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In this work, we provide a general strategy to stabilize the ground state of polyradical(oid)s and make higher spin states thermally accessible. As a proof of concept, we propose to merge two planar fully π-conjugated diradical(oid)s to obtain a planar and cross-conjugated tetraradical(oid). Using multireference quantum chemistry methods, we show that the designed tetraradical(oid) is stabilized by aromaticity and delozalization in the π-system and has six thermally accessible spin states within 1.72 kcal/mol. Analysis of the electronic structure of these six states of the tetraradical(oid) shows that its frontier π-system consists of two weakly interacting subsystems: aromatic cycles and four unpaired electrons. Conjugation between unpaired electrons, which favors closed-shell structures, is mitigated by delocalization and the aromaticity of the bridging groups, leading to the synergistic cross-coupling between two diradical(oid) subunits to stabilize the tetraradical(oid) electronic structure.

Breast cancer is one of the most prevalent tumors among women. Its prognosis and treatment outcomes depend on factors related to tumor cell biology. However, recent studies have revealed the critical role of the tumor microenvironment (TME) in the development, progression, and treatment response of breast cancer. In this review, we explore the different components of the TME and their relevance as prognostic and predictive biomarkers in breast cancer. In addition, techniques for assessing the tumor microenvironment, such as immunohistochemistry or gene expression profiling, and their clinical utility in therapeutic decision-making are examined. Finally, therapeutic strategies targeting the TME are reviewed, highlighting their potential clinical benefits. Overall, this review emphasizes the importance of the TME in breast cancer and its potential as a clinical tool for better patient stratification and the design of personalized therapies.

High efficiency and safety are critical factors in ensuring the optimal performance and reliability of systems and equipment across various industries. Fault monitoring (FM) techniques play a pivotal role in this regard by continuously monitoring system performance and identifying the presence of faults or abnormalities. However, traditional FM methods face limitations in fully capturing the complex interactions within a system and providing real-time monitoring capabilities. To overcome these challenges, Digital Twin (DT) technology has emerged as a promising solution to enhance existing FM practices. By creating a virtual replica or digital copy of a physical equipment or system, DT offers the potential to revolutionize fault monitoring approaches. This paper aims to explore and discuss the diverse range of predictive methods utilized in DT and their implementations in FM across industries. Furthermore, it will showcase successful implementations of DT in FM across a wide array of industries, including manufacturing, energy, transportation, and healthcare. The utilization of DT in FM enables a comprehensive understanding of system behavior and performance by leveraging real-time data, advanced analytics, and machine learning algorithms. By integrating physical and virtual components, DT facilitates the monitoring and prediction of faults, providing valuable insights into the system's health and enabling proactive maintenance and decision making.

By the end of 2020, there were more than 8 million women alive who had received a breast cancer diagnosis in the previous 5 years, making it the most prevalent neoplasia in the world. About 70% of breast-cancer cases present positivity for estrogen and/or progesterone receptors and a lack of HER-2 overexpression. Endocrine therapy has traditionally been the standard of care for ER-positive and HER-2-negative metastatic breast cancer. In the last 8 years, the advent of CDK4/6 inhibitors has shown that adding them to endocrine therapy doubles PFS. As a result, this combination has become the gold standard in this setting. Three CDK4/6 inhibitors have been approved by the EMA and the FDA: abemaciclib, palbociclib, and ribociclib. They all have the same indications, and it is at each physician's discretion to choose one or the other. The aim of our study was to perform a comparative efficacy analysis of the three CDK4/6i using real-world data. We selected patients diagnosed with endocrine-receptor-positive and HER2-negative breast cancer who were treated with all three CDK4/6i as first-line therapy at a reference center. After 42 months of retrospective follow up, abemaciclib was associated with a significant benefit in terms of progression-free survival in endocrine-resistant patients and in the population without visceral involvement. In our real-world cohort, we found no other statistically significant differences among the three CDK4/6 inhibitors.

The NOA (Oncological Nutrition in Andalusia) project analyses the degree of integration and areas of improvement in implementing nutritional support in the care plans of cancer patients in Andalusia. The aim was to analyse nutritional interventions for better care of cancer patients and for the improvement of the management of malnutrition in cancer. A prospective evaluation of the implementation of two areas of improvement in nutrition was conducted in three hospitals. Data were collected from each hospital over a six-month period using an online platform. A standardised care plan was designed for hospitals in Andalusia, in which proposed improvements were devised and prioritised, selecting nutritional screening in oncology services and the participation of the Nutrition Support Team (NST) on the tumour boards, as well as the assessment of the patients presented at these sessions. Our results indicated an increase in the number of medical records with nutritional evaluation results six months later, regardless of the type of tumour or hospitalisation; and there was greater participation of the NST on the tumour boards, mainly for head and neck and oesophagogastric cases. Solutions for improvement have been pinpointed and implemented that have positively impacted the nutritional care plan in the course of oncological disease.

