Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients

There is a well‐established link between inflammation and cancer of various organs, but little data are available on inflammation‐associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high‐risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high‐sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high‐risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer‐free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high‐risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.     

Epidemiology of pyoderma gangrenosum: Results from an Italian prospective multicentre study

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by painful, necrotic ulcerations. PG is described as a rare disease: the world‐wide incidence is estimated to be around 3 to 10 cases per million population per year. These estimations are based mostly on case reports and retrospective case series; there are no prospective, multicentre studies on the matter. The apparent rarity of PG is in contrast with our clinical perception as dermatologists: in our opinion, PG is not so uncommon. Therefore, we decide to investigate the epidemiology of PG in the Italian population and confirm our clinical suspicions that it is not an orphan disease. We enrolled all patients diagnosed with PG in 8 Italian Dermatological Departments from 1st October 2014 to 1st November 2015, and we recorded their features. Our data, collected from 64 patients, are in accordance with those of the published literature regarding the epidemiology and features of PG. In an Italian population of roughly 8 million inhabitants of 7 provinces, we found an incidence of 5.17 new cases per million population per year. Unlike our predictions before the study, we confirmed the world‐wide incidence of PG. To our knowledge, this is the first observational, multicentre study on PG. We hope that it provides a stimulus for further researches on PG and for the creation of an Italian register.     

Biomechanical gait features associated with hip osteoarthritis: Towards a better definition of clinical hallmarks

Critical appraisal of the literature highlights that the discriminative power of gait‐related features in patients with hip osteoarthritis (OA) has not been fully explored. We aimed to reduce the number of gait‐related features and define the most discriminative ones comparing the three‐dimensional gait analysis of 20 patients with hip osteoarthritis (OA) with those of 17 healthy peers. First, principal component analysis was used to reduce the high‐dimensional gait data into a reduced set of interpretable variables for further analysis, including tests for group differences. These differences were indicative for the selection of the top 10 variables to be included into linear discriminant analysis models (LDA). Our findings demonstrated the successful data reduction of hip osteoarthritic‐related gait features with a high discriminatory power. The combination of the top variables into LDA models clearly separated groups, with a maximum misclassification error rate of 19%, estimated by cross‐validation. Decreased hip/knee extension, hip flexion and internal rotation moment were gait features with the highest discriminatory power. This study listed the most clinically relevant gait features characteristics of hip OA. Moreover, it will help clinicians and physiotherapists understand the movement pathomechanics related to hip OA useful in the management and design of rehabilitation intervention. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1498–1507, 2015.     

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: different prion proteins determined by a DNA polymorphism.

Fatal familial insomnia and a subtype of Creutzfeldt-Jakob disease, two clinically and pathologically distinct diseases, are linked to the same mutation at codon 178 (Asp-178-->Asn) but segregate with different genotypes determined by this mutation and the methionine-valine polymorphism at codon 129 of the prion protein gene. The abnormal isoforms of the prion protein in these two diseases were found to differ both in the relative abundance of glycosylated forms and in the size of the protease-resistant fragments. The size difference was consistent with a different protease cleavage site, suggesting a different conformation of the protease-resistant prion protein present in the two diseases. These differences are likely to be responsible for the type and location of the lesions that characterize these two diseases. Therefore, the combination of the mutation at codon 178 and the polymorphism at codon 129 determines the disease phenotype by producing two altered conformations of the prion protein.     

B7 costimulatory ligand regulates development of the T-cell response to Cryptococcus neoformans

The contribution of B7 molecules to the induction and maintenance of the T-cell response to the human pathogenic fungus Cryptococcus neoformans was investigated. T-cell activation by C. neoformans was regulated by B7 molecules. This costimulatory signal was necessary for initiation and maintenance of the T-cell response, through early and late requirements for B7-CD28 interaction. Blocking B7-2 inhibited the normal T-cell proliferative response. This inhibition was due, in part, to a reduced capability of T cells to produce interleukin-2 (IL-2). In contrast, the same T-cell population produced more interferon-gamma. Suppression of the normal lymphoproliferation and IL-2 secretion responses to encapsulated C. neoformans by antibodies to B7 was largely reversed by addition of the monoclonal antibody 2H1, that is reactive with the major capsular polysaccharide, glucuronoxylomannan. Overall, our data indicate that B7 molecules play a critical role in T-cell activation by C. neoformans and suggest that appropriate manipulation could drive T helper type 1 cell development.     

