Chronic hepatitis E virus-induced spinal cord atrophy in a patient with chronic lymphatic leukemia: a case report and interdisciplinary management proposal.

Background: The hepatitis E virus (HEV) can cause acute viral hepatitis with or without neurological manifestations, and occasionally progresses to chronic infection in immunocompromised individuals. The management of chronic HEV infection in cancer patients may be challenging due to the complex immunological constellation. Furthermore, the diagnostic workflow and the impact on quality of life of neurological HEV manifestations in immunocompromised patients have not been sufficiently delineated previously. Case description: A 61-year-old male with systemically treated chronic lymphocytic leukemia (CLL) experienced a slowly progressive atrophy of the spinal cord due to a chronic HEV infection. Despite continuous antiviral treatment with ribavirin, the patient's neurological condition continued to deteriorate, particularly following subsequent attempts to treat CLL. Treatment with obinutuzumab resulted in acute bowel and urinary retention and a further deterioration of motor skills, prompting the discontinuation of obinutuzumab. The patient's neurological status improved after the administration of intravenous immunoglobulins. Conclusion: This case study provides a comprehensive long-term follow-up of a cancer patient with chronic HEV infection and associated CNS involvement, which resulted in progressive neurological disability over several years. The challenges faced in diagnosing new neurological symptoms in patients undergoing immunosuppressive cancer treatment underscore the need for an interdisciplinary diagnostic approach that includes HEV testing. We propose a diagnostic pathway for future validation in immunocompromised cohorts presenting with neurological symptoms, emphasizing its potential to enhance clinical outcomes.

Cost-benefit ratio of modern medical education using micro-costing: a model calculation using the example of an innovative breast brachytherapy workshop.

BACKGROUND AND PURPOSE: Radiation oncology is an essential component of therapeutic oncology and necessitates well-trained personnel. Multicatheter brachytherapy (MCBT) is one radiotherapeutic option for early-stage breast cancer treatment. However, specialized hands-on training for MCBT is not currently included in the curriculum for residents. A recently developed hands-on brachytherapy workshop has demonstrated promising results in enhancing knowledge and practical skills. Nevertheless, these simulation-based teaching formats necessitate more time and financial resources. Our analyses include computational models for the implementation and delivery of this workshop and can serve as a basis for similar educational initiatives. METHODS: This study aimed to assess the cost-effectiveness of a previously developed and evaluated breast brachytherapy simulation workshop. Using a micro-costing approach, we estimated costs at a detailed level by considering supplies, soft- and hardware, and personnel time for each task. This method also allows for a comprehensive evaluation of the costs associated with implementing new medical techniques. The workshop costs were divided into two categories: development and workshop execution. The cost analysis was conducted on a per-participant basis, and the impact on knowledge improvement was measured using a questionnaire. RESULTS: The total workshop costs were determined by considering the initial workshop setup expenses including the development and conceptualization of the course with all involved collaborators, as well as the costs incurred for each individual course. The workshop was found to be financially efficient, with a per-participant cost of €â€¯39, considering the industrial sponsorship provided for brachytherapy equipment. In addition, we assessed the workshop's efficacy by analyzing participant feedback using Likert scale evaluations. The findings indicated a notable enhancement in both theoretical and practical skills among the participants. Moreover, the cost-to-benefit ratio (CBFR) analysis demonstrated a CBFR of €â€¯13.53 for each Likert point increment. CONCLUSION: The hands-on brachytherapy workshop proved to be a valuable and approximately cost-effective educational program, leading to a significant enhancement in the knowledge and skills of the participants. Without the support of industrial sponsorship, the costs would have been unattainable.

The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies.

