Characteristics of vertebral osteomyelitis after liver transplantation

AbstractWe performed a retrospective single-centre 1:3 case–control study to investigate the characteristics of vertebral osteomyelitis (VO) occurring in orthotopic liver transplant (OLT) recipients between 2000 and 2012. Nine cases were identified in 752 OLT recipients (1.2%), with a median time from OLT to VO of 12 weeks. In comparison with 27 VO not occurring in OLT patients (controls), VO occurring in OLT recipients was characterized by decreased levels of inflammation biomarkers (average C-reactive protein 65.1 mg·L−1 vs. 167 mg·L−1, p 0.02; average white blood cell count 4.8 × 109·L−1 vs. 12.9 × 109·L−1, p < 0.001), higher rate of fungal infections (3/9 vs. 0/27, p 0.01), lower rate of bacterial infections (3/9 vs. 25/27, p 0.001) and decreased proportion of positive blood cultures (1/9 vs. 16/27, p 0.02) despite a trend towards higher rate of multifocal infection. Microbiologic outcomes were similar between the two groups. Overall, VO in OLT patients was more difficult to diagnose as a result of altered inflammation response and specific microbial epidemiology of causal microorganisms

Do Patients with Bronchiectasis Have an Increased Risk of Developing Lung Cancer? A Systematic Review

Background: Initial evidence supports the hypothesis that patients with non-cystic fibrosis bronchiectasis (NCFB) have a higher risk of lung cancer. We systematically reviewed the available literature to define the characteristics of lung malignancies in patients with bronchiectasis and the characteristics of patients who develop bronchiectasis-associated lung cancer. Method: This study was performed based on the PRISMA guidelines. The review protocol was registered in PROSPERO. Results: The frequency rates of lung cancer in patients with NCFB ranged from 0.93% to 8.0%. The incidence rate was 3.96. Cancer more frequently occurred in the elderly and males. Three studies found an overall higher risk of developing lung cancer in the NCFB population compared to the non-bronchiectasis one, and adenocarcinoma was the most frequently reported histological type. The effect of the co-existence of NCFB and COPD was unclear. Conclusions: NCFB is associated with a higher risk of developing lung cancer than individuals without NCFB. This risk is higher for males, the elderly, and smokers, whereas concomitant COPD’s effect is unclear

Endoscopic Technologies for Peripheral Pulmonary Lesions: From Diagnosis to Therapy

Peripheral pulmonary lesions (PPLs) are frequent incidental findings in subjects when performing chest radiographs or chest computed tomography (CT) scans. When a PPL is identified, it is necessary to proceed with a risk stratification based on the patient profile and the characteristics found on chest CT. In order to proceed with a diagnostic procedure, the first-line examination is often a bronchoscopy with tissue sampling. Many guidance technologies have recently been developed to facilitate PPLs sampling. Through bronchoscopy, it is currently possible to ascertain the PPL’s benign or malignant nature, delaying the therapy’s second phase with radical, supportive, or palliative intent. In this review, we describe all the new tools available: from the innovation of bronchoscopic instrumentation (e.g., ultrathin bronchoscopy and robotic bronchoscopy) to the advances in navigation technology (e.g., radial-probe endobronchial ultrasound, virtual navigation, electromagnetic navigation, shape-sensing navigation, cone-beam computed tomography). In addition, we summarize all the PPLs ablation techniques currently under experimentation. Interventional pulmonology may be a discipline aiming at adopting increasingly innovative and disruptive technologies

