Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

novel Gd 3+ -doped silica-based optical fiber material for dosimetry in proton therapy

International audienceOptical fibers hold promise for accurate dosimetry in small field proton therapy due to their superior spatial resolution and the lack of significant Cerenkov contamination in proton beams. One known drawback for most scintillation detectors is signal quenching in areas of high linear energy transfer, as is the case in the Bragg peak region of a proton beam. In this study, we investigated the potential of innovative optical fiber bulk materials using the sol-gel technique for dosimetry in proton therapy. This type of glass is made of amorphous silica (SiO 2) and is doped with Gd 3+ ions and possesses very interesting light emission properties with a luminescence band around 314 nm when exposed to protons. The fibers were manufactured at the University of Lille and tested at the TRIUMF Proton Therapy facility with 8.2-62.9 MeV protons and 2-6 nA of extracted beam current. Dose-rate dependence and quenching were measured and compared to other silica-based fibers also made by sol-gel techniques and doped with Ce 3+ and cu +. The three fibers present strong luminescence in the UV (Gd) or visible (Cu,Ce) under irradiation, with the emission intensities related directly to the proton flux. In addition, the 0.5 mm diameter Gd 3+-doped fiber shows superior resolution of the Bragg peak, indicating significantly reduced quenching in comparison to the Ce 3+ and cu + fibers with a Birks' constant, k B , of (0.0162 ± 0.0003) cm/MeV in comparison to (0.0333 ± 0.0006) cm/MeV and (0.0352 ± 0.0003) cm/MeV, respectively. To our knowledge, this is the first report of such an interesting k B for a silica-based optical fiber material, showing clearly that this fiber presents lower quenching than common plastic scintillators. This result demonstrates the high potential of this inorganic fiber material for proton therapy dosimetry

X-rays, γ-rays and Proton Beam Monitoring with Multimode Nitrogen-doped Optical Fiber

International audienceWe investigated the potential of a multimode (50 μ m core diameter) nitrogen doped silica-based optical fiber for X-rays, protons and γ-rays radiation detection and dosimetry. X-rays results confirm that this N-doped fiber presents a strong radioluminescence (RL) around 550 nm when exposed to radiation. The RL observed from a few cm long sample linearly depends on the dose rate at least in the 1 mGy/s to 50 Gy/s range. Low dose rate γ-ray tests demonstrate the radiation detection at dose rate as low as 40 μ Gy/s with a 2 m long fiber sample. This fiber is also associated with an optically-stimulated luminescence (OSL) when exposed to a 1064 nm laser light post-irradiation. This OSL signature provides shortly after the irradiation a precise estimation of the accumulated dose at least in the 1 Gy to 10 kGy range. Under proton exposure, we benchmarked the performances of the N-doped fiber with the ones of a conventional Markus chamber used by the TRIUMF proton-therapy team. This comparison highlights the potential of the small-size N-doped fiber to partially overcome the known limitations of commercial fiber-based dosimeters for medical applications. The obtained results are very promising for the future design of more complex spatially-resolved beam monitoring systems

Practice patterns analysis of ocular proton therapy centers the international OPTIC survey

PURPOSE To assess the planning, treatment, and follow up strategies worldwide in dedicated proton therapy ocular programs. METHODS AND MATERIALS Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system TPS , hardware software equipment, image acquisition registration, patient positioning, eye surveillance, beam delivery, quality assurance QA , clinical management, and workflow. RESULTS Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients 1729 to 6369 . Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma UM and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority 80 of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging MRI rarely being used in routine planning 20 . Increased patient to full time equivalent ratios were observed by higher accruing centers P .0161 . Generally, ophthalmologists followed up the post radiation therapy patients, though in 40 of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks range, modulation varied substantially across centers. CONCLUSIONS The first worldwide multi institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols, systematic patient centered data acquisition, and publishing guidelines on QA, staffing, treatment, and follow up parameters by dedicated ocular programs to ensure the highest level of care for ocular patient

Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study

Data are relatively scarce on gastro-intestinal tuberculosis (GITB). Most studies are old and from single centers, or did not include immunosuppressed patients. Thus, we aimed to determine the clinical, radiological, and laboratory profiles of GITB. We included adults with proven GITB treated between 2000 and 2018. Patients were enrolled from 21 referral centers in 8 countries (Belgium, Egypt, France, Italy, Kazakhstan, Saudi Arabia, UK, and Turkey). One hundred four patients were included. Terminal ileum (n = 46, 44.2%), small intestines except terminal ileum (n = 36, 34.6%), colon (n = 29, 27.8%), stomach (n = 6, 5.7%), and perianal (one patient) were the sites of GITB. One-third of all patients were immunosuppressed. Sixteen patients had diabetes, 8 had chronic renal failure, 5 were HIV positive, 4 had liver cirrhosis, and 3 had malignancies. Intestinal biopsy samples were cultured in 75 cases (78.1%) and TB was isolated in 65 patients (86.6%). PCR were performed to 37 (35.6%) biopsy samples and of these, 35 (94.6%) were positive. Ascites samples were cultured in 19 patients and M. tuberculosis was isolated in 11 (57.9%). Upper gastrointestinal endoscopy was performed to 40 patients (38.5%) and colonoscopy in 74 (71.1%). Surgical interventions were frequently the source of diagnostic samples (25 laparoscopy/20 laparotomy, n = 45, 43.3%). Patients were treated with standard and second-line anti-TB medications. Ultimately, 4 (3.8%) patients died and 2 (1.9%) cases relapsed. There was a high incidence of underlying immunosuppression in GITB patients. A high degree of clinical suspicion is necessary to initiate appropriate and timely diagnostic procedures; many patients are first diagnosed at surgery

Clinicopathological profile of gastrointestinal tuberculosis: a multinational ID-IRI study.

Data are relatively scarce on gastro-intestinal tuberculosis (GITB). Most studies are old and from single centers, or did not include immunosuppressed patients. Thus, we aimed to determine the clinical, radiological, and laboratory profiles of GITB. We included adults with proven GITB treated between 2000 and 2018. Patients were enrolled from 21 referral centers in 8 countries (Belgium, Egypt, France, Italy, Kazakhstan, Saudi Arabia, UK, and Turkey). One hundred four patients were included. Terminal ileum (n = 46, 44.2%), small intestines except terminal ileum (n = 36, 34.6%), colon (n = 29, 27.8%), stomach (n = 6, 5.7%), and perianal (one patient) were the sites of GITB. One-third of all patients were immunosuppressed. Sixteen patients had diabetes, 8 had chronic renal failure, 5 were HIV positive, 4 had liver cirrhosis, and 3 had malignancies. Intestinal biopsy samples were cultured in 75 cases (78.1%) and TB was isolated in 65 patients (86.6%). PCR were performed to 37 (35.6%) biopsy samples and of these, 35 (94.6%) were positive. Ascites samples were cultured in 19 patients and M. tuberculosis was isolated in 11 (57.9%). Upper gastrointestinal endoscopy was performed to 40 patients (38.5%) and colonoscopy in 74 (71.1%). Surgical interventions were frequently the source of diagnostic samples (25 laparoscopy/20 laparotomy, n = 45, 43.3%). Patients were treated with standard and second-line anti-TB medications. Ultimately, 4 (3.8%) patients died and 2 (1.9%) cases relapsed. There was a high incidence of underlying immunosuppression in GITB patients. A high degree of clinical suspicion is necessary to initiate appropriate and timely diagnostic procedures; many patients are first diagnosed at surgery