Relationship of Ki-67 index in biopsies of metastatic breast cancer tissue and circulating tumor cells (CTCs) at the time of biopsy collection.

BACKGROUND: The proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples. PATIENTS AND METHODS: Blood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy. RESULTS: 65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman's correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS). CONCLUSION: CTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood.

Using an Electronic Mindfulness-based Intervention (eMBI) to improve maternal mental health during pregnancy: Results from a randomized controlled trial.

Prevalence rates of peripartum depression and anxiety are high and correlate with adverse maternal and neonatal outcomes. Mindfulness-based interventions (MBI) have been shown to reduce mental distress during pregnancy. A multicenter, randomized controlled study was conducted after screening for depressive symptoms. The intervention group (IG) was given access to an 8-week supervised eMBI between weeks 29 and 36 of pregnancy and followed up to 5 months postpartum. Psychometric data were collected using the Edinburgh Postnatal Depression Scale (EPDS), the State-Trait Anxiety Inventory (STAI), the Pregnancy-Related Anxiety Questionnaire (PRAQ-R), the Freiburg Mindfulness Inventory (FMI-14) as well as the Patient Health Questionnaire (PHQ). Out of 5299 pregnant women, 1153 scored >9 on the EPDS and N = 460 were included in the RCT. No significant interaction effects for depressive symptoms and anxiety were found. Pregnancy- and birth-related anxiety decreased significantly in the IG and 6 weeks after birth, the rate of women at risk for adverse mental outcome was significantly lower compared to the CG. Mindfulness scores improved significantly in the IG. The eMBI program did not show effective regarding general depressive or anxiety symptoms, however, positive results were demonstrated regarding pregnancy and birth-related anxiety and the prevention of postpartum depression.

Current Treatment Practices and Prognostic Factors in Early-Stage Ovarian Cancer-An Analysis of the NOGGO/JAGO.

BACKGROUND: Surgery is the backbone of early-stage ovarian cancer (OC) management. However, in practice, there is disagreement about the extent of surgical staging and whether additional adjuvant treatment should be provided. As omitting relevant diagnostic or therapeutic procedures might lead to undertreatment, we aimed to structurally investigate treatment practice in addition to prognostic factors in a multicentre series of patients (pts) diagnosed with early-stage OC. PATIENTS: Within this retrospective, multicentre study, medical records of 379 pts who had undergone surgery for suspected early-stage OC between January 2014 and March 2020 were analysed. RESULTS: Of the 379 patients, 292 had pT stage 1a-2a and had complete data on the extent of surgical staging. At least one surgical step was omitted in 100 pts (34.2%). Complete surgical staging (n = 192; (65.8%)) was more often performed in high-grade serous OC and was independent of the healthcare level of the hospital where the initial diagnosis was made. Missing to take peritoneal biopsies was associated with reduced relapse-free-survival in incompletely staged, pT1 cases (p = 0.03). About every second patient (46.7%) with a final stage lower than FIGO IIB and treated with adjuvant chemotherapy received combination chemotherapy. BRCA1 and BRCA2 testing was only performed in a subset of pts, and mutations were detected in 18% (14/79) and 9% (7/85) pts, respectively. CONCLUSIONS: This study helps to increase our understanding of early-stage OC treatment and prognosis. In addition to treating patients in compliance with current guidelines, the need for BRCA testing should also be considered for early-stage OC.

Long-term effects of preeclampsia on maternal cardiovascular health and postpartum utilization of primary care: an observational claims data study.

