Levels of Soluble Endothelial Protein C Receptor Are Associated with CD4+ Changes in Maraviroc-Treated HIV-Infected Patients

BACKGROUND: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+) cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+) counts both in naïve and experienced subjects compared to traditional antiretroviral therapy. OBJECTIVES AND METHODS: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin) was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up. RESULTS: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+) cell counts (more than 500 cells/µL by week 48). CONCLUSIONS: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+) cells

The “Journal of Functional Morphology and Kinesiology” Journal Club Series: Highlights on Recent Papers in Corrective Exercise

We are glad to introduce the Journal Club of Volume Five, fourth Issue. This edition is focused on relevant studies published in the last few years in the field of corrective exercise, chosen by our Editorial Board members and their colleagues. We hope to stimulate your curiosity in this field and to share a passion for sport with you, seen also from the scientific point of view. The Editorial Board members wish you an inspiring lecture

Extended-Spectrum-Beta-Lactamases, AmpC Beta-Lactamases and Plasmid Mediated Quinolone Resistance in Klebsiella spp. from Companion Animals in Italy

We report the genetic characterization of 15 Klebsiella pneumoniae (KP) and 4 isolates of K. oxytoca (KO) from clinical cases in dogs and cats and showing extended-spectrum cephalosporin (ESC) resistance. Extended spectrum beta-lactamase (ESBL) and AmpC genes, plasmid-mediated quinolone resistance (PMQR) and co-resistances were investigated. Among KP isolates, ST101 clone was predominant (8/15, 53%), followed by ST15 (4/15, 27%). ST11 and ST340, belonging to Clonal Complex (CC)11, were detected in 2012 (3/15, 20%). MLST on KP isolates corresponded well with PFGE results, with 11 different PFGE patterns observed, including two clusters of two (ST340) and four (ST101) indistinguishable isolates, respectively. All isolates harbored at least one ESBL or AmpC gene, all carried on transferable plasmids (IncR, IncFII, IncI1, IncN), and 16/19 were positive for PMQR genes (qnr family or aac(6')-Ib-cr). The most frequent ESBL was CTX-M-15 (11/19, 58%), detected in all KP ST101, in one KP ST15 and in both KP ST340. blaCTX-M-15 was carried on IncR plasmids in all but one KP isolate. All KP ST15 isolates harbored different ESC resistance genes and different plasmids, and presented the non-transferable blaSHV-28 gene, in association with blaCTX-M-15, blaCTX-M-1 (on IncR, or on IncN), blaSHV-2a (on IncR) or blaCMY-2 genes (on IncI1). KO isolates were positive for blaCTX-M-9 gene (on IncHI2), or for the blaSHV-12 and blaDHA-1 genes (on IncL/M). They were all positive for qnr genes, and one also for the aac(6')-Ib-cr gene. All Klebsiella isolates showed multiresistance towards aminoglycosides, sulfonamides, tetracyclines, trimethoprim and amphenicols, mediated by strA/B, aadA2, aadB, ant (2")-Ia, aac(6')-Ib, sul, tet, dfr and cat genes in various combinations. The emergence in pets of multidrug-resistant Klebsiella with ESBL, AmpC and PMQR determinants, poses further and serious challenges in companion animal therapy and raise concerns for possible bi-directional transmission between pets and humans, especially at household level

Haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis

The platelet P2Y12 receptor plays a very important role both in thrombosis and hemostasis. This report describes haploinsufficiency of the platelet P2Y12 gene in a family with congenital bleeding diathesis

Use of an intraoperative wound protector to prevent surgical-site infection after pancreatoduodenectomy: randomized clinical trial

Surgical-site infection (SSI) increases treatment costs, duration of hospital stay and readmission rate after pancreatic surgery. This study aimed to assess whether a wound protector could reduce the risk of superficial incisional SSI after pancreatoduodenectomy

Age and laboratory variables at baseline of patients on ART (n = 43) or ART and MVC (n = 45).

<p>Results are presented as median and range.</p>*<p>p = 0.013 for direct comparison (Mann-Whitney).</p>§<p>p = 0.003 for direct comparison (Mann-Whitney).</p

Changes in metabolic variables and CD4⁺ cell counts over time in patients on ART (solid line, squares) or ART with MVC (broken line, circles).

<p>* denotes p<0.05 and ** p<0.01 for differences between the two patient groups at the time shown (Mann-Whitney test after non parametric analysis of variance for repeated measures).</p

HIV-RNA copy levels by time and treatment group.

<p>Data is presented as median and range. 49 copies is the lower limit of detection of the assay, and it was written in the database to indicate that the HIV-RNA was undetectable.</p

Median (range) levels of sEPCR.

<p>Median (range) levels of sEPCR.</p

CD4⁺ cell counts (solid line) and D-dimer levels (broken line) in ART treated (panel a) or ART with MVC treated (panel b) patients, by sEPCR levels at week 48 (high levels = red lines, low levels = blue lines).

<p>High or low sEPCR levels were defined as sEPCR ≥ or <300 ng/mL (corresponding to the 95^th percentile of the normal distribution). As specified in the text, D-dimers levels were measured in all patients up to week 24, while sEPCR was measured in all patients up to weel 48.</p