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Background and purpose: To assess the impact of posterior fossa pilocytic astrocytoma (PA) removal in pediatric patients, with special focus on postoperative neurological outcome after repeated surgery for tumor remnants. Methods: Our institutional database was screened for patients with PA treated between 2000 and 2019. Patients ≤ 18 years of age with complete clinical records, preoperative contrast enhanced magnetic resonance imaging (MRI) and postoperative follow-up time of ≥ 6 months were suitable for study inclusion. Functional outcome was quantified with the modified Ranking Scale (mRS) score and assessed at admission, at discharge and at every follow-up investigation. Predictors of hydrocephalus, cranial nerve deficits and tumor recurrence were evaluated. Results: A total of 57 pediatric patients with a mean age of 7.7 ± 4.8 years were included in the analysis. 27 (47.3%) children suffered from hydrocephalus at diagnosis, out of which 19 (33.3%) required a subsequent VP-Shunt. 22 (39.3%) patients had a partial resection, of which 9 (40.9%) went through second-look surgery. 2 patients with initially radiological confirmation of complete resection, had a tumor recurrence at FU and needed second-look surgery. Among the children requiring second-look surgery, 7 (63.6%) had a complete resection. Favorable outcome (mRS≤2) after initial and second-look surgery was observed in 52 patients (91.2%). Univariate analysis identified tumor location in the floor of the 4th ventricle (p = 0.030), and repeated surgery for tumor remnant removal (p = 0.043) as predictors for post-operative cranial nerve deficits. Multivariate analysis confirmed this independent association. The incidence of tumor recurrence occurred more often in patients with previous partial resection (p = 0.009) as well as in lesions located in the cerebellar peduncles (p = 0.043). Partial resection remained an independent predictor after multivariate logistic regression analysis (p = 0.045). Conclusions: Incomplete resection of posterior fossa PA is a risk factor for tumor recurrence and repeated surgery to remove tumor remnants increases the risk of new postoperative deficits. Thus, the risk of iatrogenic deterioration due to second look surgery should be implemented in the primary pre- and intraoperative decision-making. CA Santos

To evaluate the predictive value of intraoperative neuromonitoring (IONM) in brainstem cavernous malformation (BSCM) surgery.Surgically treated patients with BSCM were included. All patients received IONM consisting of motor-evoked potentials (MEPs) and somatosensory-evoked potentials (SSEPs). Neurologic examination was conducted preoperatively and at discharge and follow-up3 months after BSCM removal. Demographic, radiographic, and clinical features were assessed. Study end points were new motor or somatosensory deficits and functional disability.A total of 62 patients were included. MEP decrease was associated with new motor deficits at discharge (P = 0.022), and SSEP decrease was associated with new somatosensory deficits at discharge (P0.001) and follow-up (P0.001). Sensitivity and specificity values for MEPs (discharge: 31% and 93%; follow-up: 33% and 91%) and SSEPs (discharge: 82% and 80%; follow-up: 85% and 79%) were calculated, respectively. Receiver operating characteristic analyses with area under the curve (AUC) metrics revealed acceptable performance of MEPs (AUC, 0.75; P = 0.022) and SSEPs (AUC, 0.72; P = 0.004) in predicting early deficits. Intraoperative decrease of MEPs (P = 0.047) and SSEPs (P = 0.017) was associated with early functional disability. Surgery-related subdural air accumulation impaired IONM reliability in predicting early (P = 0.048) and long-term (P = 0.013) deficits.Established IONM warning criteria may be valid for BSCM removal. However, surgical approaches in the sitting position significantly limit the predictive value of IONM, to some extent because of intraoperative pneumocephalus.

Vitamin D (vitD) is involved in immune regulation, and its receptor has been identified in several tissues including lung, adipose tissue, brain, and skin. Based on these observations, it has been suggested that vitD has an essential role not only in bone metabolism but also in other diseases such as atopic dermatitis (AD), bronchial asthma (BA), attention-deficit/hyperactivity disorder (ADHD), and obesity because the affected tissues express vitD receptors. Furthermore, obesity, AD, and BA are regarded as inflammatory diseases. Therefore, we hypothesized that vitD concentrations are lower in children with AD, BA, ADHD, and obesity compared to healthy children. We measured 25-hydroxyvitamin D concentrations in 235 children (60% boys, age 9.3±1.7years) with obesity, BA, AD, or ADHD and compared them to those of 3352 children from a healthy population. Additionally, parathyroid hormone was measured in the children with obesity, ADHD, BA, and AD. VitD concentrations were not lower in children with obesity, ADHD, BA, and AD compared to healthy children. In multiple regression analyses adjusted to migration background, time period of blood sample, age, and sex, VitD levels correlated significantly with the severity of AD measured by SCORing Atopic Dermatitis index and attention deficit measured by Conners questionnaire in ADHD. VitD levels were not linked to hyperactivity in ADHD, the severity of BA measured as forced expiration volume in the first second, or body mass index standard deviation score. Parathyroid hormone was not associated with the activity of any analyzed disease. In conclusion, most of our findings do not support the hypothesis that vitD is involved in the pathogenesis of these entities.

