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1.
Cancers (Basel) ; 16(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38672643

RESUMO

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.

2.
Neurol Res Pract ; 6(1): 17, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38509597

RESUMO

BACKGROUND: An increasing use of newer antiseizure medication (ASM) such as SV2A ligand brivaracetam is observed. However, data on newer antiseizure medication and therapeutic drug monitoring during pregnancy is scarce. METHODS: Therapeutic drug monitoring of brivaracetam (BRV) and topiramate (TPM) serum levels were performed during pregnancy, delivery and in the umbilical cord blood at delivery in a 34-year-old female patient with severe drug-resistant epilepsy. RESULTS: During pregnancy, the serum levels of brivaracetam and topiramate remained stable. At 39th week of pregnancy, the patient gave birth to a healthy daughter. 1.5 h after the last ASM intake, the penetration rate measured in umbilical cord blood was 45% lower for BRV and 35% lower for TPM. CONCLUSIONS: While the pharmacokinetics of topiramate are well known and its use during pregnancy should only be undertaken under special circumstances, there have been few studies on newer ASM in pregnancy such as brivaracetam. Based on our results and other case reports of BRV use during pregnancy, further studies are necessary to confirm its pharmacokinetics and safety during pregnancy.

3.
Arch Gynecol Obstet ; 309(1): 195-204, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37755531

RESUMO

PURPOSE: Digitalization plays a critical role and is beginning to impact every part of the patient journey, from drug discovery and data collection to treatment and patient-reported outcomes. We aimed to evaluate the status quo and future directions of digital medicine in the specialty of gynecology and obstetrics in Germany. METHODS: An anonymous questionnaire was distributed via the German Society of Gynecology and Obstetrics newsletter in December 2022. The questionnaire covered the domains baseline demographic information, telemedicine, digital health applications (DIGAs), and future expectations. RESULTS: In all, 91 participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female and 32.6% (29 of 89) were male. About 10% (9 of 88) have prescribed DIGAs to date and 14% (12 of 86) offer telemedical appointments. Among those who do not use digital medicine, very few plan to do so in the near future. Reasons include missing software interfaces, lack of time to try out new things, lack of knowledge, lack of monetary compensation (66.3%), and employee concerns. A majority agreed that digitalization will help to save time and improve patient care and that intelligent algorithms will aid clinicians in providing patient care to women. CONCLUSIONS: The status quo and future directions of digital medicine in gynecology and obstetrics in Germany are characterized by contradicting expectations regarding the benefits of digital medicine and its actual implementation in clinical routine. This represents an important call to action to meet the requirements of modern patient care.


Assuntos
Ginecologia , Obstetrícia , Telemedicina , Gravidez , Feminino , Masculino , Humanos , Adulto , Inquéritos e Questionários , Alemanha
4.
Breast Cancer Res Treat ; 204(2): 359-365, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38141056

RESUMO

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.


Assuntos
Neoplasias da Mama , Endometriose , Feminino , Humanos , Endometriose/complicações , Endometriose/epidemiologia , Endometriose/diagnóstico , Estudos Retrospectivos , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Risco , Alemanha/epidemiologia
5.
iScience ; 26(12): 108401, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38047087

RESUMO

A crucial requirement for metastasis formation in ovarian high-grade serous carcinoma (HGSC) is the disruption of the protective peritoneal mesothelium. Using co-culture systems of primary human cells, we discovered that tumor-associated NK cells induce TRAIL-dependent apoptosis in mesothelial cells via death receptors DR4 and DR5 upon encounter with activated T cells. Upregulation of TRAIL expression in NK cells concomitant with enhanced cytotoxicity toward mesothelial cells was driven predominantly by T-cell-derived TNFα, as shown by affinity proteomics-based analysis of the T cell secretome in conjunction with functional studies. Consistent with these findings, we detected apoptotic mesothelial cells in the peritoneal fluid of HGSC patients. In contrast to mesothelial cells, HGSC cells express negligible levels of both DR4 and DR5 and are TRAIL resistant, indicating cell-type-selective killing by NK cells. Our data point to a cooperative action of T and NK in breaching the mesothelial barrier in HGSC patients.

6.
J Pers Med ; 13(10)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37888113

RESUMO

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.

