Spinal fractures in patients with ankylosing spondylitis

The ankylosed spine is prone to fracture even after minor trauma due to its changed biomechanical properties. The two central features of ankylosing spondylitis (AS) that promote the pathological remodeling of the spine are inflammation and new bone formation. AS is also associated with osteoporosis that is attributed to an uncoupling of the bone formation and bone resorption processes. Therefore, bone resorption occurs and promotes weakening of the spine as well as increased risk of vertebral fractures which can be hugely different in terms of clinical relevance. Even in the presence of symptomatic clinical vertebral fractures, the diagnosis can be overruled by attributing the pain to disease activity. Furthermore, given the highly abnormal structure of the spine, vertebral fracture diagnosis can be difficult on the basis of radiography alone. CT can show the fractures in detail. Magnetic resonance imaging is considered the method of choice for the imaging of spinal cord injuries, and a reasonable option for exclusion of occult fractures undetected by CT. Since it is equally important for radiologists and clinicians to have a common knowledge base rather than a compartmentalized view, the aim of this review article was to provide the required clinical knowledge that radiologists need to know and the relevant radiological semiotics that clinicians require in diagnosing clinically significant injury to the ankylosed spine.     

Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation and response to therapy

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET‐related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET‐related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus. In univariate analysis, ET‐related NS resulted more frequently in young people (P = 0.017) and in females (P = 0.025). We found a higher prevalence of JAK2V617F mutation in ET‐related NS patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F mutation (P = 0.041) remained significantly associated with the development of ET‐related NS, with a risk of about four times higher for JAK2V617F‐mutated patients (OR = 3.75). Ninety‐seven of 101 patients with ET‐related NS received an antiplatelet (AP) agent at the time of NS, whereas only selected high‐risk ET‐related NS patients were treated with a cytoreductive drug, according to the published guidelines and similarly to patients without NS. We observed that only 32 of 97 (33%) patients with ET‐related NS achieved a complete response after AP treatment. Among the 65 non‐responder patients, 36 (55.4%) improved NS after the introduction of cytoreductive therapy; therefore, the addition of cytoreductive treatment should be considered in this setting.     

Novel Rho kinase inhibitors with anti-inflammatory and vasodilatory activities

Increased Rho kinase (ROCK) activity contributes to smooth muscle contraction and regulates blood pressure homeostasis. We hypothesized that potent and selective ROCK inhibitors with novel structural motifs would help elucidate the functional role of ROCK and further explore the therapeutic potential of ROCK inhibition for hypertension. In this article, we characterized two aminofurazan-based inhibitors, GSK269962A [N-(3-{[2-(4-amino-1,2,5-oxadiazol-3-yl)-1-ethyl-1H-imidazo[4, 5-c]pyridin-6-yl]oxy}phenyl)-4-{[2-(4-morpholinyl)ethyl]-oxy}benzamide] and SB-7720770-B [4-(7-{[(3S)-3-amino-1-pyrrolidinyl]carbonyl}-1-ethyl-1H-imidazo[4,5-c]pyridin-2-yl)-1,2,5-oxadiazol-3-amine], as members of a novel class of compounds that potently inhibit ROCK enzymatic activity. GSK269962A and SB-772077-B have IC50 values of 1.6 and 5.6 nM toward recombinant human ROCK1, respectively. GSK269962A also exhibited more than 30-fold selectivity against a panel of serine/threonine kinases. In lipopolysaccharide-stimulated monocytes, these inhibitors blocked the generation of inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-alpha. Furthermore, both SB-772077-B and GSK269962A induced vasorelaxation in preconstricted rat aorta with an IC50 of 39 and 35 nM, respectively. Oral administration of either GSK269962A or SB-772077-B produced a profound dose-dependent reduction of systemic blood pressure in spontaneously hypertensive rats. At doses of 1, 3, and 30 mg/kg, both compounds induced a reduction in blood pressure of approximately 10, 20, and 50 mm Hg. In addition, administration of SB-772077-B also dramatically lowered blood pressure in DOCA salt-induced hypertensive rats. SB-772077-B and GSK269962A represent a novel class of ROCK inhibitors that have profound effects in the vasculature and may enable us to further evaluate the potential beneficial effects of ROCK inhibition in animal models of cardiovascular as well as other chronic diseases.     

