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Emerging digital technologies promise to improve breast cancer care, however lack of awareness among clinicians often prevents timely adoption. This study aims to investigate current awareness and intention-to-use of three technologies among breast cancer healthcare professionals (HCP): (1) digital health applications (DHA), (2) artificial intelligence (AI), and (3) blockchain technology (BC). A 22-item questionnaire was designed and administered before and after a 30 min educational presentation highlighting technology implementation examples. Technology awareness and intention-to-use were measured using 7-point Likert scales. Correlations between demographics, technology awareness, intention-to-use, and eHealth literacy (GR-eHEALS scale) were analyzed. 45 HCP completed the questionnaire, of whom 26 (57.8%) were female. Age ranged from 24 to 67 {mean age (SD): 44.93 ± 12.62}. Awareness was highest for DHA (68.9%) followed by AI (66.7%) and BC (24.4%). The presentation led to a non-significant increase of intention-to-use AI {5.37 (±1.81) to 5.83 (±1.64)}. HCPs´ intention-to-use BC after the presentation increased significantly {4.30 (±2.04) to 5.90 (±1.67), p  < 0.01}. Mean accumulated score for GR-eHEALS averaged 33.04 (± 6.61). HCPs´ intended use of AI significantly correlated with eHealth literacy (ρ = 0.383; p  < 0.01), intention-to-use BC (ρ = 0.591; p  < 0.01) and participants´ age (ρ = -0.438; p  < 0.01). This study demonstrates the effect that even a short practical presentation can have on HCPs´ intention-to-use emerging digital technologies. Training potential professional users should be addressed alongside the development of new information technologies and is crucial to increase HCPs´ corresponding awareness and intended use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Griewing, Knitza, Gremke, Wallwiener, Wagner, Lingenfelder and Kuhn.)

Background: Precision oncology treatments are being applied more commonly in breast and gynecological oncology through the implementation of Molecular Tumor Boards (MTBs), but real-world clinical outcome data remain limited. Methods: A retrospective analysis was conducted in patients with breast cancer (BC) and gynecological malignancies referred to our center's MTB from 2018 to 2023. The analysis covered patient characteristics, next-generation sequencing (NGS) results, MTB recommendations, therapy received, and clinical outcomes. Results: Sixty-three patients (77.8%) had metastatic disease, and forty-four patients (54.3%) had previously undergone three or more lines of systemic treatment. Personalized treatment recommendations were provided to 50 patients (63.3%), while 29 (36.7%) had no actionable target. Ultimately, 23 patients (29.1%) underwent molecular-matched treatment (MMT). Commonly altered genes in patients with pan-gyn tumors (BC and gynecological malignancies) included TP53 ( n = 42/81, 51.9%), PIK3CA ( n = 18/81, 22.2%), BRCA1/2 ( n = 10/81, 12.3%), and ARID1A ( n = 9/81, 11.1%). Patients treated with MMT showed significantly prolonged progression-free survival (median PFS 5.5 vs. 3.5 months, p = 0.0014). Of all patients who underwent molecular profiling, 13.6% experienced a major clinical benefit (PFSr ≥ 1.3 and PR/SD ≥ 6 months) through precision oncology. Conclusions: NGS-guided precision oncology demonstrated improved clinical outcomes in a subgroup of patients with gynecological and breast cancers.

With the recent diffusion of access to publicly available large language models (LLMs), common interest in generative artificial-intelligence-based applications for medical purposes has skyrocketed. The increased use of these models by tech-savvy patients for personal health issues calls for a scientific evaluation of whether LLMs provide a satisfactory level of accuracy for treatment decisions. This observational study compares the concordance of treatment recommendations from the popular LLM ChatGPT 3.5 with those of a multidisciplinary tumor board for breast cancer (MTB). The study design builds on previous findings by combining an extended input model with patient profiles reflecting patho- and immunomorphological diversity of primary breast cancer, including primary metastasis and precancerous tumor stages. Overall concordance between the LLM and MTB is reached for half of the patient profiles, including precancerous lesions. In the assessment of invasive breast cancer profiles, the concordance amounts to 58.8%. Nevertheless, as the LLM makes considerably fraudulent decisions at times, we do not identify the current development status of publicly available LLMs to be adequate as a support tool for tumor boards. Gynecological oncologists should familiarize themselves with the capabilities of LLMs in order to understand and utilize their potential while keeping in mind potential risks and limitations.

