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Purpose: Large language models (LLM) show potential for decision support in breast cancer care. Their use in clinical care is currently prohibited by lack of control over sources used for decision-making, explainability of the decision-making process and health data security issues. Recent development of Small Language Models (SLM) is discussed to address these challenges. This preclinical proof-of-concept study tailors an open-source SLM to the German breast cancer guideline (BC-SLM) to evaluate initial clinical accuracy and technical functionality in a preclinical simulation., Methods: A multidisciplinary tumor board (MTB) is used as the gold-standard to assess the initial clinical accuracy in terms of concordance of the BC-SLM with MTB and comparing it to two publicly available LLM, ChatGPT3.5 and 4. The study includes 20 fictional patient profiles and recommendations for 5 treatment modalities, resulting in 100 binary treatment recommendations (recommended or not recommended). Statistical evaluation includes concordance with MTB in % including Cohen's Kappa statistic (κ). Technical functionality is assessed qualitatively in terms of local hosting, adherence to the guideline and information retrieval., Results: The overall concordance amounts to 86% for BC-SLM (κ = 0.721, p < 0.001), 90% for ChatGPT4 (κ = 0.820, p < 0.001) and 83% for ChatGPT3.5 (κ = 0.661, p < 0.001). Specific concordance for each treatment modality ranges from 65 to 100% for BC-SLM, 85-100% for ChatGPT4, and 55-95% for ChatGPT3.5. The BC-SLM is locally functional, adheres to the standards of the German breast cancer guideline and provides referenced sections for its decision-making., Conclusion: The tailored BC-SLM shows initial clinical accuracy and technical functionality, with concordance to the MTB that is comparable to publicly-available LLMs like ChatGPT4 and 3.5. This serves as a proof-of-concept for adapting a SLM to an oncological disease and its guideline to address prevailing issues with LLM by ensuring decision transparency, explainability, source control, and data security, which represents a necessary step towards clinical validation and safe use of language models in clinical oncology., (© 2024. The Author(s).)

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.

Purpose: Given the relatively high incidence of both endometriosis and breast cancer, investigating the potential connection between these gynecological diseases is of substantial clinical significance. However, there is no clear consensus in the literature on the extent to which the risk of breast cancer is increased in patients with endometriosis. Therefore, we conducted a large-scale observational study investigating the association between endometriosis and breast cancer risk., Methods: This study included women aged ≥ 18 years with an initial endometriosis diagnosis from one of 315 office-based gynecologists in Germany between January 2005 and December 2021. Non-endometriosis patients were matched 1:1 to patients with endometriosis based on age, index year, average yearly consultation frequency, and predefined co-diagnoses within 12 months before or on the index date, including obesity and benign breast disorders. The association between endometriosis and the 10-year incidence of breast cancer was studied using Kaplan-Meier curves and log-rank tests. Finally, a univariable Cox regression analysis was conducted to assess the association between endometriosis and breast cancer., Results: Over a follow-up period of up to 10 years, no significant difference was observed between the endometriosis (2.4%) and the matched non-endometriosis group (2.5%) with regard to breast cancer diagnoses. Furthermore, the regression analysis revealed no significant association between endometriosis and subsequent breast cancer., Conclusion: In summary, our comprehensive 10-year study involving a substantial sample of women indicates that endometriosis is not significantly associated with an increased risk of subsequent breast cancer., (© 2023. The Author(s).)

Purpose: The aim of this study was to identify the mean age at which breast cancer (BC) was first diagnosed in 2010 or 2022, and to evaluate whether there were any changes in age groups at first BC diagnosis., Methods: This retrospective cross-sectional study included adult women (18 years or older) who were diagnosed with BC (ICD-10: C50) for the first time in 2010 or 2022 in office-based practices in Germany (in 300 general practices or 95 gynecological practices). We examined the mean age at diagnosis and the percentage of patients in three age groups (18-49, 50-65, and > 65) for both 2010 and 2022. The average age difference between 2010 and 2022 was analyzed using Wilcoxon rank tests, and the proportions of the three age groups were analyzed using chi-squared tests. These analyses were performed separately for patients in general and gynecological practices., Results: The mean age at which BC was initially diagnosed in 2022 was found to be significantly greater than that in 2010 for both general practices (66.9 years vs. 64.0 years p < 0.001) and gynecological practices (62.2 years vs. 60.3 years, p < 0.001). Early-onset BC decreased from 15.6 to 12.0% in general practices and from 23.2 to 18.2% in gynecological practices between 2010 and 2022. The proportion of new BC diagnoses in the age group 50-65 increased from 36.6 to 40.9% in gynecological practices, but did not increase in general practices., Conclusion: The study found that BC was diagnosed at an older age in 2022 than in 2010. In addition, the proportion of early-onset BC cases decreased, while the proportion of cases in the age group 50-65 increased in gynecological practices in Germany., (© 2023. The Author(s).)

