Kinase-inactivated CDK6 preserves the long-term functionality of adult hematopoietic stem cells.

Hematopoietic stem cells (HSCs) are characterized by the ability to self-renew and to replenish the hematopoietic system. The cell-cycle kinase cyclin dependent-kinase 6 (CDK6) regulates transcription, whereby it has both kinase-dependent and kinase-independent functions. We here describe the complex role of CDK6, balancing quiescence, proliferation, self-renewal and differentiation in activated HSCs. Mouse HSCs expressing kinase-inactivated CDK6 show enhanced long-term repopulation and homing, whereas HSCs lacking CDK6 have impaired functionality. The transcriptomes of basal and serially transplanted HSCs expressing kinase-inactivated CDK6 exhibit an expression pattern dominated by HSC quiescence and self-renewal, proposing a concept where MAZ and NFY-A are critical CDK6 interactors. Pharmacologic kinase inhibition with a clinically used CDK4/6 inhibitor in murine and human HSCs validated our findings and resulted in increased repopulation capability and enhanced stemness. Our findings highlight a kinase-independent role of CDK6 in long-term HSC functionality. CDK6 kinase inhibition represents a possible strategy to improve HSC fitness.

Intrauterine Detection of Ureaplasma Species after Vaginal Colonization in Pregnancy and Neonatal Outcome.

INTRODUCTION: Intrauterine infection with Ureaplasma species (U.spp.) is mostly a result of vaginal colonization with subsequent ascending infection and is associated with adverse pregnancy outcome. Little is known about rates and risk factors for ascending infection. Aim of the current study was to analyse the frequency of ascending U.spp. infection in vaginally colonized pregnant women delivering preterm and subsequent short- and long-term outcome of infants. METHODS: Women delivering ≤32 weeks of gestation with available data on vaginal U.spp. colonization in early pregnancy as well as amniotic and placental colonization screening during caesarean section were included. Neonatal short- and long-term outcome was analysed depending on vaginal and intrauterine colonization. RESULTS: Seventy-two women giving birth to 104 preterm infants were included. Intrauterine microbial invasion was found in 23/72 (31.9%) pregnancies. The most commonly detected organisms were U.spp. (52.2%), followed by E. coli (21.7%) and Enterococcus faecalis (17.4%). Intrauterine growth of U.spp. occurred exclusively after previous vaginal colonization in early pregnancy (42/72; 58.3%) and was found in 12/42 (28.6%) cases. Ascending U.spp. infection mainly occurred in pregnancies delivering <28 weeks after preterm rupture of membranes or preterm labour (9/17, 52.3%). Intrauterine detection of U.spp., but not vaginal colonization, was associated with a significantly higher rate of severe intraventricular haemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, and unfavourable psychomotor outcome. CONCLUSION: Ascending U.spp. infection after previous vaginal colonization occurred in almost one-third of pregnancies delivering ≤32 weeks, with particularly high rates in those <28 weeks, and was associated with adverse outcome of preterm infants.

Transcriptomic analysis identifies lactoferrin-induced quiescent circuits in neonatal macrophages.

Introduction: Upon birth, a hitherto naïve immune system is confronted with a plethora of microbial antigens due to intestinal bacterial colonization. To prevent excessive inflammation and disruption of the epithelial barrier, physiological mechanisms must promote immune-anergy within the neonatal gut. As high concentrations of human lactoferrin (hLF), a transferrin glycoprotein shown to modulate macrophage function, are frequently encountered in colostrum, its direct interaction with intestinal macrophages may satisfy this physiological need. Thus, the primary objective of this study was to investigate transcriptional changes induced by human lactoferrin in neonatal monocyte-derived macrophages. Methods: Cord blood-derived monocytes were differentiated with M-CSF in presence or absence of 500 µg/mL hLF for 7 days and afterwards stimulated with 1 ng/mL LPS or left untreated. RNA was then isolated and subjected to microarray analysis. Results: Differentiation of cord blood-derived monocytes in presence of hLF induced a distinct transcriptional program defined by cell cycle arrest in the G2/M phase, induction of IL-4/IL-13-like signaling, altered extracellular matrix interaction, and enhanced propensity for cell-cell interaction. Moreover, near-complete abrogation of transcriptional changes induced by TLR4 engagement with LPS was observed in hLF-treated samples. Discussion: The global transition towards an M2-like homeostatic phenotype and the acquisition of quiescence elegantly demonstrate the ontogenetical relevance of hLF in attenuating pro-inflammatory signaling within the developing neonatal intestine. The marked anergy towards proinflammatory stimuli such as LPS further underlines the glycoprotein's potential therapeutic relevance.

