Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis: A Randomized, Placebo-Controlled, Phase II Study.

Objective: To determine the effect of selexipag, an oral, selective IP prostacyclin receptor agonist, on the frequency of attacks of Raynaud's phenomenon (RP) in patients with systemic sclerosis (SSc).

Methods: Patients with SSc-related RP were randomized 1:1 to placebo (n = 38) or selexipag (n = 36) in individualized doses (maximum of 1,600 μg twice daily) during a 3-week titration period. The primary end point was the weekly average number of RP attacks during the study maintenance period, analyzed using a Bayesian approach with a negative binomial model adjusted for baseline number of RP attacks.

PET-guided treatment in patients with advanced-stage Hodgkin's lymphoma (HD18): final results of an open-label, international, randomised phase 3 trial by the German Hodgkin Study Group.

Background: The intensive polychemotherapy regimen eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in escalated doses) is very active in patients with advanced-stage Hodgkin's lymphoma, albeit at the expense of severe toxicities. Individual patients might be cured with less burdensome therapy. We investigated whether metabolic response determined by PET after two cycles of standard regimen eBEACOPP (PET-2) would allow adaption of treatment intensity, increasing it for PET-2-positive patients and reducing it for PET-2-negative patients.

3-Iodothyronamine, a Novel Endogenous Modulator of Transient Receptor Potential Melastatin 8?

The decarboxylated and deiodinated thyroid hormone (TH) derivative, 3-iodothyronamine (3-TAM), is suggested to be involved in energy metabolism and thermoregulation. G protein-coupled receptors (GPCRs) are known as the main targets for 3-TAM; however, transient receptor potential channels (TRPs) were also recently identified as new targets of 3-TAM. This article reviews the current knowledge of a putative novel role of 3-TAM in the modulation of TRPs.

A novel HPV prophylactic peptide vaccine, designed by immunoinformatics and structural vaccinology approaches.

Human papillomavirus (HPV)-caused cervical cancer is the fourth common female cancer globally. Despite availability of three effective vaccines in market, development of HPV prophylactic vaccines is still pursued due to affordability issues and type-restricted protection of the marketed vaccines. Investigational second generation prophylactic HPV vaccines are mostly exploiting epitopes from the virus minor capsid protein (L2), which despite many advantages suffer from low immunogenicity, a common problem of epitope vaccines.

Proton therapy of iris melanoma with 50 CGE : Influence of target volume on clinical outcome.

Purpose: The aim of this study was to evaluate local tumour control, incidence of radiation-induced glaucoma and associated interventions of sector-based and whole anterior segment proton beam therapy (PBT) for the treatment of iris melanoma.

Patients And Methods: We retrospectively analysed the data of 77 patients with iris melanoma who underwent PBT applied as 50 CGE in four daily fractions. Of the patients, 47 received PBT with a circular-shaped collimator and 30 with a conformal sector-shaped target volume.

Heritability and responses to high fat diet of plasma lipidomics in a twin study.

Lipidomics have a great potential as clinical tool for monitoring metabolic changes in health and disease. Nevertheless hardly anything is known about the heritability of lipids. Therefore, it is necessary to clarify how and how much we can affect these progresses in individuals.

Safety and efficacy of catheter-based left atrial appendage closure in patients with contraindications for long-term anticoagulation.

Background: Percutaneous left atrial appendage closure (LAAC) and the role of postinterventional anticoagulation often evokes controversy in daily practice. This study aimed to evaluate LAAC in patients with non-rheumatic atrial fibrillation, high thromboembolic risk and contraindications for long-term anticoagulation in a clinical scenario.

Methods: Between 2010-2015, LAAC was attempted in 118 patients (47 women).

First-in-man dose escalation and pharmacokinetic study of CAP7.1, a novel prodrug of etoposide, in adults with refractory solid tumours.

Aim: An open-label, phase I dose-escalation trial was performed in adult patients with various solid cancers to identify the maximum tolerated dose (MTD), to assess the safety, pharmacokinetic profile and anti-tumour activity of the new prodrug CAP7.1. The prodrug is converted to its active moiety etoposide via carboxylesterases in selective cells leading to a better tolerability and higher efficacy in therapeutic resistance cells and children with refractory neuroblastoma.

Transcoronary Concentration Gradient of microRNA-133a and Outcome in Patients With Coronary Artery Disease.

Circulating levels of microRNA (miR)-133a are increased in patients with coronary atherosclerotic disease (CAD). Whether the cardiac release of this miR provides any prognostic information in patients with CAD is currently unknown. We aimed to investigate if changes in concentration of miR-133a trough the coronary circulation may be associated with patients' cardiovascular outcome.

Mothers' childhood hardship forecasts adverse pregnancy outcomes: Role of inflammatory, lifestyle, and psychosocial pathways.

Research suggests the health consequences of economic hardship can be transmitted across generations. Some of these disparities are thought to be passed to offspring during gestation. But this hypothesis has not been tested in contemporary American samples, and the mechanisms of transmission have not been characterized.

Coronary Atherosclerotic Plaque Characteristics and Cardiovascular Risk Factors - Insights From an Optical Coherence Tomography Study.

Background: The association between cardiovascular risk factors (CVRF) and the risk of coronary events is widely acknowledged. Whether individual risk factors may be associated with distinct plaque characteristics is currently unclear. We investigated the relationship between CVRF and coronary plaque burden and phenotype.

Electrocorticographic Dynamics as a Novel Biomarker in Five Models of Epileptogenesis.

