Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Differential effects of acute cardiovascular exercise on explicit and implicit motor memory: The moderating effects of fitness level.

A single bout of cardiovascular exercise (CE) performed after practice can facilitate the consolidation of motor memory. However, the effect is variable and may be modulated by different factors such as the motor task's or participant's characteristics and level of awareness during encoding (implicit vs explicit learning). This study examines the effects of acute CE on the consolidation of motor sequences learned explicitly and implicitly, exploring the potential moderating effect of fitness level and awareness. Fifty-six healthy adults (24.1 ± 3.3 years, 32 female) were recruited. After practicing with either the implicit or explicit variant of the Serial Reaction Time Task (SRTT), participants either performed a bout of 16 min of vigorous CE or rested for the same amount of time. Consolidation was quantified as the change in SRTT performance from the end of practice to a 24 h retention test. Fitness level (V̇O2peak) was determined through a graded exercise test. Awareness (implicit vs explicit learning) was operationalized using a free recall test conducted immediately after retention. Our primary analysis indicated that CE had no statistically significant effects on consolidation, regardless of the SRTT's variant utilized during practice. However, an exploratory analysis, classifying participants based on the level of awareness gained during motor practice, showed that CE negatively influenced consolidation in unfit participants who explicitly acquired the motor sequence. Our findings indicate that fitness level and awareness in sequence acquisition can modulate the interaction between CE and motor memory consolidation. These factors should be taken into account when assessing the effects of CE on motor memory.

Corpus callosum-fastigium and tectal lengths in late-onset small fetuses.

OBJECTIVE: To investigate measurements on neurosonography of midbrain morphology, including corpus callosum-fastigium length and tectal length, in late-onset small fetuses subclassified as small-for-gestational-age (SGA) or growth-restricted (FGR). METHODS: This was a case-control study of consecutive singleton pregnancies delivered at term at a single center between January 2019 and July 2021, including those with late-onset smallness (estimated fetal weight (EFW) < 10th centile) and appropriate-for-gestational-age controls matched by age at neurosonography. Small fetuses were further subdivided into SGA (EFW between 3rd and 9th centile and normal fetoplacental Doppler) and FGR (EFW < 3rd centile or EFW < 10th centile with abnormal cerebroplacental ratio and/or uterine artery Doppler). Transvaginal neurosonography was performed at a mean ± SD gestational age of 33 ± 1 weeks in all fetuses to evaluate corpus callosum-fastigium length and tectal length in the midsagittal plane. Intra- and interobserver agreement was evaluated using the intraclass correlation coefficient and Bland-Altman plots. RESULTS: A total of 70 fetuses with late-onset smallness (29 with SGA and 41 with FGR) and 70 controls were included. Compared with controls, small fetuses showed significantly shorter corpus callosum-fastigium length (median (interquartile range), 44.7 (43.3-46.8) mm vs 43.7 (42.4-45.5) mm, P < 0.001) and tectal length (mean ± SD, 10.5 ± 0.9 vs 9.6 ± 1.0 mm, P < 0.001). These changes were more prominent in FGR fetuses, with a linear trend across groups according to severity of smallness. Corpus callosum-fastigium length and tectal length measurements showed excellent intra- and interobserver reliability. CONCLUSIONS: Small fetuses exhibited shorter corpus callosum-fastigium length and tectal length compared with controls, and these differences were more pronounced in fetuses with more severe smallness. These findings illustrate the potential value of midbrain measurements assessed on neurosonography as biomarkers for brain development in a high-risk population. However, further studies correlating these parameters with postnatal functional tests and follow-up are needed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Mortality and severe neurological morbidity in extremely preterm growth-restricted fetuses.

