Prenatal prediction of adverse outcome using different charts and definitions of fetal growth restriction.

OBJECTIVE: Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. METHODS: This was a retrospective cohort study of 17 261 singleton non-anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH-21st (IG-21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal-Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5-min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. RESULTS: IG-21, Hadlock and FMF fetal size references classified as growth-restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG-21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG-21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA-PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA-PI > 95th percentile and EFW < 5th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. CONCLUSIONS: The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA-PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effectiveness of contingent screening for placenta accreta spectrum disorders based on persistent low-lying placenta and previous uterine surgery.

OBJECTIVES: Maternal mortality related to placenta accreta spectrum (PAS) disorders remains substantial when diagnosed unexpectedly at delivery. The aim of this study was to evaluate the effectiveness of a routine contingent ultrasound screening program for PAS. METHODS: This was a retrospective study of data obtained between 2009 and 2019, involving two groups: a screening cohort of unselected women attending for routine mid-trimester ultrasound assessment and a diagnostic cohort consisting of women referred to the PAS diagnostic service with a suspected diagnosis of PAS. In the screening cohort, women with a low-lying placenta at the mid-trimester assessment were followed up in the third trimester, and those with a persistent low-lying placenta (i.e. placenta previa) and previous uterine surgery were referred to the PAS diagnostic service. Ultrasound assessment by the PAS diagnostic service consisted of two-dimensional grayscale and color Doppler ultrasonography, and women with a diagnosis of PAS were usually managed with conservative myometrial resection. The final diagnosis of PAS was based on a combination of intraoperative clinical findings and histopathological examination of the surgical specimen. RESULTS: In total, 57 179 women underwent routine mid-trimester fetal anatomy assessment, of whom 220 (0.4%) had a third-trimester diagnosis of placenta previa. Seventy-five of these women were referred to the PAS diagnostic service because of a history of uterine surgery, and 21 of 22 cases of PAS were diagnosed correctly (sensitivity, 95.45% (95% CI, 77.16-99.88%) and specificity, 100% (95% CI, 99.07-100%)). Univariate analysis demonstrated that parity ≥ 2 (odds ratio (OR), 35.50 (95% CI, 6.90-649.00)), two or more previous Cesarean sections (OR, 94.20 (95% CI, 22.00-656.00)) and placenta previa (OR, 20.50 (95% CI, 4.22-369.00)) were the strongest risk factors for PAS. In the diagnostic cohort, there were 173 referrals, with one false-positive and three false-negative diagnoses, resulting in a sensitivity of 96.63% (95% CI, 90.46-99.30%) and a specificity of 98.81% (95% CI, 93.54-99.97%). CONCLUSIONS: A contingent screening strategy for PAS is both feasible and effective in a routine healthcare setting. When linked to a PAS diagnostic and surgical management service, adoption of such a screening strategy has the potential to reduce the maternal morbidity and mortality associated with this condition. However, larger prospective studies are necessary before implementing this screening strategy into routine clinical practice. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Eficacia de la detección contingente para los trastornos del espectro de la placenta acreta a partir de la placenta baja persistente y en la cirugía uterina previa OBJETIVOS: La mortalidad materna relacionada con los trastornos de la gama espectral de la placenta acreta (EPA) sigue siendo considerable cuando se diagnostica de forma inesperada en el momento del parto. El objetivo de este estudio fue evaluar la efectividad de un programa rutinario de detección contingente mediante ecografía para el EPA. MÉTODOS: Este fue un estudio retrospectivo de datos obtenidos entre 2009 y 2019, en el que participaron dos grupos: una cohorte de detección de mujeres no seleccionadas que acudieron a la evaluación ecográfica rutinaria de mitad de trimestre y una cohorte de diagnóstico, integrada por mujeres remitidas al servicio de diagnóstico del EPA con un presunto diagnóstico del EPA. En la cohorte de detección, a las mujeres con una placenta baja en la evaluación de mitad de trimestre se les hizo un seguimiento en el tercer trimestre, y a aquellas con una placenta baja persistente (es decir, placenta previa) que habían tenido cirugía uterina previa se las remitió al servicio de diagnóstico del EPA. La evaluación ecográfica por el servicio de diagnóstico del EPA consistió en una ecografía Doppler bidimensional en escala de grises y en color, y a las mujeres con diagnóstico del EPA se las trató habitualmente con una resección conservadora del miometrio. El diagnóstico final del EPA se basó en una combinación de indicadores clínicos intraoperatorios y el examen histopatológico de la muestra quirúrgica. RESULTADOS: En total, 57179 mujeres se sometieron a una evaluación rutinaria de la anatomía fetal a mitad del trimestre, de las cuales a 220 (0,4%) se les diagnosticó con placenta previa en el tercer trimestre. Setenta y cinco de estas mujeres fueron remitidas al servicio de diagnóstico del EPA, debido a su historial de cirugía uterina, y 21 de los 22 casos de EPA fueron diagnosticados correctamente (sensibilidad, 95,45% (IC 95%, 77,16-99,88%) y especificidad, 100% (IC 95%, 99,07-100%)). El análisis univariante demostró que la paridad ≥2 (razón de momios (RM), 35,50 (IC 95%, 6,90-649,00)), dos o más cesáreas previas (RM, 94,20 (IC 95%, 22,00-656,00)) y la placenta previa (RM, 20,50 (IC 95%, 4,22-369,00)) fueron los factores de riesgo más fuertes para el EPA. En la cohorte de diagnóstico, se remitió a 173 mujeres, entre las cuáles hubo un diagnóstico de falso-positivo y tres diagnósticos de falsos-negativos, lo que dio como resultado una sensibilidad del 96,63% (IC 95%, 90,46-99,30%) y una especificidad del 98,81% (IC 95%, 93,54-99,97%). CONCLUSIONES: La adopción de una estrategia de detección contingente para el EPA es tanto factible como eficaz en un entorno de atención sanitaria rutinaria. Cuando se asocia a un servicio de diagnóstico y gestión quirúrgica del EPA, la adopción de esa estrategia de detección podría reducir la morbilidad y la mortalidad maternas asociadas a esta afección. Sin embargo, se necesitan estudios prospectivos más amplios antes de aplicar esta estrategia de detección en la práctica clínica habitual. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Invasive mucinous adenocarcinoma of the lung arising in a type 1 congenital pulmonary airway malformation in a 68-year-old patient: a case report.

