Simultaneous Presentation of Ankylosing Spondylitis and Pancreatic Cancer: A Case Report

A clinical case of simultaneous presentation of ankylosing spondylitis and pancreatic cancer is described. Patients with rheumatic disorders must be closely followed to screen for malignancies. Most paraneoplastic rheumatic syndromes are difficult to distinguish from autoimmune rheumatic diseases; thus, cancer occurrence may constitute a major diagnostic challenge

De Novo Variant in the <i>KCNJ9</i> Gene as a Possible Cause of Neonatal Seizures

Background: The reduction in next-generation sequencing (NGS) costs allows for using this method for newborn screening for monogenic diseases (MDs). In this report, we describe a clinical case of a newborn participating in the EXAMEN project (ClinicalTrials.gov Identifier: NCT05325749). Methods: The child presented with convulsive syndrome on the third day of life. Generalized convulsive seizures were accompanied by electroencephalographic patterns corresponding to epileptiform activity. Proband WES expanded to trio sequencing was performed. Results: A differential diagnosis was made between symptomatic (dysmetabolic, structural, infectious) neonatal seizures and benign neonatal seizures. There were no data in favor of the dysmetabolic, structural, or infectious nature of seizures. Molecular karyotyping and whole exome sequencing were not informative. Trio WES revealed a de novo variant in the KCNJ9 gene (1:160087612T > C, p.Phe326Ser, NM_004983), for which, according to the OMIM database, no association with the disease has been described to date. Three-dimensional modeling was used to predict the structure of the KCNJ9 protein using the known structure of its homologs. According to the predictions, Phe326Ser change possibly disrupts the hydrophobic contacts with the valine side chain. Destabilization of the neighboring structures may undermine the formation of GIRK2/GIRK3 tetramers necessary for their proper functioning. Conclusions: We believe that the identified variant may be the cause of the disease in this patient but further studies, including the search for other patients with the KCNJ9 variants, are needed

Correlation of surface chemical states with hydrogen isotope retention in divertor tiles of JET with ITER-Like Wall

To understand the fuel retention mechanism correlation of surface chemical states and hydrogen isotope retention behavior determined by XPS (X-ray photoelectron spectroscopy) and TDS (Thermal desorption spectroscopy), respectively, for JET ITER-Like Wall samples from operational period 2011–2012 were investigated. It was found that the deposition layer was formed on the upper part of the inner vertical divertor area. At the inner plasma strike point region, the original surface materials, W or Mo, were found, indicating to an erosion-dominated region, but deposition of impurities was also found. Higher heat load would induce the formation of metal carbide. At the outer horizontal divertor tile, mixed material layer was formed with iron as an impurity. TDS showed the H and D desorption behavior and the major D desorption temperature for the upper part of the inner vertical tile was located at 370 °C and 530 °C. At the strike point region, the D desorption temperature was clearly shifted toward higher release temperatures, indicating the stabilization of D trapping by higher heat loa

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)