS4 and Trans-AlPcS4 exhibited evident photosensitization towards mice skin, but acquiring different regions of skin.