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.

Purpose: This study investigates the impact of the COVID-19 pandemic on breast cancer (BC) care, analyzing treatment delays and factors associated with them., Methods: This retrospective cross-sectional study analyzed data from the Oncology Dynamics (OD) database. Surveys of 26,933 women with BC performed between January 2021 and December 2022 in Germany, France, Italy, the United Kingdom, and Spain were examined. The study focused on determining the prevalence of treatment delays due to the COVID-19 pandemic, considering factors such as country, age group, treating facility, hormone receptor status, tumor stage, site of metastases, and Eastern Cooperative Oncology Group (ECOG) status. Baseline and clinical characteristics were compared for patients with and without therapy delay using chi-squared tests, and a multivariable logistic regression analysis was conducted to explore the association between demographic and clinical variables and therapy delay., Results: The present study found that most therapy delays lasted less than 3 months (2.4%). Factors associated with higher risk of delay included being bedridden (OR 3.62; 95% CI 2.51-5.21), receiving neoadjuvant therapy (OR 1.79; 95% CI 1.43-2.24) compared to adjuvant therapy, being treated in Italy (OR 1.58; 95% CI 1.17-2.15) compared to Germany or treatment in general hospitals and non-academic cancer facilities (OR 1.66, 95% CI 1.13-2.44 and OR 1.54; 95% CI 1.14-2.09, respectively) compared to treatment by office-based physicians., Conclusion: Addressing factors associated with therapy delays, such as patient performance status, treatment settings, and geographic location, can help guide strategies for improved BC care delivery in the future., (© 2023. The Author(s).)

Purpose: The aim of the study was to evaluate the baseline data of women with breast cancer (BC) undergoing treatment in an intercontinental comparison., Methods: This study included 99,571 women with BC from Europe (70,834), Asia (18,208), and Latin America (10,529) enrolled between 2017 and 2021, based on data from IQVIA's Oncology Dynamics database. This source is supplied with information by means of a cross-sectional partially retrospective survey collecting anonymized data on inpatients and outpatients treated by a representative panel of oncologists. A multivariable logistic regression model was used to investigate the probability of metastases., Results: The data available in Asia (98%) and Latin America (100%) were hospital data, while in Europe, patients were treated both in hospitals and in office-based practices (62%, 38%). The mean age in Asia and Latin America (57 ± 13) was lower than in Europe (61 ± 13; p < 0.001). Lobular BC was diagnosed twice as often in Europe compared to Asia and Latin America (15.2%, 9.8%, 8.0%). The number of patients with metastasized hormone receptor-positive (HR +) BC was significantly higher in Europe and Latin America than in Asia (76%, 68%; p < 0.001). The highest number of women with metastasized BC was reported in Europe (26% compared to 14% and 20%, respectively, in Asia and Latin America). Across the continents, the percentage of women with BC who experienced metastases was 51-61% for bone, 30-39% for lung and 25-32% for liver, followed by 3-6% for skin and 3% for brain., Conclusion: Women with BC treated in Europe tend to be significantly older and more likely to develop metastases than women in Asia and Latin America, except for lung metastases., (© 2023. The Author(s).)

Purpose: The aim of this study was to analyze the persistence of women on tamoxifen (TAM) and aromatase inhibitors (AIs) in Germany, and to investigate possible determinants of non-persistence., Methods: The present retrospective cohort study was based on the IQVIA longitudinal prescription database (LRx). The study included women with an initial prescription of TAM or AIs (anastrozole, letrozole, and exemestane) between January 2016 and December 2020 (index date). Kaplan-Meier analyses were performed to show the persistence for TAM and AI, using a therapy gap of 90 or 180 days, respectively. A multivariable Cox proportional hazards regression model was further used to estimate the relationship between non-persistence and drug prescription (AI versus TAM), age, and the specialty of the physician initiating therapy (gynecologist, oncologist, or general practitioner)., Results: Up to 5 years after the index date, only 35.1% of AI and 32.5% of TAM patients were continuing therapy when therapy discontinuation was defined as at least 90 days without therapy. Using a 180-day therapy gap, 51.9% of AI and 50.4% of TAM patients remained on therapy after 5 years. Cox regression models reveal that initial therapy with TAM (HR 1.06, 95% CI 1.04-1.07), therapy initiation by oncologists (HR 1.09, 95% CI 1.07-1.11), or general practitioners (HR 1.24, 95% CI 1.21-1.27) and age ≤ 50 (HR 1.08, 95% CI 1.06-1.10) were significantly associated with an increased risk of therapy discontinuation., Conclusion: Overall, the present study indicates that persistence rates are low in all age groups for both TAM and AI treatment. We found several factors (e.g., physician specialty, younger age, and type of endocrine therapy) to be associated with an increased risk for non-persistence., (© 2022. The Author(s).)

