The Fusion of MRI and CT in the Planning of Brachytherapy for Cancer of the Uterine Cervix

Introduction: tumors of the uterine cervix are among the most common carcinomas in women. Intracervical brachytherapy is an indispensable part of curative treatment. Although the tumor is significantly more recognizable in MRI than in CT, the practical application of MRI in brachytherapy planning is still difficult. The present study examines the technical possibilities of merging CT and MRI. Materials and Methods: the treatment files and imaging of all 53 patients who had been irradiated by image-guided adaptive brachytherapy (IGABT) between January 2019 and August 2021 at the Department of Radiotherapy of the Hannover Medical School were evaluated, retrospectively. Patients were treated first with an external beam radiotherapy (EBRT) combined with simultaneous chemotherapy. After an average of 4.2 weeks, the preparation for IGABT began. The clinical target volume (CTV) for brachytherapy was contoured first in an MRI acquired before starting EBRT (MRI 1) and once more in a second MRI just before starting IGABT (MRI 2). Then, after inserting the intravaginal applicator, a CT-scan was acquired, and the CTV was contoured in the CT. Finally, the recordings of MRI 1, MRI 2, and the CT were merged, and the congruence of CTVs was quantitatively evaluated. Results: the CTV delineated in MRI 2 was, on average, 28% smaller than that in MRI 1 after an average applied radiation dose of 42 Gy. The CTV delineated in the CT covered an average of no more than 80.8% of the CTV delineated in MRI 2. The congruence of CTVs was not superior in patients with a smit sleeve in the cervical channel, with a 3D-volumetric MRI or with a contrast-enhanced sequence for MRI. Conclusion: the anatomical shape and position of the uterus is significantly changed by introducing a vaginal applicator. Despite the superior delimitability of the tumor in MRI, brachytherapy cannot be reliably planned by the image fusion of an MRI without a vaginal applicator.

Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

High Incidence of Epileptiform Potentials During Continuous EEG Monitoring in Critically Ill COVID-19 Patients

Objective: To analyze continuous 1- or 2-channel electroencephalograms (EEGs) of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) with regard to occurrence of epileptiform potentials.Design: Single-center retrospective analysis.Setting: Intensive care unit of Hannover Medical School, Hannover, Germany.Patients: Critically ill COVID-19 patients who underwent continuous routine EEG monitoring (EEG monitor: Narcotrend-Compact M) during sedation.Measurements and Main Results: Data from 15 COVID-19 patients (11 men, four women; age: 19–75 years) were evaluated. Epileptiform potentials occurred in 10 of 15 patients (66.7%).Conclusions: The results of the evaluation regarding the occurrence of epileptiform potentials show that there is an unusually high percentage of cerebral involvement in patients with severe COVID-19. EEG monitoring can be used in COVID-19 patients to detect epileptiform potentials.

Effective identification of cancer predisposition syndromes in children with cancer employing a questionnaire

Approximately 10% of children with newly diagnosed cancer have a cancer predisposition syndrome (CPS). The optimal diagnostic approach to identify them among children diagnosed with cancer is unknown. Objective: To determine whether the use of a one-page questionnaire can improve the CPS diagnosis among children with an oncologic condition. Design: Comparative effectiveness research. Setting: Referral center for children with cancer. Results: 739 children diagnosed with an oncologic condition between 2012 and 2019. All children with a newly diagnosed oncologic condition presenting to Hannover Medical School between January 1st 2017 and December 31st 2019 were prospectively evaluated with a CPS questionnaire. Children in whom the questionnaire suggested the need of a genetic workup were further evaluated. All children diagnosed with an oncologic condition between January 1st 2012 and December 31st 2016 served as control. The CPS diagnoses established during both time periods were evaluated and compared. A CPS was diagnosed in 27 out of 287 children (9.4%) during the questionnaire period versus 24 out of 452 children (5.3%) during the control period (P = 0.032). Conclusion: The CPS questionnaire appears to significantly improve the diagnosis of children with CPS among children with a newly diagnosed oncologic condition.

Defining Learning Outcomes as a Prerequisite of Implementing a Longitudinal and Transdisciplinary Curriculum with Regard to Digital Competencies at Hannover Medical School

Background: Worldwide educational programs face the challenge how to define and integrate digital competencies in medical education. This article describes the implementation of learning outcomes with respect to digital competencies in the compulsory curriculum at Hannover Medical School (MHH). Methods: An interdisciplinary MHH project group was constituted consisting of physicians and experts in medical informatics and in curriculum development. Over the course of 7 work sessions the group compared different international and national frameworks dealing with digital competencies for physicians. By a consensus driven approach the working group drew up a collection of learning outcomes which were regarded relevant to be incorporated in the curriculum at MHH. Results: The analysis of different frameworks indicated that data literacy is a central domain within all viewed preexisting catalogs. During the course of the project group analysis, 57 learning outcomes with respect to digital competencies were identified as necessary to be integrated in the compulsory curriculum. They were divided in 5 main categories: “handling of medical data,” “the digital infrastructure of the health system,” “scope of application: usage in patient care and in the field of preventive medicine,” “medico-legal and ethical basics,” and “transformation processes in medicine due to digitalization.” Conclusions: The MHH project group concluded that medical students should be taught digital competencies that enable an understanding of underlying functional principles of digital systems rather than their correct utilization. The presented project indicates that a close interdisciplinary collaboration of physicians and medical informaticians can be a promising approach to incorporate digital competencies in the undergraduate medical curriculum.