Polymicrogyria in a patient after twin-twin transfusion syndrome.

This case report presents a patient with a monochorionic twin pregnancy, development of twin-twin transfusion-syndrome (TTTS) and polymicrogyria (PMG) of one fetus. Due to TTTS grade 3, fetoscopic laser ablation was performed at gestational week 16+1. Sonographic follow-up showed a cortical malformation of the right parietal lobe in the former donor, which was identified as PMG by MRI scans. We describe the course of the pregnancy, as well as the clinical, especially neurological, development of the child over 3 years. This case report documents the power of neuroplasticity, leading to comparably good neurological outcome in an extensive, likely acquired cortical malformation. Further, it emphasises the importance of a thorough prenatal imaging characterisation of malformations of cortical development for optimal prenatal counselling of these cases.

Perinatal and postpartum care during the COVID-19 pandemic: A nationwide cohort study.

BACKGROUND: This study aimed to analyze perinatal outcomes and adverse events during the COVID-19 pandemic's first wave to help direct decision making in future waves. METHODS: This study was an epidemiological cohort study analyzing comprehensive birth registry data among all 80 obstetric departments in Austria. Out of 469 771 records, 468 348 were considered eligible, whereof those with preterm delivery, birthweight <500 g, multiple fetuses, fetal malformations and chromosomal anomalies, intrauterine fetal death, maternal cancer, HIV infection, and/or inter-hospital transfers were excluded. Women who delivered between January and June 2020 were then classified as cases, whereas those who delivered between January and June 2015-2019 were classified as controls. Perinatal outcomes, postpartum hospitalization, and adverse events served as outcome measures. RESULTS: Of 33 198 cases and 188 225 controls, data analysis showed significantly increased rates of labor induction, instrumental delivery, obstetric anesthesia, NICU transfer, and 5-min Apgar score below 7 during the COVID-19 period. There was a significantly shorter length of postpartum hospitalization during the COVID-19 period compared with the non-COVID-19 period (3.1 ± 1.4 vs 3.5 ± 1.5 days; P < .001). Significantly more women opted for short-stay delivery during the COVID-19 period (3.7% vs 2.4%; P < .001). Those who delivered during the COVID-19 period were also more likely to experience postpartum adverse events (3.0% vs 2.6%; P < .001), which was confirmed in the logistic regression model (odds ratio, 2.137; 95% confidence interval, 1.805-2.530; P < .001). CONCLUSIONS: Perinatal and postpartum care during the first wave of the COVID-19 pandemic differed significantly from that provided before. Increased rates of adverse events underline the need to ensure access to high-quality obstetric care to prevent collateral damage.

Radiotherapy-Induced Fatigue in Breast Cancer Patients.

BACKGROUND: A large proportion of breast cancer patients who undergo adjuvant radiotherapy suffer from radiotherapy-induced fatigue. The possible causative factors of this specific side effect are diverse. SUMMARY: Prevalence, duration, and severity of radiotherapy-induced fatigue are dependent on the type of radiotherapy, as well as on the irradiated volume, dose scheme, on the number of radiation fields, the combination with other treatments, diurnal rhythm, smoking, and time-to-hospitalization. Recommended treatments include non-pharmacologic interventions, such as physical and psychosocial interventions. Pharmacologic therapies include treatment with methylphenidate and modafinil. In addition to its early detection with standardized instruments, adequate education to breast cancer patients about risks and predisposing factors of radiotherapy-induced fatigue is essential. Multidimensional strategies help to maintain the patients' quality of life and therefore guarantee treatment adherence and efficacy. KEY MESSAGES: Radiotherapy-induced fatigue is an underreported, underdiagnosed, and undertreated side effect. This review provides an overview of radiotherapy-induced fatigue in breast cancer patients receiving adjuvant radiotherapy.