OBJECTIVE: To develop a model for the prediction of adverse perinatal outcome in growth-restricted fetuses requiring delivery before 28 weeks in order to provide individualized patient counseling. METHODS: This was a retrospective multicenter cohort study of singleton pregnancies with antenatal suspicion of fetal growth restriction requiring delivery before 28 weeks' gestation between January 2010 and January 2020 in six tertiary public hospitals in the Barcelona area, Spain. Separate predictive models for mortality only and mortality or severe neurological morbidity were created using logistic regression from variables available antenatally. For each model, predictive performance was evaluated using receiver-operating-characteristics (ROC)-curve analysis. Predictive models were validated externally in an additional cohort of growth-restricted fetuses from another public tertiary hospital with the same inclusion and exclusion criteria. RESULTS: A total of 110 cases were included. The neonatal mortality rate was 37.3% and, among the survivors, the rate of severe neurological morbidity was 21.7%. The following factors were retained in the multivariate analysis as significant predictors of mortality: magnesium sulfate neuroprotection, gestational age at birth, estimated fetal weight, male sex and Doppler stage. This model had a significantly higher area under the ROC curve (AUC) compared with a model including only gestational age at birth (0.810 (95% CI, 0.730-0.889) vs 0.695 (95% CI, 0.594-0.795); P = 0.016). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 66%, 80% and 66%, respectively. For the prediction of the composite adverse outcome (mortality or severe neurological morbidity), the model included: gestational age at birth, male sex and Doppler stage. This model had a significantly higher AUC compared with a model including only gestational age at birth (0.810 (95% CI, 0.731-0.892) vs 0.689 (95% CI, 0.588-0.799); P = 0.017). At a 20% false-positive rate, the model showed a sensitivity, negative predictive value and positive predictive value of 55%, 63% and 74%, respectively. External validation of both models yielded similar AUCs that did not differ significantly from those obtained in the original sample. CONCLUSIONS: Estimated fetal weight, fetal sex and Doppler stage can be combined with gestational age to improve the prediction of death or severe neurological sequelae in growth-restricted fetuses requiring delivery before 28 weeks. This approach may be useful for parental counseling and decision-making. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Corpus callosum size by neurosonography in fetuses with congenital heart defect and relationship with expected pattern of brain oxygen supply.

OBJECTIVE: To evaluate corpus callosum (CC) size by neurosonography (NSG) in fetuses with an isolated major congenital heart defect (CHD) and explore the association of CC size with the expected pattern of in-utero oxygen supply to the brain. METHODS: A total of 56 fetuses with postnatally confirmed isolated major CHD and 56 gestational-age-matched controls were included. Fetuses with CHD were stratified into two categories according to the main expected pattern of cerebral arterial oxygen supply: Class A, moderately to severely reduced oxygen supply (left outflow tract obstruction and transposition of the great arteries) and Class B, near normal or mildly impaired oxygenated blood supply to the brain (other CHD). Transvaginal NSG was performed at 32-36 weeks in all fetuses to evaluate CC length, CC total area and areas of CC subdivisions in the midsagittal plane. RESULTS: CHD fetuses had a significantly smaller CC area as compared to controls (7.91 ± 1.30 vs 9.01 ± 1.44 mm2 ; P < 0.001), which was more pronounced in the most posterior part of the CC. There was a significant linear trend for reduced CC total area across the three clinical groups, with CHD Class-A cases showing more prominent changes (controls, 9.01 ± 1.44 vs CHD Class B, 8.18 ± 1.21 vs CHD Class A, 7.53 ± 1.33 mm2 ; P < 0.05). CONCLUSIONS: Fetuses with major CHD had a smaller CC compared with controls, and the difference was more marked in the CHD subgroup with expected poorer brain oxygenation. Sonographic CC size could be a clinically feasible marker of abnormal white matter development in CHD. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Public health response to an outbreak of SARS-CoV2 infection in a Barcelona prison.

An outbreak of SARS-CoV2 infection in a Barcelona prison was studied. One hundred and forty-eight inmates and 36 prison staff were evaluated by rt-PCR, and 24.1% (40 prisoners, two health workers and four non-health workers) tested positive. In all, 94.8% of cases were asymptomatic. The inmates were isolated in prison module 4, which was converted into an emergency COVID unit. There were no deaths. Generalised screening and the isolation and evaluation of the people infected were key measures. Symptom-based surveillance must be supplemented by rapid contact-based monitoring in order to avoid asymptomatic spread among prisoners and the community at large.

