TimeTeller for timing health: The potential of circadian medicine to improve performance, prevent disease and optimize treatment.

Circadian medicine, the study of the effects of time on health and disease has seen an uprising in recent years as a means to enhance health and performance, and optimize treatment timing. Our endogenous time generating system -the circadian clock- regulates behavioural, physiological and cellular processes. Disruptions of the clock, via external factors like shift work or jet lag, or internal perturbations such as genetic alterations, are linked to an increased risk of various diseases like obesity, diabetes, cardiovascular diseases and cancer. By aligning an individual's circadian clock with optimal times for performing daily routines, physical and mental performance, and also the effectiveness of certain therapies can be improved. Despite the benefits of circadian medicine, the lack of non-invasive tools for characterizing the clock limits the potential of the field. TimeTeller is a non-invasive molecular/digital tool for the characterization of circadian rhythms and prediction of daily routines, including treatment timing, to unlock the potential of circadian medicine and implementing it in various settings. Given the multiple known and potentially yet unknown dependent health factors of individual circadian rhythms, the utility of this emerging biomarker is best exploited in data driven, personalized medicine use cases, using health information across lifestyle, care, and research settings.

Mindfulness and skills-based eHealth intervention to reduce distress in cancer-affected patients in the Reduct trial: Intervention protocol of the make it training optimized.

Introduction: Cancer-affected patients experience high distress due to various burdens. One way to expand psycho-oncological support is through digital interventions. This protocol describes the development and structure of a web-based psycho-oncological intervention, the Make It Training optimized. This intervention is currently evaluated in the Reduct trial, a multicenter randomized controlled trial. Methods: The Make It Training optimized was developed in six steps: A patient need and demand assessment, development and acceptability analysis of a prototype, the formation of a patient advisory council, the revision of the training, implementation into a web app, and the development of a motivation and evaluation plan. Results: Through a process of establishing cancer-affected patients' needs, prototype testing, and patient involvement, the Make It Training optimized was developed by a multidisciplinary team and implemented in a web app. It consists of 16 interactive self-guided modules which can be completed within 16 weeks. Discussion: Intervention protocols can increase transparency and increase the likelihood of developing effective web-based interventions. This protocol describes the process and results of developing a patient-oriented intervention. Future research should focus on the further personalization of web-based psycho-oncological interventions and the potential benefits of combining multiple psychotherapeutic approaches.

Web-based mindfulness and skills-based distress reduction for patients with cancer: study protocol of the multicentre, randomised, controlled confirmatory intervention trial Reduct.

INTRODUCTION: Many patients with cancer experience severe psychological distress, but as a result of various barriers, few of them receive psycho-oncological support. E-mental health interventions try to overcome some of these barriers and the limitation of healthcare offers, enabling patients with cancer to better cope with psychological distress. In the proposed trial, we aim to assess the efficacy and cost-effectiveness of the manualised e-mental health intervention Make It Training- Mindfulness-Based and Skills-Based Distress Reduction in Oncology. Make It Training is a self-guided and web-based psycho-oncological intervention, which includes elements of cognitive behavioural therapy, mindfulness-based stress reduction and acceptance and commitment therapy. The training supports the patients over a period of 4 months. We expect the Make It Training to be superior to treatment as usual optimised (TAU-O) in terms of reducing distress after completing the intervention (T1, primary endpoint). METHODS AND ANALYSIS: The study comprises a multicentre, prospective, randomised controlled confirmatory interventional trial with two parallel arms. The proposed trial incorporates four distinct measurement time points: the baseline assessment before randomisation, a post-treatment assessment and 3 and 6 month follow-up assessments. We will include patients who have received a cancer diagnosis in the past 12 months, are in a curative treatment setting, are 18-65 years old, have given informed consent and experience high perceived psychological distress (Hospital Anxiety and Depression Scale ≥13) for at least 1 week. Patients will be randomised into two groups (Make It vs TAU-O). The aim is to allocate 600 patients with cancer and include 556 into the intention to treat analysis. The primary endpoint, distress, will be analysed using a baseline-adjusted ANCOVA for distress measurement once the intervention (T1) has been completed, with study arm as a binary factor, baseline as continuous measurement and study centre as an additional categorical covariate. ETHICS AND DISSEMINATION: The Ethics Committee of the Medical Faculty Essen has approved the study (21-10076-BO). Results will be published in peer-reviewed journals, conference presentations, the project website, and among self-help organisations. TRIAL REGISTRATION NUMBER: German Clinical Trial Register (DRKS); DRKS-ID: DRKS00025213.