7.
Arch Gynecol Obstet ; 308(6): 1823-1830, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37740792

RESUMO

PURPOSE: Hospital information systems (HIS) play a critical role in modern healthcare by facilitating the management and delivery of patient care services. We aimed to evaluate the current landscape of HIS in the specialty of gynecology and obstetrics in Germany. METHODS: An anonymous questionnaire was distributed via the German Society of Gynecology and Obstetrics newsletter in December 2022. The questionnaire covered the domains baseline demographic information, satisfaction with daily use, satisfaction with implementation, and degree of digitization. RESULTS: Ninety-one participants completed the survey. Median age was 34 years; 67.4% (60 of 89) were female, and 32.6% (29 of 89) were male. Of the survey participants, 47.7% (42 of 88) were residents, 26.1% (23 of 91) senior physicians, and 9.1% (8 of 88) medical directors. The degree of digitization of clinical documentation is mainly mixed digital and paper-based (64.0%, 57 of 89) while 16.9% (15 of 89) operate mainly paper-based. The current HIS has been in use on average for 9 years. The median number of different software systems used in daily routine is 4. About 33.7% (30 of 89) would likely or very likely recommend their current HIS to a colleague. CONCLUSIONS: The current landscape of HIS in gynecology and obstetrics in Germany is characterized by a high heterogeneity of systems with low interoperability and long service life; thus, many healthcare professionals are not satisfied. There is both a need to enhance and an interest in modernizing the technological infrastructure to meet today's requirements for patient care.


Assuntos
Ginecologia , Internato e Residência , Obstetrícia , Médicos , Gravidez , Feminino , Masculino , Humanos , Adulto , Ginecologia/educação , Obstetrícia/educação , Inquéritos e Questionários , Alemanha
8.
J Cancer Res Clin Oncol ; 149(13): 11749-11757, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37405476

RESUMO

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.


Assuntos
Neoplasias da Mama , COVID-19 , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , COVID-19/epidemiologia , Estudos Retrospectivos , Estudos Transversais , Pandemias , Prevalência
9.
Breast Cancer Res Treat ; 202(1): 167-172, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37518826

RESUMO

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.


Assuntos
Neoplasias da Mama , Adulto , Feminino , Humanos , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos Retrospectivos , Incidência , Estudos Transversais , Alemanha/epidemiologia
10.
Healthcare (Basel) ; 11(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37372801

RESUMO

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.

11.
Breast Cancer Res Treat ; 199(3): 545-552, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37071268

RESUMO

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.


Assuntos
Neoplasias da Mama , Gota , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Mama/epidemiologia , Fatores de Risco , Gota/complicações , Gota/epidemiologia , Atenção Primária à Saúde , Incidência
12.
Cancers (Basel) ; 15(6)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36980733

RESUMO

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.

13.
Pathologie (Heidelb) ; 44(1): 39-49, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36629894

RESUMO

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.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Fosfatidilinositol 3-Quinases/genética , Mutação , Patologia Molecular
14.
J Cancer Res Clin Oncol ; 149(6): 2551-2558, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35771262

RESUMO

PURPOSE: The goal of this study is to examine the chronological development of hospitalized oncology and COVID-19 patients, and compare effects on oncology sub-disciplines for pre-pandemic (2017-19) and pandemic (2020-21) years in the setting of a German university maximum care provider. METHODS: Data were retrospectively retrieved from the hospital performance controlling system for patient collectives with oncological main (nOnco) and COVID-19 secondary diagnosis (nCOVID-19). Data analysis is based on descriptive statistical assessment. RESULTS: The oncology patient collective (nOnco = 27,919) shows a decrease of hospitalized patients for the whole pandemic (- 4% for 2020 and - 2,5% for 2021 to 2019). The number of hospitalized COVID-19 patients increases from first to second pandemic year by + 106.71% (nCOVID-19 = 868). Maximum decline in monthly hospitalized oncology patients amounts to - 19% (May 2020) during the first and - 21% (December 2020) during the second lockdown. Relative monthly hospitalization levels of oncology patients reverted to pre-pandemic levels from February 2021 onwards. CONCLUSION: The results confirm a decline in hospitalized oncology patients for the entire pandemic in the setting of a maximum care provider. Imposed lockdown and contact restrictions, rising COVID-19 case numbers, as well as discovery of new virus variants have a negative impact on hospitalized treated oncological patients.


Assuntos
COVID-19 , Neoplasias , Humanos , Estudos Retrospectivos , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Neoplasias/epidemiologia , Neoplasias/terapia , Hospitais
15.
Cancers (Basel) ; 14(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36551640

