Königstein-falkenstein, Germany

Efficacy of Transversus Thoracis Muscle Plane Block in Patients Undergoing Cardiac Surgery

Participants who undergo elective cardiac surgery with median sternotomy are eligible. They will receive general anaesthesia with multimodal analgesia as is standard in our institution. For study purposes participants will be randomized in a double blinded fashion to receive a Transversus Thoracis Muscle Plane Block with 30 mL of ropivacaine 0.5 %, or no block. As the block is carried out after induction of general anesthesia the participants will not know to which group they are assigned. all blocks will be carried out after induction of general anesthesia, under full sterile precautions, and with ultrasound guidance. multimodal analgesia intra- and postoperatively is standardized and consists of: sufentanil, ketamine, dexmedetomidine, dexamethasone, paracetamol, metamizole, IV morphine in ICU. The investigators aim for fast track surgery, i.e. extubation either in the operating room or in ICU within the first 6 postoperative hours. the primary outcome is postoperative opioid consumption over the first 24 h postoperatively, secondary outcomes are pain scores and opioid-related side effects. all outcomes will be assessed by blinded investigators.

LIBERTY: Liquid Biopsy to Diagnose and Monitor CNS Involvement in High-risk B Cell Non-Hodgkin Lymphoma

Non-Hodgkin B-cell lymphoma (B-NHL) are cancers that arise from a subtype of white blood cells (lymphocyte) and typically involve the lymphatic system; they represent 4% of all cancers [SEER database, access 2022]. Despite booming novel antineoplastic agent development, a significant number of aggressive B-NHL patients continue to succumb to their disease, experiencing rapidly progressive disease or early relapse. Central nervous system or CNS (brain, spinal cord and cerebrospinal fluid (CSF)) involvement in aggressive B-NHL is a rare (2-5%) but it is a devastating event, with a life expectancy ranging between 2 and 5 months [PMID: 30125215]. Circulating tumor DNA (ctDNA) represents fragmented DNA that originates from tumors cells, carrying specific cancer-associated mutations that can be detected in the blood or other fluids subsumed under "liquid biopsies". The role of ctDNA gained momentum with the advent of high throughput sequencing technologies, becoming increasingly relevant for clinical practice. In lymphoma, detecting and monitoring ctDNA has been shown to be feasible and of high prognostic relevance regarding response and relapse. As such, ctDNA is emerging as a promising biomarker that can provide valuable diagnostic and prognostic information [PMID: 30125215, PMID: 29449275]. Identification of patients suffering from aggressive B-NHL at high risk of CNS relapse remains extremely challenging and currently mainly relies on a clinical score (CNS-IPI) [PMID: 27382100]. The detection of asymptomatic CNS is limited to conventional techniques and is not standardized [PMID: 22927246]. In patients with biopsy-proven CNS lymphoma, ctDNA can be detected in CSF (CSF ctDNA) in approximately 95% of cases. Furthermore, CSF ctDNA is predictive of CNS relapse in a small series of neurologically asymptomatic patients with aggressive B-NHL [PMID: 36542815, PMID: 32079701, PMID: 34551072]. Prevention and treatment of CNS involvement remains a great unmet clinical need. The discovery of novel and robust biomarkers is of paramount importance for early detection and risk-adapted therapeutic strategies for CNS involvement. The investigators hypothesize that CSF ctDNA is superior to current standard diagnostic procedures (e.g., flowcytometry or cytology) to detect CNS involvement in high-risk patients. Furthermore, in patients with positive CSF ctDNA, the investigators also postulate that the concept of monitoring minimal residual disease (MRD, small amount of ctDNA that persists in patients that have no signs of active disease on standard imaging techniques) will provide additional information on patient prognosis. This is a multicenter prospective diagnostic study to compare the performance of experimental diagnostic test (ctDNA) versus conventional cytology (CC) and flow cytometry (FC). Each high-risk B-NHL participant will proceed through standard work-up to evaluate potential CNS involvement including a neurological physical examination, a brain MRI and a diagnostic lumbar puncture. Each participant's CSF will be assessed by the two diagnostic tests (CSF ctDNA and conventional test (CC/FC)); the gold standard being proven CNS lymphoma involvement.