INTRODUCTION: Congenital pulmonary airway malformation (CPAM), previously described as congenital cystic adenomatoid malformation (CCAM), is a congenital disorder of lung parenchyma. The association with the presence of a malignant transformation like rhabdomyosarcoma, pleuropulmonary blastoma, and most common invasive mucinous adenocarcinoma (IMA) is a rare development described in patients with CPAM. PATIENTS AND METHODS: Here, we report the case of a 68-year-old male patient who underwent a right lower lobectomy for a mass in the right pulmonary lobe. From his clinical history, we noted a recurrent pulmonary infection of a bullous malformation in the right lower lobe treated with antibiotics. RESULTS: The histopathological finding showed an invasive mucinous adenocarcinoma arising in a type 1 CPAM in the right lower lobe. A review of presentation, diagnosis, and treatment of this association is described in a case report. CONCLUSIONS: Surgical resection should be considered in adults with asymptomatic cysts to prevent malignant transformation. For further analysis, histopathological examination of specimen is essential for a proper diagnosis and eventually further postoperative treatment.

Comparison of different methods of measuring angle of progression in prediction of labor outcome.

OBJECTIVES: First, to compare the manual sagittal and parasagittal and automated parasagittal methods of measuring the angle of progression (AoP) by transperineal ultrasound during labor, and, second, to develop models for the prediction of time to delivery and need for Cesarean section (CS) for failure to progress (FTP) in a population of patients undergoing induction of labor. METHODS: This was a prospective observational study of transperineal ultrasound in a cohort of 512 women with a singleton pregnancy undergoing induction of labor. A random selection of 50 stored images was assessed for inter- and intraobserver reliability of AoP measurements using the manual sagittal and parasagittal and automated parasagittal methods. In cases of vaginal delivery, univariate linear, multiple linear and quantile regression analyses were performed to predict time to delivery. Univariate and multivariate binomial logistic regression analyses were performed to predict CS for FTP in the first stage of labor. RESULTS: The intraclass correlation coefficient (ICC) for the manual parasagittal method for a single observer was 0.97 (95% CI, 0.95-0.98) and for two observers it was 0.96 (95% CI, 0.93-0.98), indicating good reliability. The ICC for the sagittal method for a single observer was 0.93 (95% CI, 0.88-0.96) and for two observers it was 0.74 (95% CI, 0.58-0.84), indicating moderate reliability for a single observer and poor reliability between two observers. Bland-Altman analysis demonstrated narrower limits of agreement for the manual parasagittal approach than for the sagittal approach for both a single and two observers. The automated parasagittal method failed to capture an image in 19% of cases. The mean difference in AoP measurements between the sagittal and manual parasagittal methods was 11°. In pregnancies resulting in vaginal delivery, 54% of the variation in time to delivery was explained in a model combining parity, epidural and syntocinon use during labor and the sonographic findings of fetal head position and AoP. In the prediction of CS for FTP in the first stage of labor, a model which combined maternal factors with the sonographic measurements of AoP and estimated fetal weight was superior to one utilizing maternal factors alone (area under the receiver-operating-characteristics curve, 0.80 vs 0.76). CONCLUSIONS: First, the method of measuring AoP with the greatest reliability is the manual parasagittal technique and future research should focus on this technique. Second, over half of the variation in time to vaginal delivery can be explained by a model that combines maternal factors, pregnancy characteristics and ultrasound findings. Third, the ability of AoP to provide clinically useful prediction of CS for FTP in the first stage of labor is limited. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Prediction of large-for-gestational-age neonates: screening by maternal factors and biomarkers in the three trimesters of pregnancy.

OBJECTIVE: To develop a model based on maternal characteristics and medical history (maternal factors) for the prediction of delivery of large-for-gestational-age (LGA) neonates, and to examine the potential value of first-, second- and third-trimester fetal biometry and biomarkers in improving such a model. METHODS: This was a screening study in 76 300, 54 999, 25 727 and 6181 singleton pregnancies at 11-13, 19-24, 30-34 and 35-37 weeks' gestation, respectively. The a-priori risk for LGA with birth weight > 95(th) percentile (LGA > 95(th) ) was calculated using multivariable logistic regression analysis to determine which of the maternal factors had a significant contribution. Regression analysis was then used to determine whether screening by a combination of maternal factors, fetal biometry and various biophysical and biochemical markers had significant contribution in predicting delivery of LGA neonates. RESULTS: The likelihood of LGA > 95(th) increased with increasing maternal weight and height and was lower in women of Afro-Caribbean and South Asian racial origins, in cigarette smokers and in nulliparous women. The risk was higher in women with pre-existing diabetes mellitus Type I and lower in those with chronic hypertension. In parous women, the risk increased with birth-weight Z-score in previous pregnancy and prior history of gestational diabetes and decreased with interpregnancy interval. Screening by maternal factors at 11-13 weeks predicted 32%, 44% and 60% of LGA > 95(th) at false-positive rates (FPRs) of 5%, 10% and 20%, respectively. With the addition of fetal biometry, the detection rates improved to 37%, 51% and 68% at 19-24 weeks, 50%, 65% and 81% at 30-34 weeks and 60%, 73% and 85% at 35-37 weeks at FPRs of 5%, 10% and 20%, respectively. The addition of biomarkers did not improve the detection rates achieved when screening by a combination of maternal factors and fetal biometry. CONCLUSION: Combined screening by maternal factors and fetal biometry can predict a high proportion of pregnancies that will deliver LGA neonates. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Successful induction of labor: prediction by preinduction cervical length, angle of progression and cervical elastography.

