Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

Background: The 2 × 2 PEACE-1 study showed that combining androgen-deprivation therapy with docetaxel and abiraterone improved overall and radiographic progression-free survival in patients with de novo metastatic castration-sensitive prostate cancer. We aimed to examine the efficacy and safety of adding radiotherapy in this population.

Methods: We conducted an open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Europe.

The effectiveness of coronary computed tomography angiography and functional testing for the diagnosis of obstructive coronary artery disease: results from the individual patient data Collaborative Meta-Analysis of Cardiac CT (COME-CCT).

Aim: To determine the effectiveness of functional stress testing and computed tomography angiography (CTA) for diagnosis of obstructive coronary artery disease (CAD).

Methods And Results: Two-thousand nine-hundred twenty symptomatic stable chest pain patients were included in the international Collaborative Meta-Analysis of Cardiac CT consortium to compare CTA with exercise electrocardiography (exercise-ECG) and single-photon emission computed tomography (SPECT) for diagnosis of CAD defined as ≥ 50% diameter stenosis by invasive coronary angiography (ICA) as reference standard. Generalised linear mixed models were used for calculating the diagnostic accuracy of each diagnostic test including non-diagnostic results as dependent variables in a logistic regression model with random intercepts and slopes.

Is There a Place for De-escalating Therapy in Patients with Metastatic Hormone-sensitive Prostate Cancer?

Although intermittent androgen deprivation therapy was often recommended for metastatic hormone-sensitive cancer therapy in the past, we do not know whether its use can be extrapolated to combination therapy. Trials evaluating intermittent therapy are necessary as this strategy could improve patient quality of life and reduce adverse events and costs.

Association between in-ICU red blood cells transfusion and 1-year mortality in ICU survivors.

Background: Impact of in-ICU transfusion on long-term outcomes remains unknown. The purpose of this study was to assess in critical-care survivors the association between in-ICU red blood cells transfusion and 1-year mortality.

Methods: FROG-ICU, a multicenter European study enrolling all-comers critical care patients was analyzed (n = 1551).

Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design.

Background: Current standard of care for metastatic castration-sensitive prostate cancer supplements androgen deprivation therapy with either docetaxel, second-generation hormonal therapy, or radiotherapy. We aimed to evaluate the efficacy and safety of abiraterone plus prednisone, with or without radiotherapy, in addition to standard of care.

Methods: We conducted an open-label, randomised, phase 3 study with a 2 × 2 factorial design (PEACE-1) at 77 hospitals across Belgium, France, Ireland, Italy, Romania, Spain, and Switzerland.

Esophageal Cancer in Elderly Patients, Current Treatment Options and Outcomes; A Systematic Review and Pooled Analysis.

Esophageal cancer, despite its tendency to increase among younger patients, remains a disease of the elderly, with the peak incidence between 70-79 years. In spite of that, elderly patients are still excluded from major clinical trials and they are frequently offered suboptimal treatment even for curable stages of the disease. In this review, a clear survival benefit is demonstrated for elderly patients treated with neoadjuvant treatment, surgery, and even definitive chemoradiation compared to palliative or no treatment.

Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET.

Background: The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration.

Intracranial brain parenchymal spread of mucormycosis through olfactory tract: a diffusion-weighted imaging-based concept.

Mucormycosis is an opportunistic fungal infection involving among others the paranasal sinuses, nasal fossa and brain parenchyma. Mucor can invade the brain parenchyma by either contiguous spread from the paranasal sinuses or through vascular invasion. We report a case of fatal rhino-cerebral mucormycosis in whom cytotoxic edema at magnetic resonance diffusion-weighted imaging was symmetrically restricted to both neocortical and paleocortical primary areas of olfactory projection at earliest phase of the disease process.

Intra-Articular Osteoid Osteoma: Radiological Manifestations.

We report a case of intra-articular osteoid osteoma (IAOO) of the elbow, in order to point out the clinical and imaging features which made the case challenging and caused a diagnostic delay.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study.

Background: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.

Methods: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries.

Haploidentical transplantation and posttransplant cyclophosphamide for treating aplastic anemia patients: a report from the EBMT Severe Aplastic Anemia Working Party.