Tissue Sodium Concentration Quantification at 7.0-T MRI as an Early Marker for Chemotherapy Response in Breast Cancer: A Feasibility Study.

Background Tissue sodium concentration (TSC) is elevated in breast cancer and can determine chemotherapy response. Purpose To test the feasibility of using a sodium 23 (23Na) MRI protocol at 7.0 T for TSC quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer and to determine whether those quantitative values provide additional information about efficacy. Materials and Methods Women with primary breast cancer were included in this prospective study. From July 2017 to June 2018, participants underwent 7.0-T 23Na MRI. Multichannel data sets were acquired with a density-adapted, three-dimensional radial projection reconstruction pulse sequence. Two-dimensional tumor size and TSC were evaluated before and after the first and second chemotherapy cycle, and statistical tests were performed based on the presence or absence of a pathologic complete response (pCR). Results Fifteen women with breast cancer and six healthy women were enrolled. The mean baseline tumor size in women with a pCR was 7.0 cm2 ± 5.0 (standard deviation), and the mean baseline tumor size in women without a pCR was 19.0 cm2 ± 12.0. After the first chemotherapy cycle, women with a pCR showed a reduced tumor size of 32.9% (2.3 cm2/7.0 cm2), compared with 15.3% (2.9 cm2/19.0 cm2) in those without a pCR. The areas under the receiver operating characteristic curve for tumor size reduction after the first and second chemotherapy cycle were 0.73 (95% CI: 0.09, 0.50; P = .12) and 0.93 (95% CI: 0.04, 0.60; P < .001), respectively. Women with a pCR had a mean baseline TSC of 69.4 mmol/L ± 6.1, with a reduction of 12.0% (8.3 mmol/L), whereas those without a pCR had a mean baseline TSC of 71.7 mmol/L ± 5.7, with a reduction of 4.7% (3.4 mmol/L) after the first cycle. The areas under the receiver operating characteristic curve for TSC after the first and second cycles were 0.96 (95% CI: 0.86, 1.00; P < .001) and 1.000 (95% CI: 1.00, P < .001), respectively. Conclusion Using 7.0-T MRI for tissue sodium concentration quantification to predict early treatment outcomes of neoadjuvant chemotherapy in breast cancer is feasible, with reduced tissue sodium concentration indicative of cancer response. © RSNA, 2021 Online supplemental material is available for this article.

Receptor Discordance of Metastatic Breast Cancer Depending on the Molecular Subtype.

INTRODUCTION: Almost 30% of all women with early-stage breast cancer develop metastases. Treatment of metastatic disease is often based on the immunohistochemical information of the primary tumor, despite possible discordance of the hormone and Her2 receptor status. OBJECTIVES: The aim of this study was to compare the receptor status of the primary tumor with the metastasis, and to evaluate for receptor discordance with regard to the molecular subtype, receptor status, and the localization of the metastases. METHODS: We retrospectively analyzed the data of all consecutive women with metastatic breast cancer, who underwent treatment at the Medical University Vienna between 2009 and 2016. Associations were calculated using the χ2or Fisher's exact test; years from primary diagnosis to metastatic disease were calculated using the Kaplan-Meier method. RESULTS: We identified 213 metastatic breast cancer patients, of whom 67 (31.5%) showed a discordant receptor status. Out of 32 patients with luminal A subtype, 14 (43.8%) had a switch of at least one receptor; 27 of 53 patients (50.9%) with luminal B subtype and 21 of 32 patients (65.6%) with Her2+ subtype showed receptor discordance; for triple-negative disease, 5 of 19 patients (36.3%) had a switch of at least one receptor. In 63 samples of bone metastases, 13 (20.6%) had discordant estrogen receptor status (p = 0.04). In 55 samples of bone metastases, 35 (63.3%) had discordant Her2 status (p = 0.002). CONCLUSIONS: Our data show high rates of receptor discordance in metastatic breast cancer. Apart from the primary tumor, the immunohistochemical receptor status of the metastasis needs to be verified. This can lead to a change in treatment and prognosis.

