Suchergebnisse

Biosimilars are new drugs, highly similar copies of biological medicines, equally effective and safe but at lower prices. The aim of this brief review is to provide the current status of biosimilars approved in the European Union for dermatological use. We used PubMed for literature search up to June 2018. The keyword 'biosimilars' was searched and 1,691 items were found. From the 1,691 studies, we included 34 articles in our review. Biologics, biosimilars and generics are different types of drugs. Biosimilars are complex molecules produced by a difficult manufacturing process, and changes in product quality may affect its safety and efficacy. Now, there are 9 biosimilar medicines approved by European Medicines Agency (EMA) for plaque psoriasis and hidradenitis suppurativa: Amgevita, Solymbic, Cyltezo, Imraldi, Benepali, Erelzi, Flixabi, Inflectra and Remsima, and the number is increasing. In 2005, EMA issued the first guidelines for approval of biosimilars. Next-generation biologics, called 'biobetters', have the same target or mechanism of action as previously approved biologics, but they have structural changes and an improved formulation. The debate over the future of biosimilars is far from being finished. The explosive development of biological therapy and the emergence of biosimilars represent a significant success in the effort to provide advanced healthcare to patients all over the world.

To find sequence variants affecting prostate cancer (PCA) susceptibility in an unscreened Romanian population we use a genome‐wide association study (GWAS). The study population included 990 unrelated pathologically confirmed PCA cases and 1034 male controls. DNA was genotyped using Illumina SNP arrays, and 24.295.558 variants were imputed using the 1000 Genomes data set. An association test was performed between the imputed markers and PCA. A systematic literature review for variants associated with PCA risk identified 115 unique variants that were tested in the Romanian sample set. Thirty of the previously reported SNPs replicated (P‐value < 0.05), with the strongest associations observed at: 8q24.21, 11q13.3, 6q25.3, 5p15.33, 22q13.2, 17q12 and 3q13.2. The replicated variants showing the most significant association in Romania are rs1016343 at 8q24.21 (P = 2.2 × 10−4), rs7929962 at 11q13.3 (P = 2.7 × 10−4) and rs9364554 at 6q25.2 (P = 4.7 × 10−4). None of the variants tested in the Romanian GWAS reached genome‐wide significance (P‐value <5 × 10−8) but 807 markers had P‐values <1 × 10−4. Here, we report the results of the first GWAS of PCA performed in a Romanian population. Our study provides evidence that a substantial fraction of previously validated PCA variants associate with risk in this unscreened Romanian population. ; This study was funded in part by the European Union FP7 Program (ProMark project 202059) and by the EEA grant (ROMCAN project RO14-0017; EEAJRPRO-NO-20131-10191). ; Peer Reviewed

Gastric antral vascular ectasia (GAVE) is an important cause of gastro-intestinal bleeding. The most common clinical presentation of GAVE is chronic occult bleeding that leads to symptomatic iron deficiency anemia, but some cases could present with acute massive bleeding. Frequently, patients are dependent by iron suplimentation, or in severe cases even blood transfusions. Endoscopic therapy is frequently necessary in acute or chronic blood loss. Over the past several years, treatment for GAVE has continued to evolve as the number of available effective therapeutic interventions has increased. These included: YAG laser, argon plasma coagulation (APC), endoscopic band ligation, cryotherapy and surgical anterectomy. Argon plasma coagulation is the most commonly used technique, but has been associated with several complications like sepsis, post-APC bleeding, gastric outlet obstruction and increased incidence of hyperplastic polyps. Endoscopic band ligation (EBL), a mechanical procedure, has been reported in the past years as an effective salvage therapy for GAVE that is refractory to other approaches, or even as the first line treatment. We present a case of nodular GAVE treated succesfully with endoscopic band ligation after unsuccesufull sessions with argon plasma coagulation.