OBJECTIVE: To examine the potential value of preinduction cervical length, cervical elastography and angle of progression (AOP) in prediction of successful vaginal delivery and induction-to-delivery interval. METHODS: This was a prospective study in 99 women with singleton pregnancy undergoing preinduction ultrasound assessment at 35-42 weeks' gestation. Cervical length, elastographic score at the internal os and AOP were determined. Regression analysis was used to assess the relationship between cervical length and both AOP and elastographic score. Logistic regression analysis was used to determine which of the maternal characteristics (cervical length, AOP, elastographic score) were significant predictors of vaginal delivery and induction-to-delivery interval. RESULTS: Vaginal delivery occurred in 66 (66.7%) cases and Cesarean delivery was performed in 33 (33.3%) cases. There were significant correlations between cervical length and both AOP (r = - 0.319) and elastographic score (r = 0.368). Significant independent prediction of vaginal delivery and induction-to-delivery interval was provided by nulliparity and cervical length, with no additional significant contribution from electrographic score or AOP. CONCLUSIONS: In women undergoing induction of labor, AOP and elastographic score at the internal os are unlikely to be useful in prediction of vaginal delivery and induction-to-delivery interval.

Changes in quality of life of patients with lymphedema after lymphatic vessel transplantation.

There are multiple treatment options for patients with chronic lymphedema, and one successful approach is lymph vessel transplantation. As quality of life assessments are frequently not utilized in standard treatment regimes, we investigated the change in quality of life for patients with chronic lymphedema (total = 212) who had undergone lymphatic vessel transplantation and conservative therapy for at least 6 months prior to operation. Quality of life was assessed by a modified standard questionnaire examining the physiological and psychological status of the patients. Results document a significant improvement in quality of life and underscore success of autologous lymphatic vessel transplantation as a therapy for lymphedema.

Microsurgical lymphatic vascular grafting and secondary liposuction: Results of combination treatment in secondary lymphedema.

Surgical treatment of lymphedema with liposuction typically requires subsequent compression therapy. Here we describe an approach where secondary arm lymphedemas are initially treated by autologous lymphatic grafting to bypass the axilla and restore lymphatic flow. In the presence of excess adipose tissue, liposuction is then performed in a second procedure. To assess outcomes, the authors evaluated 28 consecutive adult patients who had undergone secondary liposuction following lymphatic grafting. Arm volumes were measured prior to lymphatic grafting and after the secondary liposuction. The necessity for additional treatment by compression garment and manual lymphatic drainage was assessed prior to lymphatic grafting and after the secondary liposuction following the direct postoperative regimen. The mean arm volumes were reduced significantly (p<0.001) from a mean of 3417± 171 (SEM) cm3 prior to lymphatic grafting to 3020±125 cm3 after reconstruction of the lymphatic vascular system and finally to 2516±104 cm3 after the secondary liposuction (SLS). All 28 adult patients underwent continuous compression and manual lymph-drainage (MLD) prior to the reconstructive surgery. All 28 patients were evaluated regarding necessity of any additional therapy more than 6 months after SLS with a median follow up period of 37 months (range, 7-160 months). 18 of 28 patients did not require any supportive therapy beyond 6 months after SLS to maintain the results. Three patients continued to utilize manual lymphatic drainage, 4 used a combination of MLD and compression therapy and 3 used elastic compression therapy (one patient only while at work). These results indicate that microsurgical restoration of lymphatic outflow followed by SLS eliminates the need for additional treatment in more than two thirds of patients.

Precisely localized LTD in the neocortex revealed by infrared-guided laser stimulation.