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.

Purpose: The aim of this retrospective cohort study was to analyze the cumulative incidence of breast cancer following gout and to investigate the association between gout and subsequent breast cancer in 67,598 primary care patients in Germany., Methods: This study included adult female patients (≥ 18 years) with an initial diagnosis of gout in 1284 general practices in Germany between January 2005 and December 2020. Individuals without gout were matched to gout patients using propensity score matching based on average yearly consultation frequency during the follow-up period, diabetes, obesity, chronic bronchitis/COPD diagnoses, and diuretic therapy. The 10-year cumulative incidence of breast cancer in the cohorts with and without gout was also studied using Kaplan-Meier curves, which were then compared using the log-rank test. Finally, a univariable Cox regression analysis was conducted to assess the association between gout and breast cancer., Results: After up to 10 years of follow-up, 4.5% of gout and 3.7% of non-gout patients were diagnosed with breast cancer. A Cox regression analysis revealed a significant association between gout and subsequent breast cancer in the total population (HR: 1.17; 95% CI: 1.05-1.31). In the age-stratified analyses, gout was only strongly associated with subsequent breast cancer in the age group ≤ 50 (HR: 1.58; 95% CI: 1.10-2.27), but the association was not significant in women over 50 years old., Conclusion: Taken together, the findings of our study provide evidence for the association between gout and subsequent breast cancer diagnosis, particularly in the youngest age group., (© 2023. The Author(s).)

Purpose: Preliminary data suggest that women with breast cancer are at particularly high risk of adhesive capsulitis of the shoulder. Therefore, this study aimed to investigate the potential association between breast cancer and adhesive capsulitis in adults from Germany., Methods: This retrospective cohort study included all women aged ≥ 18 years who were diagnosed for the first time with breast cancer in one of 1,274 general practices in Germany between January 2000 and December 2018 (index date). Women without breast cancer were matched (1:1) to those with breast cancer using a propensity score based on age at the index date, index year, and the average number of medical consultations per year during the follow-up. In women without breast cancer, the index date was a randomly selected visit date between 2000 and 2018. The association between breast cancer and the 10-year incidence of adhesive capsulitis was studied using Kaplan-Meier curves and a Cox regression model adjusted for age and several comorbidities., Results: There were 52,524 women included in this study (mean [SD] age 64.2 [12.9] years). The 10-year incidence of adhesive capsulitis was 3.6% in both the group with and the group without breast cancer (log-rank p-value = 0.317). The Cox regression analysis further showed no significant association between breast cancer and adhesive capsulitis (HR = 0.96, 95% CI = 0.86-1.08)., Conclusion: In this sample of women from Germany, breast cancer was not significantly associated with adhesive capsulitis. Although the present preliminary findings are reassuring, general practitioners should regularly assess shoulder function in breast cancer survivors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this retrospective study was to investigate the impact of a broad spectrum of antihypertensive (AH) medications on urinary tract infections (UTI) of outpatients diagnosed in general practices in Germany., Methods: This study included a total of 367,960 patients aged ≥ 18 years newly a diagnosed with UTI in 1274 general practices in Germany between January 2010 and December 2019. The analysis was conducted for five groups representing five AH therapy classes (diuretics (DIU); beta blockers (BB); calcium channel blockers (CCB); ACE inhibitors (ACEi); angiotensin II receptor blockers (ARB)), each containing 73,592 patients. A Cox regression model was used to analyze the association between each antihypertensive drug class and UTI incidence as compared to all other antihypertensive drug classes (as a group)., Results: The incidence of UTI diagnosis was slightly higher in patients treated with DIU (8.6%), followed by ACEi (8.1%), ARB (7.9%), and CCB (6.5%). Antibiotic therapy for UTI was given in 5.6% of DIU and 4.3% of CCB patients. The incidence of UTI and antibiotic therapy was much higher in women than in men across all therapy classes. No significant increase or decrease in UTI incidence or antibiotic therapy was observed in any of the AH therapy classes investigated., Conclusion: The present study did not identify a significant increase or decrease of UTI incidence or antibiotic therapy in patients treated with ACEi, ACB, CCB, beta blockers or diuretics. Across all AH classes studied, the incidence of UTI and antibiotic therapy was higher in women than in men, although not significantly., (© 2022. The Author(s).)