Sequential socioeconomic shocks, including the COVID-19 pandemic, economic recession, or energy and refugee crises in the face of violent conflicts, have led to the failure of healthcare systems in Europe. Against this background, the aim of this study was to evaluate the resilience of regional gynecological and obstetric inpatient care using the example of a regional core medical provider in central Germany. Base data were retrieved from Marburg University Hospital and underwent standardized calculation and descriptive statistical assessment pursuant to the aG-DRG catalog. The data illustrate a decline in the average length of patient stays and average case complexity in combination with increasing patient turnover for the six-year observation period of 2017-2022. Core profitability of the departments of gynecology and obstetrics deteriorated in the year of 2022. The results suggest weakened resilience of gynecological and obstetrics inpatient care in the setting of a regional core medical provider in central Germany and indicate how it may have failed in core economic profitability. This is consistent with predictions about the lack of resilience of health systems and the critical economic situation of German hospitals in the face of ongoing socioeconomic shocks that collaterally endanger women's health care., Competing Interests: The authors declare that they have no conflict of interest.

Background: The aim of this retrospective cohort study was to measure the proportion of women with an initial prescription of an antiresorptive drug (bisphosphonates or denosumab) during five years of endocrine breast cancer therapy., Methods: The study included women with an initial prescription of tamoxifen (TAM) or aromatase inhibitors (AIs) between January 2016 and December 2020. Kaplan-Meier analyses were performed to show the cumulative incidence of antiresorptive drug prescription for TAM and AIs separately for four age groups. A univariable Cox proportional hazards regression model was also used to estimate the relationship between initial endocrine drug (AIs vs. TAM) and antiresorptive drug prescription., Results: Within 5 years, 14.1% of patients on AI and 6.1% on TAM received their first prescription for an antiresorptive drug ( p < 0.001). The difference between AI and TAM was greatest in women ≤50 years (12.9% of AI and 2.8% of patients on TAM), and smallest in women >80 years (14.5% of AI and 10.3% of patients on TAM). The proportion of denosumab was 46.2% among AI patients vs. 29.1% among patients on TAM ( p < 0.001) as alendronate was prescribed to 36.9% of AI vs. 50.0% of patients on TAM., Conclusions: Across all age groups, the cumulative incidence of antiresorptive drug prescriptions was higher in patients with BC treated with AI than those receiving TAM. Denosumab was most frequently used as an antiresorptive drug in patients treated with AI, while alendronate was administered more often in patients treated with TAM.

Background: The occurrence of autonomic dysfunctions (e.g., urological dysfunctions) is a common phenomenon during the course of Parkinson's disease (PD) and resulting complications such as lower urinary tract infections (LUTI) are one of the leading causes of hospitalizations and mortality in patients with the condition. Therefore, the aim of this retrospective cohort study was to compare the most common levodopa-based treatment regimens (DOPA decarboxylase inhibitor (DCI) + carbidopa or benserazide) and to analyze the incidence of LUTI and antibiotic prescriptions in patients receiving the respective treatments., Methods: This study was based on data from the Disease Analyzer database (IQVIA) and included adult patients (≥18 years) with an initial prescription of levodopa therapy including fixed-dose levodopa/DCI combinations in 1284 general practices in Germany between January 2010 and December 2020. Conditional Cox regression models were used to analyze the association between levodopa/DCI combinations and LUTI incidence and antibiotic prescriptions., Results: Compared to levodopa + carbidopa, levodopa + benserazide therapy was significantly and negatively associated with LUTI (HR: 0.82; 95% CI: 0.71-0.95). This association was stronger in women (HR: 0.77; 95% CI: 0.65-0.92) than in men (HR: 0.93, not significant)., Conclusions: Especially in women, receiving levodopa + benserazide prescriptions was associated with a lower LUTI incidence. It is important for clinicians to keep this in mind, since LUTI is a leading cause of hospitalizations, morbidity, and mortality in patients with PD.

