A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.

BACKGROUND: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. METHODS: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. RESULTS: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. CONCLUSIONS: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.

Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

Introduction: Studies have shown that pregnant women with COVID-19 have a higher risk of intensive care unit admission and invasive mechanical ventilation support than non-pregnant women. Pregnancy-associated physiological changes in respiratory function may contribute to the elevated risk. Alteration in lung volumes and capacities are attributed to the mechanical impediment caused by the growing fetus. Multiple pregnancies may therefore compromise functional lung capacity earlier than singleton pregnancies and contribute to severe respiratory symptoms of COVID-19. Materials and Methods: A total of 5514 women with a symptomatic SARS-CoV-2 infection during pregnancy registered in the COVID-19 Related Obstetric and Neonatal Outcome Study were included. The COVID-19-related adverse maternal outcomes were compared in 165 multiple versus 5349 singleton pregnancies. Combined adverse maternal outcome was defined as presence of COVID-19-related hospitalization and/or pneumonia and/or oxygen administration and/or transfer to ICU and/or death. Multivariate logistic regression was used to estimate the odds ratios and 95% confidence intervals were calculated. Results: The frequency of dyspnea, likelihood of developing dyspnea in a defined pregnancy week and duration of the symptomatic phase of the COVID-19 infection did not differ between the two groups. On average, COVID-19-related combined adverse outcome occurred earlier during pregnancy in women expecting more than one child than in singleton pregnancies. The overall incidence of singular and combined COVID-19-associated adverse maternal outcomes was not significantly different between groups. However, regression analysis revealed that multiple gestation, preconceptional BMI > 30 kg/m 2 and gestational age correlated significantly with an increased risk of combined adverse maternal outcome. Conversely, maternal age and medically assisted reproduction were not significant risk factors for combined adverse maternal outcome. Conclusion: Our data show that multiple gestation alone is a risk factor for COVID-19-associated combined adverse maternal outcome. Moreover, severe courses of COVID-19 in women expecting more than one child are observed earlier in pregnancy than in singleton pregnancies.

Prediction of spontaneous preterm birth using CCL2 and CXCL10 in maternal serum of symptomatic high-risk pregnant women: a prospective cohort study.

INTRODUCTION: CCL2 and CXCL10 are putative biomarkers for the prediction of spontaneous preterm birth. This study evaluates these markers in a cohort of pregnant high-risk women. MATERIAL AND METHODS: In our prospective study, we included 109 women with signs of preterm labor between 20 + 0 and 31 + 6 weeks of gestation. Inclusion criteria were regular (< 3/30 min) or painful contractions, cervical length < 25 mm or a history of previous preterm birth (PTB). Blood samples were obtained upon first admission to our clinic. Biomarker concentrations were measured using pre-coated sandwich immunoassays (ELISA). Primary study outcome was spontaneous preterm birth < 34 weeks, secondary outcome was delivery < 37 weeks or within seven days after study inclusion. RESULTS: Sixteen women (14.7%) delivered < 34 weeks and twenty women between 34 + 0 and 36 + 6 weeks (18.4%). Six patients (5.5%) gave birth within seven days after study admission. CXCL10 showed higher medium serum levels in women with PTB < 34 weeks (115 pg/ml compared to 61 pg/ml ≥ 34 weeks; p < 0.001) and < 37 weeks (103 pg/ml vs. 53 pg/ml; p < 0.001). In contrary, lower CCL2 serum levels were associated with PTB < 34 weeks (46 pg/ml vs. 73 pg/ml; p = 0.032) and birth within 7 days (25 pg/ml vs. 73 pg/ml; p = 0.008). The CXCL10/CCL2-ratio further improved the predictive model with a ROC-AUC of 0.83 (95% CI 0.73-0.93, p < 0.001) for delivery < 34 weeks. These corresponds to a sensitivity, specificity and positive predictive value of 0.67, 0.86 and 0.43 at a cut-off of 2.2. CONCLUSION: Low maternal serum CCL2 levels are associated with a higher risk of preterm delivery within seven days. High CXCL10 serum levels are more associated with a high risk for preterm birth < 34 weeks. Elevated CXCL10/CCL2-ratio is showing the best predictive performance. TRIAL REGISTRATION NUMBER (DRKS-ID): DRKS00010763, Registration date: September 02, 2016.