Background: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone., Methods: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1., Results: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study., Conclusions: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2- ABC, including populations of interest (NCT02941926)., Trial Registration: ClinicalTrials.gov NCT02941926., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The ability to diagnose preeclampsia clinically is suboptimal. Our objective was to validate a novel multianalyte assay and characterize its performance, when intended for use as an aid to rule-out preeclampsia., Methods: Prospective, multicenter cohort study of pregnant individuals presenting between 28 0/7 and 36 6/7 weeks' with preeclampsia-associated signs and symptoms. Individuals not diagnosed with preeclampsia after baseline evaluation were enrolled in the study cohort, with those who later developed preeclampsia, classified as cases and compared with a negative control group who did not develop preeclampsia. Individuals with assay values at time of enrollment ≥0.0325, determined using a previously developed algorithm, considered at risk. The primary analysis was the time to develop preeclampsia assessed using a multivariate Cox regression model., Results: One thousand thirty-six pregnant individuals were enrolled in the study cohort with an incidence of preeclampsia of 30.3% (27.6%-33.2%). The time to develop preeclampsia was shorter for those with an at-risk compared with negative assay result (log-rank P <0.0001; adjusted hazard ratio of 4.81 [3.69-6.27, P <0.0001]). The performance metrics for the assay to rule-out preeclampsia within 7 days of enrollment showed a sensitivity 76.4% (67.5%-83.5%), negative predictive value 95.0% (92.8%-96.6%), and negative likelihood ratio 0.46 (0.32-0.65). Assay performance improved if delivery occurred <37 weeks and for individuals enrolled between 28 and 35 weeks., Conclusions: We confirmed that a novel multianalyte assay was associated with the time to develop preeclampsia and has a moderate sensitivity and negative likelihood ratio but high negative predictive value when assessed as an aid to rule out preeclampsia within 7 days of enrollment., Registration: The study was registered on Clinicaltrials.gov (Identifier NCT02780414).

Background: The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2., Patients and Methods: Patients with HR+, HER2- ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate., Results: 51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population., Conclusion: These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Introduction: malnutrition in cancer patients can lead to a reduction in patient quality of life, increased morbidity and mortality, and associated healthcare costs. Objective: to analyze nutritional interventions in the different phases of the oncological process, integrating the needs of patients and those of healthcare professionals. Material and methods: "Design Thinking" techniques were used to address the analysis of the current situation and identify key aspects. Thirteen professionals from 8 public health centers (endocrinology and nutrition, medical and radiotherapy oncology, primary care (PC), nursing and dietetics) participated in the study. Results: nutritional screening is not carried out in a systematic way in the different phases of the oncological process, and there is no universal consensus on the protocols for action and nutritional intervention. A wide compliance with the pathways and referral times of the selected processes has been observed. In the therapeutic phase, there is the possibility of consulting the Clinical Nutrition and Dietetics Unit (UNCYD) and 75 % have specific referral protocols. The nurse case manager is present in all hospitals and in PC. Patient access to the center psychologist was possible in 87 % of the hospitals. Participation of the UNCYD in Tumor Committees was low (only in 25 % of the centers). In all centers there is some kind of collaboration and support by patient associations and the School of Patients, especially in the therapeutic and the control and follow-up phases. Conclusions: variations are observed between the different hospitals and areas in Andalusia, both in terms of means and structures and in activities and procedures. Key points have been selected and prioritized to improve nutritional care in oncology.

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1-34) ranged from 77.8-99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences.

Background: Current therapeutic strategies that are used to combat breast cancer vary widely and largely depend on its clinicopathological features, including tumor subtype, size, stage, lymph node involvement, the presence of hormone receptors and/or HER2, as well as the degree of proliferative activity. Recent work has focused on improving our knowledge on the molecular mechanisms that underlie this complex disease. Most of the human genome is transcribed into RNAs that do not encode proteins. These noncoding RNAs may act as mediators in the regulation of gene expression. Based on their size and function, noncoding RNAs are classified into small noncoding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). LncRNAs have been found to play key roles in relevant biological processes, including breast cancer. As such, lncRNAs have been proposed as diagnostic and prognostic biomarkers, as predictive biomarkers and as putative therapeutic targets., Conclusions: In this review, we discuss the potential application of lncRNAs for the monitoring and treatment of breast cancer. We conclude that lncRNAs play important roles in the pathophysiology of this disease and may serve as putative therapeutic targets. As such, tumor-specific lncRNAs may be instrumental for improving current breast cancer clinical practices.