A relevant number of cancer patients who receive potentially neurotoxic cytostatic agents develop a chemotherapy-induced peripheral neuropathy over time. Moreover, the increasing use of immunotherapies and targeted agents leads to a raising awareness of treatment-associated peripheral neurotoxicity, e.g., axonal and demyelinating neuropathies such as Guillain-Barré-like syndromes. To date, the differentiation of these phenomena from concurrent neurological co-morbidities or (para-)neoplastic nerve affection as well as their longitudinal monitoring remain challenging. Neuromuscular ultrasound (NMUS) is an established diagnostic tool for peripheral neuropathies. Performed by specialized neurologists, it completes clinical and neurophysiological diagnostics especially in differentiation of axonal and demyelinating neuropathies. No generally approved biomarkers of treatment-induced peripheral neurotoxicity have been established so far. NMUS might significantly extend the repertoire of diagnostic and neuromonitoring methods in this growing patient group in short term. In this article, we present enlargements of the dorsal roots both in cytostatic and in immunotherapy-induced neurotoxicity for the first time. We discuss related literature regarding new integrative applications of NMUS for cancer patients by reference to two representative case studies. Moreover, we demonstrate the integration of NMUS in a diagnostic algorithm for suspected peripheral neurotoxicity independently of a certain cancer treatment regimen emphasizing the emerging potential of NMUS for clinical routine in this interdisciplinary field and prospective clinical trials.

Development and implementation of a student tumor board as a teaching format for medical students.

PURPOSE: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. METHODS: We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. RESULTS: Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. CONCLUSION: Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice.

Importance of interdisciplinarity in modern oncology: results of a national intergroup survey of the Young Oncologists United (YOU).

PURPOSE: Modern, personalized treatment concepts in oncology require an interdisciplinary and multiprofessional collaboration. In addition to its relevance in patient care, interdisciplinary collaboration is also becoming increasingly important in clinical research as well as medical education and resident training in oncology. METHODS: Between November 2021 and March 2022, an online survey was conducted among German early career research groups, represented by Young Oncologists United (YOU). The aim was to identify the status and need for interdisciplinarity at clinic, educational, and research levels. RESULTS: A total of 294 participants completed the questionnaire in full. 90.7% of the respondents fully or predominantly agreed with the statement that interdisciplinary work plays a major role in their daily clinical work. 78.9% wished for more interdisciplinary collaboration. Of the 49.7% of participants who have never participated in an interdisciplinary research project, 80.1% said they would like to participate in such a study project in the future. Lack of time resources, too much organizational effort, and possible political conflicts between institutions were identified as factors that make practical implementation difficult. 74.1% declared their willingness to become active in an oncology early career research group. CONCLUSION: Interdisciplinary collaboration has become increasingly important in oncology. Networks that span different disciplines could help to promote interdisciplinary research projects among young scientists and improve exchange in professional practice and education with the implication of improved patient care.

Can neuro-oncology teaching contribute to educate medical doctors better? A reflection on the value of neuro-oncology for student teaching.

Neuro-oncology, with its various conservative, surgical, and interventional disciplines, is ideally suited to teach basic knowledge, skills, and attitudes important to medical practice in general. However, training is less about teaching specific treatment protocols and more about fostering skills for interdisciplinary collaboration, development of treatment recommendations, communication skills, and an ethical stance. To adequately teach this content, new and innovative formats are needed to test and learn high levels of student interaction, communication, and collaboration.New teaching concepts such as inverted teaching formats as well as the use of modern media technology can be helpful to improve networking between disciplines and to improve the quality of medical education.

Complete and Incomplete Resection for Progressive Glioblastoma Prolongs Post-Progression Survival.