RESUMO

Metastasis of high-grade ovarian carcinoma (HGSC) is orchestrated by soluble mediators of the tumor microenvironment. Here, we have used transcriptomic profiling to identify lipid-mediated signaling pathways encompassing 41 ligand-synthesizing enzymes and 23 cognate receptors in tumor, immune and stroma cells from HGSC metastases and ascites. Due to its strong association with a poor clinical outcome, prostacyclin (PGI2) synthase (PTGIS) is of particular interest in this signaling network. PTGIS is highly expressed by cancer-associated fibroblasts (CAF), concomitant with elevated PGI2 synthesis, whereas tumor-associated macrophages (TAM) exhibit the highest expression of its surface receptor (PTGIR). PTGIR activation by PGI2 agonists triggered cAMP accumulation and induced a mixed-polarization macrophage phenotype with altered inflammatory gene expression, including CXCL10 and IL12A repression, as well as reduced phagocytic capability. Co-culture experiments provided further evidence for the interaction of CAF with macrophages via PGI2, as the effect of PGI2 agonists on phagocytosis was mitigated by cyclooxygenase inhibitors. Furthermore, conditioned medium from PGI2-agonist-treated TAM promoted tumor adhesion to mesothelial cells and migration in a PTGIR-dependent manner, and PTGIR activation induced the expression of metastasis-associated and pro-angiogenic genes. Taken together, our study identifies a PGI2/PTGIR-driven crosstalk between CAF, TAM and tumor cells, promoting immune suppression and a pro-metastatic environment.

16.
Healthcare (Basel) ; 10(12)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36553910

RESUMO

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 (nGynecology: -6% 2019 to 2020, -5% 2019 to 2021; nGyne-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.

17.
J Clin Med ; 11(23)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36498652

RESUMO

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.

18.
J Mol Diagn ; 24(12): 1254-1263, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36191839

RESUMO

The diagnostic evaluation of homologous recombination deficiency (HRD) is central to define targeted therapy strategies for patients with ovarian carcinoma. We evaluated HRD in 514 ovarian carcinoma samples by next-generation sequencing of DNA libraries, including BRCA1/BRCA2 and 26,523 single-nucleotide polymorphisms using the standardized Myriad HRD assay, with the predefined cut point of ≥42 for a positive genomic instability score (GIS). All samples were measured in the central Myriad laboratory and in an academic molecular pathology laboratory. A positive GIS was detected in 196 (38.1%) of tumors, whereas 318 (61.9%) were GIS negative. Combining GIS and BRCA mutations, a total of 200 (38.9%) of the 514 tumors were HRD positive. A positive GIS was significantly associated with high-grade serous histology (P < 0.000001), grade 3 tumors (P = 0.001), and patient age <60 years (P = 0.0003). The concordance between both laboratories for the GIS status was 96.9% (P < 0.000001), with a sensitivity of 94.6% and a specificity of 98.4%. Concordance for HRD status was 97.1% (499 of 514 tumors). The percentage of HRD-positive tumors in our real-life cohort was similar to the proportion observed in the recently published PAOLA-1 trial, with high concordance between central and local laboratories. Our results support introduction of the standardized HRD assay in academic molecular pathology laboratories, thus broadening access to personalized oncology strategies for patients with ovarian cancer worldwide.


Assuntos
Biomarcadores Tumorais , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Recombinação Homóloga/genética , Proteína BRCA2/genética , Proteína BRCA1/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Carcinoma Epitelial do Ovário , Instabilidade Genômica , Genômica
19.
Healthcare (Basel) ; 10(10)2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36292547

RESUMO

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.

20.
Cancer Diagn Progn ; 2(3): 308-315, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530642

RESUMO

BACKGROUND/AIM: Cervical cancer is the most common gynecological indication for pelvic exenteration (PE). It is an ultima ratio approach to cure advanced or recurring tumors. This study aimed to evaluate data from a Single Center Institution in order to assess morbidity, mortality and survival data. PATIENTS AND METHODS: Data of 24 patients, who underwent anterior (APE) or total PE (TPE) for cervical cancer at the University Hospital Marburg between 2011 and 2016, were extracted and retrospectively evaluated. Survival analysis was conducted using the Kaplan-Meyer method. RESULTS: Lymph node status was pN0, pN1 and pNX in 33.3%, 20.8% and 45.8% respectively. Negative margins could be achieved in 70.8%. A total of 16.7% of patients presented with metastatic disease, while 20.8%, 37.5% and 20.8% received 1, 2 or 3 modalities of treatment respectively; 20.8% underwent up-front PE. Predominant urinary diversion was an ileum conduit (66.7%). No complications were noted for 16.7%, major complications (≥Clavien Dindo 3) in 41.7%. Overall survival was 29.2% with a median overall survival (mOS) of 19.1 months. Curative PE was undertaken in 20 cases, with 2- and 3-year survival rates of 52.6% and 29.4% respectively. and a mOS of 24 months. Positive margins, metastatic disease, positive lymph nodes, TPE and a surgical time >6 h had a significant impact on OS. CONCLUSION: PE for cervical cancer remains a feasible option in cases of advanced or recurring tumors when alternative treatment options would fail. For selected patients it may represent a chance of cure with acceptable complication and satisfactory survival rates.

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