Importance of a detailed anomaly scan after a cfDNA test indicating fetal trisomy 21, 18 or 13.

OBJECTIVE: To investigate the effect of the presence or absence of fetal anomalies and soft markers diagnosed by ultrasound on positive predictive value (PPV) 21, 18 and 13 in pregnancies with a high-risk cfDNA result. METHODS: Retrospective study including singleton pregnancies with high-risk NIPT results for common trisomies followed by invasive testing. The cases were grouped by gestational age at the time of invasive testing and by the presence or absence of fetal abnormalities or soft markers. The ultrasound was considered abnormal if at least one major defect or a soft marker was detected. RESULTS: A total of 173 women were included. Median maternal and gestational age was 37.7 years and 14.0 weeks, respectively. CfDNA test result showed high-risk for trisomy 21 and trisomy 18 or 13 in 119 and 54 cases, respectively. The "pre-ultrasound" PPV for trisomy 21 and for trisomy 18 or 13 were 98.3% and 68.4%, respectively. In case of a high-risk result for trisomy 21 and no fetal anomalies, the PPV was 86.7% while it was 100% if there were anomalies or markers present. In the case of a high-risk result for trisomy 18 or 13, the PPV was 9.5% if the ultrasound examination was normal and 100% if the ultrasound examination was abnormal. CONCLUSION: This study suggests that a detailed ultrasound examination performed after a cfDNA result that is high-risk for one of the common autosomal trisomies adds significantly to establishing an individualized risk assessment. This is particularly true in cases with a high-risk result for trisomies 18 or 13.

Factors Associated with Increased Analgesic Use in German Women with Endometriosis during the COVID-19 Pandemic.

(1) Background: Endometriosis is a frequent chronic pain condition in women of fertile age. Pain management with analgesics is frequently used by women with endometriosis. During the COVID-19 pandemic, access to health services was temporarily restricted in various countries for persons without serious conditions, resulting in increased physical and mental health issues. The present study was conducted in order to assess the risk factors predicting increased analgesic intake by women with endometriosis during the COVID-19 pandemic. (2) Methods: The increased intake of over-the-counter (OTC) and prescription-only (PO) analgesics was assessed with an anonymous online questionnaire, along with demographic, pandemic-specific, disease-specific, and mental health characteristics. Anxiety and depression were assessed with the Generalized Anxiety Disorder Scale (GAD-2) and the Patient Health Questionnaire for Depression (PHQ-2), respectively. Pain-induced disability was assessed with the pain-induced disability index (PDI). (3) Results: A high educational level (OR 2.719; 95% CI 1.137-6.501; p = 0.025) and being at higher risk for depressive disorders, as measured by PHQ-2 ≥ 3 (OR 2.398; 95% CI 1.055-5.450; p = 0.037), were independent risk factors for an increased intake of OTC analgesics. Current global pain-induced disability (OR 1.030; 95% CI 1.007-1.054; p = 0.010) was identified as a risk factor for an increased intake of PO pain medication. The degree of reduction in social support and in social networks were independent predictors of an increased intake of PO analgesics in a univariate logistic regression analysis, but lost significance when adjusted for additional possible influencing factors. (4) Conclusions: In this population, an increased intake of OTC analgesics was related to a higher educational level and having a depressive disorder, while a higher pain-induced disability was an independent risk factor for an increased intake of PO analgesics. Pandemic-specific factors did not significantly and independently influence an increased intake of analgesics in women with endometriosis during the first wave of the COVID-19 pandemic in Germany. Healthcare providers should be aware of the possible factors related to increased analgesic use in women with endometriosis in order to identify persons at risk for the misuse of pain medication and to prevent potential adverse effects.

Resilience as a Source of Easement to Health-Related Worries in Women at Increased Risk for Breast or Ovarian Cancer During the COVID-19 Pandemic.

