Griffith University, Australia

Study Evaluating the Benefit of Adding Ipilimumab to the Combination of Atezolizumab and Bevacizumab in Patients With Hepatocellular Carcinoma Receiving First-line Systemic Therapy

Hepatocellular carcinoma (HCC) is one of the most common malignancies and ranks fourth in terms of cancer-related mortality worldwide . Unfortunately, the diagnosis of HCC is often made late in the cure of the disease when the tumour has spread outside the liver parenchyma as portal vein invasion or distant metastases. In the history of HCC patients, a significant proportion will sooner or later face systemic therapies as they are no longer eligible for radical or locoregional therapies. Cytotoxic chemotherapy and hormonal therapies have never shown significant benefit on overall survival (OS) . The first systemic therapy to show a significant beneficial impact on HCC outcome was the tyrosine kinase inhibitor (TKI) sorafenib, an anti-angiogenic agent (AAA) with anti-proliferative properties on HCC . For nearly a decade, all systemic therapies tested in randomised controlled trials as first-line systemic therapy (1L) head-to-head with sorafenib, or as 2L after sorafenib failure have not shown significant benefit. In 2018, Kudo et al. showed that lenvatinib, another TKI with anti-angiogenic properties, was at least equivalent to sorafenib in 1L in the REFLECT non-inferiority trial [5]. Other AAA TKIs with anti-cancer properties on HCC cells have demonstrated efficacy in 2L: regorafenib after progression on sorafenib in 2017 , and cabozantinib after progression on or intolerance to sorafenib in 2018 . In addition, ramucirumab, a monoclonal antibody targeting VEGFR-2, has shown significant benefit in a specific subpopulation of HCC patients with high baseline alpha-fetoprotein levels ≥ 400 ng/ml . However, all these options were strictly palliative with no long-term survivors and lack of potential recovery. Immuno-oncology (IO) approaches have completely revolutionised the paradigm of systemic HCC therapies with nonetheless a significant increase in median OS in IO-based combination strategies, but also the emergence of the possibility of long-term survivors and, for some patients, hope for a complete response and possibly a final cure.

Study to Determine the Safety and Efficacy of Ribociclib in Combination With Hormone Therapy and Hypofractionated Radiotherapy in Breast Cancer, With Positive Hormone Receptors and Negative HER2 Status, in Newly Diagnosed, Not Immediately Operable Elderly Patient (CALHYS)

Evaluation of the Impact of Case Manager Intervention on the 3-year Psychotic Episode Recurrence Rate in Patients Aged 16 to 30 Years with a First Psychotic Episode.

Biological & Fonctional Signatures for Muscle Failures, Aged People & Personalized Physical Activity

Main objective: To determine the effects of personalized physical activity management on the biological signatures of muscle failure. Secondary objectives: - Propose a support system through adapted and individualized physical activity, based on physical, biological and psycho-social indicators - Identify the biological signatures (metabolomics, epigenetic) of muscle failure in the elderly. Phenotype responders and non-responders in training 900 seniors (300 per group) APAP group: adapted and personalized physical activity APA group: adapted physical activity Control group: no physical activity Total duration of the study 5 years, duration of participation for a patient 3 months; inclusion period: 57 months Improvement of muscle failure in its broad definition (Strength, power, speed and lean mass) ) General data: description of characteristics with frequencies and percentage for categorical variables and with mean and standard deviation for quantitative variables. ii) Analysis of the primary endpoint: Machine Learning (or supervised classification) and signaling pathway prediction approaches for statistical analysis and data interpretation. iii) Analysis of secondary judgment criteria: approaches in Machine Learning (or supervised classification) and signaling pathway prediction for statistical analysis and interpretation of data with comparison of quantitative variables by Pearson correlation and categorical variables by t or chi 2 test depending on the case. Adapt and individualize physical activity support for healthy or frail elderly people

OCT-angiography as a Pronostic Marker for Visual Impairment in Patients Undergoing Neurosurgery for Compressive Macroadenoma : a Prospective Study.