Postinjury epilepsy (PIE) is a devastating sequela of various brain insults. While recent studies offer novel insights into the mechanisms underlying epileptogenesis and discover potential preventive treatments, the lack of PIE biomarkers hinders the clinical implementation of such treatments. Here we explored the biomarker potential of different electrographic features in five models of PIE.

A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial.

Background: Several studies have demonstrated the antitumor activity of first-generation somatostatin analogs (SSAs), primarily targeting somatostatin receptor (sstr) subtypes 2 and 5, in neuroendocrine tumors (NET). Pasireotide, a second-generation SSA, targets multiple sstr subtypes. We compared the efficacy and safety of pasireotide plus everolimus to everolimus alone in patients with advanced, well-differentiated, progressive pancreatic NET.

The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.

Long-term results of ultrasound guided fine needle aspiration cytology in conjunction with sentinel node biopsy support step-wise approach in melanoma.

Background: US-FNAC is a common diagnostic tool in the work-up of many cancers. Results in melanoma were initially poor (sensitivity 20-40%). Introduction of the Berlin Morphology criteria has shown potential improvement up to 65-80% in selected patients.

Timing of completion lymphadenectomy after positive sentinel node biopsy in patients with melanoma.

Background: Nodal staging with sentinel node biopsy (SNB) and completion lymph node dissection (CLND) provides prognostic information to patients with melanoma and their physicians. It is not known whether the timing of CLND is associated with survival outcome and/or CLND tumour load. This study investigated whether CLND timing is associated with CLND tumour load, disease-free survival (DFS) and/or melanoma-specific survival (MSS).

Perceived stigma of mental illness: A comparison between two metropolitan cities in India.

Purpose: An increasing number of comparative studies are conducted on the stigmatization of persons with mental illness, in particular with regard to regional and diachronic variation. So far, there have been no studies comparing stigmatization of persons with mental illness in two different regions of India. Therefore, we examined the differences in perception of stigma attached to mental illnesses in Kolkata and Chennai, with regard to cultural and geographical differences to better understand the roots and origins of this issue.

DNA Cytometry for Differentiation Between Low- and Medium-grade Dysplasia in Intraductal Papillary Mucinous Neoplasms.

Background/aim: The indication for resection of cystic pancreatic lesions is usually performed by sectional imaging criteria, such as the Sendai criteria. The aim of this study was to analyze a possible correlation between DNA cytometry and Sendai criteria for the differentiation between low-grade intraductal papillary mucinous neoplasms (IPMN-A) and medium-grade dysplasia (IPMN-B).

Materials And Methods: Histopathological analysis, DNA index and preoperative Sendai criteria were determined in 16 patients who underwent pancreatic resection for IPMN.

Myofibroblasts Are Evidence of Chronic Tissue Microtrauma at the Endometrial-Myometrial Junctional Zone in Uteri With Adenomyosis.

Background: Adenomyosis (AM) uteri exhibit hyperperistalsis. The latter causes a chronic tissue trauma at the endometrial-myometrial junctional zone (EMJZ). Upon tissue trauma, microdehiscences in the myometrium facilitate the translocation of basal endometrial fragments into the myometrium.

Independent psychometric validation of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Endometrial Cancer Module (EORTC QLQ-EN24).

The endometrial cancer (EC)-specific Quality of Life module of the European Organization for Research and Treatment of Cancer (EORTC QLQ-EN24), was developed and validated in one study. We independently validated and assessed the psychometric properties of the instrument. Two hundred and eight women with EC before surgery, during adjuvant treatment and follow-up; in three different cancer centres completed the EORTC QLQ-C30 and the EN24.

Removal torque evaluation of three different abutment screws for single implant restorations after mechanical cyclic loading.

Purpose: The aim of this study was to evaluate the removal torque of three different abutment screws and pull out strength of implant-abutment connection for single implant restorations after mechanical cyclic loading.

Methods: The study was performed in accordance with ISO 14801:2007. Three implant groups (n=15) were used: group A, PW Plus® with flat head screw; group B, PW Plus® with tapered screw; and group C, Conelog® with flat head screw.

Relation between the stability of dental implants and two biological markers during the healing period: a prospective clinical study.

Objectives: The purposes of this study were to examine the correlation between the stability of dental implants and bone formation markers during the healing period and to monitor the stability of dental implants using the resonance frequency analysis (RFA) method. The null hypothesis of the study is no correlation between the stability of dental implant and bone formation markers.

Methods: The study is a prospective clinical study during the 3-month healing period of implant.

Switching to nilotinib versus imatinib dose escalation in patients with chronic myeloid leukaemia in chronic phase with suboptimal response to imatinib (LASOR): a randomised, open-label trial.

Background: Optimal management of patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response remains undetermined. This study aimed to investigate the safety and efficacy of switching to nilotinib vs imatinib dose escalation for patients with suboptimal cytogenetic response on imatinib.

Methods: We did a phase 3, open-label, randomised trial in patients with chronic myeloid leukaemia in chronic phase with suboptimal cytogenetic response to imatinib according to the 2009 European LeukemiaNet criteria, in Latin America, Europe, and Asia (59 hospitals and care centres in 12 countries).

Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients.

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphate ribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing.

Progressive idiopathic tractional corectopia with iris thinning.

A 2-month-old boy presented with an irregular left pupil. Over the course of 3 months, progressive pupil ovalization, corectopia, and ballooning of the thinned superior iris tissue caused obstruction of the visual axis. Because of concern for deprivational amblyopia, a sectoral pupilloplasty and sphincterotomies were performed, restoring pupil shape and clearing the visual axis.