Purpose: The COVID-19 pandemic has affected individuals' and society's physical and psychological well-being. The study was conducted in order to assess the predictors for health-related worries during the COVID-19 pandemic in vulnerable populations. Patients and Methods: A cross-sectional web-based survey of women who had a higher risk of developing breast cancer (BC) or ovarian cancer (OC) was conducted, regardless of whether they had experienced an active malignant disease during the pandemic. A self-reported questionnaire was designed for this study to assess health-related worries. The PHQ-4 questionnaire was used to evaluate mental health, and the Brief Resilience Scale (BRS) questionnaire was employed to investigate resilience. Results: History of BC or OC was recognized as an independent significant risk factor for worries regarding being more susceptible to a more severe course of COVID-19 disease (OR 3.593; 95% CI 1.030-12.536; p = 0.045). High scores in the BRS questionnaire were negatively correlated with health-related worries, such as an increased risk for occurrence of BC or OC (OR 0.332; 95% CI 0.118-0.933; p = 0.37) or worsening of oncological outcome as a result of an infection with the SARS-CoV-2 virus (OR 0.330; 95% I 0.114-0.956; p = 0.041). Conclusion: The obtained findings determined resilience as an independent and potent protective parameter in terms of health-related concerns in women at high risk for BC and OC. The results may assist in identifying women at risk for health-related concerns during adverse life events, allowing healthcare providers to respond fast and according to the patients´ needs.

Determinants of Pain-Induced Disability in German Women with Endometriosis during the COVID-19 Pandemic.

(1) Background: The main aim of this research was to examine the factors leading to pain-induced disability by assessing the impact of demographic, endometriosis-specific, pandemic-specific, and mental health factors. (2) Methods: Women with endometriosis who attended online support groups were invited to respond to an online survey during the first wave of the COVID-19 pandemic in Germany. The Pain Disability Index (PDI) was employed to assess disability-related daily functioning. Independent predictors of pain-induced disability were determined using univariate and multivariate logistic regression analyses. (3) Results: The mean PDI score of the study population was 31.61 (SD = 15.82), which was significantly higher (p < 0.001) than that reported in a previously published normative study of the German population. In the present study, a high level of pain-induced disability, as defined by scores equal to or higher than the median of the study population, older age (OR 1.063, 95% CI 1.010−1.120, p = 0.020), dysmenorrhea (OR 1.015, 95% CI 1.005−1.026, p = 0.005), dysuria (OR 1.014; 95% CI 1.001−1.027, p = 0.029), lower back pain (OR 1.018, 95% CI 1.007−1.029, p = 0.001), and impaired mental health (OR 1.271, 95% CI 1.134−1.425, p < 0.001) were found to be independent risk factors. Pandemic-specific factors did not significantly influence the pain-induced disability of the participants in this study. (4) Conclusions: The level of pain-induced disability was significantly higher among the women with endometriosis than among women in the normative German validation study. Our findings identified risk factors for experiencing a high level of pain-induced disability, such as demographic and specific pain characteristics. Pandemic-specific factors did not significantly and independently influence the pain-induced disability during the first wave of the COVID-19 pandemic in Germany. Impaired mental health negatively influenced functioning during daily activities. Thus, women with endometriosis should be managed by a multidisciplinary team of healthcare professionals to prevent negative effects of pain-induced disability on their quality of life.

Mental Health and Social Support Are Key Predictors of Resilience in German Women with Endometriosis during the COVID-19 Pandemic.

Background: Endometriosis is a multifaceted chronic pain disorder that can have an impact on both physical and mental health. Women suffering from chronic pain may be more susceptible to various health disorders, especially during adversity, such as the COVID-19 pandemic. Previous research has identified resilience as a mediator between internal or external stressors and well-being. Methods: An online survey was conducted during the first wave of the COVID-19 pandemic in Germany through patient support groups of women with endometriosis. The Brief Resilience Score (BRS) was employed to evaluate resilience, while the PHQ-4 questionnaire was used to assess self-reported mental health. Univariate and multivariate logistic regression analyses were applied to determine resilience's independent risk and protective parameters. Results: High educational level was found to be an independent supportive moderator of high resilience in women with a resilience score greater than the study population's median (BRS > 2.66; OR 2.715; 95% CI 1.472−5.007; p = 0.001) but not in women in the highest resilience score quartile (BRS > 3.33). A decrease in perceived social support was detected to be the most powerful independent risk factor for low resilience: OR 0.541, 95% CI 0.307−0.952, p = 0.033 for predicting BRS > 2.66, and OR 0.397, 95% CI 0.189−0.832, p = 0.014 for predicting scores > 3.33 on the BRS scale. A high burden of mental health symptoms, as measured by the PHQ-4 scale, was negatively associated with resilience. Conclusions: Satisfying social support and good mental health were shown to be key resources for resilience. The results of this study may assist in the identification of women at risk for low resilience and the development of resilience-building strategies in patients with endometriosis.