PURPOSE: Preeclampsia occurs in up to 15% of pregnancies and constitutes a major risk factor for cardiovascular disease. This observational cohort study aimed to examine the association between preeclamptic pregnancies and cardiovascular outcomes as well as primary and specialized care utilization after delivery. METHODS: Using statutory claims data we identified women with singleton live births between 2010 and 2017. Main outcomes included the occurrence of either hypertension or cardiovascular disease after one or more preeclamptic pregnancies, number of contacts to a general practitioner or cardiologist after delivery and prescribed antihypertensive medication. Data were analyzed using Cox proportional hazard regression models adjusted for maternal age, diabetes, dyslipidemia, and obesity. RESULTS: The study cohort consisted of 181,574 women with 240,698 births. Women who experienced preeclampsia once had an increased risk for cardiovascular (hazard ratio, HR = 1.29) or hypertensive (HR = 4.13) events. In women affected by recurrent preeclampsia, risks were even higher to develop cardiovascular disease (HR = 1.53) or hypertension (HR = 6.01). In the following years after delivery, general practitioners were seen frequently, whereas cardiologists were consulted rarely (0.3 and 2.4%). CONCLUSION: Women affected by preeclampsia experience an increased risk of developing chronic hypertension and cardiovascular disease, especially those with recurrent preeclampsia. Future medical guidelines should take this potential risk into account.

Comorbidity, life-style factors and healthcare utilization in incident chronic kidney disease: sex-specific analyses of claims data.

BACKGROUND: Chronic kidney disease (CKD) is common in aging men and women. In contrast to other European countries, Germany lacks CKD registries. The aim of this study was to determine the incidence of CKD stages 2-5 in men and women in Germany. Furthermore, differences between the sexes in terms of comorbidities, potentially inappropriate medications (PIM), and healthcare utilization were examined. METHODS: In this retrospective observational study, claims data from members of a statutory health insurance fund aged 18 years or older with incident CKD between 2011 and 2018 were analyzed. Incident CKD was defined as having two confirmed diagnoses of CKD stages 2-5 from outpatient care or one primary or secondary diagnosis from inpatient care. RESULTS: The age- and sex-standardized incidence of all CKD stages was 945/100 000 persons between 2011 and 2018. Incident CKD, especially stages 3 and 4, occurred more frequently in women, while the incidence of stages 2 and 5 was higher in men. While women visited their GP more frequently and were prescribed PIMs more often, men were more likely to visit a nephrologist and were more often hospitalized after the incident CKD diagnosis. CONCLUSION: More awareness needs to be raised towards the early detection of CKD and the use of PIMs, especially in women. Improved care coordination is needed to avoid an overprovision of patients with uncomplicated incident stages and ensure that patients with advanced CKD stages get timely access to specialist care.

Observational database study on preeclampsia and postpartum medical care up to 7.5 years after birth.

Preeclampsia is associated with a substantially increased long-term risk for cardiovascular, cerebrovascular and renal disease. It remains unclear whether and to which extent specialized medical postpartum care is sought. We aimed to assess current utilization of postpartum primary and specialized care and medication prescription behavior in women who experienced preeclampsia. This retrospective observational study based on statutory claims data included 193,205 women with 258,344 singleton live births between 2010 and 2017 in Southern Germany. Postpartum care was evaluated by analyzing and comparing the frequency of medical consultations in primary and specialized care and prescriptions for antihypertensive medication among women with and without preeclampsia up to 7.5 years after delivery. Gynecologists and general practitioners were the main health care providers for all women. Although specialized postpartum care was sought by more women after preeclampsia, the effect size indices revealed no considerable association between a history of preeclampsia and the utilization of specialized outpatient aftercare (e.g. 2% vs. 0.6% of patients with and without preeclampsia who consulted a nephrologist during the first year postpartum, r = 0.042). Preeclampsia was associated with an increased risk to take any antihypertensive medication after delivery (HR 2.7 [2.6; 2.8]). Postpartum referral to specialized outpatient care and quarterly prescriptions of antihypertensives following preeclampsia failed to match the early and rapidly increased incidence and risk of hypertension. These data highlight the missed opportunity to implement a reasonable follow-up strategy and prevention management in order to achieve long-term clinical benefits.

Implementing a Perinatal Depression Screening in Clinical Routine: Exploring the Patient's Perspective.