The non-convex shape of (234) Barbara, the first Barbarian

Asteroid (234) Barbara is the prototype of a category of asteroids that has been shown to be extremely rich in refractory inclusions, the oldest material ever found in the Solar System. It exhibits several peculiar features, most notably its polarimetric behavior. In recent years other objects sharing the same property (collectively known as "Barbarians") have been discovered. Interferometric observations in the mid-infrared with the ESO VLTI suggested that (234) Barbara might have a bi-lobated shape or even a large companion satellite. We use a large set of 57 optical lightcurves acquired between 1979 and 2014, together with the timings of two stellar occultations in 2009, to determine the rotation period, spin-vector coordinates, and 3-D shape of (234) Barbara, using two different shape reconstruction algorithms. By using the lightcurves combined to the results obtained from stellar occultations, we are able to show that the shape of (234) Barbara exhibits large concave areas. Possible links of the shape to the polarimetric properties and the object evolution are discussed. We also show that VLTI data can be modeled without the presence of a satellite.Comment: 10 pages, 6 figure

A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion

Strong evidence suggests that phospholipase Cγ1 (PLCγ1) is a suitable target to counteract tumourigenesis and metastasis dissemination. We recently identified a novel signalling pathway required for PLCγ1 activation which involves formation of a protein complex with 3-phosphoinositide-dependent protein kinase 1 (PDK1). In an effort to define novel strategies to inhibit PLCγ1-dependent signals we tested here whether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCγ1 interaction and impair PLCγ1-dependent cellular functions in cancer cells. Here, we demonstrate that 2-O-Bn-InsP5 interacts specifically with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCγ1 complex. 2-O-Bn-InsP5 is able to inhibit the epidermal growth factor-induced PLCγ1 phosphorylation and activity, ultimately resulting in impaired cancer cell migration and invasion. Importantly, we report that 2-O-Bn-InsP5 inhibits cancer cell dissemination in zebrafish xenotransplants. This work demonstrates that the PDK1/PLCγ1 complex is a potential therapeutic target to prevent metastasis and it identifies 2-O-Bn-InsP5 as a leading compound for development of anti-metastatic drugs

Treating hyperglycemia improves skeletal muscle protein metabolism in cancer patients after major surgery

Objective: Cancer and surgical stress interact to aggravate insulin resistance, protein catabolism, and glutamine depletion in skeletal muscle. We compared the effects of insulin-mediated euglycemia and moderate hyperglycemia on kinetics of protein and selected amino acids in skeletal muscle of female cancer patients after major surgery. Design: In each patient, a 24-hr period of insulin-mediated tight euglycemia (mean blood glucose, 5.8 0.4 mmol/L) preceded or followed a 24-hr control period of moderate hyperglycemia (mean blood glucose, 9.6 0.6 mmol/L) on the first and second day after surgery, in randomized order, according to a crossover experimental design. Setting: Intensive care unit, cancer ospital. Patients: Cancer patients after abdominal radical surgery combined with intraoperative radiation therapy. Interventions: Intensive (57 +/- 11 units/24 hrs) and conventional (25 +/- 5 units/24 hrs) insulin treatment during total parenteral nutrition. Measurements and Main Results: Muscle metabolism was assessed at the end of each 24-hr period of euglycemia and of hyperglycemia by leg arteriovenous catheterization with stable isotopic tracers. We found that euglycemia as compared with hyperglycemia was associated with higher (p < .05) fractional glucose uptake (16% +/- 4% vs. 9% +/- 3%); higher (p < .05) muscle protein synthesis and neutral net protein balance (-3 +/- 3 vs. -11 +/-3 nmol phenylalanine·100 (mL-1)·(min-1), respectively); lower (-52% +/- 12%, p < .01) muscle nonprotein leucine disposal (an index of leucine oxidation) and higher (p < .05) plasma leucine concentrations; and higher (3.6 +/- 1.7 times, p < .01) net de novo muscle glutamine synthesis and plasma glutamine concentrations (p < .05). Euglycemia was associated with higher (23% +/- 7%, p < .05) plasma concentrations of arginine but did not affect either arginine release from muscle or plasma concentration and muscle flux of asymmetrical dimethylarginine. Rate of muscle proteolysis correlated (p < .05) with muscle release of asymmetrical dimethylarginine. Conclusions: Treating hyperglycemia improves skeletal muscle protein and amino acid metabolism in cancer patients after major surgery

The complex TIE between macrophages and angiogenesis

Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway