Medical Progress Research Articles

Abstract PO4-01-10: Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer

Abstract Background: Prognostic assessment in HR+ HER2- early breast cancer (EBC) remains challenging given relatively low rates of disease progression. Nuanced risk stratification is needed for decisions regarding systemic therapy. Modern artificial intelligence (AI)-based techniques have already provided substantial medical progress, particularly in prostate cancer. Here, we leverage multi-modal artificial intelligence (MMAI) trained using digital histopathology and clinical data to evaluate whether the MMAI technology can be expanded to other disease indications by applying the technology to the WSG PlanB and ADAPT trials in HR+ HER2- EBC. Methods: Pre-treatment breast biopsy and surgical hematoxylin and eosin (H&E) slides were digitized from the WSG PlanB and ADAPT trials for HR+ HER2- EBC patients receiving endocrine therapy +/- chemotherapy. Median follow-up in both trials exceeded 5 years. A multi-modal artificial intelligence architecture was developed and validated on predicting risk of distant recurrence (DR). Time-to-event endpoints were summarized using cumulative incidence curves. Univariable and multivariable Fine-Gray models were used to assess performance; hazard ratios were reported per standard deviation increase of the model score. Results: A total of 5539 patients from the two trials with H&E images and available follow-up data were used for development and validation of a multi-modal artificial intelligence architecture. The MMAI score derived using the training set was significantly associated with risk of DR in a validation cohort. To put the results into the clinical context in HR+ HER2- EBC, comprehensive validation analyses are currently ongoing and will be presented at the meeting. Conclusions: We have successfully developed a multiple-instances, learning-based deep neural network for outcome prediction using H&E-stained images. This study provides important evidence that MMAI technology can further personalize breast cancer management by adding standardizable information. Citation Format: Daniel Kates-Harbeck, Hans-Heinrich Kreipe, Oleg Gluz, Matthias Christgen, Sherko Kuemmel, Monika Graeser, Ulrike Nitz, Sven Mahner, Doris Mayr, Rachel Wuerstlein, Akinori Mitani, Jingbin Zhang, Hans Pinckaers, Yi Ren, Peter Wood, Jacqueline Griffin, Felix Feng, Andre Esteva, Jess Keim-Malpass, Ronald Kates, Nadia Harbeck. Multi-modal artificial intelligence models from baseline histopathology predict prognosis in HR+ HER2- early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-10.

Trace compounds in the urban water cycle in the Freiberg region, Germany

Trace compounds in the urban water cycle in the Freiberg region, Germany

Evaluation of drug related problems among hospitalised elderly patients at a secondary hospital in East Borneo

Background: The elderly population often requires increased drug intake (polypharmacy) due to diminished organ function, particularly in the liver and kidneys, responsible for processing medications. Identifying drug-related problems (DRPs) in this demographic is crucial for mitigating morbidity, mortality, and overall drug therapy costs. Objective: This study aimed to identify DRPs and their determinants in hospitalised geriatric patients. Methods: An observational retrospective study was conducted in the Secondary Hospital in East Borneo from January 2019 - December 2021. Data were collected from medication charts, including patients aged 60-79, medical progress notes, and laboratories. DRPs were identified and classified using Pharmaceutical Care Network Europe’s (PCNE) classification V9.0. Results: Of the 614 included patients, 79% were aged 60-69 years, 56.0% were male, and 73% were prescribed ≥ five medications. DRPs were identified in 75.2% of patients, primarily related to treatment effectiveness (27.19%) and treatment safety (53.42%). Causes included inappropriate monitoring (14.5%), improper drug combinations (51.79%), excessive drug dosage (16.61%), and inadequate drug dosage (13.51%). Conclusion: The high frequency of DRPs, specifically concerning treatment effectiveness and safety, highlights the need for enhanced monitoring and prescribing procedures, contributing to preventing and treating future DRPs in the elderly population.

Impossible Yet Possible—Orthotopic Liver Transplantation in a Patient With Complete Portal Vein Thrombosis: A Case Report and Literature Review

This case study presents a liver transplantation (LT) in a patient with incidentally, intraoperatively detected complete portal vein thrombosis (PVT), classified as YERDEL stage 4, challenging traditional surgical boundaries. The patient's resilience and the innovative approach adopted by the surgical team exemplify the evolving complexities of LT in the context of advanced PVT. This report underscores the significance of detailed case documentation in medical literature, especially for complex transplant scenarios. It contributes to a broader understanding of surgical techniques and patient-centered approaches in LT. The narrative highlights the dynamic interplay between surgical advancements and vascular complications, advocating for the refinement of surgical methods and a reevaluation of conventional perspectives in transplantation. This case is pivotal in illustrating medical progress and the persistent pursuit of better outcomes in complex transplant situations.

Assessment of postoperative morbidity in Spanish hospitals: Results from a national survey

BackgroundThe methodology used for recording, evaluating and reporting postoperative complications (PC) is unknown.The aim of the present study was to determine how PC are recorded, evaluated, and reported in General and Digestive Surgery Services (GDSS) in Spain, and to assess their stance on morbidity audits. MethodsUsing a cross-sectional study design, an anonymous survey of 50 questions was sent to all the heads of GDSS at hospitals in Spain. ResultsThe survey was answered by 67 out of 222 services (30.2%). These services have a reference population (RP) of 15 715 174 inhabitants, representing 33% of the Spanish population.Only 15 services reported being requested to supply data on morbidity by their hospital administrators. Eighteen GDSS, with a RP of 3 241 000 (20.6%) did not record PC. Among these, 7 were accredited for some area of training. Thirty-six GDSS (RP 8 753 174 (55.7%) did not provide details on all PC in patients’ discharge reports. Twenty-four (37%) of the 65 GDSS that had started using a new surgical procedure/technique had not recorded PC in any way. Sixty-five GDSS were not concerned by the prospect of their results being audited, and 65 thought that a more comprehensive knowledge of PC would help them improve their results. Out of the 37 GDSS that reported publishing their results, 27 had consulted only one source of information: medical progress records in 11 cases, and discharge reports in 9. ConclusionsThis study reflects serious deficiencies in the recording, evaluation and reporting of PC by GDSS in Spain.

An online survey on public awareness of drug clinical trials in inland cities of northern China.

The aims of this survey were to investigate the public awareness of drug clinical trials (DCTs) and willingness to participate the DCTs, and provide references for propaganda and science popularization of DCTs. A self-designed questionnaire named "an online survey questionnaire on public awareness of DCTs" was used to conduct an online survey from January to March 2022. The demographic characteristics and the response of participants to the awareness and willingness to participate the DCTs were collected. The factors affecting the public awareness of DCTs were analyzed by single factor and binary logistic regression analysis. One thousand three hundred eighty valid questionnaires were collected, and the respondents' awareness rate of DCTs was 61.1%. Thirteen demographic characteristics including age, gender, education, occupation, work fields, household type, marital status, city type, income, medical insurance, medical expenditure, pressure to seek medical care, financial pressure, both significantly affected the qualified rate of participants' awareness of DCTs (p < 0.001) by single factor analysis. Binary logistic regression analysis indicated that education level, work fields, city type, medical insurance, and medical expenditure affected independently the participants' awareness rate of DCTs (p < 0.001). 52.9% of the participants were willing to take part in DCTs. "to promote medical progress" (54.4%) or "believe doctors" (31.1%) were the most frequent reasons for subjects participating in DCTs. The public awareness rate of DCTs and the willingness to participate in drug clinical were significantly affected by the demographic characteristics of subjects. Thus, targeting the needs of the public, propaganda, and science popularization of DCTs should be carried out and served public health.

Speak up & reach out: In defense of biomedical research

Scientists face challenges in communicating about their careers in biomedical research to the public, despite the importance of doing so. Here, we discuss tools and resources for outreach, such as posters, videos, and presentations that can be leveraged by scientists to help educate communities about the pivotal role of animals in medical progress.

Surgical treatment of invasive fungal infection in pediatric oncology.

Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome. From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days. Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy.

Far Out: The Extended Denial of Public Access to Psychedelic Therapeutics

The United States patent regime is designed to promote dissemination of information that undergirds a particular innovation. To incentivize disclosure, inventors are granted a time-limited right to exclude others from practicing the invention, thereby affording the inventor a period in which to commercialize and financially benefit from their inventive contribution. The disclosure provides information sufficient for one of skill in the relevant art to make and use the invention, and the public may freely do so upon the patent’s expiry. Global advancement of human medicine is fundamentally intertwined with the United States patent system; medical progress largely depends upon the exclusionary protections United States patents confer. Ordinarily, the expiry of patents covering therapeutic products and methods yields substantial price reduction, as new market participants seek to establish market share by undercutting the expired patent holder and others. The patent system also yields to the public not only access to new and improved medical technology but also a delayed, unencumbered freedom to make and use the invention upon the patent’s exhaustion. Recently, psychoactive chemical compounds have garnered renewed and international attention. Although many psychedelic substances have had a long history of human use, including within therapeutic contexts, the Controlled Substances Act and related legislation significantly stifled research directed toward developing these substances for medical use. This “artificial” impediment to therapeutic innovation effectively delayed public access to the fruits of earlier innovation.

MRNA vaccination, a model of transition from basic biology to medicine

Sixty years elapsed between the discovery of messenger RNA (mRNA) and the use of this molecule in an unprecedented global vaccination campaign that brought the Covid-19 pandemic under control. Sixty years of doubts for some and certainties for others about the possibility of using mRNA-an example of synthetic biology-in therapeutic medicine and vaccinology. Years of "translational" research and development have culminated in the success of anti-Covid-19 mRNA vaccines and the promise of more to come against emerging pathogens. A new paradigm in vaccinology, enabling pandemics to be tackled as they emerge. A lesson to be learned: medical progress is less a question of time than of the critical nature of the biological discovery that underpins it. Before leaving us, François Gros, who played a key role in the discovery of mRNA, was able to appreciate the relevance of this obvious fact.

Does 'summative' count? The influence of the awarding of study credits on feedback use and test-taking motivation in medical progress testing.

Despite the increasing implementation of formative assessment in medical education, its' effect on learning behaviour remains questionable. This effect may depend on how students value formative, and summative assessments differently. Informed by Expectancy Value Theory, we compared test preparation, feedback use, and test-taking motivation of medical students who either took a purely formative progress test (formative PT-group) or a progress test that yielded study credits (summative PT-group). In a mixed-methods study design, we triangulated quantitative questionnaire data (n = 264), logging data of an online PT feedback system (n = 618), and qualitative interview data (n = 21) to compare feedback use, and test-taking motivation between the formative PT-group (n = 316), and the summative PT-group (n = 302). Self-reported, and actual feedback consultation was higher in the summative PT-group. Test preparation, and active feedback use were relatively low and similar in both groups. Both quantitative, and qualitative results showed that the motivation to prepare and consult feedback relates to how students value the assessment. In the interview data, a link could be made with goal orientation theory, as performance-oriented students perceived the formative PT as not important due to the lack of study credits. This led to low test-taking effort, and feedback consultation after the formative PT. In contrast, learning-oriented students valued the formative PT, and used it for self-study or self-assessment to gain feedback. Our results indicate that most students are less motivated to put effort in the test, and use feedback when there are no direct consequences. A supportive assessment environment that emphasizes recognition of the value of formative testing is required to motivate students to use feedback for learning.

Japanese guidelines for the treatment of idiopathic pulmonary fibrosis 2023:Revised edition

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease with a poor prognosis and an unknown cause that generally progresses to pulmonary fibrosis and leads to irreversible tissue alteration. The "Guidelines for the treatment of idiopathic pulmonary fibrosis 2017," specializing in the treatment of IPF for the first time in Japan and presenting evidence-based standard treatment methods suited to the state of affairs in Japan, was published in 2017, in line with the 2014 version of "Formulation procedure for Minds Clinical Practice Guidelines."Because new evidence had accumulated, we formulated the “Guidelines for the treatment of Idiopathic Pulmonary Fibrosis 2023 (revised 2nd edition).” While keeping the revision consistent with the ATS/ERS/JRS/ALAT IPF treatment guidelines, new clinical questions (CQs) on pulmonary hypertension were added to the chronic stage, in addition to acute exacerbation and comorbid lung cancer, which greatly affect the prognosis but are not described in the ATS/ERS/JRS/ALAT IPF guidelines. Regarding the advanced stages, we additionally created expert consensus-based advice for palliative care and lung transplantation. The number of CQs increased from 17 in the first edition to 24. It is important that these guidelines be used not only by respiratory specialists but also by general practitioners, patients, and their families; therefore, we plan to revise them appropriately in line with ever-advancing medical progress.

A Framework for Future Analysis of Ophthalmology Fellowships in Iran: Call for Action, Implications and Recommendations.

Ophthalmology fellowship is focusing on the educational advancement, medical research progress and academic productivity by transforming general ophthalmologists into superior clinical capacities in ophthalmology. There is a vast majority of ophthalmologists who wish to undertake fellowship degrees. The fellowship programs have several benefits for ophthalmologists and medical institutions. However, the expansion of ophthalmic fellowships has resulted in a greater number of ophthalmology visits, the possibility of unnecessary subspecialty eye examinations, induced demand and increasing eye-care costs. Moreover, sub-specialized ophthalmic services are not accessible to patients in remote regions. This can lead to a degree of inequity in the provision of healthcare services in the healthcare system. The massive expansion of fellowships in ophthalmology is revitalizing the necessity for evaluation of the need for post-residency education and providing effective planning for the future of the ophthalmic human-resource for eye health. This narrative review includes an integration and descriptive summary of the existing evidence on trends and different aspects that affect the future of ophthalmic fellowship education. Moreover, we pinpointed challenges such as maintaining standards in fellowship education, keeping an efficient production of graduates, and improving productivity in both patient care and education. We explored potential solutions to overcome these challenges. The 7-step framework for future analysis suggested here includes Determining educational needs and desired outcomes, Evaluating the current status of fellowship education, determining the gaps, and appropriate solutions, analyzing possible future trends and their impact on ophthalmology practice, investing in virtual educational technology, developing new educational horizons by foresight expert panels, and human-resource planning.

Understanding students' feedback use in medical progress testing: A qualitative interview study.

Active engagement with feedback is crucial for feedback to be effective and improve students' learning and achievement. Medical students are provided feedback on their development in the progress test (PT), which has been implemented in various medical curricula, although its format, integration and feedback differ across institutions. Existing research on engagement with feedback in the context of PT is not sufficient to make a definitive judgement on what works and which barriers exist. Therefore, we conducted an interview study to explore students' feedback use in medical progress testing. All Dutch medical students participate in a national, curriculum-independent PT four times a year. This mandatory test, composed of multiple-choice questions, provides students with written feedback on their scores. Furthermore, an answer key is available to review their answers. Semi-structured interviews were conducted with 21 preclinical and clinical medical students who participated in the PT. Template analysis was performed on the qualitative data using a priori themes based on previous research on feedback use. Template analysis revealed that students faced challenges in crucial internal psychological processes that impact feedback use, including 'awareness', 'cognizance', 'agency' and 'volition'. Factors such as stakes, available time, feedback timing and feedback presentation contributed to these difficulties, ultimately hindering feedback use. Notably, feedback engagement was higher during clinical rotations, and students were interested in the feedback when seeking insights into their performance level and career perspectives. Our study enhanced the understanding of students' feedback utilisation in medical progress testing by identifying key processes and factors that impact feedback use. By recognising and addressing barriers in feedback use, we can improve both student and teacher feedback literacy, thereby transforming the PT into a more valuable learning tool.

Focus on senescence: Clinical significance and practical applications.

The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well-being and minimizing the impact of aging-related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra- and inter-individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age-related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age-dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity-driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age-related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age-related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

Analysis of pharmaceutical interventions in chemotherapy prescriptions of adult and pediatric patients at an oncology reference institute.

Chemotherapy, one of the primary cancer treatments, has a high risk of causing significant harm in cases of its misuse. Pharmaceutical intervention is one of the strategies used to prevent medication errors from reaching the patient by identifying drug-related problems or other discrepancies related to patient data or medical progress. The primary objective of this study was to analyze the profile of the pharmaceutical intervention made in chemotherapy prescriptions for adult and pediatric patients in order to measure its impact on patient safety. A retrospective cross-sectional and observational study was conducted at a reference center for cancer treatment in Rio de Janeiro, Brazil. Pharmaceutical interventions performed in chemotherapy prescriptions from January to October 2022 were quantified, classified, and analyzed by their type, most common medicine, and acceptability. From the patients treated in the period, 220 (14.8%) adults and 64 (23.4%) children and teenagers received at least one pharmaceutical intervention. The most common types for adults were dose adjustments: overdose (22.5%) and underdose (22.5%). However, in pediatry, incompleteness of supporting drug protocol (22.1%) was the most registered. The most common medicines involved in pharmaceutical intervention were carboplatin (for adults) and electrolytes/hydration (for pediatric patients). Pharmaceutical intervention acceptability by prescriptors was very similar, reaching 80.4% for adults and 77.9% for pediatrics. The pharmaceutical intervention profile was quite distinct by virtue of the singularities of each population. The pharmacists' role was shown to be paramount in intercepting medication errors in the prescription of chemotherapy protocols, contributing to patient safety.

A dynamic fuzzy rule-based inference system using fuzzy inference with semantic reasoning

The challenge of making flexible, standard, and early medical diagnoses is significant. However, some limitations are not fully overcome. First, the diagnosis rules established by medical experts or learned from a trained dataset prove static and too general. It leads to decisions that lack adaptive flexibility when finding new circumstances. Secondly, medical terminological interoperability is highly critical. It increases realism and medical progress and avoids isolated systems and the difficulty of data exchange, analysis, and interpretation. Third, criteria for diagnosis are often heterogeneous and changeable. It includes symptoms, patient history, demographic, treatment, genetics, biochemistry, and imaging. Symptoms represent a high-impact indicator for early detection. It is important that we deal with these symptoms differently, which have a great relationship with semantics, vary widely, and have linguistic information. This negatively affects early diagnosis decision-making. Depending on the circumstances, the diagnosis is made solo on imaging and some medical tests. In this case, although the accuracy of the diagnosis is very high, can these decisions be considered an early diagnosis or prove the condition is deteriorating? Our contribution in this paper is to present a real medical diagnostic system based on semantics, fuzzy, and dynamic decision rules. We attempt to integrate ontology semantics reasoning and fuzzy inference. It promotes fuzzy reasoning and handles knowledge representation problems. In complications and symptoms, ontological semantic reasoning improves the process of evaluating rules in terms of interpretability, dynamism, and intelligence. A real-world case study, ADNI, is presented involving the field of Alzheimer’s disease (AD). The proposed system has indicated the possibility of the system to diagnose AD with an accuracy of 97.2%, 95.4%, 94.8%, 93.1%, and 96.3% for AD, LMCI, EMCI, SMC, and CN respectively.

Advancing Evidence-based Palliative Care Research: Navigating Challenges and Proposing Solutions.

Amid the increasing demand for palliative care, driven by demographic shifts and medical progress, evidence-based practices face obstacles due to limited research. Complex patient conditions and ethical considerations challenge traditional methodologies, while the absence of comprehensive clinical trials hinders innovative interventions. Empowering practitioners with research skills and establishing a palliative care research network are efforts aimed at bridging these gaps. It is important to emphasise that these initiatives collectively aspire to enhance evidence-based practices, ensuring quality care for individuals facing severe illnesses.

Device innovation in cardiovascular medicine: a report from the European Society of Cardiology Cardiovascular Round Table.

Research performed in Europe has driven cardiovascular device innovation. This includes, but is not limited to, percutaneous coronary intervention, cardiac imaging, transcatheter heart valve implantation, and device therapy of cardiac arrhythmias and heart failure. An important part of future medical progress involves the evolution of medical technology and the ongoing development of artificial intelligence and machine learning. There is a need to foster an environment conducive to medical technology development and validation so that Europe can continue to play a major role in device innovation while providing high standards of safety. This paper summarizes viewpoints on the topic of device innovation in cardiovascular medicine at the European Society of Cardiology Cardiovascular Round Table, a strategic forum for high-level dialogue to discuss issues related to the future of cardiovascular health in Europe. Devices are developed and improved through an iterative process throughout their lifecycle. Early feasibility studies demonstrate proof of concept and help to optimize the design of a device. If successful, this should ideally be followed by randomized clinical trials comparing novel devices vs. accepted standards of care when available and the collection of post-market real-world evidence through registries. Unfortunately, standardized procedures for feasibility studies across various device categories have not yet been implemented in Europe. Cardiovascular imaging can be used to diagnose and characterize patients for interventions to improve procedural results and to monitor devices long term after implantation. Randomized clinical trials often use cardiac imaging-based inclusion criteria, while less frequently trials randomize patients to compare the diagnostic or prognostic value of different modalities. Applications using machine learning are increasingly important, but specific regulatory standards and pathways remain in development in both Europe and the USA. Standards are also needed for smart devices and digital technologies that support device-driven biomonitoring. Changes in device regulation introduced by the European Union aim to improve clinical evidence, transparency, and safety, but they may impact the speed of innovation, access, and availability. Device development programmes including dialogue on unmet needs and advice on study designs must be driven by a community of physicians, trialists, patients, regulators, payers, and industry to ensure that patients have access to innovative care.

Ethical Principles in Plastic Surgery Research.

Research is an integral part of medical progress that leads to better understanding of disease processes and the development of therapies to improve patient care. The medical community has an obligation and societal responsibility to review its practices and advance its knowledge to optimize care for those who entrust it with their health and well-being. While ultimately intended to benefit patients specifically and society as a whole, every laboratory and clinical investigation inherently carries an element of uncertainty and has attendant risks. These can have unintended and, at times, harmful consequences that cannot justify the knowledge gained. In order to mitigate these risks and protect human subjects involved in clinical research studies, a basic framework of ethical principles has been developed to guide responsible experimental design, execution, and data dissemination. This article provides a review of these principles and the historical context from which they were derived and explores the persistent challenges and cognitive biases that can increase susceptibility to unethical research practices.