Ten-year experience of protocol-based management of small-for-gestational-age fetuses: perinatal outcome in late-pregnancy cases diagnosed after 32 weeks.

OBJECTIVE: To report our 10-year experience of protocol-based management of small-for-gestational-age (SGA) fetuses, based on standardized clinical and Doppler criteria, in late-pregnancy cases. METHODS: A retrospective cohort was constructed of consecutive singleton pregnancies referred for late-onset (> 32 weeks) SGA (defined as estimated fetal weight (EFW) < 10th centile) that were classified as fetal growth restriction (FGR) or low-risk SGA, based on the severity of smallness (EFW < 3rd centile) and the presence of Doppler abnormalities (uterine artery pulsatility index (UtA-PI) ≥ 95th centile or cerebroplacental ratio (CPR) < 5th centile). Low-risk SGA pregnancies were followed at 2-week intervals and delivered electively at 40 weeks. FGR pregnancies were followed at 1-week intervals, or more frequently if there were signs of fetal deterioration, and were delivered electively after 37 + 0 weeks' gestation. The occurrence of stillbirth and composite adverse outcome (CAO; defined as neonatal death, metabolic acidosis, need for endotracheal intubation or need for admission to the neonatal intensive care unit) was analyzed in low-risk SGA and FGR pregnancies. RESULTS: A total of 1197 pregnancies with EFW < 10th centile were identified and classified at diagnosis as low-risk SGA (n = 619; 51.7%) or FGR (n = 578; 48.3%). Of these, 160 were delivered before 37 weeks' gestation; for obstetric reasons in 93 (58.1%) cases, severe pre-eclampsia in 33 (20.6%), FGR with severe hypoxia in 47 (29.4%) and stillbirth in four (2.5%) (indications are non-exclusive). During follow-up, 52/574 (9.1%) low-risk SGA pregnancies were reclassified as FGR, whereas 22/463 (4.8%) FGR pregnancies were reclassified as low-risk SGA. Overall, there were no stillbirths in the low-risk SGA group and four in the FGR group, all of which occurred before 37 weeks. There were no instances of neonatal death in pregnancies delivered ≥ 37 weeks. The risk of CAO was higher in those meeting antenatal criteria for FGR at 37 weeks than in those classified as low-risk SGA (32/493 (6.5%) vs 15/544 (2.8%); odds ratio, 2.5 (95% CI, 1.3-4.6)). In FGR pregnancies, the adjusted odds ratio (95% CI) for CAO was 6.3 (1.8-21.1) in those with EFW < 3rd centile, while it was 3.2 (1.5-6.8) and 4.2 (1.9-8.9) in those with UtA-PI ≥ 95th centile and CPR < 5th centile, respectively, as compared to FGR pregnancies without each of these criteria. CONCLUSION: Protocol-based risk stratification with different management and monitoring schemes for late pregnancy with a suspected SGA baby, based on clinical and Doppler criteria, enables identification and tailored assessment of high-risk FGR, while allowing expectant management with safe perinatal outcome for low-risk SGA fetuses. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Environmental Exposure during Pregnancy: Influence on Prenatal Development and Early Life: A Comprehensive Review.