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

The Role of Acetylsalicylic Acid in the Prevention of Pre-Eclampsia, Fetal Growth Restriction, and Preterm Birth.

BACKGROUND: Recent studies suggest that low-dose acetylsalicylic acid (ASA) can lower pregnancy-associated morbidity. METHODS: This review is based on pertinent publications that were retrieved by a selective search in PubMed, with special attention to systematic reviews, metaanalyses, and randomized controlled trials. RESULTS: Current meta-analyses document a reduction of the risk of the occurrence of pre-eclampsia (RR 0.85, NNT 50), as well as beneficial effects on the rates of preterm birth (RR 0.80, NNT 37), fetal growth restriction (RR 0.82, NNT 77), and perinatal death (RR 0.79, NNT 167). Moreover, there is evidence that ASA raises the rate of live births after a prior spontaneous abortion, while also lowering the rate of spontaneous preterm births (RR 0.89, NNT 67). The prerequisites for therapeutic success are an adequate ASA dose, early initiation of ASA, and the identification of women at risk of pregnancy-associated morbidity. Side effects of treatment with ASA in this patient group are rare and mainly involve bleeding in connection with the pregnancy (RR 0.87, NNH 200). CONCLUSION: ASA use during pregnancy has benefits beyond reducing the risk of pre-eclampsia. The indications for taking ASA during pregnancy may be extended at some point in the future; at present, in view of the available evidence, it is still restricted to high-risk pregnancies.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Prediction of recurrent gestational diabetes mellitus: a retrospective cohort study.

BACKGROUND: Women after gestational diabetes mellitus (GDM) are at increased risk for development of GDM recurrence. It was the aim of our study to evaluate factors for prediction of risk of recurrence. METHODS: In this retrospective cohort study we included 159 women with GDM and a subsequent pregnancy. Putative risk factors for GDM recurrence were analyzed by logistic regression models. Results were compared to a cohort of age-matched women without GDM as controls (n = 318). RESULTS: The overall risk of GDM recurrence was 72.3% (115/159). Risk factors of recurrence were a body mass index (BMI) ≥ 30 kg/m2 before the index pregnancy (odds ratio (OR) 2.8 [95% CI 1.3-6.2], p = 0,008), a BMI ≥ 25 kg/m2 before the subsequent pregnancy (OR 2.7 [95% CI 1.3-5.8]. p = 0.008), a positive family history (OR 4.3 [95% CI 1.2-15.4], p = 0.016) and insulin treatment during the index pregnancy (OR 2.3 [95% CI 1.1-4.6], p = 0.023). Delivery by caesarean section (index pregnancy) was of borderline significance (OR 2.2 [95% CI 0.9-5.2], p = 0.069). Interpregnancy weight gain, excessive weight gain during the index pregnancy and fetal outcome where not predictive for GDM recurrence. Neonates after GDM revealed a higher frequency of transfer to intensive care unit compared to healthy controls (OR 2.3 [95% CI 1.1-4.6], p = 0.0225). The best combined risk model for prediction of GDM recurrence including positive family history and a BMI ≥ 25 kg/m2 before the subsequent pregnancy revealed moderate test characteristics (positive likelihood ratio 7.8 [95% CI 1.1-54.7] and negative likelihood ratio 0.7 [95% CI 0.6-0.9]) with a positive predictive value of 96.6% in our cohort. CONCLUSIONS: A positive family history of diabetes mellitus in combination with overweight or obesity were strongly associated with recurrence of a GDM in the subsequent pregnancy. Normalization of the pregravid BMI should be an effective approach for reducing the risk of GDM recurrence.

Assessment of Quality of Life in Gestational Diabetes Mellitus Care-Study Protocol of the GDM-QOL Project.