Automatic multi-model-based segmentation of the left atrium in cardiac MRI scans.

Model-based segmentation approaches have been proven to produce very accurate segmentation results while simultaneously providing an anatomic labeling for the segmented structures. However, variations of the anatomy, as they are often encountered e.g. on the drainage pattern of the pulmonary veins to the left atrium, cannot be represented by a single model. Automatic model selection extends the model-based segmentation approach to handling significant variational anatomies without user interaction. Using models for the three most common anatomical variations of the left atrium, we propose a method that uses an estimation of the local fit of different models to select the best fitting model automatically. Our approach employs the support vector machine for the automatic model selection. The method was evaluated on 42 very accurate segmentations of MRI scans using three different models. The correct model was chosen in 88.1% of the cases. In a second experiment, reflecting average segmentation results, the model corresponding to the clinical classification was automatically found in 78.0% of the cases.

Fully automatic geometry planning for cardiac MR imaging and reproducibility of functional cardiac parameters.

PURPOSE: To establish operator-independent, fully automated planning of standard cardiac geometries and to determine the impact on interstudy reproducibility of cardiac functional parameters. MATERIALS AND METHODS: Cardiac MR imaging was done in 50 patients referred for left-ventricular function assessment. In all patients, first standard manual planning was performed followed by automatic planning (AUTO1) and repeat automatic planning (AUTO2) after repositioning the patient to investigate interstudy reproducibility. Cardiac functional parameters were assessed and cine scans were visually graded on a 4-point scale from nondiagnostic to excellent. RESULTS: Overall success rate of AUTO was 94% with good to excellent geometry planning in >94% of cine standard views. Comparing manual versus fully automated planning, a high agreement of cardiac functional parameters (Lin's concordance correlation coefficient, 0.91 to 0.99) with minimal percent bias (0.24 to 3.84%) was found. In addition, a high interstudy reproducibility of automatic planning was demonstrated (Lin's concordance correlation coefficient, 0.89 to 0.99; percent bias, 0.38 to 5.04%; precision, 3.46 to 9.09%). CONCLUSION: Fully automated planning of cardiac geometries could reliably be performed in patients showing a variety of cardiovascular pathologies. Standard cardiac geometries were precisely replicated and functional parameters were highly accurate.

One year after navigated total knee replacement, no clinically relevant difference found between fixed bearing and mobile bearing knee replacement in a double-blind randomized controlled trial.

BACKGROUND: The mobile bearing designs have not yet been shown to improve clinical outcome of total knee arthroplasty (TKA). In this prospective randomized study, we compared the short-term clinical results of a mobile bearing implant with those of the fixed bearing version of the same implant. METHODS: We randomized 100 knees into two double-blind groups who received either the fixed (FB, 52 knees) or the mobile bearing (MB, 48 knees) version of the same implant. We used navigation to standardize the surgical technique. For up to one year, we recorded the Knee Society (KSS) and Oxford (OXF) scores. We performed an exploratory analysis of variance (ANOVA) to determine the influence of baseline scores as covariate and the extent of improvement in clinical outcome over time. RESULTS: After one year, we did not detect any statistically significant difference between the two groups. The KSS scores differed by 2 points, the OXF scores by 1.1 points. CONCLUSION: Even with identical geometry of implant surfaces and a navigated surgical technique, first-year results do not support a preference for either a fixed or a mobile design.

Towards automatic patient positioning and scan planning using continuously moving table MR imaging.

A concept is proposed to simplify patient positioning and scan planning to improve ease of use and workflow in MR. After patient preparation in front of the scanner the operator selects the anatomy of interest by a single push-button action. Subsequently, the patient table is moved automatically into the scanner, while real-time 3D isotropic low-resolution continuously moving table scout scanning is performed using patient-independent MR system settings. With a real-time organ identification process running in parallel and steering the scanner, the target anatomy can be positioned fully automatically in the scanner's sensitive volume. The desired diagnostic examination of the anatomy of interest can be planned and continued immediately using the geometric information derived from the acquired 3D data. The concept was implemented and successfully tested in vivo in 12 healthy volunteers, focusing on the liver as the target anatomy. The positioning accuracy achieved was on the order of several millimeters, which turned out to be sufficient for initial planning purposes. Furthermore, the impact of nonoptimal system settings on the positioning performance, the signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) was investigated. The present work proved the basic concept of the proposed approach as an element of future scan automation.

Assessment of anterior cruciate ligament reconstruction using 3D ultrashort echo-time MR imaging.