Preconception and prenatal exposure to environmental contaminants may affect future health. Pregnancy and early life are critical sensitive windows of susceptibility. The aim of this review was to summarize current evidence on the toxic effects of environment exposure during pregnancy, the neonatal period, and childhood. Alcohol use is related to foetal alcohol spectrum disorders, foetal alcohol syndrome being its most extreme form. Smoking is associated with placental abnormalities, preterm birth, stillbirth, or impaired growth and development, as well as with intellectual impairment, obesity, and cardiovascular diseases later in life. Negative birth outcomes have been linked to the use of drugs of abuse. Pregnant and lactating women are exposed to endocrine-disrupting chemicals and heavy metals present in foodstuffs, which may alter hormones in the body. Prenatal exposure to these compounds has been associated with pre-eclampsia and intrauterine growth restriction, preterm birth, and thyroid function. Metals can accumulate in the placenta, causing foetal growth restriction. Evidence on the effects of air pollutants on pregnancy is constantly growing, for example, preterm birth, foetal growth restriction, increased uterine vascular resistance, impaired placental vascularization, increased gestational diabetes, and reduced telomere length. The advantages of breastfeeding outweigh any risks from contaminants. However, it is important to assess health outcomes of toxic exposures via breastfeeding. Initial studies suggest an association between pre-eclampsia and environmental noise, particularly with early-onset pre-eclampsia. There is rising evidence of the negative effects of environmental contaminants following exposure during pregnancy and breastfeeding, which should be considered a major public health issue.

The protective effects of acute cardiovascular exercise on the interference of procedural memory.

Numerous studies have reported a positive impact of acute exercise for procedural skill memory. Previous work has revealed this effect, but these findings are confounded by a potential contribution of a night of sleep to the reported exercise-mediated reduction in interference. Thus, it remains unclear if exposure to a brief bout of exercise can provide protection to a newly acquired motor memory. The primary objective of the present study was to examine if a single bout of moderate-intensity cardiovascular exercise after practice of a novel motor sequence reduces the susceptibility to retroactive interference. To address this shortcoming, 17 individuals in a control condition practiced a novel motor sequence that was followed by test after a 6-h wake-filled interval. A separate group of 17 individuals experienced practice with an interfering motor sequence 45 min after practice with the original sequence and were then administered test trials 6 h later. One additional group of 12 participants was exposed to an acute bout of exercise immediately after practice with the original motor sequence but prior to practice with the interfering motor sequence and the subsequent test. In comparison with the control condition, increased response times were revealed during the 6-h test for the individuals that were exposed to interference. The introduction of an acute bout of exercise between the practice of the two motor sequences produced a reduction in interference from practice with the second task at the time of test, however, this effect was not statistically significant. These data reinforce the hypothesis that while there may be a contribution from exercise to post-practice consolidation of procedural skills which is independent of sleep, sleep may interact with exercise to strengthen the effects of the latter on procedural memory.

A new classification system for the restoration of root filled teeth.

The aim of this report is to (i) review the current literature on the status of root filled teeth, (ii) analyse the most important factors in decision-making, (iii) discuss the current restorative concepts, and (iv) classify both the evidence and clinical practice in a way that seeks to be clear, understandable and helpful for clinicians. Restoration of root filled teeth represents a challenge for the clinician and remains a controversial subject. The guidelines describe a new classification that is drawn from evidence presented in the literature and also from clinical expertise-based reviews. It describes five categories of teeth.

Postoperative pain after removal of gutta-percha from root canals in endodontic retreatment using rotary or reciprocating instruments: a prospective clinical study.

OBJECTIVES: The aim of this clinical study was to evaluate and compare the incidence and intensity of postoperative pain following removal of gutta-percha from root canals using rotary and reciprocating instruments. MATERIALS AND METHODS: One hundred and sixty patients scheduled for a non-surgical endodontic retreatment were included for evaluation. Preoperative pain was recorded with using a questionnaire with a 10-cm visual analogical scale (VAS). Endodontic filling material was removed with Reciproc (VDW, Munich, Germany) or ProFile (Dentsply Tulsa Dental Specialties, Tulsa, OK) instruments. Patients then recorded their postoperative pain in a VAS pain scale at 4, 8, 16, 24, 48, and 72 h post-treatment. Results were analyzed using the Mann-Whitney U, Kruskal-Wallis, and Chi-square tests. Multivariate logistic and a multiple regression analysis were used to detect the effect of confounding factors. RESULTS: Results showed a direct relation between the intensity of pre-operative pain and that of postoperative pain (P < .05). No significant differences were observed between the two groups regarding postoperative pain (P > .05) as a qualitative variable. As numerical values, statistically significant differences were found regarding sex and the system used (P < .05). CONCLUSIONS: The method for pain evaluation was determinant in postoperative pain findings. Endodontic retreatment preparation with Reciproc results in lower values of postoperative pain compared with ProFile. Women are more susceptible to postoperative pain than are men. CLINICAL RELEVANCE: One of the most significant contributions of this research is the importance given to the method used for pain evaluation. The present study analyzed postoperative pain resulting from the use of reciprocating or continuous rotary instruments during removal of gutta-percha in retreatment procedures.

