Venous Thromboembolism and Cerebrovascular Events in Patients with Giant Cell Arteritis: A Population-Based Retrospective Cohort Study

Objective

To investigate the incidence of venous thromboembolism (VTE) and cerebrovascular events in a community-based incidence cohort of patients with giant cell arteritis (GCA) compared to the general population.

Methods

A population-based inception cohort of patients with incident GCA between January 1, 1950 and December 31, 2009 in Olmsted County, Minnesota and a cohort of non-GCA subjects from the same population were assembled and followed until December 31, 2013. Confirmed VTE and cerebrovascular events were identified through direct medical record review.

Results

The study population included 244 patients with GCA with a mean ± SD age at diagnosis of 76.2 ± 8.2 years (79% women) and an average length of follow-up of 10.2 ± 6.8 years. Compared to non-GCA subjects of similar age and sex, patients diagnosed with GCA had a higher incidence (%) of amaurosis fugax (cumulative incidence ± SE: 2.1 ± 0.9 versus 0, respectively; p = 0.014) but similar rates of stroke, transient ischemic attack (TIA), and VTE. Among patients with GCA, neither baseline characteristics nor laboratory parameters at diagnosis reliably predicted risk of VTE or cerebrovascular events.

Conclusion

In this population-based study, the incidence of VTE, stroke and TIA was similar in patients with GCA compared to non-GCA subjects.     

Treatment of hepatitis C virus genotype 4 in the DAA era

The recently approved interferon-free DAA (direct antiviral agents) regimens have shown not only to be effective in terms of sustained virological response (SVR) rates (>?90%) but also well tolerated in most hepatitis C virus (HCV) infected patients. Nevertheless HCV genotypes are different and only a small percentage of trials consider genotype 4 (GT4), which was associated with lower rates of SVR compared with other genotypes before the arrival of the DAA’s. In this review, we discuss the efficacy of DAA therapy in GT4 HCV infection with specific reference to more recent studies, including those conducted in a ‘field-practice’ scenario. Overall, DAA-based regimens appear more effective also in the poorly-explored setting of patients with HCV GT4 infection. Despite an overall limited number of patients was evaluated, favorable results are being derived from studies on ombitasvir/paritaprevir/ritonavir, sofosbuvir and velpatasvir, whether or not in association with voxilaprevir, and with the new combined therapy glecaprevir + pibentasvir.     

Connexin 26 (GJB2) mutations as a cause of the KID syndrome with hearing loss

KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea. These channels play a role in the coordinated exchange of molecules and ions occurring in a wide spectrum of cellular activities. In this paper we describe two patients with Cx26 mutations cause cell death by the alteration of protein trafficking, membrane localization and probably interfering with intracellular ion concentrations. We discuss the pathogenesis of both the hearing and skin phenotypes.     

A study on oral rehabilitation in stroke patients: analysis of a group of 33 patients

doi:10.1111/j.1741‐2358.2009.00322.x
A study on oral rehabilitation in stroke patients: analysis of a group of 33 patients Background: Stroke is the third leading cause of death in the world after cardiovascular disease and cancer. This study aimed to investigate the oro‐dental status and removable denture conditions in stroke survivors. Methods: At the Department of Vascular Disease of the Neurological Clinic of the Polyclinic Hospital of Bari, from January 2003 to May 2008, 189 consecutive patients were examined who had had a stroke, to select removable denture wearers. The oro‐dental examination was performed in a period between 12 and 60 months after the stroke and among these 189 patients, 60 were wearing a removable denture, but only 33 participated in our research. All the patients gave written informed consent. Results: It was observed that in 42.4%, removable dentures needed to be remade, in 27.3%, they needed to be rebased and in 30.3%, they were adequate. Conclusion: The role of oral health providers is fundamental in order to maintain good oral health and to avoid oral diseases in stroke patients. They should, indeed, monitor these patients with a regular follow‐up after 1 month and every 3–4 months.     