Colorectal cancer is the third most common cancer worldwide and represents a significant major public health issue.
Therefore, the interest in detecting the multiple factors implied in the development of cancer has increased recently. One of the
factors could be the Helicobacter pylori infection, but a direct causal connection is missing. This gram-negative bacterium infects
approximately 4 billion individuals globally and various conditions such as gastroduodenal ulcers or gastric adenocarcinomas can
be induced by it. Some of the reported carcinogenic effects of Helicobacter pylori bacterium are hypergastrinemia, chronic
inflammation, dysbiosis, and toxin production. Each of these elements involved in the pathogenesis has various mechanisms of
action. Dysbiosis can occur due to various treatments for the eradication of the Helicobacter pylori infection. This bacterium also
has a proinflammatory effect at the gastric level which can predispose to the development of dysplasia or even neoplasia. The
toxins produced by this bacterium, such as the vacuolating cytotoxin A, promote inflammation. In this review, we discuss the
possible connections between the Helicobacter pylori infection, through its diverse pathogenic mechanisms, and colorectal
neoplasm. Prospective studies are necessary to determine whether there certainly is a direct link between the two conditions.

Publisher's version (útgefin grein) ; Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high‐risk CRC mutations in the Romanian population. We performed whole‐genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559‐1G>C). ; This study was funded in part by the European Union FP7 Program (ProMark project 202059) and by the EEA grant (ROMCAN project RO14‐0017; EEAJRP‐RO‐NO‐20131‐10191). We thank the study participants, the staff at deCODE Genetics Iceland and Landspitali University Hospital. ; Peer Reviewed

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download ; Two familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C). ; European Union EEA

Introduction: Our objective is to review current international guidelines for Helicobacter Pylori treatment and our department`s experience in this field. Materials and methods: Helicobacter pylori is a Gram-negative, microaerophilic bacterium that can be found mainly in the gastric mucus or on the inner surface of the gastric epithelium, infecting up to 50% of the population. Colonization with this bacterium is not a disease in itself, but can cause chronic gastritis, peptic ulcer, gastric cancer and MALToma. Because of this, infection with H. pylori continues to be a major healthcare burden, especially in less-developed countries. A multitude of non-invasive tests are available for the diagnosis of Helicobacter pylori infection (blood antibody, stool antigen or urea breath test), but the most reliable method of diagnosis is histological examination from two sites after endoscopic biopsy, combined with either a microbial culture or rapid urease test. Treatment of Helicobacter pylori infection is becoming a challenge, as eradication following standard triple therapy is decreasing worldwide due to increased bacterial resistance against antibiotics, which has led to the development of newer therapies such as the sequential treatment in which a PPI and amoxicillin is given for 5 days followed by a PPI, clarithromycin and metronidazole for another 5 days, or the quadruple therapy based on a PPI, bismuth subcitrate, metronidazole and tetracycline for 10 days. Results and conclusion: H. pylori infection remains one of the most challenging infectious diseases, causing high morbidity and mortality, mainly because none of the actual antibiotic therapies can provide successful eradication.

Autoimmune cholangitis defines a spectrum of cholestatic liver diseases that are characterized by inflammation of bile ducts and a reasonable response to immunosuppressive therapy. The two most common diseases associated with this term in the literature are: an overlap syndrome of primary biliary cirrhosis and autoimmune hepatitis and a form of hyper IgG4 syndrome (currently associated with autoimmune pancreatitis). Liver biopsy is mandatory for the diagnosis. There are, whatsoever, in clinical practice, many cases that do not meet current diagnostic criteria but that have a good response to corticosteroid treatment. Keywords: autoimmune cholangitis, primary biliary cirrhosis, hyper IgG4 syndrome.

