TSH-receptor antibodies may prevent bone loss in pre- and postmenopausal women with Graves' disease and Graves' orbitopathy.

Objective: Thyrotoxicosis is established risk factor for osteoporosis due to increased bone turnover. Glucocorticoids often administered for Graves' orbitopathy (GO) have additional negative effect on bone mineral density (BMD). Our aim was to examine the influence of thyroid hormones, TSH, TSH-receptor antibodies (TRAb) and glucocorticoid treatment on bone in women with Graves' thyrotoxicosis and Graves' orbitopathy (GO).

Comorbidities of COPD in Bulgarian Patients - Prevalence and Association with Severity and Inflammation.

Background: wis a disease with constantly rising economic and social burden; it is associated with multiple comorbidities which contribute to the disease severity.

Aim: To investigate the prevalence of co-morbidities in COPD patients and their association with the disease severity and CRP levels.

Patients And Methods: We conducted a retrospective study among 338 COPD patients (mean age 65.

Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.

Pontocerebellar hypoplasia type 1 (PCH1) is a major cause of non-5q spinal muscular atrophy (SMA). We screened 128 SMN1-negative SMA patients from Bulgaria for a frequent mutation -p.G31A in EXOSC3, and performed a literature review of all genetically verified PCH1 cases.

Origin and Spread of HIV-1 Subtype B Among Heterosexual Individuals in Bulgaria.

Human immunodeficiency virus (HIV) was originally introduced in Bulgaria through heterosexual transmission (HET) and later transferred to other vulnerable groups along with numerous more recent introductions from outside Bulgaria. To define the diversity, origins, and dynamics of the HIV-1 subtypes prevalent in HET population in Bulgaria, we applied phylogenetic and phylodynamic analyses using polymerase (pol) sequences from HET individuals to infer the spatiotemporal evolutionary history of the HIV-1 epidemic in this population in Bulgaria. High genetic diversity was found, including 13 different HIV-1 subtypes: 45.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries.

Dissemination of successful international clone ST15 and clonal complex 17 among Bulgarian CTX-M-15 producing K. pneumoniae isolates.

A total of 82 extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae and 4 Klebsiella oxytoca isolates were collected in 2014 from four geographical areas in Bulgaria and their multilocus sequence type (MLST) and transferability of the ESBL encoding genes were investigated. The predominant type was CTX-M-15 (87%), followed by CTX-M-3 (9%), SHV-12 or SHV-2 (2%) and CTX-M-14 (1%). The CTX-M-15 producers belonged to ST15 (34.

The Role of Cytomegalovirus in Congenital and Early Postnatal Infections in Northeastern Bulgaria.

Background: Human cytomegalovirus is a ubiquitous, large enveloped DNA β-herpesvirus that, like other herpesviruses, establishes lifelong latency following primary infection. It is the most frequent cause of congenital, neonatal and early postnatal infections with long lasting sequelae.

Aim: The aim of the present study was to assess the prevalence of cytomegalovirus among a cohort of newborns and 1-3-month-old children with neurological symptoms, physical retardation, prolonged jaundice, thrombocytopenic purpura and other disabilities.

Effect and process evaluation of a kindergarten-based, family-involved cluster randomised controlled trial in six European countries on four- to six-year-old children's steps per day: the ToyBox-study.

Background: The ToyBox-intervention is a theory- and evidence-based intervention delivered in kindergartens to improve four- to six-year-old children's energy balance-related behaviours and prevent obesity. The current study aimed to (1) examine the effect of the ToyBox-intervention on increasing European four- to six-year-old children' steps per day, and (2) examine if a higher process evaluation score from teachers and parents was related to a more favourable effect on steps per day.

Methods: A sample of 2438 four- to six-year-old children (51.

Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation.

Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab-lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study.

Chronic Hepatitis Due to Gluten Enteropathy - a Case Report.

Background: Celiac disease is an immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals.

Case Description: A 45-year-old Caucasian woman presented with severe iron-deficient anemia and mild elevation of liver enzymes. Upper endoscopy was done in the context of evaluation of anemia, which revealed reduced duodenal folds and mosaic pattern of the mucosa, but also grade II esophageal varices and portal hypertensive gastropathy.

Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy.

Background: Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations.

Methods: In this phase 1 dose-escalation study, we enrolled 4 healthy volunteers and 25 participants with moderate or severe hemophilia A or B who did not have inhibitory alloantibodies.

A benchmarking project on the quality of previous guidelines about the management of malignant pleural effusion from the European Society of Thoracic Surgeons (ESTS) Pleural Diseases Working Group.

Objectives: In the European Society of Thoracic Surgeons (ESTS) survey about management of malignant pleural effusions (MPE), 56% of respondents are not informed of any relevant clinical guidelines and 52%, who are aware of the existence of guidelines, declared that they are in need of updating or revision. The ESTS Pleural Diseases Working Group developed a benchmarking project on quality of previous guidelines on the management of MPE.

Methods: The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument was used to assess each guideline.

Low grade astrocytoma causing dural and calvarial destruction.

This case report describes destruction of overlying dura and calvaria by a low grade glioma in the absence of prior surgery or radiation. Bone and dural involving is known to occur with some malignant tumors, but due to low grade glioma is very rare. The initial radiologic examinations demonstrated a heterogeneous mass in the right parietal region with both extra- and intra-axial components.

