a case of angioinvasive cutaneous anaplastic large cell lymphoma completely regressed after low dose systemic methotrexate

n/

VP50.10: Predicting fetal and maternal complications with sFlt1/PlGF ratio in hypertensive disorders of pregnancy

n/

Predictive value of hematological and phenotypical parameters on postchemotherapy leukocyte recovery

Background: Grade IV chemotherapy toxicity is defined as absolute neutrophil count <500/μL. The nadir is considered as the lowest neutrophil number following chemotherapy, and generally is not expected before the 7th day from the start of chemotherapy. The usual prophylactic dose of rHu-G-CSF (Filgrastim) is 300 μg/day, starting 24-48 h after chemotherapy until hematological recovery. However, individual patient response is largely variable, so that rHu-G-CSF doses can be different. The aim of this study was to verify if peripheral blood automated flow cytochemistry and flow cytometry analysis may be helpful in predicting the individual response and saving rHu-G-CSF. Methods: During Grade IV neutropenia, blood counts from 30 cancer patients were analyzed daily by ADVIA 120 automated flow cytochemistry analyzer and by Facscalibur flow cytometer till the nadir. "Large unstained cells" (LUCs), myeloperoxidase index (MPXI), blasts, and various cell subpopulations in the peripheral blood were studied. At nadir rHu-G-CSF was started and 81 chemotherapy cycles were analyzed. Cycles were stratified according to their number and to two dose-levels of rHuG-CSF needed to recovery (300-600 vs. 900-1200 μg) and analyzed in relation to mean values of MPXI and mean absolute number of LUCs in the nadir phase. The linear regressions of LUCs % over time in relation to two dose-levels of rHu-G-CSF and uni-multivariate analysis of lymphocyte subpopulations, CD34+ cells, MPXI, and blasts were also performed. Results: In the nadir phase, the increase of MPXI above the upper limit of normality (>10; median 27.7), characterized a slow hematological recovery. MPXI levels were directly related to the cycle number and inversely related to the absolute number of LUCs and CD34 +/CD45+ cells. A faster hematological recovery was associated with a higher LUC increase per day (0.56% vs. 0.25%), higher blast (median 36.7/μL vs. 19.5/μL) and CD34+/CD45+ cell (median 2.2/μL vs. 0.82/μL) counts. Conclusions: Our study showed that some biological indicators such as MPXI, LUCs, blasts, and CD34 +/CD45+ cells may be of clinical relevance in predicting individual hematological response to rHu-G-CSF. Special attention should be paid when nadir MPXI exceeds the upper limit of normality because the hematological recovery may be delayed. © 2009 Clinical Cytometry Society

Current use and performance of the different fetal growth charts in the Italian population

Objectives: The choice of growth charts impacts on screening, diagnosis and clinical management of fetal growth abnormalities. The objectives of the study were to evaluate: 1) the clinical practice at a national level among tertiary referral centers in the use of fetal biometric growth charts; and 2) the impact on fetal growth screening of existing national and international growth charts. Study design: A questionnaire was sent to 14 Italian tertiary referral centers to explore biometric reference growth charts used in clinical practice. National and international (Intergrowth-21st and World Health Organization) fetal growth charts were tested on a large national cohort of low risk women with singleton uneventful pregnancy derived from a retrospective cross-sectional multicenter study (21 centers). The percentage of fetuses with biometric measurements below and above the 10th and 90th percentile for each biometric parameter and gestational week were calculated for each growth chart. The percentile curves of the study population were calculated by non-linear quantile regressions. Results: Twelve Italian centers (86 %) answered to the questionnaire showing a wide discrepancy in the use of growth charts for fetal biometry. The cohort included 7347 pregnant women. By applying Intergrowth-21st growth charts the percentage of fetuses with head circumference, abdominal circumference and femur length below the 10th centile was 3.9 %, 3.6 % and 2.3 %, and above the 90th centile 29.9 %, 32.5 % and 46 %, respectively. The percentages for the World Health Organization growth charts for head and abdominal circumferences and femur length were: below the 10th centile 6.3 %, 7.2 % and 5.3 %, and above 90th centile 22.8 %, 21.3 % and 31.9 %, respectively. Conclusions: The wide discrepancy in clinical use of fetal growth charts in Italian centers warrants the adoption of an uniform set of charts. Our data suggest that immediate application into clinical practice of international growth charts might result into an under-diagnosis of small for gestational age fetuses and, especially, in an over-diagnosis of large for gestational age fetuses with major consequences for clinical practice. On these grounds, there is an urgent need for a nationwide study for the prospective evaluation of international growth charts and, if needed, the construction and adoption of methodologically robust national growth charts

