Haemophilia therapies

In the last few decades dramatic improvements in the management of haemophilia patients have occurred. Haemophilia has moved from a fatal or disabling disease to a hereditary disorder with available treatment and much better clinical outcomes. The safety of antihaemophilic factor concentrates has been dramatically improved and, in a multidisciplinary environment including haematologists, orthopaedic surgeons, paediatrics, infectiologists, specialised nurses and physiotherapists, complications related to haemophilia are now limited, markedly improving the quality of life of haemophiliacs. One can even think that the cure of haemophilia through gene therapy might occur in the next decades. Keeping this ultimate aim in mind, efforts at present are mainly focused on bioengineered Factor VIII/Factor IX concentrates with increased efficacy or longer half-life or decreased immunogenicity. In addition, several preclinical and clinical studies are being carried out for optimising and individually tailoring the therapeutic regimens of antihaemophilic therapies using global haemostasis tests in combination with the routine coagulation assays.     

The Effect of Gene Mutations on Metastasis and Overall Survival in Metastatic and Nonmetastatic Colon Cancers

Objective: It is known that many genes are associated with colon cancer. We aimed to investigate the effect of gene mutations on metastasis and overall survival in metastatic and non metastatic colon cancers. Methods: A total of 50 patients with metastatic (n=25) and non metastatic (n=25) diagnosed with colon cancer between 2010 and 2018 were included in the study. APC, MUTYH, RAD50, MEN1, ATM, PALB2, NSH2, BRCA1, BRCA2, MLH1, BRIP1, TP53, PTEN, BARD1, MSH6, PMS2, NBN, and FAM175A gene mutations were evaluated using the next generation sequencing method. The effect of gene mutations on metastasis and overall survival were evaluated. Results: The mean age of patients with colon cancer without distant metastasis was 48.64±14.72 years and for patients with distance metases was 56.68±11.65. The mean survival time of colon cancer patients with distant organ metastasis after the metastasis date was 104.36±58.59 weeks. The presence of APC, MUTYH, and TP53 genetic mutations was observed with a higher rate in metastatic colon cancer (p<0.05). Conclusion: We showed that APC, MUTYH, and TP53 mutations are associated with distant organ metastasis.     

Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed. The IU-TAB-1 cell line was noted to be resistant to everolimus (mTORC1 inhibitor) and sensitive to nelfinavir (AKT1 inhibitor) across the endpoints measured. Sensitivity to nelfinavir was due to the IU-TAB-1 cell line’s gain-of function (GOF) mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization (aCGH), including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition. We present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.     

Telaprevir Experience From Turkey

Background:

In patients with chronic hepatitis C, triple drug regimens containing a protease inhibitor, peginterferon and ribavirin were found to significantly increase sustained virologic response rates compared to dual drug regimen containing pegylated interferon and ribavirin, especially in genotype 1.

Objectives:

In Turkey, telaprevir has been used since March 2013. We aimed to evaluate results of patients with chronic hepatitis C treated with telaprevir, peginterferon and ribavirin.

Patients and Methods:

We evaluated 28 patients with genotype 1 chronic hepatitis C infection treated with triple drug regimen containing telaprevir, in three medical centers in Turkey, retrospectively. Demographic data of patients, treatment indications, adverse events and outcomes were recorded.

Results:

Of 28 patients intended to treat, 25 (89.2%) patients completed the treatment. Overall, 21 (82.1%) patients had relapse and five patients were non-responder. Regarding the treatment outcomes of Telaprevir based regimen, 20/26 patients achieved sustained virological response. Pruritus, rash, dysgeusia, anorectal discomfort and anemia were main adverse effects. Blood transfusion and ribavirin dose reduction required for 7 and 11 patients, respectively. Due to several adverse effects, 10 patients were hospitalized.

Conclusions:

Although more frequent and severe adverse effects, telaprevir has been promising for patients with treatment-experienced hepatitis C.     

Mechanical and optical properties of monolithic CAD-CAM restorative materials

Statement of problem

Achieving natural tooth appearance with sufficient mechanical strength is one of the most challenging issues of computer-assisted design and computer-assisted manufacturing (CAD-CAM) materials. However, limited evidence is available regarding their optical and mechanical properties for proper and evidence-based material selection in clinical practice.

The effects of extraction methods on the contents of fatty acids, especially EPA and DHA in marine lipids

This study aims to evaluate the efficiency of trans-methylation methods in fish oil obtained using Soxhlet extraction method and Bligh and Dyer method and also to observe the effects of extraction methods on the contents of polyunsaturated fatty acids [PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] in five marine species: sardine (Sardinella aurita), anchovy (Engraulis encrasicolus), sea bream (Sparus aurata), brushtooth lizardfish (Saurida undosquamis) and chub mackerel (Scomber japonicus). The results showed that Bligh and Dyer extraction method was more efficient in extracting polar and non-polar lipids than Soxhlet method and also prevented losses of PUFAs by a reduction in the oxidation. The level of EPA showed fluctuations for the two extraction methods. However, Soxhlet method showed significant decrease (p?相似文献   

Prosthetic valve endocarditis caused by Salmonella enteritidis

Until now, only 12 cases of prosthetic valve endocarditis caused by Salmonella spp. have been reported in the English literature. High complication and mortality rates, a fulminant course and the requirement for early surgical intervention deserve special attention in this kind of infective endocarditis. A new case of Salmonella prosthetic valve endocarditis complicated by sepsis-induced cholestasis and a literature review are presented in this report.