Complete populations of virtual patients for in silico clinical trials

Motivation Model-based approaches to safety and efficacy assessment of pharmacological drugs, treatment strategies or medical devices (In Silico Clinical Trial, ISCT) aim to decrease time and cost for the needed experimentations, reduce animal and human testing, and enable precision medicine. Unfortunately, in presence of non-identifiable models (e.g. reaction networks), parameter estimation is not enough to generate complete populations of Virtual Patients (VPs), i.e. populations guaranteed to show the entire spectrum of model behaviours (phenotypes), thus ensuring representativeness of the trial. Results We present methods and software based on global search driven by statistical model checking that, starting from a (non-identifiable) quantitative model of the human physiology (plus drugs PK/PD) and suitable biological and medical knowledge elicited from experts, compute a population of VPs whose behaviours are representative of the whole spectrum of phenotypes entailed by the model (completeness) and pairwise distinguishable according to user-provided criteria. This enables full granularity control on the size of the population to employ in an ISCT, guaranteeing representativeness while avoiding over-representation of behaviours. We proved the effectiveness of our algorithm on a non-identifiable ODE-based model of the female Hypothalamic-Pituitary-Gonadal axis, by generating a population of 4 830 264 VPs stratified into 7 levels (at different granularity of behaviours), and assessed its representativeness against 86 retrospective health records from Pfizer, Hannover Medical School and University Hospital of Lausanne. The datasets are respectively covered by our VPs within Average Normalized Mean Absolute Error of 15%, 20% and 35% (90% of the latter dataset is covered within 20% error). Availability and implementation. Our open-source software is available at https://bitbucket.org/mclab/vipgenerator Supplementary information Supplementary data are available at Bioinformatics online.

Drug safety profiles in geriatric patients with Parkinson’s disease using the FORTA (Fit fOR The Aged) classification: results from a mono-centric retrospective analysis

To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with different labels, namely A (indispensable), B (beneficial), C (questionable), and D (avoid). The aims of our study were to assess the medication appropriateness in PD inpatients applying the FORTA list and drug-drug interaction software, further to assess the adequacy of FORTA list for patients with PD. We retrospectively collected demographic data, comorbidities, laboratory values, and the medication from the discharge letters of 123 geriatric inpatients with PD at the university hospital of Hannover Medical School. Patients suffered on average from 8.2 comorbidities. The majority of the medication was labeled A (60.6% of PD-specific and 40.9% of other medication) or B (22.3% of PD-specific and 26.9% of other medication). Administered drugs labeled with D were amantadine, clozapine, oxazepam, lorazepam, amitriptyline, and clonidine. Overall, 545 interactions were identified, thereof 11.9% severe interactions, and 1.7% contraindicated combinations. 81.3% of patients had at least one moderate or severe interaction. The FORTA list gives rational recommendations for PD-specific and other medication, especially for general practitioners. Considering the demographic characteristics and the common multimorbidity of geriatric PD patients, this study underlines the importance of awareness, education, and preventive interventions to increase drug safety.

Targeting FGFR2 in advanced cholangiocarcinoma: an interview with Arndt Vogel

Professor Arndt Vogel, a senior consultant and professor of gastrointestinal oncology in the Department of Gastroenterology, Hepatology and Endocrinology at Hannover Medical School, Germany, speaks with Rachel Jenkins (Senior Editor of Oncology Central) about cholangiocarcinoma, the challenges of the field and some promising avenues for therapy. To listen to the full podcast interview, visit Oncology Central ( www.oncology-central.com/ ) now.

Students as advocates of global health goals: the case of medical education in Germany

Background Germany has started to take on greater responsibility in global health policy. Furthermore, new threats, such as climate change, have increased sensitivity. However, health professionals are not well prepared to respond to the new tasks and the changing needs of the population. Global health is still largely missing from the education and training programmes of the vast majority of professional groups in Germany. This paper aims to illustrate how students can become advocates of global health education and enhance institutional change, when health policy fails to act effectively. Methods An elective programme introduced in September 2019 in the undergraduate medical curriculum at Hannover Medical School, Germany, serves as a case study to explore the tools and substance of the programme, as well as the stakeholders involved. Results The new global health programme utilises a window of opportunity in the curriculum, which includes a small number of mandatory seminars which students can chose from. It builds on five major pillars: collaboration between students and the programme coordinator and participatory curriculum development; the SDGs as framework and guidance of the curriculum; a multiprofessional and transsectoral teaching team; collaboration with NGOs; strong networks through collaboration with the national German medical students' association. Sustainability remains a major challenge, yet there is now institutional and financial support at Hannover Medical School and the new German National Competence Based Catalogue of Learning Objectives for Undergraduate Medical Education also includes global health issues. Conclusions Students as advocates for global health can make a difference and enhance institutional change through transsectoral, participatory teaching programmes.