Modelling the progression of cervical dilatation in spontaneous labour

Introduction The first attempt to model the progression of cervical dilation during spontaneous labour of pregnant women dates back to 1955 [1]. From the graphical analysis of the time profiles of dilation observed in 500 women aged 13 to 42 years, the Author derived a mean labour sigmoid curve, consisting in a latent phase followed by an active phase ending in a deceleration phase. This cervimetric graph, or cervicogram, is still reported in current manuals of obstetrics. Zhang et al [2, 3] fitted cervical dilation profiles with mixed models based on 10th or 8th degree polynomials, and concluded that the duration of latent and active phases largely differs from woman to woman, and that there is no deceleration at the end of the active phase. For this reason, these Authors supply charts reporting the empirical 95th centile of the distribution of labour duration for different values of cervical dilation at admission to labour room, thus abandoning the idea of modelling the progression of cervical dilation. The aim of this presentation is to show the use of parsimonious nonlinear mixed models to trace cervimetric charts, reporting current cervical dilation vs time to full dilation. Data and methods Data here used derive from an observational study including 328 low-risk women (146 primiparae and 182 multiparae), who delivered at Buzzi Children\u2019s Hospital between April and June 2013 [4]. All women delivered vaginally at term, after uncomplicated single pregnancy and spontaneous labour managed by midwives, without any kind of medical intervention. We had to take into account a lot of difficulties and hindrances to construct a model for the progression of cervical dilation. The time of the beginning of labour is unknown (1); women are admitted to labour room at different degrees of dilation (2); cervical dilation measures are taken at irregular intervals as required by clinical practice (3); midwives usually assess cervical dilation with fingers, though the measure is reported in cm, from 0 (no dilation) to 10 (full dilation) (4); full cervical dilation is not indicated with a measure, but with a value of 10 cm, arbitrarily assigned to all women (5); individual dilation profiles are largely incomplete, a maximum of 5 measures per woman was recorded before full dilation, and only 60 women (18%) were assessed twice or more (6); the progression of cervical dilation is extremely erratic (7). Since dilation cannot be related to the unknown time from the onset of labour, we considered, as already suggested by Zhang et al [2], the time remaining to the attainment of full cervical dilation (t, time to full dilation), and expressed current dilation (yi(t), from 1 to 9 cm) observed in the ith woman as a function of a parsimonious nonlinear model (3 parameters only), instead of the 9 to 11 parameters of the polynomials used by Zhang et al [2, 3]: i i i i i(t) logit(y (t)/10) \u3b1= 7\u3b2+ log(t \u3b4+ ) \u3b5+ In {1}, logit(yi(t)/10) is a linear function of the log-transformation of time: parameter \u3b2i is the dilation velocity constant, the ratio \u3b1 \u3b2ii determines the time at maximum dilation velocity, and \u3b4i modulates the shape of the log-transformation of time; intra-individual random terms \u3b5i(t) were assumed to approximate a normal distribution, with variance proportional to {[E(yi(t))/10][1\u2013E(yi(t))}-1. When back-transformed to the original scale, expression {1} defines a family of strongly asymmetrical never-decreasing (since cervical dilation is an irreversible process) sigmoid curves, with a slight slowdown of dilation velocity a little before, or at full dilation, in this latter case the curve presents an exponential shape. Because cervical dilation profiles were largely incomplete, we could not resort to the usual two-stage models [5] to trace cervimetric charts, but we were forced to adopt a nonlinear mixed model [6], which can obtain estimates of the parameters of the individual cervical dilation curves also for the women with profiles made up by a number of observations lower the number of paramtes (in our case 1 or 2 assesments only): i 0 i P 0 i P 0 P i(t) logit(y (t)/10) \u3b1= \u3b1+ \u3b1+ x (\u3b2+ \u3b2+\u3b2+ x)log(t \u3b4+ \u3b4+ x) \u3b5+ {2} Parity (x=0 for primiparae, x=1 for multiparae) was included as a covariate into model {2}, since multiparae are known to progress somewhat faster in active-phase labour [7]. Parameters \u3b10 and \u3b20 refer to primiparae, \u3b1P and \u3b2P refer to the difference between multiparae and primiparae, whereas \u3b40 and \u3b4P modulate the log-transformation of time by parity. Random terms \u3b1i and \u3b2i, which model inter-individual differences, are assumed to have bivariate normal distribution with E(\u3b1i)=E(\u3b2i)=0 and unstructered covariance matrix Cov(\u3b1i,\u3b2i)=[ ] 2 2 \u3c3\u3b1 \u3c3\u3b1\u3b2 \u3c3\u3b2 , , . Models {1} and {2} were fitted using PROC NLIN and NLMIXED of SAS/STAT\uae software (SAS Institute, Cary, NC; v.9.4, 2013). Results Although based on 3 parameters only, model {1} proved to be flexible enough to describe cervical dilation profiles of rather different shape. As shown in figure 1 (left), concerning primiparous women, profiles may present an inflection point (i.e. a maximum dilation velocity) already 4 hours before the attainment of full dilation (orange curve) or at about 1 hour (dark red and green curves) or in the last half hour of the dilation process (the