In recent years, the concept of quality of life (QoL) has gained significant importance within health care and clinical research, e.g., as in patient-reported outcomes. In gestational diabetes mellitus (GDM) care, enhancing QoL through reasonable interventions is considered equally important as achieving metabolic control and preventing complications in the treatment process, leading to the suggestion that QoL assessment should be implemented as a clinical standard in GDM care. Although a considerable number of questionnaires for the measurement of general as well as health-related and diabetes-specific QoL are frequently used in GDM research, a validated QoL questionnaire tailored to women with GDM does not exist in German-speaking countries. To develop and test such an instrument, we plan to conduct the following steps: (a) translate the Persian questionnaire GDMQ-36, the only GDM-specific questionnaire to date; (b) conduct expert ratings as well as pretests featuring cognitive debriefings and structured interviews with women suffering from GDM for evaluating comprehensibility, face and content validity; (c) pilot and validate the preliminary questionnaire in terms of testing its psychometric performance (e.g., via confirmatory factor analysis). The resulting GDM-specific questionnaire will facilitate a broader perspective of the pregnant women's expectations, needs, impairments, and burdens related to their disease, and its treatment. This enables physicians and other health professionals to establish an individualized treatment plan and to provide customized information, support, and psychological counseling, which helps to optimize the provided care.

Correction: Multiple Gestation as a Risk Factor for SARS-CoV-2-Associated Adverse Maternal Outcome: Data From the COVID-19 Related Obstetric and Neonatal Outcome Study (CRONOS).

[This corrects the article DOI: 10.1055/a-2196-6224.].

Risk Factors of Preterm Birth in Women After Local Treatment of Cervical Intraepithelial Neoplasia - a Retrospective Cohort Study.

Purpose A previous cervical intraepithelial neoplasia is associated with an increased obstetrical risk. It was the aim of the study to identify risk factors of preterm birth in patients with cervical intraepithelial neoplasia in dependence of the treatment modality (excisional vs. ablative). Methods Women with treated cervical intraepithelial neoplasia and subsequent pregnancy (n = 155) were included in this retrospective study. Methods of treatment were either conization by large loop excision of the transformation zone (LLETZ) or ablative laser vaporization. Results Of the total population 60.6% (n = 94) had a conization and 39.4% (n = 61) a laser vaporization alone. The frequency of preterm birth < 37 weeks was 9.7% (n = 15) without differences between conization and laser (11.7 vs. 6.7%, p = 0.407) with an odds ratio (OR) of 1.9 (95% confidence interval [CI] 0.6-6.2). Preterm birth < 34 weeks was found in 2.6% (n = 4), of which all had a conization (4.3 vs. 0%, p = 0.157). Risk factors for preterm birth were repeated cervical intervention (OR 4.7 [95% CI 1.5-14.3]), especially a combination of conization and laser ablation (OR 14.9 [95% CI 4.0-55.6]), age at intervention < 30 years (OR 6.0 [95% CI 1.3-27.4]), a history of preterm birth (OR 4.7 [95% CI 1.3-17.6]) and age at delivery < 28 years (OR 4.7 [95% CI 1.5-14.3]). Conclusion The large loop excision of the transformation zone as a modern, less invasive ablative treatment did not obviously increase the risk of preterm birth compared to laser vaporization. The most important risk factor for preterm delivery was the need of a repeated intervention, especially at younger age. We assume that the persistence or recurrence of the cervical intraepithelial neoplasia following a high-risk human papillomavirus infection is mainly responsible for the observed effect.

Radiopaque tissue transfer and X-ray system versus standard specimen radiography for intraoperative margin assessment in breast-conserving surgery: randomized clinical trial.

