Entwicklung und Validierung eines Algorithmus zur automatisierten Auswertung der autonomen Funktion des Herzens

Die Beurteilung der autonomen Funktion des Herzens hat in den letzten Jahren zunehmend an Bedeutung gewonnen. Sie wird zur Diagnostik und zum Therapie-Monitoring sowie zur Prognoseabschätzung in vielen Bereichen der Medizin eingesetzt. Für eine weitere Verbreitung und den regelmäßigen Einsatz in der Routineversorgung ist die unkomplizierte Erhebung dieser Parameter entscheidend. Die bislang existierenden Parameter sind jedoch relativ empfindlich gegenüber Artefakten und bedürfen daher einer aufwendigen manuellen Nachbearbeitung des erhobenen EKG-Signals. Im Rahmen dieser Studie haben wir einen Auswertungsalgorithmus entwickelt und validiert, der es erlaubt, die autonome Funktion des Herzens vollautomatisch aus einem Routine-EKG mit geringer Auflösung zu bestimmen. Die verwendeten EKGs zur Entwicklung und Validierung des Mechanismus stammen aus einer Studie an Patienten in einer Notaufnahme. Alle Daten wurden im klinischen Alltag und ohne zusätzlichen Aufwand für das Personal oder die Patienten erhoben. Zur Erkennung der QRS Komplexe haben wir einen bestehenden und validierten Algorithmus überarbeitet. Als Vergleich haben wir einen etablierten und weit verbreiteten Algorithmus zur Erkennung von QRS-Komplexen gewählt. Unser Verfahren zeigte eine höhere Korrelation mit der manuellen Auswertung für mehrere HRV-Parameter. Um die Zuverlässigkeit weiter zu steigern, haben wir anschließend die Dezelerationskapazität des Herzens (DC) als etablierten Marker für die HRV um einen Tiefpassfilter erweitert. Hier zeigte sich eine außerordentlich hohe Korrelation mit dem manuell ausgewerteten EKG-Signal. Durch das beschriebene Verfahren kann die autonome Funktion des Herzens deutlich schneller, einfacher und kostengünstiger ermittelt werden als mit den Standardverfahren. Als Grundlage diente eine EKG-Aufzeichnung aus dem klinischen Alltag in niedriger Qualität. Diese Methode stellt also eine Möglichkeit dar, aus den Daten, die aktuell schon in großer Zahl in vielen medizinischen Einrichtungen anfallen, die autonome Funktion des Herzens zu bestimmen. Die DC mit Tiefpassfilter ist bislang nicht bezüglich ihrer klinischen Bedeutung untersucht worden. In weiteren Studien sollte dieser Parameter und seine Bedeutung für die Diagnostik sowie Therapieüberwachung bei unterschiedlichen Krankheitsbildern untersucht werden

Stress Urinary Incontinence: An Unsolved Clinical Challenge

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective

A non‐inferiority comparative analysis of micro‐ultrasonography and MRI‐targeted biopsy in men at risk of prostate cancer

Objective: To compare the efficacy of multiparametric magnetic resonance imaging (mpMRI)-directed and micro-ultrasonography (micro-US)-directed biopsy for detecting clinically significant (Grade Group >1) prostate cancer (csPCa). Materials and methods: A total of 203 patients were prospectively enrolled at three institutions across Germany and Austria in the period from January 2019 to December 2019. During each biopsy, the urologist was blinded to the mpMRI report until after the micro-US targets had been assessed. After unblinding, targets were then sampled using software-assisted fusion, followed by systematic samples. The primary outcome measure was non-inferiority of micro-US to detect csPCa, with a detection ratio of at least 80% that of mpMRI. Results: A total of 79 csPCa cases were detected overall (39%). Micro-US-targeted biopsy detected 58/79 cases (73%), while mpMRI-targeted biopsy detected 60/79 (76%) and non-targeted (completion sampling) samples detected 45/79 cases (57%). mpMRI-targeted samples alone detected 7/79 (9%) csPCa cases which were missed by micro-US-targeted and non-targeted samples. Three of these seven were anterior lesions with 2/7 in the transition zone. Micro-US-targeted samples alone detected 5/79 (6%) and completion sampling alone detected 4/79 cases (5%). Micro-US was non-inferior to mpMRI and detected 97% of the csPCa cases detected by mpMRI-targeted biopsy (95% CI 80-116%; P = 0.023). Conclusions: This is the first multicentre prospective study comparing micro-US-targeted biopsy with mpMRI-targeted biopsy. The study provides further evidence that micro-US can reliably detect cancer lesions and suggests that micro-US biopsy might be as effective as mpMRI for detection of csPCA. This result has significant implications for increasing accessibility, reducing costs and expediting diagnosis