Antibody to capsular polysaccharide enhances the function of neutrophils from patients with AIDS against Cryptococcus neoformans.

OBJECTIVE: To determine the contribution of anti-glucuronoxylomannan monoclonal antibody (MAb18B7) to the fungicidal capacity of polymorphonuclear leukocytes (PMNL) from HIV-infected patients towards Cryptococcus neoformans. DESIGN: Killing activity and superoxide anion generation were evaluated in the presence or absence of MAb18B7 in an in vitro system. METHODS: Killing activity was determined by colony forming unit inhibition assay. Superoxide generation was measured in the presence or absence of zymosan, C. neoformans, or Candida albicans. CD16, CD32, and CD64 molecules on PMNL were evaluated by cytofluorometric analysis. RESULTS: MAb18B7 strongly influenced the phagocytic and killing activities against encapsulated C. neoformans and consistently enhanced superoxide anion generation. Expression of CD16, and to a lesser extent CD64, on PMNL was required for MAb18B7-induced superoxide generation. By blocking CD16 and CD64 molecules with anti-CD16 and anti-CD64 MAb, a significant down-regulation of MAb18B7-induced fungicidal activity was observed. CONCLUSIONS: Our results demonstrate that MAb18B7 selectively enhances the killing mechanisms of PMNL from HIV-infected patients against encapsulated C. neoformans. The availability of CD16 and CD64 molecules on PMNL plays a critical role.     

Interdependency of Interleukin-10 and Interleukin-12 in Regulation of T-Cell Differentiation and Effector Function of Monocytes in Response to Stimulation with Cryptococcus neoformans

We previously demonstrated that the principal component of capsular material of Cryptococcus neoformans, glucuronoxylomannan (GXM), induces interleukin-10 (IL-10) secretion from human monocytes. Here we report that encapsulation of the yeast with GXM is able to down-regulate interleukin-12 (IL-12) production by monocytes that would normally occur in the absence of encapsulation. This phenomenon appeared to be the result of inhibition of the phagocytic process by encapsulation with GXM as well as of negative signals such as IL-10 secretion produced by interaction of GXM with leukocytes. Decreased secretion of IL-12 correlated with decreased release of gamma interferon (IFN-gamma) from T cells, suggesting a role for encapsulation with GXM in hindering a T helper type 1 (Th1) response. This is supported by the ability of encapsulation with GXM to limit increased expression of B7-1 costimulatory molecules that otherwise might limit IL-10 secretion. Endogenous IL-10 played a critical role in modulatory activity associated with encapsulation with GXM. Blocking IL-10 with monoclonal antibody to IL-10 resulted in increased (i) IL-12 secretion, (ii) IFN-gamma release from T cells, and (iii) killing of C. neoformans by monocytes. These results suggest that encapsulation with GXM limits development of a protective Th1-type response, an inhibitory process in which IL-10 plays a critical role. Scavengers of GXM and/or IL-10 could be useful in a protective Th1-type response in patients with cryptococcosis.     

Abnormal platelet mitochondrial function in patients affected by migraine with and without aura

To investigate energy metabolism in migraine, we determined platelet mitochondrial enzyme activities in 40 patients with migraine with aura and in 40 patients with migraine without aura during attack-free intervals and in 24 healthy control subjects. NADH-dehydrogenase, citrate synthase and cytochrome-c-oxidase activities in both patient groups were significantly lower than in controls ( p < 0.01), while NADH-cytochrome-c-reductase activity was reduced only in migraine with aura ( p <0.01). No alteration in succinate-dehydrogenase was observed. Monoamine-oxidase activity differed between sexes (p < 0.05) but within each sex group no difference was observed between patients and controls. We hypothesize that the defect in mitochondrial enzymes observed indicates a systemic impairment of mitochondrial function in migraine patients.     

25-Hydroxyvitamin D levels in the outpatient population of a northern Italy region

Vitamin D deficiency is common, though its prevalence varies depending on the characteristics of the study population and the reference values adopted. We have analyzed the data of 25(OH)D levels collected in our laboratory to define the status in an outpatient population and the best cut-point for clinical practice.