In a direct approach to elucidate the origin of long-term depression (LTD), glutamate was applied onto dendrites of neurons in rat neocortical slices. An infrared-guided laser stimulation was used to release glutamate from caged glutamate in the focal spot of an ultraviolet laser. A burst of light flashes caused an LTD-like depression of glutamate receptor responses, which was highly confined to the region of "tetanic" stimulation (<10 micrometers). A similar depression of glutamate receptor responses was observed during LTD of synaptic transmission. A spatially highly specific postsynaptic mechanism can account for the LTD induced by glutamate release.

Robotics in gynecologic surgery.

Robotic surgery has evolved from an investigational surgical approach to a clinically useful adjunct in multiple surgical specialties over the past decade. Advocates of robotic-assisted gynecologic surgery revere the system's wristed instrumentation, ergonomic positioning, and three-dimensional high-definition vision system as significant improvements over laparoscopic equipment's four degrees of freedom and two-dimensional laparoscope that demand the surgeon stand throughout a procedure. The cost, lack of haptic feedback, and the bulky size of the equipment make robotics less attractive to others. Studies evaluating outcomes in robotic-assisted gynecologic surgery are limited. Multiple small retrospective studies demonstrate the safety and feasibility of robotic hysterectomy. With increased surgeon experience, operative times are similar to, or shorter than, laparoscopic cases. Robotic assistance can facilitate suturing in laparoscopic myomectomies, and is associated with decreased blood loss and a shorter hospital stay, although may require longer operative times. Robotic assistance has also been applied to multiple procedures in the subspecialties of infertility, urogynecology and gynecologic oncology with good success and relatively low morbidity. However, further research is warranted to better evaluate the relative benefits and costs of robotic assisted gynecologic surgery.

Pregnancy outcomes after maternal Zika virus infection in a non-endemic region: prospective cohort study.

OBJECTIVES: The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region. METHODS: According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained. RESULTS: Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies. CONCLUSION: The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.

Fluctuation and reproducibility of exposure and effect of insulin glargine in healthy subjects.

AIM: Low diurnal fluctuation and high day-to-day reproducibility in exposure and effect characterize beneficial basal insulin products. Two insulin glargine (LANTUS) formulations [without (R) or with polysorbate-20 (T)], added to minimize unfolding of proteins and subsequent formation of fibril structures, were assessed for equivalence in exposure and effect, and aspects of fluctuation and reproducibility in time-concentration and time-action profiles. METHODS: A dose of 0.4 U/kg was subcutaneously administered to 24 healthy subjects in a two-sequence (R-T-R-T or T-R-T-R), randomized, four-way crossover trial utilizing 30-h Biostator-based euglycaemic glucose clamps. RESULTS: Identical serum insulin glargine concentration and time-action profiles established average, individual and population equivalence in insulin exposure and effect. Point estimates for 24-h area under the curve for insulin (INS-AUC(0-24) (h)) and glucose infusion rates (GIR-AUC(0-24) (h)) were 97% [90% confidence interval (CI): 91-103%] and 100% (88-114%), respectively. Within-subject variability (coefficient of variation) for INS-AUC(0-24) (h) and GIR-AUC(0-24) (h) were 19% (95% CI: 14-25%) and 34% (24-43%), respectively. The diurnal relative fluctuation of the serum insulin glargine concentration was 20% (95% CI: 19-21%). CONCLUSION: Insulin glargine in either formulation presents with a high day-to-day reproducibility of a uniform release after injection enabling an effective basal insulin supplementation.

A comparison of hormone therapies on the urinary excretion of prostacyclin and thromboxane A2.