A difficult diagnosis of Hodgkin lymphoma due to immune thrombocytopenia

We report a rare clinical presentation of childhood Hodgkin lymphoma with immune thrombocytopenia. Diagnostic biopsy of the abdominal mass was performed after administration of intravenous immunoglobulins, steroids, and platelet transfusion. Concomitant thrombocytopenia complicated the whole diagnosis work up and the initial management of neoplasia.     

Effects of coffee consumption in chronic hepatitis C: A randomized controlled trial

BackgroundCoffee is associated with a reduced risk of hepatocellular carcinoma in patients with chronic C hepatitis. This prospective trial was aimed at assessing the mechanisms underlying coffee-related protective effects.MethodsForty patients with chronic hepatitis C were randomized into two groups: the first consumed 4 cups of coffee/day for 30 days, while the second remained coffee “abstinent”. At day 30, the groups were switched over for a second month.ResultsAt baseline, aspartate aminotransferase and alanine aminotransferase were lower in patients drinking 3–5 (Group B) than 0–2 cups/day (Group A) (56 ± 6 vs 74 ± 11/60 ± 3 vs 73 ± 7 U/L p = 0.05/p = 0.04, respectively). HCV-RNA levels were significantly higher in Group B [(6.2 ± 1.5) × 10⁵ vs (3.9 ± 1.0) × 10⁵ UI/mL, p = 0.05]. During coffee intake, 8-hydroxydeoxyguanosine and collagen levels were significantly lower than during abstinence (15 ± 3 vs 44 ± 16 8-hydroxydeoxyguanosine/10⁵ deoxyguanosine, p = 0.05 and 56 ± 9 vs 86 ± 21 ng/mL, p = 0.04). Telomere length was significantly higher in patients during coffee intake (0.68 ± 0.06 vs 0.48 ± 0.04 Arbitrary Units, p = 0.006). Telomere length and 8-hydroxydeoxyguanosine were inversely correlated.ConclusionIn chronic hepatitis C coffee consumption induces a reduction in oxidative damage, correlated with increased telomere length and apoptosis, with lower collagen synthesis, factors that probably mediate the protection exerted by coffee with respect to disease progression.     

TLR2 activation in corneal stromal cells by Staphylococcus aureus‐induced keratitis

The Toll‐Like Receptor 2 (TLR2) plays an active and important role in Staphylococcus aureus‐induced chronic ocular inflammation. The aim of this study was to investigate the expression and function of TLR2 of corneal stromal cells in ex vivo rabbit model of S. aureus keratitis. Corneal buttons with sclera rims placed in an ex vivo air‐interface organ culture were assigned to two groups: corneas with epithelial and stromal abrasions. Each group was then divided into two sub‐groups exposed to UV‐killed S. aureus ATCC 6538P and S. aureus ATCC 29213, respectively. TLR2 and IL‐8 mRNA expressions were analyzed by quantitative real‐time RT‐PCR. TLR2 localization was visualized by immunofluorescence analysis. The results demonstrated that TLR2 and IL‐8 mRNA were significantly expressed in the stromal cells of the groups exposed to S. aureus strains. Moreover, it has been demonstrated that, after corneal injury, keratocytes differentiated into myofibroblasts became able to express TLR2 only when exposed to S. aureus. Identification of mechanisms regulation of corneal TLRs may lead to development of therapeutic interventions aimed at controlling corneal inflammation. This ex vivo model can be used to clarify the molecular events of bacterial‐corneal tissue interactions and their inflammatory consequences.