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.

In breast cancer, the current guideline for pathological workup includes recommendations for advanced molecular analysis of certain predictive molecular markers in addition to basic immunohistochemical diagnostics. These markers are determined depending on tumor stage, including sequencing techniques and immunohistochemical methods. This comprises the systematic investigation of molecular alterations such as PIK3CA or BRCA1,2 mutations, NTRK fusions, or microsatellite instability as a basis for targeted therapy. Further alterations, for example in the PI3K pathway, ESR1 alterations, or ERBB2 mutations, may also be relevant for individual therapy decisions especially in the context of resistant or relapsed disease. Thus, particularly in advanced stages, a more comprehensive molecular characterization of the tumor may reveal genetic alterations that act as tumor drivers and provide targets for personalized therapies. Due to the large number of potential molecular targets, NGS panel diagnostics are a suitable approach in this conjunction with immunohistochemical characterization and the individual clinical situation. Molecular based therapeutical strategies outside of entity-specific approvals should be discussed in an interdisciplinary team within the framework of a molecular tumor board., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

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.

Purpose: The aim of this study was to analyze the prevalence of breast cancer in relation to body height and to investigate associations between body height and breast cancer in Germany., Methods: This retrospective cohort study included 135,741 adult women followed in one of 161 gynecology practices in Germany between January 2019 and December 2021. The 3 year prevalence of breast cancer (ICD-10: C50) during the study period was shown in relation to body height, which was included in this study as a five-category variable for women: ≤ 160 cm, 161-165 cm, 166-170 cm, 171-175 cm, > 175 cm. The associations between height and breast cancer were analyzed using logistic regression models adjusted for age and BMI., Results: The prevalence of breast cancer increased from 5.1% in women ≤ 160 cm to 6.8% in women > 175 cm in the age group 51-60, and from 9.2% in women ≤ 160 cm to 12.2% in women 171-175 cm in the age group > 60 years. The OR for breast cancer was 1.18 (95% CI 1.12-1.24) for every 10 cm increase in height. Compared to height ≤ 160 cm, the OR for height 166-170 cm was 1.26 (1.15-1.39), for 171-175 cm 1.43 (1.27-1.61), and for > 175 cm 1.49 (1.28-1.74)., Conclusion: The results of this study suggest that greater body height in women is significantly related to an increased breast cancer risk., (© 2022. The Author(s).)

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.

Purpose: The aim of this retrospective study was to analyze the incidence of lower urinary tract infections (LUTI) and antibiotic prescriptions within 12 months after initial prescription of anti-seizure medication (ASM) between January and December 2020 (index date) and to investigate the association between a broad spectrum of ASMs and the risk of LUTI in patients with epilepsy., Methods: This retrospective cohort study included a total of 9186 adult patients (≥18 years) with an initial diagnosis of epilepsy and a prescription of an ASM treated in 1284 general practices in Germany between January 2010 and December 2020 (index date). Six frequently prescribed ASMs with at least 1000 available patients were analyzed. Patients treated with one of six ASMs were matched to each other by propensity scores based on sex, age, and secondary diagnoses. Cox regression models were used to analyze the association between the use of ASM and LUTI risk., Results: The cumulative LUTI incidence 12 months after the start of therapy was highest in patients treated with pregabalin (16.7%), followed by valproate (11.6%) and gabapentin (10.2%). A similar trend was observed for LUTI with antibiotic prescription (9.2% pregabalin, 6.8% valproate, 6.8% gabapentin). Conditional regression analyses revealed that pregabalin therapy was significantly positively associated with LUTI (HR: 1.76; 95% CI 1.29-2.39) and LUTI-based antibiotic prescription (HR: 2.16; 95% CI 1.43-3.27). Carbamazepine was associated with a significantly lower incidence of LUTI in women (HR: 0.47; 95% CI: 0.30-0.75), but not in men. No significant associations were observed for other ASMs., Conclusion: The present study identifies a significant positive association between ASM and LUTI incidence and antibiotic prescriptions in patients with epilepsy treated with pregabalin, whereas a protective effect was found for carbamazepine in women only. No significant associations were observed for the four remaining ASMs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.