BACKGROUND: Reduction of positive margin rate (PMR) in breast-conserving surgery (BCS) of non-palpable breast cancer remains a challenge. The efficacy of intraoperative specimen radiography (SR) is unclear. This randomized trial evaluated whether the PMR was reduced by the use of devices that allow precise localization of the affected margins. METHODS: Patients with microcalcification-associated breast cancer undergoing planned BCS were enrolled. Study participants were randomized to receive either SR with radiopaque tissue transfer and X-ray system (KliniTrayTM) or the institutional standard procedure (ISO). In all patients with a radiological margin less than 5 mm, an immediate re-excision was conducted. The primary outcome was the PMR. Risk factors for positive margins and the effect of immediate re-excision on final surgery were secondary analyses. RESULTS: Among 122 randomized patients, 5 patients were excluded due to the extent of primary surgery and 117 were available for analysis. Final histopathology revealed a PMR of 31.7 per cent for the KliniTrayTM group and 26.3 per cent for the ISO group (P = 0.127). Independent factors for positive margins were histological tumour size more than 30 mm (adjusted OR (aOR) 10.73; 95 per cent c.i. 3.14 to 36.75; P < 0.001) and specimen size more than 50 mm (aOR 6.65; 95 per cent c.i. 2.00 to 22.08; P = 0.002). Immediate re-excision due to positive SR led to an absolute risk reduction in positive margins of 13.6 per cent (from 42.7 to 29.1 per cent). CONCLUSION: Specimen orientation with a radiopaque tissue transfer and X-ray system did not decrease the PMR in patients with microcalcification-associated breast cancer; however, SR and immediate re-excision proved to be helpful in the reduction of PMR. REGISTRATION NUMBER: DRKS00011527 (https://www.drks.de).

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Radiological Underestimation of Tumor Size as a Relevant Risk Factor for Positive Margin Rate in Breast-Conserving Therapy of Pure Ductal Carcinoma In Situ (DCIS).

Background: Radiological underestimation of the actual tumor size is a relevant problem in reaching negative margins in ductal carcinoma in situ (DCIS) associated with microcalcifications in breast-conserving therapy (BCT). The aim of this study is to evaluate whether the radiological underestimation of tumor size has an influence on the histopathological margin status. Methods: Patients who underwent BCT with preoperatively diagnosed pure DCIS were included (pooled analysis of two trials). Multiple factors were analysed regarding radiological underestimation ≥10 mm. Radiological underestimation was defined as mammographic minus histological tumor size in mm. Results: Positive margins occurred in 75 of 189 patients. Radiological underestimation ≥10 mm was an independent influencing factor (OR 5.80; 95%CI 2.55−13.17; p < 0.001). A radiological underestimation was seen in 70 patients. The following parameters were statistically significant associated with underestimation: pleomorphic microcalcifications (OR 3.77; 95%CI 1.27−11.18), clustered distribution patterns (OR 4.26; 95%CI 2.25−8.07), and mammographic tumor sizes ≤20 mm (OR 7.47; 95%CI 3.49−15.99). Only a mammographic tumor size ≤20 mm was an independent risk factor (OR 6.49; 95%CI 2.30−18.26; p < 0.001). Grading, estrogen receptor status, and comedo necrosis did not influence the size estimation. Conclusion: Radiological underestimation is an independent risk factor for positive margins in BCT of DCIS associated with microcalcifications predominantly occurring in mammographic small tumors.

Prevalence, Clinical Significance and Risk Factors for Developing Scar Pain and Sensibility Disorders in Breast Cancer Patients after Breast-Conserving Therapy and Mastectomy.

INTRODUCTION: The aim of this study was to gather information on the prevalence and risk factors for scar pain and sensibility disorders after breast cancer surgery, as only limited information of these complaints are available. MATERIAL AND METHODS: A clinical cohort study using a non-validated questionnaire was conducted among women who presented to routine follow-up at the Breast Cancer Center Rostock, Germany. The subjects were informed that the subjective perception and sensation were in the foreground and that the questionnaire had to be filled out independently according to the current feeling. RESULTS: Overall 175 patients could be evaluated. The prevalence of scar pain was 30.8% after breast conserving therapy (BCT) and 34.5% after mastectomy. Following BCT 87.5%, respectively 81.8% of women after mastectomy were very satisfied or satisfied with the scarring. Sensory disorders were increased in the mastectomy group (p = 0.001). Scar pain after previous surgery was a risk factor to develop sensory disorders after BCT (p = 0.008) and mastectomy (p = 0.029). For patients receiving mastectomy, sensory disorders after previous breast surgeries increased the risk for sensory disorders (p = 0.029). Smoking was a risk factor for sensory disorders after mastectomy (p = 0.048). Multivariate analysis could not confirm any of the risk factors. CONCLUSION: This study demonstrated a high satisfaction with scarring after breast surgery and a low level of scar pain. A lack of postoperative information, as well as a low level of actually performed scar care after surgery were observed. Increased focus should be on improved information on postoperative scare care.