Unveiling Physiological and Psychosocial Pain Components with an Artificial Intelligence Based Telemonitoring Tool

Chronic pain has long been known as one of the major health concerns, impacting psychological health, functioning, and quality of life. However, its treatment is complex and is challenged by a complex interplay between biological, psychological, and social factors. Common pain treatments present significant medical and technological limitations, reflected in unspecific drug usage and an extremely high number of medical examinations that patients face regularly, with a huge cost burden on the healthcare system. Furthermore, the overall efficacy of pain management is often limited (73% dissatisfaction with treatment), leaving the patient in poor life conditions. Designing individualized targeted therapies requires understanding each subject's multidimensional pain experience, taking into consideration both the physical and emotional aspects involved. However, today, the golden standard measurement for pain is self-reports, which inherently suffer from subjective differences in perception and reporting. Healthcare systems advocate for the discovery of biomarkers and reliable clinical trial endpoints for pain to foster diagnosis, monitor pain progression, assess new treatments, and personalized therapeutic response. Nevertheless, most of the evidence today comes from inpatient settings or controlled laboratory environments. The pAIn-sense study aims at providing a radically novel approach in the monitoring and treatment of pain patients: a novel telemonitoring system allowing to understand the real nature of the pain (emotional vs physical), leveraging the use of advanced Artificial Intelligence techniques and wearable sensing technology collecting biometric data, therefore enabling efficient personalized treatments. To achieve this goal, the investigators will combine real patient data both from a physical and emotional perspective, to characterize the pain nature of patients and provide a tailored continuum-of-care. The system will include: 1. Robotic wearable sensors (Hardware): wearable technology for physiological monitoring (e.g., skin conductance, blood volume pressure and heart rate, activity) 2. Digital platform (Software): a customized application that collects psychological assessments, psychological status, medication, subjective pain level and sleep quality. 3. AI-based engine: advanced AI models take all the previous physical and psychological information and model it to provide an outline of what is the nature of the pain level of the subject. The system will be used to monitor the patient during normal activities (day and night) while collecting physiological, psychosocial, and pain information.

Early Minimally Invasive Image Guided Endoscopic Evacuation of Intracerebral Haemorrhage (EMINENT-ICH)

Spontaneous supratentorial intracerebral haemorrhage (SSICH) is the second most common form of stroke and accounts for approximately 2500 cases in Switzerland annually. The prognosis is very poor with nearly half of the patients dying within one year after haemorrhage. Treatment options for SSICH consist of either the current gold standard, best medical treatment (BMT), or surgical hematoma evacuation. Neither the best medical treatment nor the established surgical mainstay (conventional craniotomy) have shown relevant improvement of survival or functional outcome rates. A minimal invasive approach with early image-guided endoscopic surgery conducted within 24 hours after bleeding onset is therefore proposed. Endoscopic surgery was shown to be safe and effective, however large trials analyzing the benefits of endoscopic surgery are lacking. An earlier, more complete and more rapid hematoma evacuation could improve the functional outcome and mortality rates in affected patients. The primary objective of this two-armed, open-labelled, single centre randomised controlled trial is to show superiority of early minimally invasive image-guided hematoma evacuation additionally to BMT compared to BMT alone in improving functional outcome rates at 6 months in patients with SSICH. The study procedures include 6 visits in total, 4 of them during hospital stay, 2 of them as follow-up visits within the clinical routine. Each visit consists of assessing Glasgow Coma Scale (GCS), modified Rankin Scale (mRS) and National Institute of Health Stroke Scale (NIHSS), three visits include CT scans (before intervention, directly postoperative and during follow up) and blood sampling (before intervention, postoperative and during follow up). Three visits include assessing patient satisfaction and cognition, and two visits include patient quality of life assessments. This study was designed in collaboration with Patient and Public representatives.