remaining profiles). Ten hours before the attainment of full dilation there are women with no more than 1 cm dilation and women with so much as 4 cm dilation. During the labour, dilation velocity may vary considerably from woman to woman: 10 hours before the attainment of full dilation, dilation velocity is always less than 0.5 cm/hr, but maximum velocity may be more than 3.5 cm/hr when initial dilation is 1 cm (red and blue curves) or be about 1 cm/hr when initial dilation is 4 cm (green curve). It is worth noting that women with different initial dilation (red curve: 1.7 cm, olive green curve: 2.7 cm) may present the same maximum velocity (1.7 cm/hr), since their dilation profiles differ in convexity. Figure 1 (right) shows, plotted on the cervicometric charts traced with mixed model {2}, the cervical dilation profiles (green lines) of the 95 primiparous women with 2 or more assessments and the dilation values (green dots) of the 51 women with 1 assessment only, predicted on the basis of model {2}. Green dots As expected, though individual profiles differ largely, the large majority of them lies completely within the interval 3rd \u2013 97th centile of the cervicometric charts. At 10 hours, the distribution of dilation values conditional on time to full dilation is highly right skewed, then positive skewness decreases and the distribution becomes symmetrical when median dilation is 5 cm, and left skewed subsequently. The same results were observed in the 182 multiparous women included in the study. We observe that a 4 cm dilation is the 97th centile 10 hours before the attainment of full dilation, and is the 3 rd centile at 0.5 hours. This means that, at 10 hours, 3% of women present more than 4 cm dilation, but that another 3% of women still present a 4 cm dilation half an hour before the end of dilation process. So a 4 cm dilation observed from 10 to 0.5 hours before the attainment of full dilation cannot be regarded as unusual. Analogously, at 10 hours, 10% and 25% of women present more than 3 and 2 cm dilation, respectively, but 10% and 25% of women still present a 3 or 2 cm dilation, 1 and 3 hours before the end of dilation process. Our data confirm that labour progresses faster in multiparae than in primiparae: e.g. a 5 cm dilation is achieved 45 min vs 1 hour and half before the end of dilation process in multiparae. Primiparae present a wider variability (+30% in terms of interquartile range) in the distribution of dilation values conditional on time to full dilation. Conclusions In 1955 Friedman [1] wrote: \u201cThe dynamic nature of parturitional change has, in the past, rendered exceedingly difficult the detailed and critical analysis of its vagaries\u201d. Actually, try to model the kinetics of the cervical dilation process turned out still to be a very hard task. Nonetheless some important points were established: (1) a parsimonious nonlinear parametric model is suitable to describe very different shapes of the dilation process, (2) mixed nonlinear models allow to trace plausible cervimetric charts even in the case of dilation profiles largely incomplete, (3) the above model provide quantitative estimates of the inter-individual variability and of the difference in the progression of cervical dilation between primiparae and multiparae. Unfortunately, the classical cervicograms give an unrealistic and useless picture of labour progression when referred to a single patient, the course of cervical dilation being largely erratic even in the case of spontaneous labour in uncomplicated pregnancies. In the first place, during labour the time remaining to the attainment of full cervical dilation is unknown, so the charts cannot be used in obstetric practice; in the second place a subsequent value of dilation cannot be predicted on the basis of the previous assessments. For these reasons, Ferrazzi et al [4] proposed cervimetric charts reporting the distribution of time needed to gain 1 cm in cervical dilation as a function of current dilation. Although theoretically usable, the practical value of these charts remains very low. In primiparous women, the time needed to gain 1 cm in dilation ranges from 10 (10th centile) to 110 min (90th centile) when current dilation is 1 cm, and from 5 to 70 min when current dilation is 9 cm. In multiparous women, the reference interval is somewhat narrower, the time needed ranging from 3 to 70 min when current dilation is 1 cm, and from 2 to 45 min when current dilation is 9 cm. On the basis of these results they concluded that the progression of cervical dilatation in normal human labour is unpredictable. References 1. Friedman EA. Primigravid labor. A graphicostatistical analysis. Obstetrics and Gynecology 1955; 6:567-589. 2. Zhang J, Troendle JF, Yancey MK. Reassessing the labor curve in nulliparous women. American Journal of Obstetrics and Gynecology 2002; 187:824-828. 3. Zhang J, Landy HJ, Branch DW, et al. Contemporary patterns of spontaneous labor with normal neonatal outcomes. Obstetrics and Gynecology 2010; 116:1281-1287. 4. Ferrazzi E, Milani S, Cirillo F, at al. Progression of cervical dilatation in normal human labor is unpredictable. Acta Obstet Gynecol Scand 2015; 94:1136-1144. 5. Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics 1982; 38:963-974. 6. Goldstein H. Nonlinear multilevel models, with an application to discrete response data. Biometrika 1991; 78:45-51. 7. Friedman EA. An objective approach to the diagnosis and management of abnormal labor. Bull N Y Acad Med 1972; 48:842-858