Challenge of diagnosing pyoderma gangrenosum after caesarean section.

Pyoderma gangrenosum is a neutrophilic skin disease that leads to extensive, painful, necrotic ulcerations, particularly at surgical sites. As obstetric cases with pyoderma gangrenosum are rare and, therefore, often misdiagnosed initially, it is important to raise awareness about this rare complication. Here, we describe a patient who presented with pyoderma gangrenosum at the surgical site 4 days after undergoing a caesarean section. The erythema was initially misdiagnosed as wound infection, and the patient, who was experiencing pain, underwent antibiotic treatment and surgical wound debridement. When the wound was unresponsive to these treatments, a dermatologist was consulted who suspected pyoderma gangrenosum and began a high-dose corticosteroids therapy, which led to a fulminant improvement of the local wound. In conclusion, the rare diagnosis of pyoderma gangrenosum should be considered in the differential diagnosis of a suspected surgical wound infection. Early interdisciplinary treatment is essential to avoid further complications.

7T CEST MRI: A potential imaging tool for the assessment of tumor grade and cell proliferation in breast cancer.

OBJECTIVES: To investigate the feasibility of chemical exchange saturation transfer (CEST) MRI in patients with breast carcinomas and possible correlations between magnetization transfer asymmetry (MTRasym) values and histological features, such as tumor grade and the Ki-67 proliferation index. MATERIALS AND METHODS: Nine healthy subjects and 18 female patients were enrolled for this study. The imaging protocol for the patients consisted of diffusion-weighted imaging (DWI), CEST imaging, and T1-weighted, contrast-enhanced (CE)-MRI. CEST was performed using a 3D gradient echo (GRE) sequence, employing eight pre-saturation pulses of a duration of 50 ms and a duty cycle (DC) of 80%, with a mean amplitude of the saturation pulse train of 1 µT. The Z-spectrum was plotted and MTRasym values calculated for the frequency of the maximum of MTRasym curve, were correlated with the Ki-67 proliferation index and apparent diffusion coefficient (ADC). Patient data were statistically assessed using the Games-Howell post-hoc and Pearson's correlation test. RESULTS: Different tumor types had asymmetry peaks at different positions of Z-spectrum. MTRasym (mean ±â€¯SD) (%) calculated for G1 (3.0 ±â€¯0.3; range: 2.70-3.50) was not significantly lower than for G2 (4.50 ±â€¯1.30; range: 3.20-6.50; p = 0.066). In contrast, the increase in MTRasym between G1 and G3 (6.40 ±â€¯1.70; range: 4.80-9.80) lesions was significant (p = 0.007). No significant difference was observed between G2 and G3 with regard to MTRasym (p = 0.089). There was a strong positive correlation between the MTRasym, and Ki-67 proliferation index (r = 0.890; p = 0.001), while there was a moderate negative correlation between MTRasym and ADC values (r = -0.506; p = 0.027). CONCLUSIONS: Calculated MTRasym demonstrates a strong positive correlation with tumor proliferation and has the potential to become a valuable biomarker for breast tumor characterization.

Evaluation of Reproductive Concerns and Biographical Impact of Breast Cancer in Young Patients.