Neural injury markers in intrauterine growth restriction and their relation to perinatal outcomes.

BACKGROUNDThe aims of this study were to (i) compare the concentrations of two neural injury markers, S100B protein and neuron-specific enolase (NSE), in intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate growth-for-gestational-age (AGA), and (ii) investigate potential relationships between concentrations of these markers, Doppler abnormalities, and adverse perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative, prospective study among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler were measured. At the time of delivery, maternal venous blood and fetal umbilical arterial blood samples were collected. S100B and NSE concentrations were determined from these samples.RESULTSIn total, 254 pregnancies were included. Among these, 147 were classified as IUGR and 107 as AGA. There were no differences between the groups in S100B concentrations. However, levels of NSE in maternal and umbilical cord serum differed significantly between these groups (2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR (P<0.05), respectively). No differences were observed in these neurological markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough some variations exist in these neurological markers, they did not correlate with perinatal or neonatal complications.

Acute exercise and motor memory consolidation: Does exercise type play a role?

A single bout of high-intensity exercise can augment off-line gains in skills acquired during motor practice. It is currently unknown if the type of physical exercise influences the effect on motor skill consolidation. This study investigated the effect of three types of high-intensity exercise following visuomotor skill acquisition on the retention of motor memory in 40 young (25.3 ±3.6 years), able-bodied male participants randomly assigned to one of four groups either performing strength training (STR), circuit training (CT), indoor hockey (HOC) or rest (CON). Retention tests of the motor skill were performed 1 (R1h) and 24 h (R1d) post acquisition. For all exercise groups, mean motor performance scores decreased at R1h compared to post acquisition (POST) level; STR (P = 0.018), CT (P = 0.02), HOC (P = 0.014) and performance scores decreased for CT compared to CON (P = 0.049). Mean performance scores increased from POST to R1d for all exercise groups; STR (P = 0.010), CT (P = 0.020), HOC (P = 0.007) while performance scores for CON decreased (P = 0.043). Changes in motor performance were thus greater for STR (P = 0.006), CT (P < 0.001) and HOC (P < 0.001) compared to CON from POST to R1d. The results demonstrate that high-intensity, acute exercise can lead to a decrease in motor performance assessed shortly after motor skill practice (R1h), but enhances offline effects promoting long-term retention (R1d). Given that different exercise modalities produced similar positive off-line effects on motor memory, we conclude that exercise-induced effects beneficial to consolidation appear to depend primarily on the physiological stimulus rather than type of exercise and movements employed.

Risk factors to develop multicentric lesions of the lower genital tract.

Purpose ofinvestigation: To analyze which are the risk factors in developing multicentric lesions of lower genital tract. MATERIALS AND METHODS: A prospective study of 1,011 patients was conducted at the low genital tract pathology clinic of Sant Joan de Deu Hospital between 2003-2011. A complete assessment of cervix, vagina, and vulva was carried out including HPV-DNA testing, cytology study, colposcopy, and biopsy in case of atypical findings. The statistical analysis was done with SPSS v.19 software. Differences between groups were considered statistically significant atp < 0.05. RESULTS: Twenty-two patients presented multicentric lesions (2.2%). The average age was 43 years. Most of the lesions were bicentric affecting cervix and vagina and cervix and vulva. Only in two cases (9%) there were three sites of genital neoplasia. The authors found four cervical cancer, 17 high grade, and one low grade lesions of the cervix. Eighteen vaginal intraepithelial neoplasia (VAIN), six high grade, 14 low grade, and four vulvar intraepithelial neoplasia (VIN) were found. HPV infection, age > 35 years, multiparity, contraceptive method, immunodeficiency, and level of studies were significantly correlated with multicentric lesions. High percentage of affected margins were found. VIN cases were treated with surgical excision and in two cases microinvasion was found. VAIN III cases were treated with surgical excision or with laser and one case progressed to vaginal cancer. Recurrence after treatment was 27%. CONCLUSION: Age, multiparity, contraceptive method, immunodeficiency, and level of studies were significantly correlated with multicentric lesion. Multicentric lesions had an increased risk of recurrence and progression to cancer.