Early Changes in the Antithrombin and Thrombin-Antithrombin Complex in Patients With Paroxysmal Atrial Fibrillation.

Background: Data on coagulation changes in paroxysmal atrial fibrillation (PAF) are scarce. The aim of this study was to examine plasma antithrombin (AT) levels and activity as well as thrombin-antithrombin (TAT) complex levels in the early hours of the clinical manifestation of PAF.

Methods: Fifty-one patients (26 men and 25 women; mean age 59.

Significant Increase in C-Reactive Protein and Serum Amyloid A in the Early Hours of Paroxysmal Atrial Fibrillation.

Background: A number of data have been accumulated on inflammation in persistent and permanent atrial fibrillation (AF). Our aim was to study the process in paroxysmal AF (PAF) by measuring plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA) and fibrinogen in dynamics.

Methods: The markers were investigated in 51 patients (26 males and 25 females; 59.

Early effects of paroxysmal atrial fibrillation on plasma markers of fibrinolysis.

There are no studies to date on the early changes in the hemostasis profile of patients with paroxysmal atrial fibrillation (PAF).Given the key role of the fibrinolytic system in maintaining blood fluidity, our aim was to examine its activity in patients with clinical manifestation of the disease <24 hours.We studied 51 nonanticoagulated patients with a first episode of the disease (26 men, 25 women; mean age 59.

Analysis of cell-free fetal DNA for non-invasive prenatal diagnosis in a family with neonatal diabetes.

Aims: An early genetic diagnosis of neonatal diabetes guides clinical management and results in improved treatment in ~ 40% of patients. In the offspring of individuals with neonatal diabetes, a prenatal diagnosis allows accurate estimation of the risk of developing diabetes and, eventually, the most appropriate treatment for the baby. In this study, we performed non-invasive prenatal genetic testing for a fetus at risk of inheriting a paternal KCNJ11 p.

Rituximab maintenance versus observation alone in patients with chronic lymphocytic leukaemia who respond to first-line or second-line rituximab-containing chemoimmunotherapy: final results of the AGMT CLL-8a Mabtenance randomised trial.

Background: In many patients with chronic lymphocytic leukaemia requiring treatment, induction therapy with rituximab plus chemotherapy improves outcomes compared with chemotherapy alone. In this study we aimed to investigate the potential of rituximab maintenance therapy to prolong disease control in patients who respond to rituximab-containing induction regimens.

Methods: In this randomised, international, multicentre, open-label, phase 3 clinical trial, we enrolled patients who had achieved a complete response (CR), CR with incomplete bone marrow recovery (CRi), or partial response (PR) to first-line or second-line rituximab-containing chemoimmunotherapy and randomly assigned them in a 1:1 ratio (central block randomisation in the electronic case report form system) to either intravenous rituximab 375 mg/m(2) every 3 months, or observation alone, for 2 years.

Cross-cultural measurement invariance of the Revised Child Anxiety and Depression Scale across 11 world-wide societies.

Background: In order to compare estimates by one assessment scale across various cultures/ethnic groups, an important aspect that needs to be demonstrated is that its construct across these groups is invariant when measured using a similar and simultaneous approach (i.e., demonstrated cross-cultural measurement invariance).

Decreased Activity of the Protein C Anticoagulant Pathway in the Early Hours of Paroxysmal Atrial Fibrillation.

Background: Increased coagulation activity has been established in paroxysmal atrial fibrillation (PAF), but data on the anticoagulant system are scarce.

Purpose: To examine the protein C anticoagulant pathway in the early hours of the disease.

Materials And Methods: Fifty-one patients (26 men and 25 women; mean age 59.

Clinical and genetic challenges in a family with history of childhood polyp, aortopathy, and clinical diagnosis of hereditary hemorrhagic teleangiectasia (HHT).

Hereditary hemorrhagic teleangiectasia (HHT) is a genetic disorder, characterized by abnormal vessel formation and arteriovenous malformations (AVMs). The so-called "Curaçao criteria" are most commonly employed for the purposes of clinical diagnosis. However, children may not exhibit the full magnitude of symptoms and the Curaçao criteria appear to be less sensitive in this setting.

A phase III randomized study to evaluate the efficacy and safety of CT-P13 compared with reference infliximab in patients with active rheumatoid arthritis: 54-week results from the PLANETRA study.

Background: CT-P13 (Remsima®, Inflectra®) is a biosimilar of the infliximab reference product (RP; Remicade®). The aim of this study was to compare the 54-week efficacy, immunogenicity, safety, pharmacokinetics (PK) and pharmacodynamics (PD) of CT-P13 and RP in patients with active rheumatoid arthritis (RA).

Methods: In this multinational phase III double-blind study, patients with active RA and an inadequate response to methotrexate (MTX) were randomized (1:1) to receive CT-P13 (3 mg/kg) or RP (3 mg/kg) at weeks 0, 2, 6 and then every 8 weeks to week 54 in combination with MTX (12.

Dual-time point 18FDG-PET/CT imaging may be useful in assessing local recurrent disease in high grade bone and soft tissue sarcoma.

Background: Sarcomas comprise 1% of malignant tumors in adults but represent a significant diagnostic and therapeutic challenge. Molecular imaging with ¹⁸FDG PET/CT is a powerful modality in oncology. Its use for initial assessment, evaluation of response to therapy and recurrent disease in most tumors is essential for therapeutic decisions.