OBJECTIVE: The role of resection in progressive glioblastoma (GBM) to prolong survival is still controversial. The aim of this study was to determine 1) the predictors of post-progression survival (PPS) in progressive GBM and 2) which subgroups of patients would benefit from recurrent resection. METHODS: We have conducted a retrospective bicentric cohort study on isocitrate dehydrogenase (IDH) wild-type GBM treated in our hospitals between 2006 and 2015. Kaplan-Maier analyses and univariable and multivariable Cox regressions were performed to identify predictors and their influence on PPS. RESULTS: Of 589 patients with progressive IDH wild-type GBM, 355 patients were included in analyses. Median PPS of all patients was 9 months (95% CI 8.0-10.0), with complete resection 12 months (95% CI 9.7-14.3, n=81), incomplete resection 11 months (95% CI 8.9-13.1, n=70) and without resection 7 months (95% CI 06-08, n=204). Multivariable Cox regression demonstrated a benefit for PPS with complete (HR 0.67, CI 0.49-0.90) and incomplete resection (HR 0.73, 95% CI 0.51-1.04) and confirmed methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene promoter, lower age at diagnosis, absence of deep brain and multilocular localization, higher Karnofsky Performance Status (KPS) and recurrent therapies to be associated with longer PPS. In contrast, traditional eloquence and duration of progression-free survival had no effect on PPS. Subgroup analyses showed that all subgroups of confirmed predictors benefited from resection, except for patients in poor condition with a KPS <70. CONCLUSIONS: Out data suggest a role for complete and incomplete recurrent resection in progressive GBM patients regardless of methylation of MGMT, age, or adjuvant therapy but not in patients with a poor clinical condition with a KPS <70.

Tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and treatment.

The discovery of the oncometabolite 2-hydroxyglutarate in isocitrate dehydrogenase 1-mutated (IDH1-mutated) tumor entities affirmed the role of metabolism in cancer. However, large databases with tissue metabolites that are modulated by IDH1 mutation remain an area of development. Here, we present an unprecedented and valuable resource for tissue metabolites in diffuse glioma and their modulations by IDH1 mutation, histology, and tumor treatments in 101 tissue samples from 73 diffuse glioma patients (24 astrocytoma, 17 oligodendroglioma, 32 glioblastoma), investigated by NMR-based metabolomics and supported by RNA-Seq. We discovered comparison-specific metabolites and pathways modulated by IDH1 (IDH1 mutation status cohort) and tumor entity. The Longitudinal investigation cohort provides metabolic profiles of untreated and corresponding treated glioma samples at first progression. Most interestingly, univariate and multivariate cox regressions and Kaplan-Meier analyses revealed that tissue metabolites correlate with progression-free and overall survival. Thus, this study introduces potentially novel candidate prognostic and surrogate metabolite biomarkers for future prospective clinical studies, aiming at further refining patient stratification in diffuse glioma. Furthermore, our data will facilitate the generation of so-far-unanticipated hypotheses for experimental studies to advance our molecular understanding of glioma biology.

A Continuous Correlation Between Residual Tumor Volume and Survival Recommends Maximal Safe Resection in Glioblastoma Patients: A Nomogram for Clinical Decision Making and Reference for Non-Randomized Trials.

OBJECTIVE: The exact role of the extent of resection or residual tumor volume on overall survival in glioblastoma patients is still controversial. Our aim was to create a statistical model showing the association between resection extent/residual tumor volume and overall survival and to provide a nomogram that can assess the survival benefit of individual patients and serve as a reference for non-randomized studies. METHODS: In this retrospective multicenter cohort study, we used the non-parametric Cox regression and the parametric log-logistic accelerated failure time model in patients with glioblastoma. On 303 patients (training set), we developed a model to evaluate the effect of the extent of resection/residual tumor volume on overall survival and created a score to estimate individual overall survival. The stability of the model was validated by 20-fold cross-validation and predictive accuracy by an external cohort of 253 patients (validation set). RESULTS: We found a continuous relationship between extent of resection or residual tumor volume and overall survival. Our final accelerated failure time model (pseudo R2 = 0.423; C-index = 0.749) included residual tumor volume, age, O6-methylguanine-DNA-methyltransferase methylation, therapy modality, resectability, and ventricular wall infiltration as independent predictors of overall survival. Based on these factors, we developed a nomogram for assessing the survival of individual patients that showed a median absolute predictive error of 2.78 (mean: 1.83) months, an improvement of about 40% compared with the most promising established models. CONCLUSIONS: A continuous relationship between residual tumor volume and overall survival supports the concept of maximum safe resection. Due to the low absolute predictive error and the consideration of uneven distributions of covariates, this model is suitable for clinical decision making and helps to evaluate the results of non-randomized studies.