Predictors of Psychological Distress in Women with Endometriosis during the COVID-19 Pandemic.

Background: Endometriosis is a multifaceted chronic pain condition that can have a negative impact on mental health. Patients suffering from chronic pain may face an additional psychological burden during adversity, such as the COVID-19 pandemic. The main aim of this research was to evaluate the prevalence of self-reported depression and anxiety, the influence of demographic, endometriosis-specific, pandemic-specific factors, and resilience on mental health outcomes of patients with endometriosis. Methods: An online survey was conducted through patient support groups of women suffering from endometriosis during the first wave of the COVID-19 pandemic. The PHQ-4 questionnaire, which combines two items of the Patient Health Questionnaire for Depression (PHQ-2) and two items from the Generalized Anxiety Disorder Scale (GAD-2) was used to assess self-reported mental health. The Brief Resilience Score (BRS) was employed to evaluate resilience. Independent risk and protective factors for mental health were investigated by multivariate logistic regression analyses. Results: The PHQ-4 questionnaire was completed by 274 respondents. More than 40% reached depression (PHQ-2) and anxiety (GAD-2) scores of ≥3, and more than 20% achieved PHQ-2 and GAD-2 scores of ≥5. High resilience was found to be a reliable and strong independent protector for the probability of developing adverse psychological outcomes: OR 0.295, p < 0.001 for developing generalized anxiety disorder (GAD-2 ≥ 3), and OR 0.467, p < 0.001 for having major depression (PHQ-2 ≥ 3). Conclusions: Pain-induced disability is an independent risk factor for developing major depression and anxiety, while resilience was identified as a potential protective parameter in terms of positive psychological outcomes in women with endometriosis. The results of this study may help to identify women at risk for adverse mental health outcomes and should encourage healthcare practitioners to establish strategies for the reduction of negative psychological and psychiatric impacts on patients with endometriosis.

First-Trimester Screening for Gestational Diabetes Mellitus in Twin Pregnancies.

We previously reported a logistic regression model for prediction of GDM from maternal characteristics and medical history in 75,161 singleton pregnancies. In this study of 1376 twin and 13,760 singleton pregnancies recruited at 11-13 weeks' gestation, we extend the model to include terms for twin pregnancies. We found the respective odds of GDM in dichorionic and monochorionic twin pregnancies to be 1.36 (95% CI: 1.02-1.81) and 2.78 (95% CI: 1.72-4.48) times higher than in singleton pregnancies. In both singleton and twin pregnancies, the risk for GDM increased with maternal age and weight and birth weight z-score of a baby in a previous pregnancy and is higher in women with a previous pregnancy complicated by GDM; in those with a first- or second-degree relative with diabetes mellitus; in women of Black, East Asian, and South Asian racial origin; and in pregnancies conceived through the use of ovulation-induction drugs. In singleton pregnancies, at 10% and 20% false-positive rate, the detection rate was 43% and 58%, respectively. In twin pregnancies, using risk cut-offs corresponding to 10% and 20% false-positive rates in singletons, the respective false-positive rates were 27% and 47%, and the detection rates were 63% and 81%.

A retrospective analysis of immunohistochemically determined IRF4 (interferon regulating factor 4) expression in a consecutive cohort of 114 ovarian cancer patients.