Bariatric surgery represents one of the most efficient treatments addressing obesity and its associated complications
with an increasing trend. Even if the medical benefits for patients are huge, due to weight loss and despite technical improvements
in bariatric procedures, it is still associated with diverse types of complications. Most of the complications appear due to nutrient
deficiency, as absorption is compromised after surgical anatomy modification. Neurological complications after bariatric surgery
are very diverse with an occurrence within days to years after surgery, most frequently in patients with gastrointestinal or surgical
complications. Any segment of the nervous system can be affected with distinct types of manifestations ranging from peripheral
axonal neuropathy, nerve palsy secondary to compartment syndrome, encephalopathy, and myelopathy, to psychiatric and
demyelinating central nervous system diseases. Identifying patients at risk and systematic screening for nutrient deficiency with
proper supplementation is essential for preventing neurological complications and lifelong sequelae. In this paper, we present
the spectrum of neurological complications reported after bariatric surgery.

Chronic liver disease is a late stage of progressive hepatic fibrosis. It consists of functional and structural disruptions in most chronic liver diseases. An accurate diagnosis allows us to establish the degree of fibrosis and the stage of the disease, the prognosis of the patient and to predict a treatment response. Despite the fact that liver biopsy is considered a gold standard, noninvasive methods for diagnosing liver fibrosis have gained more and more importance. Whether we talk about serum biomarkers or imagistic methods from transient elastography to 3-D magnetic resonance elastography, the question remains: are these useful or useless? Serum biomarkers represent blood components that can reflect liver histological changes, thus they can monitor the continuous process of fibrosis. These can be subcategorized in direct (that show extracellular matrix turnover) and indirect markers (that reflect disturbances in the hepatic function). However these markers alone are not as accurate in the staging of fibrosis, only help differentiate patients without or with low grade of fibrosis from those with significant fibrosis and cannot be considered alone in the diagnosis of liver fibrosis. Imagistic methods include: ultrasound-based transient elastography, magnetic resonance elastography (MRE), 2D-shear wave elastography, acoustic radiation impulse imaging (ARFI) and cross sectional imaging, the first being the most used. Using a combination of non-invasive tools allows us to diminish the number of patients in need of liver biopsy. However, the patient must always be informed of the advantages and disadvantages of each method and its limitations.

The burden of colorectal cancer (CRC) is increasing all over the world. The prevalence of diabetes mellitus is increasing. It is estimated that diabetes affects 387 million people worldwide. It is predicted that 552 million people worldwide will develop diabetes by 2030. A large pool of data indicate that DM increases by 2 fold the risk of CRC. This is the reason to firmly suggest the inclusion of DM in the criteria for CRC screening as an important measure to decrease the mortality of this ailment.

The infection caused by H. pylori appears secondary after a bacterial colonization of the stomach and the initial portion of the small bowel. H. pylori –infected patients can develop gastritis, peptic ulcer, stomach cancer or MALT lymphoma. H. pylori infection is defined by WHO like a type I carcinogen, its role in gastric carcinogenesis being supported by the greatest researchers. Objectives: In this study our purpose was to determine the endoscopic appearances in H. pylori infection quoted in medical literature until now and the frequency of their appearance in our group of interest. Materials and methods: In this study it was made an analytic study in which it was realized a retrospective cohort investigation at the Emergency Central Military and University Hospital "Dr. Carol Davila" Bucharest, gastroenterology branch –endoscopic department between 18.12.2012- 21.08.2013 on 1694 patients between 18 and 92 years old, with the medium age of 55 years old. As a diagnostic method for H. pylori infection we used superior digestive endoscopy during which were taken biopsies and it was made a fast urease test. Results: Regarding the variation of the endoscopic aspects at the population of study, we have found gastritis with all its aspects (which was Sidney classified) in the biggest percentage meaning 59.3% of the cases, followed with a percentage of 18.8% by those without any endoscopic abnormality, and then in 10,33% of the cases we have found peptic ulcer. With a smaller percentage, under 10%, we have found duodenitis at 8.67% of this patients, and finally the most severe lesions represented by gastric cancer and lymphoma were found at 2,7% of the H.pylori infected patients.