Micro-Ultrasound: a way to bring imaging for prostate cancer back to urology

Only a decade ago, there were insufficient imaging options for the detection and local staging of prostate cancer. However, the introduction of multiparametric magnetic resonance imaging (mpMRI) has advanced a much-needed tool for this scope of application. The possibilities and limitations of mpMRI have been well studied. Imaging must be acquired and evaluated using a standardized protocol (the latest version of Prostate Imaging–Reporting and Data System). Sensitivity has been shown to increase with higher grades and larger tumors, and while the detection rate on a per patient basis is relatively high, the per-lesion detection rate is far inferior. Various specialists have attempted to elevate the use of transrectal ultrasound, a tool frequently used by all urologists. Encouragement for this idea comes from a recently introduced system of high frequency transrectal ultrasound. The level of evidence supporting its use in the detection and staging of prostate cancer is not comparable with mpMRI yet, but initial prospective studies indicate good potential. The sensitivity of micro-ultrasound and mpMRI for clinically significant prostate cancer ranges from 94% to 100% and from 88% to 90%, respectively. Further areas of application, such as local staging for prostate and bladder cancer, are currently being evaluated. In summary, microultrasound presents a promising technology for further improving urological imaging and allows for the possibility of returning prostate cancer imaging to urologists. This review will summarize the current scientific basis for the use of micro-ultrasound in the detection of prostate cancer

Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI

Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI

Proceedings of the 18th ECOOP Doctoral Symposium and PhD Students Workshop

Proceedings of the 18th ECOOP Doctoral Symposium and PhD Students WorkshopAITOunpublishedis peer reviewe

Production of Proliferation- and Differentiation-Competent Porcine Myoblasts for Preclinical Studies in a Porcine Large Animal Model of Muscular Insufficiency

Muscular insufficiency is observed in many conditions after injury, chronic inflammation, and especially in elderly populations. Causative cell therapies for muscle deficiencies are not state of the art. Animal models to study the therapy efficacy are, therefore, needed. We developed an improved protocol to produce myoblasts suitable for pre-clinical muscle therapy studies in a large animal model. Myoblasts were isolated from the striated muscle, expanded by employing five different protocols, and characterized on transcript and protein expression levels to determine procedures that yielded optimized regeneration-competent myoblasts and multi-nucleated myotubes. We report that swine skeletal myoblasts proliferated well under improved conditions without signs of cellular senescence, and expressed significant levels of myogenic markers including Pax7, MyoD1, Myf5, MyoG, Des, Myf6, CD56 (p ≤ 0.05 each). Upon terminal differentiation, myoblasts ceased proliferation and generated multi-nucleated myotubes. Injection of such myoblasts into the urethral sphincter complex of pigs with sphincter muscle insufficiency yielded an enhanced functional regeneration of this muscle (81.54% of initial level) when compared to the spontaneous regeneration in the sham controls without myoblast injection (67.03% of initial level). We conclude that the optimized production of porcine myoblasts yields cells that seem suitable for preclinical studies of cell therapy in a porcine large animal model of muscle insufficiency