The study pursues the objective of drawing a comparison between the data of gyne-oncology, gynecology, and obstetrics patient collectives of a German university hospital regarding the progression of patient number and corresponding treatment data during the five-year period of 2017-2021 to assess the impact of the COVID-19 pandemic on gyne-oncological treatment. Descriptive assessment is based on data extracted from the database of the hospital controlling system QlikView ® for patients hospitalized at the Department of Gynecology and Obstetrics of Marburg University Hospital. Gynecology and gyne-oncology experience a maintained decline in patient number (n Gynecology : -6% 2019 to 2020, -5% 2019 to 2021; n Gyne-Oncology : -6% 2019 to 2020, -2% 2019 to 2021) with varying effects on the specific gyne-oncological main diagnoses. Treatment parameters remain unchanged in relative assessment, but as gyne-oncology constitutes the dominating revenue contributor in gynecology (35.1% of patients, 52.9% of revenue, 2021), the extent of the decrease in total revenue (-18%, 2019 to 2020, -14%, 2019 to 2021) surpasses the decline in patient number. The study displays a negative impact on the gynecology care situation of a German university hospital for the entire pandemic, with an even greater extent on gyne-oncology. This development not only endangers the quality of medical service provision but collaterally pressurizes gynecology service providers.

Background: Antihypertensive pharmacological therapy includes diuretics, beta-blockers, ACE inhibitors, calcium channel blockers and angiotensin II receptor blockers. Besides their use in arterial hypertension, these drugs also play a major role in the therapy of portal hypertension, heart failure and coronary artery disease. Systematic analyses on the possible influence of these medications on cancer incidence are lacking. Methods: By utilizing the Disease Analyzer database (IQVIA), 349,210 patients with antihypertensive drug prescriptions between 2010 and 2020 without a diagnosis of cancer prior to or at the date of initial drug prescription were included. Propensity score matching was carried out by 1:1:1:1:1 according to the five antihypertensive treatments. Cox regression analyses were performed to investigate an association between antihypertensive drugs and the incidence of cancer. Results: Patients who were diagnosed with cancer were treated with diuretics in 19.9% of cases, calcium channel blockers in 16.9% of cases, and angiotensin II receptor blockers, ACE inhibitors, or beta-blockers in 13.9%, 13.2% and 12.8% of cases, respectively. Cox regression models revealed that diuretic use positively correlated with liver cancer incidence (HR: 1.31, 95%CI: 1.12-2.63) and lymphoid/haematopoietic tissue cancer incidence (HR: 1.27, 95%CI: 1.10-1.46). Use of diuretics negatively correlated with the incidence of prostate (HR: 0.64, 95%CI: 0.53-0.78) and skin cancer (HR: 0.81, 95%CI: 0.72-0.92). Finally, a positive association was found between angiotensin II receptor inhibitors and prostate cancer incidence (HR: 1.50, 95%CI: 1.28-1.65). Conclusions: These data suggest that diuretic use might be associated with liver cancer and lymphoid/haematopoetic tissue cancer development.

This study aims at evaluating the use case potential of breast cancer care for artificial intelligence and blockchain technology application based on the patient data analysis at Marburg University Hospital and, thereupon, developing a digital workflow for breast cancer care. It is based on a retrospective descriptive data analysis of all in-patient breast and ovarian cancer patients admitted at the Department of Gynecology of Marburg University Hospital within the five-year observation period of 2017 to 2021. According to the German breast cancer guideline, the care workflow was visualized and, thereon, the digital concept was developed, premised on the literature foundation provided by a Boolean combination open search. Breast cancer cases display a lower average patient case complexity, fewer secondary diagnoses, and performed procedures than ovarian cancer. Moreover, 96% of all breast cancer patients originate from a city with direct geographical proximity. Estimated circumference and total catchment area of ovarian present 28.6% and 40% larger, respectively, than for breast cancer. The data support invasive breast cancer as a preferred use case for digitization. The digital workflow based on combined application of artificial intelligence as well as blockchain or distributed ledger technology demonstrates potential in tackling senological care pain points and leveraging patient data safety and sovereignty., Competing Interests: The authors declare that they have no conflict of interest.