BACKGROUND: Tumor-infiltrating lymphocytes influence the prognosis of solid tumors, including ovarian cancer (OC). The immunoregulatory transcription factor (IRF4) is mainly expressed in plasma cells and regulates immunoglobulin class switch recombination as well as plasma cell differentiation. Therefore, we analyzed the impact of IRF4 expression in a consecutive cohort of OC patients. METHODS: IRF4 expression was evaluated by immunostaining. Differences in IRF4 expression among the subgroups of the established clinical-pathological features like age, histological subtype, tumor stage, histological grading, postoperative tumor burden, and completeness of chemotherapy were determined by χ2 test. The impact of IRF4 expression on progression-free survival (PFS) and overall survival (OS) was examined by univariate and multivariate Cox analysis adjusted for established clinical-pathological factors and Kaplan-Meier survival analysis. RESULTS: 114 patients entered this study. IRF4 was expressed in 51.7% of the entire cohort. 72.3% patients with high-grade serous OC showed IRF4 expression compared to 37.3% patients with a non-high-grade serous OC (p < 0.001). Univariate Cox-regression analysis revealed no prognostic impact of IRF4 expression in terms of PFS (p = 0.35) and OS (p = 0.98). Kaplan-Meier plots failed to show any prognostic impact for PFS (p = 0.35) and OS (p = 0.98), too. Established clinical-pathological factors retained their prognostic impact as tumor stage in terms of PFS (< 0.001) and as postoperative residual tumor burden (p = 0.04), tumor stage (< 0.001), histological grade (p = 0.02), and completeness of chemotherapy (p < 0.001) in terms of OS, respectively. CONCLUSION: Immunohistochemically determined IRF4 expression correlated with high-grade serous OC. However, it failed to show any prognostic impact in this cohort of 114 patients.

Explorative Analysis of Low-Dose Metronomic Chemotherapy with Cyclophosphamide and Methotrexate in a Cohort of Metastatic Breast Cancer Patients.

BACKGROUND: Low-dose metronomic chemotherapy (LDMC) is increasingly used in metastatic breast cancer (MBC). In this retrospective analysis, we examined the therapeutic effects and side effects of LDMC in a cohort of MBC patients. METHODS: Patients with MBC were included when LDMC with oral cyclophosphamide (CTX) and methotrexate (MTX) was administered between 2009 and 2015. The primary endpoint was disease control rate (DCR) ≥ 24 weeks after the start of LDMC. Secondary endpoints were duration of progression-free survival (PFS), rates of discontinuation due to side effects, and DCR with regard to subgroups. RESULTS: Retrospective data of 35 patients were available for this analysis. 31% patients achieved DCR. The median PFS was 12 weeks. 9% of patients discontinued LDMC due to adverse events. DCR was 37% in the first 2 lines and 25% in further lines of therapy. 22% of patients with multiple metastases and 35% with ≤2 different metastatic sites achieved DCR. DCR was achieved in 33% of hormone receptor(HR)-positive patients and 27% of HR-negative patients. CONCLUSION: The DCR of 31% is in line with the results of previous phase II studies. LDMC was well tolerated. Subgroup analysis was not able to identify a group in which LDMC was more efficient.

The value of advanced MRI techniques in the assessment of cervical cancer: a review.

OBJECTIVES: To assess the value of new magnetic resonance imaging (MRI) techniques in cervical cancer. METHODS: We searched PubMed and MEDLINE and reviewed articles published from 1990 to 2016 to identify studies that used MRI techniques, such as diffusion weighted imaging (DWI), intravoxel incoherent motion (IVIM) and dynamic contrast enhancement (DCE) MRI, to assess parametric invasion, to detect lymph node metastases, tumour subtype and grading, and to detect and predict tumour recurrence. RESULTS: Seventy-nine studies were included. The additional use of DWI improved the accuracy and sensitivity of the evaluation of parametrial extension. Most studies reported improved detection of nodal metastases. Functional MRI techniques have the potential to assess tumour subtypes and tumour grade differentiation, and they showed additional value in detecting and predicting treatment response. Limitations included a lack of technical standardisation, which limits reproducibility. CONCLUSIONS: New advanced MRI techniques allow improved analysis of tumour biology and the tumour microenvironment. They can improve TNM staging and show promise for tumour classification and for assessing the risk of tumour recurrence. They may be helpful for developing optimised and personalised therapy for patients with cervical cancer. TEACHING POINTS: • Conventional MRI plays a key role in the evaluation of cervical cancer. • DWI improves tumour delineation and detection of nodal metastases in cervical cancer. • Advanced MRI techniques show promise regarding histological grading and subtype differentiation. • Tumour ADC is a potential biomarker for response to treatment.