A Study for Observing Severe Asthma in Patients Treated With Tezepelumab

This is a 12-month, multi-country, multi-center, prospective, non-comparative and non-interventional (observational), post-reimbursement real-world evidence study that will assess asthma symptom control, lung function, and patient-reported outcomes including health-related quality of life after tezepelumab treatment initiation in participants with severe asthma in Europe and Canada. This study is planned to be conducted in several countries including but not limited to Canada, Germany, Denmark, Switzerland, and Sweden. Participants will be followed for a maximum period of 52 weeks after tezepelumab treatment initiation, irrespective of treatment discontinuation.

DESTINY Breast Respond HER2-low Europe

This non-interventional study will investigate the effectiveness withT-DXd, the demographic and clinical characteristics of the patients, treatment patterns, tolerability, management of adverse drug reactions (ADRs), and patient experience of T-DXd in patients with HER2-low unresectable and/or metastatic breast cancer. Patients will be treated according to the proposed indication statement in the Summary of Product Characteristics (SmPC). No drug product will be administered as part of this study. Data on conventional chemotherapy (i.e., including but not limited to capecitabine, eribulin, gemcitabine, paclitaxel and nab-paclitaxel) will also be collected in a disease registry part of the study.

Clinical Surveillance Vs. Anticoagulation for Low-risk Patients with Isolated Subsegmental Pulmonary Embolism

Transcutaneous Tibial Nerve Stimulation in Acute Spinal Cord Injury

Swiss Severe Asthma Register

The overall objective is to establish a clinical register for patients with severe asthma. Since the number of patients with severe asthma at a single center is usually low, it will be important to collect data in a multi-center system to optimize the diagnostic evaluation and treatment of patients with severe asthma. So far, there is little reliable information about the frequency, phenotype and therapy of patients with severe asthma. The construction of a clinical register should close this gap. The primary objective is to show changes in symptoms control during follow up period and at study end by using the Asthma Control Test (ACT). Secondary endpoints are to collect data to better understand asthma's natural history in patients with severe asthma. The examination will be based on the assessment of the parameters specified under "outcomes". Patients presenting to participating study center (pulmonologists in private practice or in pulmonary departments in hospital within Switzerland) with severe asthma will be asked to take part in this study when corresponding to the eligibility criteria. All patients with severe asthma will be included in the register only after detailed information and written consent. After four months (for specific therapies) and after 12 months, patients should be re-evaluated for up to 15 years. These follow-up data will also be recorded in the register. During the follow-up visits, the same parameters will be collected as during the initial Baselineexamination (some parameters will be omitted, for example, therapy received or requested for the defined period of the last 12 months, etc.). Severe asthma patients receiving a new specific therapy, e.g. obtained with antibodies, but who cannot be included in the register with the complete parameter profile due to time or capacity reasons of the centers, should be recorded at least with defined basic data and a reduced number of parameters in the register. These parameters include according to the specific asthma approved specific therapies, socio-demographic data, lung function values, laboratory values, parameters of asthma control, smoking status and add-on- therapy. This should make it possible to record a subgroup of severe asthmatics that are suitable for antibody therapy and at the same time offer the attending physician the opportunity to adequately document these complex and expensive therapies by recording the defined parameters. In these patients, an evaluation of the therapy response should be carried out after four months and documented in the register. Thereafter, there is an annual follow-up. At any time, these patients can be transferred to the full version of the register by entering the missing parameters. Patients for whom only the basic data is available (basic version) as well as patients with complete parameter profile in the register are kept in the same database and can be evaluated together. In general, no register-specific examinations will be carried out, but only parameters anyway recorded routinely. Since this is a cohort study, no sample size calculation can be calculated. Evaluations are carried out continuously. The collective of the data should be described by descriptive statistics concerning the basic data as well as the data of the function diagnostics. Subentities of severe asthma should be identified by a cluster analysis.