Prediction of Spontaneous Preterm Birth in At-risk Women Using Thrombospondin 1 from Cervicovaginal Fluid: A Prospective Observational Study.

Introduction Thrombospondin 1, desmoplakin and stratifin are putative biomarkers for the prediction of preterm birth. This study aimed to validate the predictive capability of these biomarkers in patients at risk of preterm birth. Materials and Methods We included 109 women with symptoms of threatened spontaneous preterm birth between weeks 20 0/7 and 31 6/7 of gestation. Inclusion criteria were uterine contractions, cervical length of less than 25 mm, or a personal history of spontaneous preterm birth. Multiple gestations were also included. Samples of cervicovaginal fluid were taken before performing a digital examination and transvaginal ultrasound. Levels of cervicovaginal thrombospondin 1, desmoplakin and stratifin were quantified by enzyme-linked immunosorbent assays. The primary endpoint was spontaneous preterm birth before 34 + 0 weeks of gestation. Results Sixteen women (14.7%) delivered before 34 + 0 weeks. Median levels of thrombospondin 1 were higher in samples where birth occurred before 34 weeks vs. ≥ 34 weeks of gestation (4904 vs. 469 pg/mL, p < 0.001). Receiver operator characteristics analysis resulted in an area under the curve of 0.86 (p < 0.0001). At an optimal cut-off value of 2163 pg/mL, sensitivity, specificity, positive predictive value and negative predictive value were 0.94, 0.77, 0.42 and 0.99, respectively, with an adjusted odds ratio of 32.9 (95% CI: 3.1 - 345, p = 0.004). Multiple gestation, cervical length, and preterm labor had no impact on the results. Survival analysis revealed a predictive period of more than eight weeks. Levels of desmoplakin and stratifin did not differ between groups. Conclusion Thrombospondin 1 allowed long-term risk estimation of spontaneous preterm birth.

[Management of Infection in Threatened Preterm Birth - A Survey of German Perinatal Centers]. / Infektionsmanagement bei drohender Frühgeburt ­ eine Umfrage an deutschen Perinatalzentren.

INTRODUCTION: In spite of insufficient evidence, we assume a high willingness to diagnose and treat vaginal infections in threatened preterm births in Germany. METHODS: Online survey on the management of infection in threatened preterm birth in all 212 German perinatal centers. RESULTS: The response rate was 31.6% (n=67). 78.8% disclaim an empirical antibiotic treatment in threatened preterm birth below 34 weeks of gestation. Half of the remaining 14 centers always start an antibiotic treatment in cases with signs or symptoms of threatened preterm birth. 94% perform vaginal swabs for culture. 37.3% use a microscopic assessment by vaginal Nugent score or Amsel score. An abnormal vaginal microbiota is mostly treated (bacterial vaginosis 79.1%, n=53, Candida spp. 77.6%, n=52, Ureaplasma spp. 49.3%, n=33). After treatment, 70.1% agree with repeating the culture diagnosis. There is common consensus for antibiotic treatment in cases with preterm premature rupture of membranes. 72.6% favor a monotherapy with a ß-lactam antibiotic. Statements on duration of therapy were inconsistent, whereby 58% of centers treat for more than 7 days. CONCLUSION: In German perinatal centers, we observed a great willingness to diagnose and treat infections in threatened preterm birth. However, the management of infection is heterogeneous and partly contradicts the present guidelines.