BACKGROUND: This study evaluates interventions offered to young breast cancer (BC) patients, including fertility preservation, genetic testing, and counseling for parenthood concerns, and analyzes the effect of BC on biographical issues. METHODS: Women who were diagnosed with BC at the age of 18-40 years and who underwent treatment at the Breast Center, Ludwig-Maximilian University (LMU) in Munich between 2006 and 2013, were eligible for this study. Patients received a self-developed questionnaire which covered the following topics: fertility preservation, family planning, genetic testing, parenthood concerns and children's needs, partnership status, and employment situation. RESULTS: Re-evaluating their initial decision on fertility preservation, 76.4% of patients reported satisfaction with their decision. After BC diagnosis, 45.8% reported to have maternal desire, but only 21.7% actually planned to have children. 41.7% of patients missed sufficient counseling regarding parenthood concerns. Analysis of individual employment situations showed that the time period until the return to work was longer in patients who received chemotherapy. The majority of patients (71.6%) did not report changes in their partnership status. CONCLUSION: Young BC survivors report a lack of communication related to parenthood concerns and future conception, but are satisfied with counseling regarding fertility preservation and genetics.

MRI-based quantification of residual fibroglandular tissue of the breast after conservative mastectomies.

PURPOSE: Skin-sparing and nipple-sparing mastectomies (SSM; NSM) remove the breast's fibroglandular tissue (FGT), thereby reducing breast cancer risk. The postoperative presence of residual FGT (RFGT) is associated with remaining cancer risk. This study evaluated the role of MRI in the quantitative assessment of RFGT and its impact on the estimation of the remaining breast cancer risk. METHODS: The postoperative MRI scans (following EUSOMA recommendations) of 58 patients who had undergone SSM or NSM between 2003 and 2013, as well as preoperative MRI scans that were available in 25 of these patients, were retrospectively evaluated for the presence and location of RFGT by three radiologists. Two different observers quantitatively assessed the volume and percentage of retromamillary and other RFGT (RFGTrm and RFGTother) were assessed. The Fisher's exact test, the Student's t-test, and intraclass coherence were used to compare patient groups and to assess reproducibility. RESULTS: RFGT was found in 20% of all breasts and significantly more frequently after NSM than SSM (50% vs. 13%, p = .003). RFGTrm and RFGTother were more prevalent after NSM (p < 0.001; p = .127). RFGT ranged from 0.5 to 26% of the preoperative FGT, with higher percentages after NSM than SSM (p = .181). CONCLUSIONS: The prevalence and percentage of RFGT found on MRI indicate a considerable remaining postoperative breast cancer risk in some women.

An sFlt-1:PlGF ratio of 655 is not a reliable cut-off value for predicting perinatal outcomes in women with preeclampsia.

OBJECTIVES: The ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) is increased in preeclampsia. This study evaluated perinatal outcomes in cases with an sFlt-1:PlGF ratio above 655. STUDY DESIGN: We retrospectively analyzed data from all consecutive women with singleton pregnancies who presented with clinically manifest preeclampsia and underwent immediate sFlt-1:PlGF assessment. Cases with an sFlt-1:PlGF ratio ≥ 655 were matched 1:1 for gestational age to controls with a ratio < 655. MAIN OUTCOME MEASURES: The 5-min Apgar score and the arterial cord pH. RESULTS: There was a significant association of sFlt-1:PlGF ratios ≥ 655 with fetal distress (40% in cases vs. 3.3% in controls; p < .01) and neonatal sepsis (23.3% vs. 0%; p = .02), but not with impaired Apgar score (9 vs. 9 at 5 min; p = .45) or lower arterial cord pH (7.24 ±â€¯0.09 vs. 7.26 ±â€¯0.08; p = .73). Perinatal mortality (20% vs. 16.7%; p = .9), intrauterine growth restriction (IUGR; 30% vs. 13.3%; p = .2), and small-for-gestational-age fetuses (SGA; 30% vs. 16.7%; p = .35) were proportionally distributed among cases and controls. IUGR and SGA diagnoses were most common in cases with sFlt1:PlGF ratios ≥ 1000, as was respiratory distress. CONCLUSIONS: An sFlt-1:PlGF ratio above 655 is not predictive of impaired perinatal outcomes, and insufficiently reliable for predicting outcomes in cases with clinical signs of preeclampsia. Our data suggest that an extremely high sFlt-1:PlGF ratio above 1000 might be more useful.