Success of benznidazole chemotherapy in chronic Trypanosoma cruzi-infected patients with a sustained negative PCR result.

Cure assessment in chronic Trypanosoma cruzi infection is controversial, mainly because of the lack of reliable tests to ensure parasite elimination. Here, we assess the impact of benznidazole therapy on the conventional serology and parasitaemia in chronic Chagas disease. A total of 455 patients with long-term Trypanosoma cruzi infection underwent specific chemotherapy with benznidazole. Their parasitological status was assessed by polymerase chain reaction (PCR) detection of T. cruzi DNA. Drops in the titres of antibody levels were serially measured by indirect immunofluorescence assay (IFI) and chemiluminescent microparticle immunoassay (CMIA). Patients were monitored during the treatment period and for a further 90, 150 and 240 days. Controls were repeated yearly during the 7-year follow-up. The PCR result was negative in all patients between 60-day (n = 22) and 90-day (n = 294) controls. Treatment failure was detected in 45 patients and was significantly more frequent in those who did not complete the therapy [12 out of 13 (92 %) vs. 33 out of 442 (7 %)] (p = 0.0001). A significant drop in serum titres was detected after the first follow-up year in patients with sustained negative PCR results: 2nd year (p = 0.029 by IFI; p = 0.002 by CMIA), 5th year (p = 0.036 by IFI; p = 0.039 by CMIA) and 6th year (p = 0.028 by IFI; p = 0.019 by CMIA). The results point to a beneficial effect of benznidazole and may be the cure of chronic patients who had a consistently negative PCR result throughout the follow-up period.

Do knowledge of uterine artery resistance in the second trimester and targeted surveillance improve maternal and perinatal outcome? UTOPIA study: a randomized controlled trial.

OBJECTIVES: To ascertain whether screening for pre-eclampsia (PE) and intrauterine growth restriction (IUGR) by uterine artery (UtA) Doppler in the second trimester of pregnancy and targeted surveillance improve maternal and perinatal outcomes in an unselected population. METHODS: This was a multicenter randomized open-label controlled trial. At the routine second-trimester anomaly scan, women were assigned randomly to UtA Doppler or non-Doppler groups. Women with abnormal UtA Doppler were offered intensive surveillance at high-risk clinics of the participating centers with visits every 4 weeks that included measurement of maternal blood pressure, dipstick proteinuria, fetal growth and Doppler examination. The primary outcome was a composite score for perinatal complications, defined as the presence of any of the following: PE, IUGR, spontaneous labor < 37 weeks' gestation, placental abruption, stillbirth, gestational hypertension, admission to neonatal intensive care unit and neonatal complications. Secondary outcomes were a composite score for maternal complications (disseminated intravascular coagulation, maternal mortality, postpartum hemorrhage, pulmonary edema, pulmonary embolism, sepsis), and medical interventions (for example, corticosteroid administration and induction of labor) in patients developing placenta-related complications. RESULTS: In total, 11 667 women were included in the study. Overall, PE occurred in 348 (3.0%) cases, early-onset PE in 48 (0.4%), IUGR in 722 (6.2%), early-onset IUGR in 93 (0.8%) and early-onset PE with IUGR in 32 (0.3%). UtA mean pulsatility index > 90(th) percentile was able to detect 59% of early-onset PE and 60% of early-onset IUGR with a false-positive rate of 11.1%. When perinatal and maternal data according to assigned group (UtA Doppler vs non-Doppler) were compared, no differences were found in perinatal or maternal complications. However, screened patients had more medical interventions, such as corticosteroid administration (relative risk (RR), 1.79 (95% CI, 1.4-2.3)) and induction of labor for IUGR (RR, 1.36 (95% CI, 1.07-1.72)). In women developing PE or IUGR, there was a trend towards fewer maternal complications (RR, 0.46 (95% CI, 0.19-1.11)). CONCLUSIONS: Routine second-trimester UtA Doppler ultrasound in an unselected population identifies approximately 60% of women at risk for placental complications; however, application of this screening test failed to improve short-term maternal and neonatal morbidity and mortality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Placental 11B-Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Intrauterine Growth Restriction versus Small-for-Gestational-Age Fetuses.