OBJECTIVE: To evaluate the effect of estradiol, estradiol and norethisterone acetate (NETA), raloxifene and tibolone on the prostacyclin (PGI(2))/thromboxane A2 (TxA(2)) ratio in postmenopausal women after 8 weeks of treatment. DESIGN: This was a randomized, double-blind, cross-over study. Each patient took 8-week courses of estradiol 2 mg, estradiol 2 mg + NETA 1 mg, tibolone 2.5 mg, and raloxifene 60 mg; there was an 8-week placebo wash-out between each different intervention. All volunteers took all four treatment options and were randomized to one of three possible sequences. Urine was collected and frozen at each visit. Urinary metabolites of PGI(2) and TxA(2) were then assessed at the end of the study. RESULTS: The ratio of PGI(2)/TxA(2) was significantly increased for raloxifene. No other treatments showed statistically significant changes. CONCLUSIONS: The relationship between cardiovascular risk and hormone replacement therapy remains poorly understood. Raloxifene may have additional cardioprotective effects that the other treatments did not demonstrate, and none of the treatments statistically worsened the PGI(2)/TxA(2) ratio. This ratio may be under-utilized as a marker of net effect on cardiovascular health, but more research is needed to link it to health outcomes.

Hysteropexy. A review.

Uterine prolapse is a common problem in women that negatively affects one's quality of life. Surgical treatment commonly involves a hysterectomy followed by vaginal vault suspension of some type. Hysteropexy to treat uterovaginal prolapse has a long history dating back to the 1800s and has gone through many changes. Recent literature describes vaginal, open abdominal and laparoscopic approaches. Vaginal sacrospinous hysteropexy is well-supported by the scientific literature. Favorable postoperative outcomes range from 62-100% and additional data show improved quality of life and sexual function. Anatomic outcomes appear to be comparable to vaginal hysterectomy with sacrospinous ligament vault suspension. Additionally, encouraging outcomes following pregnancy have been described. The sacrohysteropexy, performed through a laparotomy incision or laparoscopically, also has favorable data, with cure rates ranging from 91-100%. Studies supporting this procedure also describe improvements in quality of life and sexual function. Complications related to these procedures are similar to those described after vaginal vault suspension using comparable techniques, although most studies report shorter operative times and less blood loss. At the present time, hysteropexy, either transvaginal or abdominal, seems to be a safe procedure with acceptable results in women who desire uterine preservation. As these procedures gain popularity and data become available, questions related to patient selection, surgical durability, outcomes following pregnancy, and complications related to risk of uterine pathology will likely be answered.

[Community-acquired, methicillin-resistant Staphylococcus aureus acute osteomyelitis and pneumonia]. / Osteomielitis aguda y neumonía comunitaria por Staphylococcus aureus resistente a meticilina.

The appearance of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is a increasingly important problem. We describe the case of a child suffering a CA-MRSA osteomyelitis complicated with a non-necrotizing pneumonia. The fast resolution of the pulmonary infection contrasts with the poor evolution of the septic bone. We emphasise the importance of correct surgical drainage to clear the infection. We review the literature on this emergent pathogen.

[Re-intervention after carpal tunnel release]. / Revisionseingriffe nach Karpaldachspaltung.

In the last eight years we performed 63 re-interventions because of recurrent carpal tunnel syndromes. Intact parts of the retinaculum were the reason for persistent symptoms in 38 patients. 21 patients suffered from scar tethering, two patients from circumferential fibrosis of the nerve. In one patient a ganglion and in another patient a direct injury to the median nerve was detected. In 21 patients short incisions were performed in the primary procedures. Since the introduction of endoscopic carpal tunnel release, an open decompression via a short incision is recommended as an alternative. Since then we encounter an increase of necessary operative revisions after short incisions. Optical tools may increase the survey especially in short incisions. In extended teno-synovialitis of the flexor tendons, a longer incision over the wrist enables adequate conditions for a safe teno-synovialectomy. The length of the incision has to be chosen according to the pathologic-anatomic situation, the disposable equipment and the experience of the surgeon.

Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder.

Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain's adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure-function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time × treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P(FWE) = 0.02) and BOLD responsivity (P(FWE) = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P(FWE)=0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P(FWE) ⩽ 0.05). In addition, we observed greater amygdala neural responsivity to self-referential criticism in socially anxious participants, as compared with controls (P(FWE) = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT.