Evidence of brain injury in fetuses of mothers with preterm labor with intact membranes and preterm prelabor rupture of membranes.

BACKGROUND: Brain injury and poor neurodevelopment have consistently been reported in infants and adults born preterm. These changes occur at least in part prenatally and are associated with intra-amniotic inflammation. The pattern of brain changes has been partially documented by magnetic resonance imaging but not with neurosonography in combination with amniotic fluid brain injury biomarkers. OBJECTIVES: To evaluate the prenatal features of brain remodeling and injury in fetuses from patients with preterm labor with intact membranes or preterm prelabor rupture of membranes and to investigate the potential influence of intra-amniotic inflammation as a mediator of risk. STUDY DESIGN: In this prospective cohort study, fetal brain remodeling and injury was evaluated by neurosonography and amniocentesis in singleton pregnant patients with preterm labor with intact membranes or preterm prelabor rupture of membranes between 24.0-34.0 weeks, with (n=41) and without (n=54) intra-amniotic inflammation. Controls for neurosonography were outpatient pregnant patients without preterm labor or preterm prelabor rupture of membranes matched 2:1 by gestational age at ultrasound. Amniotic fluid controls were patients with an amniocentesis performed for indications other than preterm labor or preterm prelabor rupture of membranes without brain or genetic defects whose amniotic fluid was collected in our biobank for research purposes matched by gestational age at amniocentesis. The group with intra-amniotic inflammation included those with intra-amniotic infection (microbial invasion of the amniotic cavity and intra-amniotic inflammation) and those with sterile inflammation. Microbial invasion of the amniotic cavity was defined as a positive amniotic fluid culture and/or positive 16S ribosomal RNA gene. Inflammation was defined by amniotic fluid interleukin-6 >13.4 ng/ml in preterm labor and >1.43 ng/ml in preterm prelabor rupture of membranes. Neurosonography included the evaluation of brain structure biometric parameters and cortical development. As amniotic fluid brain injury biomarkers we selected neuron-specific enolase, protein S100B and glial fibrillary acidic protein. Data was adjusted for cephalic biometrics, fetal growth centile, fetal sex, non-cephalic presentation and preterm prelabor rupture of membranes at admission. RESULTS: Fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes had signs of brain remodeling and injury. First, they had a smaller cerebellum. Thus, in intra-amniotic inflammation, non- intra-amniotic inflammation and control groups, transcerebellar diameter (median (25th; 75th percentile)) was 32.7mm (29.8; 37.6), 35.3mm (31.2;39.6) and 35.0mm (31.3;38.3), respectively (p=0.019); vermian height was 16.9 mm (15.5 ;19.6), 17.2 mm (16.0;18.9) and 17.1mm (15.7;19.0), respectively (p=0.041). Second, they presented a lower corpus callosum area (0.72mm2 (0.59;0. 81), 0.71mm2 (0.63;0.82) and 0.78mm2 (0.71;0. 91), respectively (p=0.006). Third, they showed a delayed cortical maturation (Sylvian fissure depth / biparietal diameter ratio was 0.14 (0.12;0.16), 0.14 (0.13;0.16) and 0.16 (0.15;0.17), respectively (p<0.001), and right parieto-occipital sulci depth ratio was 0.09 (0.07;0.12), 0.11 (0.09;0.14) and 0.11 (0.09;0.14), respectively (p=0.012)). Finally, regarding amniotic fluid brain injury biomarkers, fetuses from mothers with preterm labor with intact membranes or preterm prelabor rupture of membranes, had higher concentrations of neuron-specific enolase (11804.6pg/ml (6213.4;21098.8), 8397.7 pg/ml (3682.1;17398.3) and 2393.7pg/ml (1717.1;3209.3), respectively (p<0.001)); protein S100B (2030.6 pg/ml (993;4883.5), 1070.3pg/ml (365.1-1463.2) and 74.8pg/ml (44.7;93.7), respectively (p<0.001)), and glial fibrillary acidic protein (1.01ng/ml (0.54;3.88), 0.965ng/ml (0.59;2.07) and 0.24mg/ml (0.20;0.28), respectively (p=0.002)). CONCLUSION: Fetuses with preterm labor with intact membranes or preterm prelabor rupture of membranes had prenatal signs of brain remodeling and injury at the time of clinical presentation. These changes were more pronounced in those with intra-amniotic inflammation.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

A multivariable prediction model for intra-amniotic infection in patients with preterm labor and intact membranes including a point of care system that measures amniotic fluid MMP-8.