INTRODUCTION: The objective of this study was to evaluate placental 11B-hydroxysteroid dehydrogenase type 2 (11B-HSD-2) mRNA levels in intrauterine growth-restricted fetuses (IUGR) as compared with small-for-gestational-age (SGA) fetuses according to clinical criteria. MATERIAL AND METHODS: Placental levels of 11B-HSD-2 mRNA levels were measured in SGA (birth weight <10th centile) and gestational-age-matched, appropriate-for-gestational-age (AGA) births. SGA was classified as IUGR (birth weight <3rd centile or <10th percentile with abnormal uterine artery Doppler or cerebroplacental ratio) or non-IUGR SGA. After RNA extraction, mRNA levels were determined by reverse transcription and quantitative PCR. RESULTS: A total of 38 placentas were analyzed (20 AGA and 18 SGA). Among the SGA pregnancies, 13 qualified as IUGR. The activity of 11B-HSD-2 in IUGR pregnancies [0.105 (SD 0.328)] was significantly reduced compared to non-IUGR SGA [0.304 (SD 0.261); p = 0.018] and AGA [0.294 (SD 0.328); p = 0.001]. These differences remained significant after adjusting for potential confounders (such as smoking or maternal cortisol levels). Activity levels did not significantly differ between non-IUGR SGA and AGA. DISCUSSION: IUGR fetuses had reduced 11B-HSD-2 activity in comparison with SGA and normally grown fetuses. This finding provides opportunities to develop new placental biomarkers for the phenotypic characterization of fetal smallness.

Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

OBJECTIVE: Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. METHODS: A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. RESULTS: Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). CONCLUSIONS: Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed.

Relationship between Foetal Growth Restriction and Maternal Nutrition Status Measured by Dual-Energy X-Ray Absorptiometry, Leptin, and Insulin-Like Growth Factor.

AIMS: The aim of this study was to determine if maternal nutritional status, as defined by body composition, leptin, and insulin-like growth factor (IGF)-I levels, relates to foetal growth. METHODS: In this prospective study, mothers of foetuses with foetal growth restriction (FGR; cases; n = 46) and mothers of appropriate-for-gestational-age (AGA) foetuses (controls; n = 81) were consecutively recruited over a 14- month period. A maternal blood sample was obtained during the third trimester (between 32 and 34 weeks of gestation) for the assessment of IGF-I and leptin. Body composition was assessed by dual-energy X-ray absorptiometry within the first 15 days after delivery. The study used the SPSS-PC statistical package, version 19.0, and p < 0.05 was considered statistically significant. RESULTS: Mean serum IGF-I levels were lower in the cases than in the controls (p < 0.05), whereas leptin concentrations were higher in the cases after adjusting for age, body mass index and cigarette consumption (p < 0.05). Cases had less lean and fat tissue than controls (p < 0.05) but a relatively higher fat percentage. CONCLUSIONS: The mothers of foetuses with FGR have a body composition pattern characterized by a slightly increased fraction of fat mass, lower IGF-I concentrations, and increased serum leptin levels. Optimization of maternal nutritional status should be considered, as the nutritional status may be involved in the pathogenesis of FGR.