Influence of Orally Administered Probiotic Lactobacillus Strains on Vaginal Microbiota in Women with Breast Cancer during Chemotherapy: A Randomized Placebo-Controlled Double-Blinded Pilot Study.

BACKGROUND: Due to chemotherapy and estrogen deprivation therapy, genitourinary syndrome of menopause is a common condition in breast cancer patients. We aimed to determine the effect of an orally administered Lactobacillus preparation on the vaginal microbiota in breast cancer patients. METHODS: Postmenopausal breast cancer patients receiving chemotherapy, with vaginal atrophy and an intermediate vaginal microbiota (Nugent score 4-6), were either randomized to the intervention group receiving probiotic capsules of 4 Lactobacillus species or to the control group receiving placebo twice daily for 2 weeks. Consecutive vaginal swabs were taken at baseline, 1 day after administration of the last capsule (follow-up 1), and after 1 week (follow-up 2) in 22 patients (11 vs. 11). RESULTS: We observed a positive influence on the vaginal microbiota in 7/11 (63%) women in the intervention group, and 4/11 (36%) women in the control group. There was a shift in Nugent score towards normal microbiota levels in the intervention group (-1.3 at follow-up 1, -0.45 at follow-up 2) and a significant deterioration of the Nugent score in the control group (+0.4 at follow-up 1, +2.5 at follow-up 2). CONCLUSION: The orally administered Lactobacillus preparation has the potential to improve the vaginal microbiota in women undergoing chemotherapy for breast cancer.

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

PURPOSE: The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. METHODS: We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m2 at baseline were considered obese, whereas those with a BMI <30 kg/m2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. RESULTS: Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10-4-0.81; p = 0.025). CONCLUSIONS: Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity.

Adverse Events of Trastuzumab Emtansine (T-DM1) in the Treatment of HER2-Positive Breast Cancer Patients.

The human epidermal growth factor receptor 2 (HER2) is commonly associated with poor prognosis and is overexpressed in approximately 15-20% of all breast cancers. The introduction of HER2-targeted therapies led to significant improvement in the prognosis of patients with HER2-positive breast cancer, for both early and advanced disease. These targeted therapies include the antibodies trastzumab and pertuzumab, the tyrosine kinase inhibitor lapatinib, and the antibody-drug conjugate trastuzumab emtansine (T-DM1). T-DM1 combines the anti-tumor activity of trastuzumab with that of DM1, a highly potent derivative of the anti-microtubule agent maytansine, resulting in increased anti-tumor activity. Notably, this agent has been demonstrated to be safe and is associated with low toxicity rates. However, maytansinoid, the cytotoxic component of T-DM1, does have the potential to induce various adverse events, particularly radiation necrosis, when used in combination with stereotactic radiosurgery. In this review, we aimed to summarize the current literature regarding T-DM1 safety and toxicity, with special emphasis on the existing landmark studies.

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

BACKGROUND: Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. METHODS: A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. RESULTS: In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were inconclusive regarding bacterial vaginosis (± candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. CONCLUSIONS: Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

Quantitative Sodium MR Imaging at 7 T: Initial Results and Comparison with Diffusion-weighted Imaging in Patients with Breast Tumors.