OBJECTIVES: Among patients with preterm labor and intact membranes (PTL), those with intra-amniotic infection (IAI) present the highest risk of adverse perinatal outcomes. Current identification of IAI, based on microbiological cultures and/or polymerase chain reaction amplification of the 16S ribosomal RNA gene, delay diagnosis and, consequently, antenatal management. The aim to of the study was to assess the performance of a multivariable prediction model for diagnosing IAI in patients with PTL below 34.0 weeks using clinical, sonographic and biochemical biomarkers. METHODS: From 2019 to 2022, we prospectively included pregnant patients admitted below 34.0 weeks with diagnosis of PTL and had undergone amniocentesis to rule in/out IAI. The main outcome was IAI, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. Based on the date of admission, the sample (n=98) was divided into a derivation (2019-2020, n=49) and validation cohort (2021-2022, n=49). Logistic regression models were developed for the outcomes evaluated. As predictive variables we explored ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, and amniotic fluid glucose and matrix metalloproteinase-8 (MMP-8) levels. The model was developed in the derivation cohort and applied to the validation cohort and diagnostic performance was evaluated. Clinical management was blinded to the model results. RESULTS: During the study period, we included 98 patients admitted with a diagnosis of PTL. Of these, 10 % had IAI. The final model included MMP-8 and amniotic fluid glucose levels and showed an area under the receiver operating characteristic curve to predict the risk of IAI of 0.961 (95 % confidence interval: 0.860-0.995) with a sensitivity of 75 %, specificity of 93.3 %, positive likelihood ratio (LR) of 11.3 and negative LR of 0.27 in the validation cohort. CONCLUSIONS: In patients with PTL, a multivariable prediction model including amniotic fluid MMP-8 and glucose levels might help in the clinical management of patients undergoing amniocentesis to rule in/out IAI, providing results within a few minutes.

Preterm Prelabour Rupture of Membranes before Viability in Twin Pregnancies: What Can We Expect?

Preterm prelabour rupture of membranes (PPROMs) before viability carries significant perinatal mortality and morbidity. Clinical management and prenatal counselling are a challenge, especially in twin pregnancies, due to scarce evidence on how previable PPROM affects this population. The aim of this study was to describe pregnancy outcomes of twin pregnancies complicated with previable PPROM and evaluate potential prognostic factors that may predict perinatal mortality. A retrospective cohort including dichorionic and monochorionic diamniotic twin pregnancies complicated with PPROM before 24 + 0 weeks of pregnancy was evaluated. Perinatal outcomes of pregnancies managed expectantly were described. Factors predicting perinatal mortality or reaching periviability (defined from 23 + 0 weeks onwards) were evaluated. Of the 45 patients included, 7 (15.6%) spontaneously delivered within the first 24 h after diagnosis. Two patients (5.3%) requested selective termination of the affected twin. In the 36 ongoing pregnancies that opted for expectant management, the overall survival rate was 35/72 (48.6%). There were 25/36 (69.4%) patients who delivered after 23 + 0 weeks of pregnancy. When periviability was achieved, neonatal survival increased up to 35/44 (79.5%). Gestational age at delivery was the only independent risk factor of perinatal mortality. The overall survival rate of twin pregnancies complicated with previable PPROM is poor but similar to singletons. No prognostic factors, apart from achieving periviability, were identified as individual predictors of perinatal mortality.

Outpatient management of preterm prelabor rupture of membranes before 34 weeks: Maternal and neonatal outcomes.

OBJECTIVE: To evaluate the maternal, fetal, and neonatal outcomes of pregnant women complicated with preterm prelabor rupture of membranes (PPROM) eligible for outpatient care. METHODS: This study included a retrospective cohort of patients with singleton pregnancies with PPROM between 23+0 to 34+0 weeks who remained pregnant after the first 72 h. Outpatient management was considered in women with clinical, ultrasound and analytical stability, and easy access to hospital. Maternal, fetal, and neonatal results were compared between women managed as inpatients versus those managed as outpatients. RESULTS: Women eligible for the outpatient management had a better prognostic profile (no anhydramnios, longer cervical length, less intraamniotic infection, and clinical, ultrasound, and analytical stability) and presented a lower gestational age at admission and longer latency to delivery, resulting in a similar gestational age at delivery as the inpatient group. Postpartum curettage, uterine atony, respiratory distress syndrome, and bronchopulmonary dysplasia were less frequent in the outpatient group. Composite maternal-fetal morbidity and mortality outcomes were similar in both groups, while composite neonatal morbidity and mortality outcomes were significantly lower in the outpatient group. CONCLUSION: Outpatient management may be an option for women presenting stable PPROM before 34 weeks when adequate selection criteria are fulfilled. Differences in perinatal outcomes in the outpatient group compared with the inpatient group are probably attributable to baseline characteristics. Further prospective randomized studies are needed to confirm the benefits of outpatient management in PPROM.

Noninvasive prediction models of intra-amniotic infection in women with preterm labor.

BACKGROUND: Among women with preterm labor, those with intra-amniotic infection present the highest risk of early delivery and the most adverse outcomes. The identification of intra-amniotic infection requires amniocentesis, perceived as too invasive by women and physicians. Noninvasive methods for identifying intra-amniotic infection and/or early delivery are crucial to focus early efforts on high-risk preterm labor women while avoiding unnecessary interventions in low-risk preterm labor women. OBJECTIVE: This study modeled the best performing models, integrating biochemical data with clinical and ultrasound information to predict a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days. STUDY DESIGN: From 2015 to 2020, data from a cohort of women, who underwent amniocentesis to rule in or rule out intra-amniotic infection or inflammation, admitted with a diagnosis of preterm labor at <34 weeks of gestation at the Hospital Clinic and Hospital Sant Joan de Déu, Barcelona, Spain, were used. At admission, transvaginal ultrasound was performed, and maternal blood and vaginal samples were collected. Using high-dimensional biology, vaginal proteins (using multiplex immunoassay), amino acids (using high-performance liquid chromatography), and bacteria (using 16S ribosomal RNA gene amplicon sequencing) were explored to predict the composite outcome. We selected ultrasound, maternal blood, and vaginal predictors that could be tested with rapid diagnostic techniques and developed prediction models employing machine learning that was applied in a validation cohort. RESULTS: A cohort of 288 women with preterm labor at <34 weeks of gestation, of which 103 (35%) had a composite outcome of intra-amniotic infection and/or spontaneous delivery within 7 days, were included in this study. The sample was divided into derivation (n=116) and validation (n=172) cohorts. Of note, 4 prediction models were proposed, including ultrasound transvaginal cervical length, maternal C-reactive protein, vaginal interleukin 6 (using an automated immunoanalyzer), vaginal pH (using a pH meter), vaginal lactic acid (using a reflectometer), and vaginal Lactobacillus genus (using quantitative polymerase chain reaction), with areas under the receiving operating characteristic curve ranging from 82.2% (95% confidence interval, ±3.1%) to 85.2% (95% confidence interval, ±3.1%), sensitivities ranging from 76.1% to 85.9%, and specificities ranging from 75.2% to 85.1%. CONCLUSION: The study results have provided proof of principle of how noninvasive methods suitable for point-of-care systems can select high-risk cases among women with preterm labor and might substantially aid in clinical management and outcomes while improving the use of resources and patient experience.

Intra- and interobserver reproducibility of second trimester ultrasound cervical length measurement in a general population.

OBJECTIVES: To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester. METHODS: A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed. RESULTS: Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used. CONCLUSION: Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.

Latency to delivery in physical examination-indicated cerclage in twins is similar to that in singleton pregnancies.

OBJECTIVE: To compare latency to delivery and perinatal outcomes between twin and singleton pregnancies undergoing physical examination-indicated cerclage. METHODS: Retrospective observational study (2007-2017) of women who underwent physical examination-indicated cerclage at the Hospital Clinic of Barcelona. Primary outcomes were latency from cerclage to delivery and gestational age at delivery. Secondary outcomes included: neonatal morbidity and mortality, preterm prelabor rupture of membranes, clinical chorioamnionitis and cerclage displacement. Wilcoxon-test and χ2 test were used to compare continuous and categorical variables. RESULTS: Sixty women were included (17 twins and 43 singletons). There were no differences in gestational age at cerclage or presence of bulging membranes between groups. Median (25th;75th percentile) gestational age at delivery was 27.1 (24.5;32.3) weeks in the twin group and 27.6 (25.3;35.3) weeks in the singleton group (P = 0.594). There were no statistically significant differences in latency from cervical cerclage to delivery between the two groups (43 days [21;64] vs. 29 days [16;76], respectively; P = 0.938). There were no differences in neonatal mortality (2/26 [7.7%] vs. 1/33 [3.1%]; P = 0.578) or in composite neonatal morbidity (14 [53.9%] vs. 14 [42.4%]; P = 0.283) between groups, respectively. CONCLUSION: These results suggest that physical examination-indicated cerclage placement in twins could prolong latency to delivery similarly to singleton pregnancies.

Perinatal outcome after selective termination in dichorionic twins discordant for congenital anomalies.

INTRODUCTION: Our objective was to evaluate the perinatal outcome of selective termination of dichorionic twin pregnancies with discordant anomalies, according to gestational age at time of procedure. MATERIAL AND METHODS: Retrospective review of 147 dichorionic twin pregnancies referred to our Fetal Medicine Unit between 2003 and 2018 for selective termination. Gestational age at delivery, fetal loss, and overall and 28-day post-delivery survival rates, were evaluated according to gestational age at time of procedure. Selective termination procedure was defined as early, intermediate, and late when performed before 18 weeks, between 18 and 23 weeks, and after 23 weeks, respectively. Kruskal-Wallis and chi-squared test were used to compare groups. RESULTS: Overall survival at 28 days post-delivery, pregnancy loss, and preterm delivery before 32 weeks of gestation rates were 93.4%, 6.9%, and 15.5%, respectively. When stratified by gestational age at procedure, intermediate selective termination was associated with a lower survival rate than early and late procedures (86% vs. 96.9% and 100%, respectively; p = 0.035), and a nonsignificant trend for higher pregnancy loss (12% vs. 3.1%). Preterm delivery before 32 weeks of gestation occurred in 27% of late procedures, which was significantly higher than in early (9.5%) and intermediate (18.2%) procedures. CONCLUSIONS: Selective termination in dichorionic twin pregnancies with discordant fetal anomaly is associated with low pregnancy loss and preterm delivery rate, primarily when performed before 18 weeks. When legally possible, late procedures can be a good alternative, particularly in those cases diagnosed beyond the 18th week of gestation.

Mid-trimester prediction of spontaneous preterm birth with automated cervical quantitative ultrasound texture analysis and cervical length: a prospective study.

The objective of this study was to evaluate a novel automated test based on ultrasound cervical texture analysis to predict spontaneous Preterm Birth (sPTB) alone and in combination with Cervical Length (CL). General population singleton pregnancies between 18 + 0 and 24 + 6 weeks' gestation were assessed prospectively at two centers. Cervical ultrasound images were evaluated and the occurrence of sPTB before weeks 37 + 0 and 34 + 0 were recorded. CL was measured on-site. The automated texture analysis test was applied offline to all images. Their performance to predict the occurrence of sPTB before 37 + 0 and 34 + 0 weeks was evaluated separately and in combination on 633 recruited patients. AUC for sPTB prediction before weeks 37 and 34 respectively were as follows: 55.5% and 65.3% for CL, 63.4% and 66.3% for texture analysis, 67.5% and 76.7% when combined. The new test improved detection rates of CL at similar low FPR. Combining the two increased detection rate compared to CL alone from 13.0 to 30.4% for sPTB < 37 and from 14.3 to 42.9% sPTB < 34. Texture analysis of cervical ultrasound improved sPTB detection rate compared to cervical length for similar FPR, and the two combined together increased significantly prediction performance. This results should be confirmed in larger cohorts.