The RESPOND Outcomes Study

The specific objectives, falling into three main categories, are as follows: 1. Monitor the uptake of newer antiretroviral treatment (ART) drugs and drugs for treatment of co-infections and co-morbidities; 2. To evaluate the safety profiles of the newer individual ART drugs when used in routine clinical practice as part of either first-line or subsequent treatment regimens. 3. Investigate long term outcomes and clinical disease progression overall and in specific sub-groups The Outcomes study is a collaboration between investigators from clinics and cohorts across Europe, Australia and South America with a willingness to share data and to use a common follow-up schedule and assessment. Participating sites have a commitment to continue to follow this large cohort that is heterogeneous in both its demographic profile and in ART prescribing patterns thus resulting in enough power to answer many key clinical questions. The Outcomes study is a study in the RESPOND International Cohort Consortium of Infectious Diseases. RESPOND is an innovative, flexible and dynamic cohort consortium for the study of infectious diseases, including HIV, built as a generic structure for facilitating multi stakeholder involvement. In RESPOND all collected data is part of a common data repository or 'data lake', which is stored in a database located at CHIP, Rigshospitalet, Copenhagen, Denmark. Data collection in RESPOND is modular with a core data collection module onto which additional modules/studies can be added. Pseudonymised patient data can be entered manually via an online secure platform or be electronically transferred from existing local, regional or national data structures to the data lake. In the Outcomes study data will be collected at enrolment and at annual follow-up (FU) visits. For patients living with HIV-1 enrolled and under FU, demographic, laboratory, therapeutic and clinical data on HIV and viral hepatitis will be collected once a year. Clinical event data (except AIDS other than AIDS defining malignancies) will be collected in real-time on RESPOND event forms.

Brain-injured Patients Extubation Readiness Study

Severe brain-injured patients need mechanical ventilation with tracheal intubation. After treatment of the acute neurological condition, weaning of the mechanical ventilation has to be initiated notably to prevent ventilator associated pneumonia and others complications. Nevertheless, extubation failure is very common in this population due to residual neurological impairment with airway control alteration. Guidelines about weaning of mechanical ventilation and extubation exclude brain-injured patients with a residual impaired consciousness. In 2017, a simple and pragmatic extubation readiness clinical score was validated in a prospective observational cohort study of 140 brain injured patients. (Godet et al. Anesthesiology. 2017 Jan;126(1):104-114) In this study, brain injured patients with residual impaired consciousness who succeeded a spontaneous breathing trial were extubated. In multivariate analysis, 4 clinical elements were associated with extubation success. A prediction score was determined using the odds ratio such as followed : 1. Deglutition: 3 points if present 2. Gag reflex: 4 points if present 3. Cough: 4 points if present 4. CRS-R Score, visual item > 2, 3 points if present, 1 point if not For a cut-off value of 9, extubation failure could be predicted with a sensibility of 84%, a specificity of 75%, a positive predictive value of 89% and a negative predictive value of 66%. In order to participate, brain-injured patients will have to succeed a spontaneous breathing trial and meet all inclusion criteria, including not being able to obey to simple orders without sedation. Using a stepped wedge randomisation process with intensive care units as clusters, patients will be weaned and extubated under usual care or using the extubation readiness clinical score. The authors' hypothesis is that this clinical score will allow physicians to extubate patients at the right time interval and prevent extubation failure in this frail population.

Biological Markers of Functional Effects of Physical Activity in an Elderly Population

Circulating biomarkers are promising tools for early diagnosis of pathologies associated with aging. Inflammation and immunity are associated with the risk of sarcopenia and frailty in elderly patients. The investigators investigate the effect of an adapted physical activity program on the metabolism and function of circulating immune cells and miRNA in frail and non-frail elderly subjects. The main objective is to establish the link between biological markers of aging (immune cells phenotypes and function, miRNA) and motor capacities alteration/improvement. The secondary objectives are: (1) to characterize the functional and immunometabolic dimensions of frailty from objective indicators; (2) to propose a management system through adapted and individualized physical activity, based on objective indicators; (3) to evaluate the clinical impact of both frailty and its preventative management through physical activity; and (4) to identified new biomarkers of frailty. A total of 100 patients categorized as frail, pre-frail, and non-frail after a standardized geriatric evaluation are included in a comparative and interventional study. Exercise intervention consists in a 12-weeks physical activity program. Blood sample and physical/psychological functional measurements are performed before and after the 12-weeks physical activity program. ANOVA tests and correlational analysis will be performed. The finality of the study is to improve the medical prescription of physical activities in elderly patients.