The Significance of Preoperative Computed Tomography for Predicting Optimal Cytoreduction in Advanced Ovarian Cancer.

Introduction Optimal cytoreduction is the most important prognostic factor in advanced ovarian cancer. Although staging and assessment of operability are made by exploratory surgery, preoperative computed tomography (CT) of the abdomen is regarded as standard. The aim of this study was to examine various CT parameters with regard to prediction of optimal cytoreduction. Patients and Methods The retrospective study included 131 patients with ovarian cancer newly diagnosed between 2010 and 2014. Of these, n = 36 with FIGO stage I to IIB were excluded from the study. A preoperative abdominal CT was available for n = 75 of the 95 patients with FIGO stage IIC to IV. The CT scans underwent blinded review. The 11 evaluated CT parameters were examined by means of χ 2 test and logistic regression analysis with regard to the endpoints of macroscopic residual tumour and residual tumour > 1 cm. Survival analyses used the Kaplan-Meier method and log rank test. Results Of 75 patients, 28 (37.3%) had complete tumour resection and 26 (34.7%) had residual tumour ≤ 1 cm. Residual tumours > 1 cm were found in 21 (28%) patients, five of which were not resectable. Overall survival with residual tumour > 1 cm differed significantly from the group with no macroscopic residual tumour (p = 0.003) and with residual tumour ≤ 1 cm (p = 0.04). The CT parameters tumour foci in the diaphragm, mesocolon, greater omentum and peritoneum as well as ascites correlated with macroscopic residual tumour. In the multivariate logistic regression analysis only the CT parameter intraparenchymal liver metastasis was statistically significant with regard to prediction of suboptimal tumour resection (> 1 cm) (OR 8.04; 95% CI 1.57 - 42.4; p = 0.0134). The sensitivity, specificity, PPV and NPV were 37.5, 89.7, 66.7 and 72.2%. Conclusion Although risk parameters for suboptimal tumour reduction can be identified by CT of the abdomen, surgical exploration with histological confirmation of the diagnosis is essential because of the poor diagnostic accuracy.

Uterocervical angle as a predictor of preterm birth on a high-risk collective between 20 and 31 weeks of gestation: A cohort analysis.

INTRODUCTION: The cervical length (CL) measurement is a widely used method to estimate the risk of preterm birth. Due in particular to the high false-positive rate, the establishment of markers with improved test characteristics is a great challenge. A potential predictor of preterm birth is the uterocervical angle (UCA) and this additional measurement may improve the risk assessment. It was the aim of this study to compare the test properties of CL and UCA on patients at risk for preterm birth. MATERIAL AND METHODS: 109 patients with at least one of the following signs of threatening preterm birth between 20+0/7 and 31+6/7 weeks were included in a prospective cohort analysis: regular (>3/30 min) or painful uterine contractions, CL below 25 mm or a history of preterm birth. Exclusion criteria were premature rupture of membranes, hypertensive disorders, vaginal bleeding, surgical cerclage, Arabin pessary or cervical dilation of more than 30 mm. The determination of the UCA was carried out in a standardized manner using the image documents captured by vaginal sonographic CL measurement. The primary endpoint was preterm birth <34 weeks, secondary endpoints were delivery <37 weeks and within 7 days. RESULTS: The UCA was on average 103° and the mean UCA in preterm and term groups did not differ significantly (P = .924). The UCA was not predictive for threatened preterm birth, even if only singletons were considered. For CL the best predictive accuracy for preterm birth <34 weeks was observed at a cut-off value of 14 mm with sensitivity 0.50, specificity 0.80, positive predictive value 0.30, negative predictive value 0.90, positive likelihood ratio 2.4, negative likelihood ratio 0.6 and an odds ratio of 3.9 (95% confidence interval 1.3-11.7, P = .016). CONCLUSIONS: The assessment of UCA in patients at risk for preterm birth was not suitable to predict the probability of a threatened preterm birth. Measurement of UCA cannot be recommended in this situation.