[Overview of the interstitial lung disease in the Southeast of Mexico]. / Panorama de la enfermedad pulmonar intersticial en el sureste de México.

Background: Interstitial lung disease (ILD) corresponds to a heterogeneous group of pathologies that differ in etiology with common clinical and radiological manifestations. In Latin America and Mexico, reports are scarce and the need for studies to understand the scenario is emphasized. Objective: To analyze a multidimensional profile in patients with interstitial lung disease in Yucatan. Method: This is an observational, prospective, analytic, descriptive study including consecutive patients diagnosed with ILD over a 4-year period. Demographic and clinical data, lung function tests, chest imaging, serum immunological profile, and echocardiographic findings were recorded. Differences between subgroups were analyzed performing a one-way analysis of variance (ANOVA). Results: 110 patients were included. The median age was 60 years and women were most affected. The main cause of ILD was related with connective tissue diseases (CTD). A group subanalysis revealed that Idiopathic pulmonary fibrosis (IPF) was common in males with a history of smoking and an imaging pattern of usual interstitial pneumonia. Lung function tests showed a moderate-to-severe pulmonary restriction (FVC 55%p) and mild hypoxemia (PaO2 79mmHg). Positive antinuclear antibodies are less likely in cases with IPF (20 vs. 65%; p = 0.006). Conclusion: In Southeastern Mexico, ILD occurs in women in their seventh decade of life; the most common cause is related with CTD. Our results support that ILD has a heterogeneous expression and is relevant the need for subsequent studies characterizing each ILD.

Introducción: La enfermedad pulmonar intersticial (EPI) corresponde a un grupo heterogéneo de patologías que difieren en su etiología pero tienen manifestaciones clínicas y radiológicas comunes. En Latinoamérica y México los reportes son escasos, enfatizando la necesidad de estudios que permitan conocer su escenario clínico-epidemiológico. Objetivo: Realizar un análisis multidimensional y contrastado de la EPI en la población de la Península de Yucatán. Método: Estudio observacional, prospectivo, analítico y descriptivo, que incluye la totalidad de pacientes diagnosticados de EPI en un período de 4 años. Se registraron datos demográficos y clínicos, pruebas de función pulmonar, imagenología del tórax, perfil inmunológico y ecocardiografía transtorácica. Se analizaron las diferencias según la etiología mediante análisis de la varianza de una sola vía (ANOVA). Resultados: Se incluyeron 110 pacientes con una mediana de edad de 60 años y predominio del sexo femenino. La causa principal de la EPI fue relacionada con enfermedad del tejido conectivo. El subanálisis de grupos mostró que la fibrosis pulmonar idiopática (FPI) es frecuente en los varones con antecedente de tabaquismo y patrón tomográfico de neumonía intersticial usual. Las pruebas de función pulmonar demostraron restricción pulmonar moderadamente grave (FVC 55%p) e hipoxemia leve (PaO2 79 mmHg). La positividad de anticuerpos antinucleares ocurre en menor proporción en la FPI (20 vs. 65%, p = 0.006). Conclusiones: En el sureste de México, la EPI ocurre en mujeres de la séptima década de la vida y se relaciona con enfermedad del tejido conectivo. Nuestros resultados respaldan que la EPI tiene expresión heterogénea y se requieren estudios subsecuentes sobre cada tipo de enfermedad.

Characterization of vaginal microbiota in women with preterm labor with intra-amniotic inflammation.