In the absence of an HLA-matched donor, the best treatment for acquired aplastic anemia patients refractory to immunosuppression is unclear. We collected and analyzed data from all acquired aplastic anemia patients who underwent a haploidentical transplantation with posttransplant cyclophosphamide in Europe from 2011 to 2017 (n = 33). The cumulative incidence of neutrophil engraftment was 67% (CI: 51-83%) at D +28 and was unaffected by age group, stem cell source, ATG use, or Baltimore conditioning regimen.

Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy.

Chronic vascular rejection characterized by the myointimal proliferation of smooth muscle cells that progressively obstruct the arterial graft lumen may become the main cause of long-term graft loss in vascularized composite allotransplantation (VCA), as observed in solid organ transplantation. As such, new diagnostic tools are required. The objective of this study was to evaluate the usefulness of flow magnetic resonance imaging (MRI) in the qualitative and quantitative monitoring of VCA in three patients transplanted between 2005 and 2012.

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data.

Objective: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients.

Design: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies.

Data Sources: Medline, Embase, and Web of Science for published studies.

Selepressin, a novel selective vasopressin V agonist, is an effective substitute for norepinephrine in a phase IIa randomized, placebo-controlled trial in septic shock patients.

Background: Vasopressin is widely used for vasopressor support in septic shock patients, but experimental evidence suggests that selective V agonists are superior. The initial pharmacodynamic effects, pharmacokinetics, and safety of selepressin, a novel V-selective vasopressin analogue, was examined in a phase IIa trial in septic shock patients.

Methods: This was a randomized, double-blind, placebo-controlled multicenter trial in 53 patients in early septic shock (aged ≥18 years, fluid resuscitation, requiring vasopressor support) who received selepressin 1.

Altered inhibitory control and increased sensitivity to cross-modal interference in tinnitus during auditory and visual tasks.

Tinnitus is the perception of sound in the absence of external stimulus. Currently, the pathophysiology of tinnitus is not fully understood, but recent studies indicate that alterations in the brain involve non-auditory areas, including the prefrontal cortex. In experiment 1, we used a go/no-go paradigm to evaluate the target detection speed and the inhibitory control in tinnitus participants (TP) and control subjects (CS), both in unimodal and bimodal conditions in the auditory and visual modalities.

Further delineation of the KAT6B molecular and phenotypic spectrum.

KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B.

Percutaneous pedicle screw implantation for refractory low back pain: from manual 2D to fully robotic intraoperative 2D/3D fluoroscopy.

Many surgical treatments for chronic low back pain that is refractory to medical treatments focus on spine stabilization. One of the main surgical procedures consists of placing an interbody cage with bone grafts associated with pedicle screws [2, 25, 30]. This technique can be performed using different approaches: a large open posterior approach, tubular approaches (minimal open) or percutaneously (minimally invasive percutaneous or MIP) [5, 28].

Effects of helium-oxygen on respiratory mechanics, gas exchange, and ventilation-perfusion relationships in a porcine model of stable methacholine-induced bronchospasm.

Objective: To explore the consequences of helium/oxygen (He/O(2)) inhalation on respiratory mechanics, gas exchange, and ventilation-perfusion (VA/Q) relationships in an animal model of severe induced bronchospasm during mechanical ventilation.

Design: Prospective, interventional study.

Setting: Experimental animal laboratory, university hospital.

[Food deficiencies in children--multicenter survey in the school environment. Analysis of the daily diet of adolescents].

The aim of this work is to study the food habits in a group of 131 children of school ages (11-14 years); they had to take notice of their food, with control by interview; results shown a shortage in calories (80% of normal supply for age), but also a severe imbalance: too many lipids, too few complex sugars, deficiencies in calcium, phosphorus, iron, iodine, vitamins A and C, fibers (30% of normal supply); alcohol has been used by 35 children. A nutritional education is recommended for this age group.

[Role of freedom in psychiatric theories].

All the theories of mind used in the treatment of mental illnesses are based on one or another kind of determinism. Therefore, psychiatrists are obliged to conceive the subjective free will of their patients as a psychological function that their theories do not explain. As a result of it, they encounter many difficulties in the ethical aspects of their therapeutical choices.