Purpose To investigate the clinical feasibility of a quantitative sodium 23 ((23)Na) magnetic resonance (MR) imaging protocol developed for breast tumor assessment and to compare it with 7-T diffusion-weighted imaging (DWI). Materials and Methods Written informed consent in this institutional review board-approved study was obtained from eight healthy volunteers and 17 patients with 20 breast tumors (five benign, 15 malignant). To achieve the best image quality and reproducibility, the (23)Na sequence was optimized and tested on phantoms and healthy volunteers. For in vivo quantification of absolute tissue sodium concentration (TSC), an external phantom was used. Static magnetic field, or B0, and combined transmit and receive radiofrequency field, or B1, maps were acquired, and image quality, measurement reproducibility, and accuracy testing were performed. Bilateral (23)Na and DWI sequences were performed before contrast material-enhanced MR imaging in patients with breast tumors. TSC and apparent diffusion coefficient (ADC) were calculated and correlated for healthy glandular tissue and benign and malignant lesions. Results The (23)Na MR imaging protocol is feasible, with 1.5-mm in-plane resolution and 16-minute imaging time. Good image quality was achieved, with high reproducibility (mean TSC values ± standard deviation for the test, 36 mmol per kilogram of wet weight ± 2 [range, 34-37 mmol/kg]; for the retest, 37 mmol/kg ± 1 [range, 35-39 mmol/kg]; P = .610) and accuracy (r = 0.998, P < .001). TSC values in normal glandular and adipose breast tissue were 35 mmol/kg ± 3 and 18 mmol/kg ± 3, respectively. In malignant lesions (mean size, 31 mm ± 24; range, 6-92 mm), the TSC of 69 mmol/kg ± 10 was, on average, 49% higher than that in benign lesions (mean size, 14 mm ± 12; range, 6-35 mm), with a TSC of 47 mmol/kg ± 8 (P = .002). There were similar ADC differences between benign ([1.78 ± 0.23] × 10(-3) mm(2)/sec) and malignant ([1.03 ± 0.23] × 10(-3) mm(2)/sec) tumors (P = .002). ADC and TSC were inversely correlated (r = -0.881, P < .001). Conclusion Quantitative (23)Na MR imaging is clinically feasible, may provide good differentiation between malignant and benign breast lesions, and demonstrates an inverse correlation with ADC. (©) RSNA, 2016 Online supplemental material is available for this article.

Role of Lactobacillus Species in the Intermediate Vaginal Flora in Early Pregnancy: A Retrospective Cohort Study.

BACKGROUND: Poor obstetrical outcomes are associated with imbalances in the vaginal flora. The present study evaluated the role of vaginal Lactobacillus species in women with intermediate vaginal flora with regard to obstetrical outcomes. METHODS: We retrospectively analysed data from all women with singleton pregnancies who had undergone routine screening for asymptomatic vaginal infections at our tertiary referral centre between 2005 and 2014. Vaginal smears were Gram-stained and classified according to the Nugent scoring system as normal flora (score 0-3), intermediate vaginal flora (4-6), or bacterial vaginosis (7-10). Only women with intermediate vaginal flora were investigated. Women with a Nugent score of 4 were categorised into those with and without Lactobacilli. Follow-up smears were obtained 4-6 weeks after the initial smears. Descriptive data analysis, the Welch's t-test, the Fisher's exact test, and multiple regression analysis with adjustment for confounders were performed. Gestational age at delivery and birth weight were the outcome measures. RESULTS: At antenatal screening, 529/8421 women presented with intermediate vaginal flora. Amongst these, 349/529 (66%) had a Nugent score of 4, 94/529 (17.8%) a Nugent score of 5, and 86/529 (16.2%) a Nugent score of 6. Amongst those with a Nugent score of 4, 232/349 (66.5%) women were in the Lactobacilli group and 117/349 (33.5%) in the Non-Lactobacilli group. The preterm delivery rate was significantly lower in the Lactobacilli than in the Non-Lactobacilli group (OR 0.34, CI 0.21-0.55; p<0.001). Mean birth weight was 2979 ± 842 g and 2388 ± 1155 g in the study groups, respectively (MD 564.12, CI 346.23-781.92; p<0.001). On follow-up smears, bacterial vaginosis rates were 9% in the Lactobacilli and 7.8% in the Non-Lactobacilli group. CONCLUSIONS: The absence of vaginal Lactobacillus species and any bacterial colonisation increases the risks of preterm delivery and low birth weight in women with intermediate vaginal flora in early pregnancy.