This study aims to investigate the relation between vaginal microbiota and exposition to intra-amniotic inflammation (IAI). We conducted a prospective cohort study in women with preterm labor <34 weeks who had undergone amniocentesis to rule out IAI. Vaginal samples were collected after amniocentesis. Women with IAI included those with positive amniotic fluid (AF) for a microorganism identified by specific culture media and Sanger sequencing 16S ribosomal RNA gene and/or high AF interleukin (IL)-6 levels. Vaginal microbiota was characterized by 16S ribosomal RNA gene amplicon sequencing. Specific quantitative PCR targeted to Lactobacillus spp. was also performed. Regression models were used to evaluate associations between vaginal microbiota and exposition to IAI. Concerning our results, 64 women were included. We observed an inverse association between AF IL-6 levels and load of Lactobacillus spp. Depletion in Lactobacillus spp. load was significantly associated with an early gestational age at delivery and a short latency to delivery. Microbial-diversity was found to be a risk factor for the subsequent occurrence of clinical chorioamnionitis. To the contrary, higher Lactobacillus spp. load had a protective role. In conclusion, the study identifies reduced bacterial load of Lactobacillus spp. in women exposed to IAI and found microbial-diversity and Lactobacillus spp. depletion to be associated with a worse perinatal outcome.

Critical pathway for primary open angle glaucoma diagnosis.

AIM: To develop a critical pathway for primary open angle glaucoma (POAG) diagnosis intended to be efficient, to unify criteria, reduce resource use and minimize costs to the health system. METHODS: We performed a systematic search on PubMed, Cochrane, Embase and ClinicalTrials.org databases and classified the quality of evidence from level I through III. RESULTS: A critical pathway was designed by setting a key-decision step by step model on the basis of the best current evidence. CONCLUSION: A critical pathway, evidence-based guideline, may be a useful tool intended to reduce costs while maintaining or even improving the quality of care for diagnosing a highly prevalent pathology such as open angle glaucoma.

Fast redox-triggered shuttling motions in a copper rotaxane based on a phenanthroline-terpyridine conjugate.

Fast shuttling motions in solution have been observed by cyclic voltammetry in a Cu(I/II)-based [2] rotaxane. In the reported system, the different coordination preferences of both copper oxidation states are exploited to promote the electrochemically-triggered gliding of the ring from a tetra to a pentacoordinated site and vice versa. The thread of this rotaxane consists of a tridentate 2,2':6',2''-terpyridine chelating unit directly bonded through its 5-position to the 3-position of the bidentate 1,10-phenanthroline unit. This distribution reduces to a minimum the distance between the two coordination sites and lessens the congestion around the tetrahedral environment. These two factors have been demonstrated to highly increase the kinetics of the switching process. In addition, the electrochemical experiments carried out in different solvent mixtures evidenced the influence of the solvent on the shuttling mechanism.

Non steroidal anti-inflammatory drugs in the prevention of cystoid macular edema after uneventful cataract surgery.

BACKGROUND: Cystoid macular edema (CME) remains an important complication after cataract surgery. There is no consensus about how to prevent this frequent complication. The purpose of this study was to conceive an effective anti-inflammatory strategy using nonsteroidal anti-inflammatory drugs (NSAIDs) together with regular treatment with corticosteroids to prevent CME and improve visual acuity after cataract surgery in patients without risk factors. MATERIALS AND METHODS: We searched the PubMed, Cochrane, and Google Scholar databases focused on prospective, controlled, randomized, double-blind clinical trials published in the last 10 years, with a minimum follow-up of 4 weeks. RESULTS: A total of nine clinical trials, one systematic review, and two reviews satisfied our search criteria. Most studies highlighted that NSAIDs are as powerful as corticosteroids to diminish postoperative inflammation, and demonstrated an additional benefit when used in combination with standard corticosteroid postsurgical therapy. In addition, the use of NSAIDs in the perioperative period seems to significantly improve the outcome after surgery and helps prevent CME in low-risk patients. CONCLUSION: The prophylactic use of NSAIDs in combination with the standard postoperative steroid scheme appears to be a positive course of action for preventing CME after cataract surgery. We suggest a therapeutic scheme based on the administration of one drop four times a day, beginning the day before surgery and for 4 weeks after the procedure. It is also advisable to administer one drop every 15 minutes in the hour prior to surgery in order to obtain better anti-inflammatory efficacy.

Effect of metal complexation on the conductance of single-molecular wires measured at room temperature.