This work demonstrates the potential of ultrashort TE (UTE) imaging for visualizing graft material and fixation elements after surgical repair of soft tissue trauma such as ligament or meniscal injury. Three asymptomatic patients with anterior cruciate ligament (ACL) reconstruction using different graft fixation methods were imaged at 1.5T using a 3D UTE sequence. Conventional multislice turbo spin-echo (TSE) measurements were performed for comparison. 3D UTE imaging yields high signal from tendon graft material at isotropic spatial resolution, thus facilitating direct positive contrast graft visualization. Furthermore, metal and biopolymer graft fixation elements are clearly depicted due to the high contrast between the signal-void implants and the graft material. Thus, the ability of UTE MRI to visualize short-T(2) tissues such as tendons, ligaments, or tendon grafts can provide additional information about the status of the graft and its fixation in the situation after cruciate ligament repair. UTE MRI can therefore potentially support diagnosis when problems occur or persist after surgical procedures involving short-T(2) tissues and implants.

Automated planning of scan geometries in spine MRI scans.

Consistency of MR scan planning is very important for diagnosis, especially in multi-site trials and follow-up studies, where disease progress or response to treatment is evaluated. Accurate manual scan planning is tedious and requires skillful operators. On the other hand, automated scan planning is difficult due to relatively low quality of survey images ("scouts") and strict processing time constraints. This paper presents a novel method for automated planning of MRI scans of the spine. Lumbar and cervical examinations are considered, although the proposed method is extendible to other types of spine examinations, such as thoracic or total spine imaging. The automated scan planning (ASP) system consists of an anatomy recognition part, which is able to automatically detect and label the spine anatomy in the scout scan, and a planning part, which performs scan geometry planning based on recognized anatomical landmarks. A validation study demonstrates the robustness of the proposed method and its feasibility for clinical use.

Accuracy of implant alignment and early results after minimally invasive vs conventional OrthoPilot-navigated Columbus TKA.

The goal of this study was to evaluate potential risks and benefits of minimally invasive vs conventional approaches in navigated total knee arthroplasty (TKA) in 50 patients. Preoperatively, no statistically significant differences between the two groups were found for deformity, range of motion (ROM), clinical scores, and ligament stability in the native joint or after prosthesis implantation measurements intraoperatively. Postoperatively, there were no significant differences between the two groups for deformity and clinical scores. In contrast, significantly less pain according to VAS measures and quicker improvements in ROM during the first 10 postoperative days were experienced in the minimally invasive group. Complication rates were similar in both groups. According to our results, minimally invasive navigated TKA is characterized by high implant positioning accuracy, soft tissue management quality, and complication rates similar to those for conventional approaches. Compared with the conventional approach, minimally invasive TKA provides superior functional results and less pain in the early postoperative period.

Automated model-based rib cage segmentation and labeling in CT images.

We present a new model-based approach for an automated labeling and segmentation of the rib cage in chest CT scans. A mean rib cage model including a complete vertebral column is created out of 29 data sets. We developed a ray search based procedure for rib cage detection and initial model pose. After positioning the model, it was adapted to 18 unseen CT data. In 16 out of 18 data sets, detection, labeling, and segmentation succeeded with a mean segmentation error of less than 1.3 mm between true and detected object surface. In one case the rib cage detection failed, in another case the automated labeling.

Spine detection and labeling using a parts-based graphical model.

The detection and extraction of complex anatomical structures usually involves a trade-off between the complexity of local feature extraction and classification, and the complexity and performance of the subsequent structural inference from the viewpoint of combinatorial optimization. Concerning the latter, computationally efficient methods are of particular interest that return the globally-optimal structure. We present an efficient method for part-based localization of anatomical structures which embeds contextual shape knowledge in a probabilistic graphical model. It allows for robust detection even when some of the part detections are missing. The application scenario for our statistical evaluation is spine detection and labeling in magnetic resonance images.

The water jet as a new tool for endoprosthesis revision surgery--an in vitro study on human bone and bone cement.

In revision surgeries of endoprostheses, the interface between implant and bone cement or bone must be loosened. Conventional tools have many disadvantages because of their size and limited range. Taking advantage of the selective and athermic cutting process, a plain water jet is already used in order to cut soft tissues. This study investigates the possibilities of both a plain and an abrasive water jet as cutting tools for revision surgery. Samples of the mid-diaphysis of human femora and bone cement (CMW3) were cut with a plain water jet (PWJ) and an abrasive water jet (AWJ) at two different jet-to-surface angles (30 degrees,90 degrees ) and at five different pressure levels (30, 40, 50, 60, 70 MPa). For a PWJ a selective pressure range was identified, where only bone cement was cut. Injecting a bio-compatible abrasive (lactose) to the jet stream resulted in significantly higher cut depths in both materials. Material removal in bone was significantly less at the smaller jet-to-surface angle for both techniques. No clear selectivity between bone and bone cement was observed for application of the AWJ. However, the material removal rate was significantly higher for bone cement than for bone at all pressure levels. The results indicate that an AWJ might be an alternative tool for cement removal. The possibility for localised cutting at interfaces could be an advantage for revision of a non-cemented prosthesis.