Role of interleukin-23 circulating levels increase in resected colorectal cancer before and after chemotherapy: preliminary data and future perspectives

Expression of IL‐23, a heterodimeric cytokine involved in the induction of Th17 cells, is increased in human tumors. Although the endogenous IL‐23 expression has been reported to promote tumor development and growth, the studies using local and systemic administration of IL‐23 have shown that its application at the excessive amount induces antitumor immune responses. IL‐23 is, today, considered the key driver of intestinal inflammation and its role in inflammatory responses is tissue‐specific. The aim of this study was to investigate the role of circulating levels of IL‐23 in patients with resected colorectal cancer (CRC) before and after chemotherapy, respect to healthy controls. Twenty‐five patients were enrolled between June 2007 and January 2009, and followed through 2010. All patients underwent chemotherapy, mostly FOLFOX4. Twenty‐sex and age‐matched healthy donors were recruited as controls. IL‐23 serum concentrations, measured by a quantitative enzyme immunoassay technique, were significantly higher in patients with resected CRC (26.02 ± 28.63 pg/ml versus 7.1 ± 6.4 pg/ml, P < 0.001) and after chemotherapy respect to controls (21.74 ± 23.82 pg/ml versus 7.17 ± 6.43 pg/ml, P < 0.001). An increase was documented also before chemotherapy (26.02 ± 28.63 pg/ml versus 21.74 ± 23.82 pg/ml, P = 0.7) but not statistically significant. This work investigated, for the first time, the role of IL‐23 in CRC resection and chemotherapy, showing no correlation with the severity of disease, tumor removal, and chemotherapeutic treatment. However, other works are needed to better clarify if IL‐23 could be considered a key‐molecule in human CRC and a target for tumor treatment. J. Cell. Physiol. 226: 3032–3034, 2011. © 2011 Wiley‐Liss, Inc.     

Fast flexible modeling of RNA structure using internal coordinates

Modeling the structure and dynamics of large macromolecules remains a critical challenge. Molecular dynamics (MD) simulations are expensive because they model every atom independently, and are difficult to combine with experimentally derived knowledge. Assembly of molecules using fragments from libraries relies on the database of known structures and thus may not work for novel motifs. Coarse-grained modeling methods have yielded good results on large molecules but can suffer from difficulties in creating more detailed full atomic realizations. There is therefore a need for molecular modeling algorithms that remain chemically accurate and economical for large molecules, do not rely on fragment libraries, and can incorporate experimental information. RNABuilder works in the internal coordinate space of dihedral angles and thus has time requirements proportional to the number of moving parts rather than the number of atoms. It provides accurate physics-based response to applied forces, but also allows user-specified forces for incorporating experimental information. A particular strength of RNABuilder is that all Leontis-Westhof basepairs can be specified as primitives by the user to be satisfied during model construction. We apply RNABuilder to predict the structure of an RNA molecule with 160 bases from its secondary structure, as well as experimental information. Our model matches the known structure to 10.2 Angstroms RMSD and has low computational expense.     

Proteomic analysis identifies differentially expressed proteins after HDAC vorinostat and EGFR inhibitor gefitinib treatments in Hep-2 cancer cells

Several solid tumors are characterized by poor prognosis and few effective treatment options, other than palliative chemotherapy in the recurrent/metastatic setting. Epidermal growth factor receptor (EGFR) has been considered an important anticancer target because it is involved in the development and progression of several solid tumors; however, only a subset of patients show a clinically meaningful response to EGFR inhibition, particularly to EGFR tyrosine kinase inhibitors such as gefitinib. We have recently demonstrated synergistic antitumor effect of the histone deacetylase inhibitor vorinostat combined with gefitinib. To further characterize the interaction between these two agents, cellular extracts from Hep‐2 cancer cells that were untreated or treated for 24 h with either vorinostat or gefitinib alone or with a vorinostat/gefitinib combination were analyzed using 2‐D DIGE. Software analysis using DeCyder was performed, and numerous differentially expressed protein spots were visualized between the four examined settings. Using MALDI‐TOF MS and ESI‐Ion trap MS/MS, several differentially expressed proteins were identified; some of these were validated by Western blotting. Finally, a pathway analysis of experimental data performed using MetaCore highlighted a relevant relationship between the identified proteins and additional potential effectors. In conclusion, we performed a comprehensive analysis of proteins regulated by vorinostat and gefitinib, alone and in combination, providing a useful insight into their mechanisms of action as well as their synergistic interaction.