Introduction Perinatal depression (PND) is a frequently observed mental disorder, showing a prevalence of up to 20% and resulting in unfavorable maternal and neonatal outcomes. Targeted screening for PND offers the potential to identify and treat undiagnosed cases and help prevent its deleterious consequences. The aim of the present study was to evaluate participants' personal attitudes and acceptance of a routine screening program for PND in pregnancy care, identify any potential underlying factors, and appraise the general perspective on perinatal mental health problems. Methods In total, 732 women in their second trimester of pregnancy took part in a PND screening program that was incorporated in routine prenatal care using the Edinburgh Postnatal Depression Scale (EPDS) and completed a web-based survey on screening acceptance. Results Participants viewed PND screening as useful (78.7%, n = 555/705), especially in terms of devoting attention to perinatal mental health problems (90.1%, n = 630/699), easy to complete (85.4%, n = 606/710), and without feelings of discomfort (88.3%, n = 628/711). Furthermore, women with previous or current mental health issues rated the usefulness of screening significantly higher, as did women with obstetric risks (p < 0.01 - p = 0.04). The final regression model explained 48.4% of the variance for screening acceptance. Conclusion Patient acceptance for PND screening was high in our study cohort, supporting the implementation of screening programs in routine pregnancy care with the potential to identify, sensitize, and treat undiagnosed patients to reduce stigmatization and offer access to tailored dedicated PND care programs.

Circulating miR-200 Family and CTCs in Metastatic Breast Cancer before, during, and after a New Line of Systemic Treatment.

The extracellular circulating microRNA (miR)-200 regulates epithelial-mesenchymal transition and, thus, plays an essential role in the metastatic cascade and has shown itself to be a promising prognostic and predictive biomarker in metastatic breast cancer (MBC). Expression levels of the plasma miR-200 family were analyzed in relationship to systemic treatment, circulating tumor cells (CTC) count, progression-free survival (PFS), and overall survival (OS). Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429, and CTC status (CTC-positive ≥ 5 CTC/7.5 mL) was assessed in 47 patients at baseline (BL), after the first completed cycle of a new line of systemic therapy (1C), and upon the progression of disease (PD). MiR-200a, miR-200b, and miR-141 expression was reduced at 1C compared to BL. Upon PD, all miR-200s were upregulated compared to 1C. At all timepoints, the levels of miR-200s were elevated in CTC-positive versus CTC-negative patients. Further, heightened miR-200s expression and positive CTC status were associated with poorer OS at BL and 1C. In MBC patients, circulating miR-200 family members decreased after one cycle of a new line of systemic therapy, were elevated during PD, and were indicative of CTC status. Notably, increased levels of miR-200s and elevated CTC count correlated with poorer OS and PFS. As such, both are promising biomarkers for optimizing the clinical management of MBC.

Acceptance, experiences, and needs of hospitalized pregnant women toward an electronic mindfulness-based intervention: A pilot mixed-methods study.

Background: Anxiety disorders and depression during pregnancy are highly prevalent. Hospitalized pregnant women with high maternal or fetal risk represent a particularly vulnerable population often excluded from research samples. Screening for mental health disorders is not routinely offered for this particular patient group. Electronic mindfulness-based interventions constitute an accessible, convenient, and cost-effective mental health resource but have not yet been evaluated for acceptance in inpatient settings. To date, little is known about the needs and perceptions of this group of women. Objective: The aim of this study was to examine whether a brief electronic mindfulness-based intervention (eMBI) is accepted among hospitalized high-risk pregnant women. We assessed personal motivation and barriers, experiences, usability requirements, and overall acceptance of the eMBI, as well the specific needs and demands of patients with high-risk pregnancies regarding mental health services. Methods: An exploratory pilot study with a mixed-methods study design was carried out among 30 women hospitalized with a high obstetric risk. The study participants were given access to an eMBI with a 1-week mindfulness program on how to deal with stress, anxiety, and depressive symptoms. Semi-structured interviews were conducted with the 30 participants and analyzed using systematic content analysis. In addition, acceptance and usability were assessed via questionnaires. Results: Study findings showed a high level of acceptance of the eMBI. Most of the respondents were satisfied with the usability and considered the eMBI program to be helpful. The greatest barriers to using the eMBI were a general negative attitude toward using apps, preference for personal contact, or no current need for psychotherapy. Participants criticized the lack of awareness of mental health issues during pregnancy and expressed a need for low-threshold treatment offers, especially during hospitalization. Conclusions: There is a strong need for mental health services in pregnancy care, especially for pregnant women with risk profiles. An eMBI offers an acceptable means of providing mental health support for hospitalized women with a severe obstetric risk.