High Dose Steroids in Children With Stroke

Background: Arterial ischemic stroke (AIS) is a rare but devastating condition affecting 2-5/100,000 children/year. Children do not recover better than adults with 2/3 suffering long term neurological, cognitive and behavioural problems. The economic cost of stroke is substantial. Arteriopathy is identified as AIS aetiology in 60-80% of previously healthy children and is the strongest predictor of recurrent events. 30-40% of these children will have a focal cerebral arteriopathy (FCA). FCA in childhood is shown to be an inflammatory vessel wall pathology provoked by infections. This encourages treatment with steroids, despite lack of evidence. Rationale: There is increasing evidence that etiologically inflammatory processes play a crucial role in childhood stroke, and influence outcome. Retrospective analyses suggest improved outcome and less recurrence with steroid treatment. With the exception of sickle cell disease, this study will be the first randomized clinical trial in children with arterial ischemic stroke. It will provide high-level evidence for the most appropriate treatment for children with AIS due to FCA. Alignment of interventions and outcome as well as pooled analysis with the planned Focal Cerebral Arteriopathy Steroid (FOCAS) study in North America will allow pooled analysis results.This is very important in view of the marked neurological, social and economic burden of childhood AIS for patients and families. This project has been identified as the most important AIS treatment trial by a Delphi survey of international paediatric stroke experts and is one of the most important research priorities identified by parents. In addition, the study will provide insights into the pathogenesis of inflammatory vasculopathies.The objective of this trial is to show that children with first stroke event due to unilateral FCA treated with a combination of high dose steroid and aspirin will have better and quicker recovery of arteriopathy, better clinical functional outcome, and less recurrence compared to children treated with aspirin alone. The proposed study is a prospective multicentre, parallel group, two-arm, randomized controlled, open-label clinical trial with blinded outcome assessment, comparing a high dose course of methylprednisolone / prednisolone plus standard of care with standard of care alone in children with unilateral arteriopathy and acute ischemic stroke. Measurements and procedures: Participants will be randomized within 48 hours after diagnosis (maximum 96 hours after stroke onset) to standard of care (SC) alone (control group) or SC plus steroids (experimental group). SC will be harmonized among the study centres to include aspirin treatment. Patients will be assessed at 1, 3, 6 and 12 months. Magnetic imaging and angiography (MRI/MRA) will be done at 1, (3) and 6 months. Number of Participants: 70 participants in total, 35 per treatment arm Study duration: 48 months Study Centre(s): International multi-centre study with approximately 20 to 30 centres Participating countries:Switzerland, Germany, France, Austria, Great Britain & Australia Centres in additional countries might be considered. Statistical Considerations: The sample size is based on the comparison of the primary outcome - the change in FCASS from baseline to 1 month - between the two treatment groups. The standard deviation from 13 patients of a retrospective study was calculated. The standard deviation of the baseline and follow-up FCASS was 3.0 and 3.3, respectively. The standard deviation of the change in FCASS from baseline was 2.8. Based on the standard deviation of 2.8 and a two-sample means test, 64 patients (32 in each group) are required to detect a difference of 2.0 with a power of 80% at a two-sided alpha-level of 0.05. To account for dropouts (8%), we enlarge the sample size to 70 patients (35 in each group). The primary analysis will follow the intention-to-treat (ITT) principle, i.e. all patients will be analysed in the allocated group regardless of any protocol violations such as cross-overs. The primary outcome (change in FCASS from baseline to 1 month) as well as other secondary continuous score outcomes that are measured multiple times during follow-up (RRQ, mRS, Pediatric Stroke Outcome Measure (PSOM), VABS, modAspect) will be assessed in a repeated-measure, mixed-effects linear model. Good Clinical Practice (GCP) Statement: This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH-GCP) as well as all national legal and regulatory requirements.