Purpose: the aim of this cross-sectional study was to analyze the impact of the COVID-19 pandemic on Cervical Cancer Screening (CCS) in gynecological practices in Germany. Methods: The basis of the analysis was the Uniform Evaluation Standard (EBM) of the Statutory Health Insurance Scheme. This cross-sectional study included all women aged ≥20 years with at least one CCS (clinical and cytological examination) in 223 gynecological practices in Germany during the period 2018−2021. The number of patients with CCS per practice was shown for each year. The average number of patients per year was compared between the pre-pandemic time period (2018, 2019) and the pandemic time period (2020, 2021) using Wilcoxon tests. Analyses were conducted separately for clinical investigations and cytological investigations and were also stratified by age group (20−34, 35−50, >50 years). Results: CCS in gynecological practices significantly decreased in Germany between the pre-pandemic time period of 2018−2019 and the pandemic years of 2020−2021. This decrease was observed in all age groups but was stronger in women aged 20−34 (−25.6%) and weaker in women aged >50 (−15.2%). Conclusions: We found a statistically and clinically relevant decrease of patients receiving CCS in gynecological practices in Germany. This finding is even more exceptional because the new screening algorithm with direct invitations for each patient started in 2020 and was supposed to lead to a higher number of patients in its first years. However, the observed decline in the detection of cervical precancer lesions may lead to increased cervical cancer burden. Risk-based screening strategies and further measures are necessary to adapt to the ongoing COVID-19 pandemic and return to pre-pandemic CCS numbers.

This study aims at examining the chronological development of hospitalized cardiovascular and COVID-19 patients and comparing the effects on related sub-disciplines and main diagnoses for pre-pandemic (2017-2019) and pandemic (2020-2021) years in the setting of a German university maximum care provider. Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with main diagnosis of diseases of the circulatory system (n Circulatory ) and COVID-19 secondary diagnosis (n COVID-19 ). The cardiovascular patient collective (n Circulatory = 25,157) depicts a steady state in terms of relative yearly development of patient numbers (+0.4%, 2019-2020, +0.1%, 2020-2021). Chronological assessment points towards monthly decline during lockdowns and phases of high regional incidence of COVID-19 (i.e., 2019-2020: March -10.2%, April -12.4%, December -14.8%). Main diagnoses of congestive heart failure (+16.1% 2019/2020; +19.2% 2019/2021) and acute myocardial infarction show an increase in case numbers over the course of the whole pandemic (+15.4% 2019/2020; +9.4% 2019/2021). The results confirm negative effects on the cardiovascular care situation during the entire pandemic in the setting of a university maximum care provider. A general increase in cardiac disorders and a worrisome turn in case development of acute myocardial infarction emphasize the feared cardiovascular burden of COVID-19.

Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept., Methods: We retrospectively analyzed all patients referred to our center's Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel's target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS., Results: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy ( n = 30) had significantly longer progression-free survival than patients treated with other therapies ( n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits., Conclusion: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.

Tissue-resident immune cells have been shown to play an important role in skin health and disease. However, owing to limited access to human skin samples and time-consuming, technically demanding protocols, the characterization of tissue-derived cells remains challenging. For this reason, blood-derived leukocytes are frequently used as a surrogate specimen, although they do not necessarily reflect local immune responses in the skin. Therefore, we aimed to establish a rapid protocol to isolate a sufficient number of viable immune cells from 4-mm skin biopsies that can be directly used for a deeper characterization such as comprehensive phenotyping and functional studies of T cells. In this optimized protocol, only two enzymes, type IV collagenase and DNase I, were used to achieve both the highest possible cellular yield and marker preservation of leukocytes stained for multicolor flow cytometry. We further report that the optimized protocol may be used in the same manner for murine skin and mucosa. In summary, this study allows a rapid acquisition of lymphocytes from human or mouse skin suitable for comprehensive analysis of lymphocyte subpopulations, for disease surveillance, and for identification of potential therapeutic targets or other downstream applications., (© 2022 The Authors.)