[The pulsed water jet for selective removal of bone cement during revision arthroplasty]. / Der gepulste Wasserstrahl zur selektiven Knochenzemententfernung in der Revisionsendoprothetik.

Conventional tools used in prosthetic revision surgery have a limited range of action within the narrow cement mantle. Water jet cutting technology permits tiny and precisely controlled cuts, and may therefore be an alternative method of bone cement removal. Our study compares the cutting performance on bone cement (PMMA) and bone of a pulsed water jet and a continuous water jet. The aim of the study was to establish whether selective removal of PMMA is possible. 55 bone specimens (bovine femora) and 32 specimens of PMMA were cut with a continuous and a pulsed water jet at different pressures (40 MPa, 60 MPa) and pulse frequencies (0Hz, 50Hz, 250Hz). To ensure comparability of the results, the depths of cut were related to the hydraulic power of that part of the jet actually impinging on the material. While for PMMA the power-related depth of cut increased significantly with the pulse frequency, this did not apply to bone. The cuts produced in bone were sharp-edged. Since PMMA is more brittle than bone, the water jet caused cracks that enlarged further until particles of bone broke away. Although selective removal of PMMA without doing damage to the bone was not possible at the investigated settings of the jet parameters, the results do show that a pulsed water jet can cut bone cement much more effectively than bone. This is an important advantage over conventional non-selective tools for the removal of bone cement.

Comparison of robotic-assisted and manual implantation of a primary total hip replacement. A prospective study.

BACKGROUND: Robotic-assisted total hip replacement has become a common method of implantation, especially in Europe. It frequently has been postulated that robotic reaming would result in an improved clinical outcome due to the better fit of the prosthesis, but that has never been demonstrated in a prospective study, to our knowledge. The purpose of this study was to compare robotic-assisted implantation of a total hip replacement with conventional manual implantation. METHODS: One hundred and fifty-four patients scheduled for total hip replacement were randomly assigned to undergo either conventional manual implantation of an S-ROM prosthesis (eighty patients) or robotic-assisted implantation of such a prosthesis (seventy-four patients). The five-axis ROBODOC was used for the robotic-assisted procedures. Preoperatively as well as at three, six, twelve, and twenty-four months after surgery, the scores according to the Harris and Merle d'Aubigné systems and the Mayo clinical score were determined. Radiographs made at these intervals were analyzed for evidence of loosening, prosthetic alignment, and heterotopic ossification. RESULTS: Thirteen (18%) of the seventy-four attempted robotic implantations had to be converted to manual implantations as a result of failure of the system. The duration of the robotic procedures was longer than that of the manual procedures (mean and standard deviation,107.1 +/- 29.1 compared with 82.4 +/- 23.4 minutes, p < 0.001). Limb-length equality (mean discrepancy, 0.18 +/- 0.30 compared with 0.96 +/- 0.93 cm, p < 0.001) and varus-valgus orientation of the stem (mean angle between the femur and the shaft of the prosthesis, 0.34 degrees +/- 0.67 degrees compared with 0.84 degrees +/- 1.23 degrees, p < 0.001) were better after the robotic procedures. At six months, slightly more heterotopic ossification was seen in the group treated with robotic implantation. The group treated with robotic implantation had a better Mayo clinical score at six and twelve months and a better Harris score at twelve months; however, by twenty-four months, no difference was found between the groups with regard to any of the three scores. Dislocation was more frequent in the group treated with robotic implantation: it occurred in eleven of the sixty-one patients in that group compared with three of eighty in the other group (p < 0.001). Recurrent dislocation and pronounced limping were indications for revision surgery in eight of the sixty-one patients treated with robotic implantation compared with none of the seventy-eight (excluding two with revision for infection) treated with manual insertion (p < 0.001). Rupture of the gluteus medius tendon was observed during all of the revision operations. CONCLUSIONS: The robotic-assisted technology had advantages in terms of preoperative planning and the accuracy of the intraoperative procedure. Disadvantages were the high revision rate; the amount of muscle damage, which we believe was responsible for the higher dislocation rate; and the longer duration of surgery. This technology must be further developed before its widespread usage can be justified.