The present work aims to give insight into the effect that metal coordination has on the room-temperature conductance of molecular wires. For that purpose, we have designed a family of rigid, highly conductive ligands functionalized with different terminations (acetylthiols, pyridines, and ethynyl groups), in which the conformational changes induced by metal coordination are negligible. The single-molecule conductance features of this series of molecular wires and their corresponding Cu(I) complexes have been measured in break-junction setups at room temperature. Experimental and theoretical data show that no matter the anchoring group, in all cases metal coordination leads to a shift toward lower energies of the ligand energy levels and a reduction of the HOMO-LUMO gap. However, electron-transport measurements carried out at room temperature revealed a variable metal coordination effect depending on the anchoring group: upon metal coordination, the molecular conductance of thiol and ethynyl derivatives decreased, whereas that of pyridine derivatives increased. These differences reside on the molecular levels implied in the conduction. According to quantum-mechanical calculations based on density functional theory methods, the ligand frontier orbital lying closer to the Fermi energy of the leads differs depending on the anchoring group. Thereby, the effect of metal coordination on molecular conductance observed for each anchoring could be explained in terms of the different energy alignments of the molecular orbitals within the gold Fermi level.

Fast pirouetting motion in a pyridine bisamine-containing copper-complexed rotaxane.

The present work reports the introduction of pyridine bisamine terdentate ligands in the structure of a pirouetting copper rotaxane. Rotaxane 2[PF6] constitutes the first example of the incorporation of imine-based dynamic covalent chemistry in the synthesis of switchable copper-complexed interlocked systems. In this rotaxane, the substitution of the classical terpyridine terdentate unit by a pyridine bisamine moiety has led to a significant stabilization of the pentacoordinated site. That fact has been evidenced by EPR spectroscopy and cyclic voltammetry. Regarding the tetracoordinated site, the congestion around the coordination sphere has been reduced to accelerate the typically slow reorganization of the Cu(II). Ethynyl-3,8-substitution on the axis phenanthroline along with the 2,9-diphenyl-1,10-phenanthroline (dpp) present in the macrocycle afforded a very stable coordination environment for Cu(I), which is at the same time labile upon oxidation. In summary, the incorporation of a pyridine bisamine unit as a terdentate ligand and the optimization of the bidentate ligand of the axle not only has led to a simplification of the synthetic procedures, but it has also given rise to a bistable systems with an enhanced energetic separation between states and an acceleration of the reorganization processes. Thus far, rotaxane 2[PF6] presents the fastest switching cycle reported to date in copper-interlocked dynamic systems.

Self-assembly of an iron(II)-based M5L6 metallosupramolecular cage.

A pentanuclear M(5)L(6) coordination cage is self-assembled in solution from a rigid linear heteroditopic phen-tpy ligand and an iron (II) salt.

Meningitis tuberculosa: determinación de resistencia del mycobacterium tuberculosis a las drogas antibacilares / Tuberculosis meningitis: assay of the antimicrobial resistance of M tuberculosis to antituberculous agents

Se determinó la magnitud de la resistencia del Mycobacterium tuberculosis a las drogas antibacilares en pacientes con meningitis tuberculosa con y sin antecedentes de tratamiento. Se estableció una resistencia de 20,0 y 9,9 por ciento respectivamente. Estas cifras coinciden en las encontradas en las otras localizaciones de tuberculosis por lo que no debe esperarse un mayor porcentaje de fracasos terapéuticos por esta causa. A pesar de ello, dada la gravedad de la localización meníngea continuaremos determinando el patrón de resistencia en todo nuevo caso de meningitis tuberculosa

Meningitis tuberculosa: determinación de resistencia del mycobacterium tuberculosis a las drogas antibacilares / Tuberculous meningitis: resistence determination of mycobacterium tuberculosis to antibacillar agents

Se determinó la magnitud de la resistencia del Mycobacterium tuberculosis a las drogas antibacilares en pacientes con meningitis tuberculosa, con y sin antecedentes de tratamiento. Se estableció una resistencia de 20,0 y 9,9%respectivamente. Estas cifras coinciden con las encontradas en las otras localizaciones de tuberculosis, por lo que no debe esperarse un mayor porcentaje de fracasos terapéuticos por esta causa. A pesar de ello, dada la gravedad de la localización meníngea continuaremos determinando el patrón de resistencia en todo nuevo caso de meningitis tuberculosa