Objectives The aim of this study was to investigate, whether maternal serum levels of sFlt-1, PlGF and PAPP-A at third trimester of pregnancy are associated with late-onset PE and intrauterine growth retardation (IUGR) after 34 weeks of pregnancy. Methods This was a prospective study measuring the maternal serum levels of soluble tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF) and pregnancy-associated plasma protein-A (PAPP-A) at 32–37 weeks of pregnancy: 730 patients were enrolled and 676 had neither intrauterine growth restriction (IUGR) nor preeclampsia (PE) or pregnancy induced hypertension (PIH) throughout the pregnancy. 22 patients developed IUGR, 32 PE and 24 PIH. Results Linear regression analyses after adjusting for maternal age, gestational age at the blood sampling and maternal BMI showed associations between PE and serum sFlt-1 levels (Exp(s) = 3.29; 95% CI: 2.69–4.04), serum PlGF levels (Exp(s) = 0.18; 95% CI: 0.13–0.24), sFlt-1/PlGF ratio (Exp(s) = 15.59; 95% CI: 10.64–22.84) and serum PAPP-A (Exp(s) = 1.48; 95% CI 1.15–1.89). sFlt-1, PlGF and sFlt-1/PlGF-Ratio showed comparable area under the curve (AUC) estimates with a predictive ability to discriminate pregnancies developing PE and IUGR from controls. The predictive ability of PAPP-A for PE was only slightly better than chance. Conclusions This study supported the ability of a single measurement of sFlt-1/PlGF ratio at third trimester to predict PE and IUGR occurring after 34 weeks of pregnancy. However, larger multicentre studies are needed to replicate our results.

One measure to quantify the degree of dysregulation is allostatic load (AL). Typically, AL incorporates information on diverse biomarkers and is associated with health outcomes such as cardiovascular diseases or the incidence of coronary events (C-E).This study investigates the predictive performance of different AL scoring methods on the incidence of coronary events (C-E). This study also elaborates sex differences in the baseline risks of C-E and the AL associated risks of C-E.Longitudinal data analysis of the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcification, and Lifestyle) of 4327 participants free of C-E at study baseline aged 45-75. The data contains over 13 biomarkers measuring AL.After conducting multiple imputations on missing values on AL for 826 participants, the analysis sample consisted of N = 4327 participants. We applied the two most commonly used methods of AL scoring AL (count-based and Z-score) and a recently developed logistic regression weighting method (LRM) approach. Cox regression was used to predict the incidence of C-E for each AL score. Results were estimated without (M0) and with (M1) covariate adjustment, and in a final model (M2), with an interaction between AL and sex.We found no violation of the proportional hazard assumption and significant differences in the survival curves between the sexes for C-E (Log-rank test: prob. ChiAL scores are suitable for predicting C-E. Differences between the AL-scoring algorithms were only present after including interactions. We value the count-based method as suitable for clinical practice since its calculation is relatively simple, and performance was among the best. Interaction analysis revealed that despite strong sex differences in baseline C-E, the effect of AL is more pronounced for females at high levels of AL; thus, females could benefit more from a potential intervention on AL. We suggest further investigation of sex differences concerning the mediation by physiological and psychological intermediates.