Autophagy allows cells to temporarily tolerate energy stress by replenishing critical metabolites through self-digestion, thereby attenuating the cytotoxic effects of anticancer drugs that target tumor metabolism. Autophagy defects could therefore mark a metabolically vulnerable cancer state and open a therapeutic window. While mutations of autophagy genes (ATGs) are notably rare in cancer, haploinsufficiency network analyses across many cancers have shown that the autophagy pathway is frequently hit by somatic copy number losses of ATGs such as MAP1LC3B/ATG8F ( LC3 ), BECN1/ATG6 (Beclin-1), and ATG10 . Here, we used CRISPR/Cas9 technology to delete increasing numbers of copies of one or more of these ATGs in non-small cell lung cancer cells and examined the effects on sensitivity to compounds targeting aerobic glycolysis, a hallmark of cancer metabolism. Whereas the complete knockout of one ATG blocked autophagy and led to profound metabolic vulnerability, this was not the case for combinations of different nonhomozygous deletions. In cancer patients, the effect of ATG copy number loss was blunted at the protein level and did not lead to the accumulation of p62 as a sign of reduced autophagic flux. Thus, the autophagy pathway is shown to be markedly robust and resilient, even with the concomitant copy number loss of key autophagy genes.

Cancer cells have a characteristic metabolism, mostly caused by alterations in signal transduction networks rather than mutations in metabolic enzymes. For metabolic drugs to be cancer-selective, signaling alterations need to be identified that confer a druggable vulnerability. Here, we demonstrate that many tumor cells with an acquired cancer drug resistance exhibit increased sensitivity to mechanistically distinct inhibitors of cancer metabolism. We demonstrate that this metabolic vulnerability is driven by mTORC1, which promotes resistance to chemotherapy and targeted cancer drugs, but simultaneously suppresses autophagy. We show that autophagy is essential for tumor cells to cope with therapeutic perturbation of metabolism and that mTORC1-mediated suppression of autophagy is required and sufficient for generating a metabolic vulnerability leading to energy crisis and apoptosis. Our study links mTOR-induced cancer drug resistance to autophagy defects as a cause of a metabolic liability and opens a therapeutic window for the treatment of otherwise therapy-refractory tumor patients.

TP63, a member of the p53 gene family gene, encodes the ΔNp63 protein and is one of the most frequently amplified genes in squamous cell carcinomas (SCC) of the head and neck (HNSCC) and lungs (LUSC). Using an epiallelic series of siRNAs with intrinsically different knockdown abilities, we show that the complete loss of ΔNp63 strongly impaired cell proliferation, whereas partial ΔNp63 depletion rendered cells hypersensitive to cisplatin accompanied by an accumulation of DNA damage. Expression profiling revealed wide-spread transcriptional regulation of DNA repair genes and in particular Fanconi anemia (FA) pathway components such as FANCD2 and RAD18 - known to be crucial for the repair of cisplatin-induced interstrand crosslinks. In SCC patients ΔNp63 levels significantly correlate with FANCD2 and RAD18 expression confirming ΔNp63 as a key activator of the FA pathway in vivo Mechanistically, ΔNp63 bound an upstream enhancer of FANCD2 inactive in primary keratinocytes but aberrantly activated by ΔNp63 in SCC. Consistently, depletion of FANCD2 sensitized to cisplatin similar to depletion of ΔNp63. Together, our results demonstrate that ΔNp63 directly activates the FA pathway in SCC and limits the efficacy of cisplatin treatment. Targeting ΔNp63 therefore would not only inhibit SCC proliferation but also sensitize tumors to chemotherapy., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)