Evaluation of Repeated Web-Based Screening for Predicting Postpartum Depression: Prospective Cohort Study.

BACKGROUND: Postpartum depression (PPD) is a severe mental disorder that often results in poor maternal-infant attachment and negatively impacts infant development. Universal screening has recently been recommended to identify women at risk, but the optimal screening time during pregnancy has not been defined so far. Thus, web-based technologies with widespread use among women of childbearing age create new opportunities to detect pregnancies with a high risk for adverse mental health outcomes at an early stage. OBJECTIVE: The aim of this study was to stratify the risk for PPD and to determine the optimal screening time during pregnancy by using a web-based screening tool collecting electronic patient-reported outcomes (ePROs) as the basis for a screening algorithm. METHODS: In total, 214 women were repeatedly tested for depressive symptoms 5 times during and 3 times after pregnancy by using the Edinburgh Postnatal Depression Scale (EPDS), accessible on a web-based pregnancy platform, developed by the authors of this study. For each prenatal assessment, the area under the curve (AUC), sensitivity, specificity, and predictive values for PPD were calculated. Multivariate logistic regression analyses were applied to identify further potential predictors, such as age, education, parity, relationship quality, and anxiety, to increase predictive accuracy. RESULTS: Digitally collected data from 214 pregnant women were analyzed. The predictive accuracy of depressive symptoms 3 and 6 months postpartum was reasonable to good regarding the screening in the second (AUC=0.85) and third (AUC=0.75) trimester. The multivariate logistic regression analyses resulted in an excellent AUC of 0.93 at 3 months and a good AUC of 0.87 at 6 months postpartum. CONCLUSIONS: The best predictive accuracy for PPD has been shown for screening between the 24th and the 28th gestational week (GW) and seems to be beneficial for identifying women at risk. In combination with the aforementioned predictive factors, the discriminatory power improved, particularly at 3 months postpartum. Screening for depression during pregnancy, combined with the women's personal risk profile, can be used as a starting point for developing a digital screening algorithm. Thereby, web-based assessment tools constitute feasible, efficient, and cost-effective approaches. Thus, they seem to be beneficial in detecting high-risk pregnancies in order to improve maternal and infant birth outcomes in the long term.

An observational claims data analysis on the risk of maternal chronic kidney disease after preterm delivery and preeclampsia.

Women with complications of pregnancy such as preeclampsia and preterm birth are at risk for adverse long-term outcomes, including an increased future risk of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). This observational cohort study aimed to examine the risk of CKD after preterm delivery and preeclampsia in a large obstetric cohort in Germany, taking into account preexisting comorbidities, potential confounders, and the severity of CKD. Statutory claims data of the AOK Baden-Wuerttemberg were used to identify women with singleton live births between 2010 and 2017. Women with preexisting conditions including CKD, ESKD, and kidney replacement therapy (KRT) were excluded. Preterm delivery (< 37 gestational weeks) was the main exposure of interest; preeclampsia was investigated as secondary exposure. The main outcome was a newly recorded diagnosis of CKD in the claims database. Data were analyzed using Cox proportional hazard regression models. The time-dependent occurrence of CKD was analyzed for four strata, i.e., births with (i) neither an exposure of preterm delivery nor an exposure of preeclampsia, (ii) no exposure of preterm delivery but exposure of at least one preeclampsia, (iii) an exposure of at least one preterm delivery but no exposure of preeclampsia, or (iv) joint exposure of preterm delivery and preeclampsia. Risk stratification also included different CKD stages. Adjustments were made for confounding factors, such as maternal age, diabetes, obesity, and dyslipidemia. The cohort consisted of 193,152 women with 257,481 singleton live births. Mean observation time was 5.44 years. In total, there were 16,948 preterm deliveries (6.58%) and 14,448 births with at least one prior diagnosis of preeclampsia (5.61%). With a mean age of 30.51 years, 1,821 women developed any form of CKD. Compared to women with no risk exposure, women with a history of at least one preterm delivery (HR = 1.789) and women with a history of at least one preeclampsia (HR = 1.784) had an increased risk for any subsequent CKD. The highest risk for CKD was found for women with a joint exposure of preterm delivery and preeclampsia (HR = 5.227). These effects were the same in magnitude only for the outcome of mild to moderate CKD, but strongly increased for the outcome of severe CKD (HR = 11.90). Preterm delivery and preeclampsia were identified as independent risk factors for all CKD stages. A joint exposure or preterm birth and preeclampsia was associated with an excessive maternal risk burden for CKD in the first decade after pregnancy. Since consequent follow-up policies have not been defined yet, these results will help guide long-term surveillance for early detection and prevention of kidney disease, especially for women affected by both conditions.