Background One measure to quantify the degree of dysregulation is allostatic load (AL). Typically, AL incorporates information on diverse biomarkers and is associated with health outcomes such as cardiovascular diseases or the incidence of coronary events (C-E). Aims This study investigates the predictive performance of different AL scoring methods on the incidence of coronary events (C-E). This study also elaborates sex differences in the baseline risks of C-E and the AL associated risks of C-E. Design Longitudinal data analysis of the Heinz Nixdorf Recall Study (Risk Factors, Evaluation of Coronary Calcification, and Lifestyle) of 4327 participants free of C-E at study baseline aged 45–75. The data contains over 13 biomarkers measuring AL. Methods After conducting multiple imputations on missing values on AL for 826 participants, the analysis sample consisted of N = 4327 participants. We applied the two most commonly used methods of AL scoring AL (count-based and Z-score) and a recently developed logistic regression weighting method (LRM) approach. Cox regression was used to predict the incidence of C-E for each AL score. Results were estimated without (M0) and with (M1) covariate adjustment, and in a final model (M2), with an interaction between AL and sex. Results We found no violation of the proportional hazard assumption and significant differences in the survival curves between the sexes for C-E (Log-rank test: prob. > Chi2 = 0.000). In M0, all AL-scoring methods predicted C-E significantly, with the LRM based AL-score having the best performance (hazard ratio = 3.133; CI: [2.630, 3.732]; Somer's D = 0.717). After covariate inclusion, differences between the scoring methods levelled, though the count-based method and LRM performed better than the Z-scoring method. The interaction analysis in M2 showed a significant multiplicative interaction for the count-based method (1.254; [1.066, 1.475]) and for the LRM (1.746; [1.132, 2.692]). The additive relative excess risk due to interaction (RERI) measure was negative for the count-based method (RERI = −1.967; [-3.778; −0.156]) and the LRM (RERI = −1.909 [-3.910; 0.091]), indicating subadditivity. Conclusion AL scores are suitable for predicting C-E. Differences between the AL-scoring algorithms were only present after including interactions. We value the count-based method as suitable for clinical practice since its calculation is relatively simple, and performance was among the best. Interaction analysis revealed that despite strong sex differences in baseline C-E, the effect of AL is more pronounced for females at high levels of AL; thus, females could benefit more from a potential intervention on AL. We suggest further investigation of sex differences concerning the mediation by physiological and psychological intermediates.

Sonographic features of polycystic ovaries consist of elevated antral follicle count or ovarian volume of at least one ovary. The aim of this prospective cross-sectional study was to estimate intraindividual differences in sonographic measurements between the both ovaries of PCOS patients and controls and clinical consequences.Both ovaries of 85 PCOS patients and 48 controls were scanned transvaginally and agreement of sonographic measurements was analyzed using the Bland-Altman method. Concordance correlation coefficients (CCC) were computed.Mean differences between right and left ovaries were 0.24 (95% confidence interval [95% CI]: -0.32-0.80) follicles for AFC and 1.14 (95% CI: 0.34-1.92)ml for OV in the whole study population, 0.14 (95% CI: -0.68-0.96) follicles for AFC and 1.48 (95% CI: 0.39-2.58)ml for OV in PCOS patients, 0.42 (95% CI: -0.19-1.02) follicles for AFC and 0.53 (95% CI: -0.50-1.56)ml for OV in controls. Rather wide limits of agreement and low CCCs (0.7 for all estimates) indicated poor agreement between the ovaries for both sonographic measurements. Width between lower and upper limits of agreement was higher for PCOS patients than for controls. 23.5% of the PCOS patients showed polycystic ovarian morphology (PCOM) only in one ovary, resulting in 9.4% potentially missed PCOS diagnosis according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group.Substantial differences in antral follicle count and ovarian volume between the right and left ovary were observed. In approximately 10% of the PCOS patients in our study only the examination of both ovaries has led to a reliable diagnosis of PCOS. In clinical practice it is recommended to scan both ovaries for a reliable diagnosis of abnormal sonographic findings in PCOM and PCOS diagnosis.

Introduction The successful outcome of pregnancy requires adequate immune tolerance. A lack of appropriate tolerance might cause placental dysfunction and pregnancy complications such as preeclampsia (PE). Members of the B7 family play an essential role in maintaining immune tolerance in pregnancy by effecting T cells. Objectives B7-H4 is responsible for the negative regulation of T-cell-mediated immune response and might play an important role in PE. We currently revealed that sB7-H4 is involved in the spontaneous onset of labor and is elevated in early pregnancy in women with a preterm premature rupture of the amniotic membranes (pPROM). Thus, here we investigated the association between PE and sB7-H4 levels. Material and methods Maternal serum levels of sB7-H4 were determined by enzyme-linked immunosorbent assay in first trimester with elevated risk for PE Results In women at elevated risk for PE in first trimester significantly higher levels of sB7-H4 were detected compared to controls (p Conclusion sB7-H4 is involved in the regulation of immune tolerance in women with PE in the third trimester. In the first trimester, sB7-H4 might serve as a predictive immunological biomarker for women who are at elevated risk of developing PE.