A case of ultrasound diagnosis of fetal hiatal hernia in late third trimester of pregnancy

Congenital hiatal hernia is a condition characterized by herniation of the abdominal organs, most commonly the stomach, through a physiological but overlax esophageal hiatus into the thoracic cavity. Prenatal diagnosis of this anomaly is unusual and only eight cases have been reported in the literature. In this paper we describe a case of congenital hiatal hernia that was suspected at ultrasound at 39 weeks' gestation, on the basis of a cystic mass in the posterior mediastinum, juxtaposed to the vertebral body. Postnatal upper gastrointestinal tract series confirmed the prenatal diagnosis. Postnatal management was planned with no urgency. Hiatal hernia is not commonly considered in the differential diagnosis of fetal cystic chest anomalies. This rare case documents the importance of prenatal diagnosis of this anomaly for prenatal counseling and postnatal management

Methylglyoxal, Glycated Albumin, PAF, and TNF-α: Possible Inflammatory and Metabolic Biomarkers for Management of Gestational Diabetes

Background: In gestational diabetes mellitus (GDM), pancreatic \u3b2-cell breakdown can result from a proinflammatory imbalance created by a sustained level of cytokines. In this study, we investigated the role of specific cytokines, such as B-cell activating factor (BAFF), tumor necrosis factor \u3b1 (TNF-\u3b1), and platelet-activating factor (PAF), together with methylglyoxal (MGO) and glycated albumin (GA) in pregnant women affected by GDM. Methods: We enrolled 30 women whose inflammation and metabolic markers were measured at recruitment and after 12 weeks of strict dietetic therapy. We compared these data to the data obtained from 53 randomly selected healthy nonpregnant subjects without diabetes, hyperglycemia, or any condition that can affect glycemic metabolism. Results: In pregnant women affected by GDM, PAF levels increased from 26.3 (17.4-47.5) ng/mL to 40.1 (30.5-80.5) ng/mL (p < 0.001). Their TNF-\u3b1 levels increased from 3.0 (2.8-3.5) pg/mL to 3.4 (3.1-5.8) pg/mL (p < 0.001). The levels of methylglyoxal were significantly higher in the women with GDM (p < 0.001), both at diagnosis and after 12 weeks (0.64 (0.46-0.90) \u3bcg/mL; 0.71 (0.47-0.93) \u3bcg/mL, respectively) compared to general population (0.25 (0.19-0.28) \u3bcg/mL). Levels of glycated albumin were significantly higher in women with GDM (p < 0.001) only after 12 weeks from diagnosis (1.51 (0.88-2.03) nmol/mL) compared to general population (0.95 (0.63-1.4) nmol/mL). Conclusion: These findings support the involvement of new inflammatory and metabolic biomarkers in the mechanisms related to GDM complications and prompt deeper exploration into the vicious cycle connecting inflammation, oxidative stress, and metabolic results