Challenges in Acceptance and Compliance in Digital Health Assessments During Pregnancy: Prospective Cohort Study.

BACKGROUND: Pregnant women are increasingly using mobile apps to access health information during the antenatal period. Therefore, digital health solutions can potentially be used as monitoring instruments during pregnancy. However, a main factor of success is high user engagement. OBJECTIVE: The aim of this study was to analyze engagement and factors influencing compliance in a longitudinal study targeting pregnant women using a digital health app with self-tracking. METHODS: Digitally collected data concerning demographics, medical history, technical aspects, and mental health from 585 pregnant women were analyzed. Patients filling out ≥80% of items at every study visit were considered to be highly compliant. Factors associated with high compliance were identified using logistic regression. The effect of a change in mental and physical well-being on compliance was assessed using a one-sample t test. RESULTS: Only 25% of patients could be considered compliant. Overall, 63% left at least one visit blank. Influential variables for higher engagement included higher education, higher income, private health insurance, nonsmoking, and German origin. There was no relationship between a change in the number of physical complaints or depressive symptoms and study dropout. CONCLUSIONS: Maintaining high engagement with digital monitoring devices over a long time remains challenging. As cultural and socioeconomic background factors had the strongest influence, more effort needs to be directed toward understanding the needs of patients from different demographic backgrounds to ensure high-quality care for all patients. More studies need to report on compliance to disclose potential demographic bias.

Reduction in physical activity significantly increases depression and anxiety in the perinatal period: a longitudinal study based on a self-report digital assessment tool.

PURPOSE: Physical activity can reduce pregnancy-related complications and contributes substantially to improving maternal mental health. A reduction in activity encompassing exercise and daily household tasks throughout the course of pregnancy increases the risk of depression and anxiety. The following research examines the longitudinal interaction between exercise, general physical activity, and mental health outcomes in pregnant women. METHODS: This prospective longitudinal study was conducted at the maternity departments of two major university hospitals in Germany. Self-reported data of 597 women were digitally assessed every 4 weeks from the second trimester until birth as well as 3 and 6 months postnatally. Depressive and anxiety symptoms were assessed using the EPDS, PRAQ, and STAI and physical activity levels were measured using the PPAQ questionnaire. Cross-sectional and longitudinal analyses using Pearson's correlation coefficient and multiple regression models were conducted. RESULTS: We found a significant reduction in general physical activity in the period from the 20th to 32nd gestational week. Women who reported a greater decline during pregnancy showed significantly higher depression and anxiety scores. In stratified analyses, only baseline mental health scores proved to be variables with stronger impact on postnatal depression and anxiety outcomes. CONCLUSION: General physical activity and maternal mental health significantly influence each other during and after pregnancy. Both physical activity and the prevention of perinatal mental disorders should be systematically encouraged during perinatal care to prevent adverse maternal and fetal birth outcomes.