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Introduction: This study aimed to describe the efficacy of fulvestrant 500 mg in postmenopausal women with estrogen receptor (ER)-positive advanced/metastatic breast cancer who had disease progression after receiving anti-estrogen therapy in clinical practice, getting real-world data., Materials and Methods: Multicenter, retrospective, observational study conducted in Spain. Postmenopausal women with locally advanced/metastatic ER-positive breast cancer who received treatment with fulvestrant 500 mg after progression with a previous anti-estrogen therapy were eligible. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), clinical benefit rate (CBR), duration of clinical benefit (DoCB), and safety profile., Results: A total of 263 women were evaluated (median age, 65.8 years). At a median follow-up of 21.5 months, median PFS and OS were 10.6 and 43.2 months, respectively. PFS according to 1st, 2nd, 3rd, and ≥ 4th lines were 11.5, 10.6, 9.9, and 8.5 months, respectively (p = 0.0245). PFS in patients with visceral involvement was 10 months vs 10.6 months in patients without visceral involvement (p = 0.6604), 9.6 months in patients with high Ki67 vs 10 months in patients with low Ki67 (p = 0.7224), and 10.2 months in HER2+ patients vs 10.3 months in HER2- patients (p = 0.6809). The CBR was 56.5% and the DoCB was 18.4 months. The most frequently adverse events were injection site pain (10.3%) and musculoskeletal disorders (7.6%)., Conclusions: Fulvestrant 500 mg administered in clinical practice was shown to be effective (PFS, 10.6 months; CBR, 56.5%) and well tolerated, in accordance with previous trials.

Cyclopropyl cyanide and other simple nitriles detected in Titan's atmosphere could be precursors leading to the formation of organic macromolecules in the atmosphere of Saturn's largest satellite. Proposing a thermodynamically possible mechanism that explains their formation and supports experimental results represents a difficult challenge. Experiments done in the Atomic and Molecular Physics Laboratory at the University of Trento (AMPL) have studied the ion-molecule reaction between cyclopropyl cyanide and its protonated form, with reaction products being characterized by mass spectrometry. In addition to the expected ion-molecule adduct stabilized by non-covalent long-range interactions, in this work we prove that another distinct species having the same mass to charge ratio (m/z) of 135 is also produced. Moreover, from a previous study of the neutral cyclopropyl cyanide potential energy surface (PES) which shows a partial biradical character it has been possible to characterize the formation through the bimolecular reaction of a new covalent cyclic organic molecule. Calculations have been carried out at the ab initio Møller-Plesset (MP2) level of theory, ensuring the connectivity of the stationary points by using the intrinsic reaction coordinate (IRC) procedure. In order to characterize the reaction transition state, multireference calculations were done using a complete active space involving six electrons and six molecular orbitals [CAS (6 e - , 6 m.o.)]. This study opens the possibility of exploring the formation of new organic molecules by gaseous phase ion-molecule interaction schemes, with such molecules having relevance in interstellar space and in astrobiology (and may be involved in prebiotic molecular evolution).

Gas phase reactive collisions between lithium ions and i-C 3 H 7 X (X = Br, OH) molecules have been studied under single collision conditions in the center of mass (CM) 0.01-10.00 eV energy range using a radiofrequency-guided ion beam apparatus. Mass spectrometry analysis of the products did show the presence of [C 3 H 6 -Li] + , [HX-Li] + , C 3 H 7 + , and C 2 H 3 + as well as of the [Li-i-C 3 H 7 Br] + adduct while [Li-i-C 3 H 7 OH] + was hardly detected. For all these reactive processes, the corresponding cross sections have been measured in absolute units as a function of the CM collision energy. Quantum chemistry ab initio calculations done at the second order Möller Plesset level have provided relevant information on the topology of the potential energy surfaces (PESs) where a reaction takes place allowing the characterization of the stationary points on the respective PESs along their reaction pathways. The connectivity of the different stationary points localized on the PESs was ensured by using the intrinsic reaction coordinate (IRC) method, confirming the adiabatic character of the reactions. The main topology features of the reactive PESs, in the absence of dynamical calculations, were used to interpret at the qualitative level the behavior of the experimental excitations functions, evidencing the role played by the potential energy barriers on the experimental dynamics of the reactions. Reaction rate constants at 303.2 K for different reactions have been calculated from measured excitation functions.

Metastatic breast cancer is a heterogeneous disease that presents in varying forms, and a growing number of therapeutic options makes it difficult to determine the best choice in each particular situation. When selecting a systemic treatment, it is important to consider the medication administered in the previous stages, such as acquired resistance, type of progression, time to relapse, tumor aggressiveness, age, comorbidities, pre- and post-menopausal status, and patient preferences. Moreover, tumor genomic signatures can identify different subtypes, which can be used to create patient profiles and design specific therapies. However, there is no consensus regarding the best treatment sequence for each subgroup of patients. During the SABCC Congress of 2014, specialized breast cancer oncologists from referral hospitals in Europe met to define patient profiles and to determine specific treatment sequences for each one. Conclusions were then debated in a final meeting in which a relative degree of consensus for each treatment sequence was established. Four patient profiles were defined according to established breast cancer phenotypes: pre-menopausal patients with luminal subtype, post-menopausal patients with luminal subtype, patients with triple-negative subtype, and patients with HER2-positive subtype. A treatment sequence was then defined, consisting of hormonal therapy with tamoxifen, aromatase inhibitors, fulvestrant, and mTOR inhibitors for pre- and post-menopausal patien ts; a chemotherapy sequence for the first, second, and further lines for luminal and triple-negative patients; and an optimal sequence for treatment with new antiHER2 therapies. Finally, a document detailing all treatment sequences, that had the agreement of all the oncologists, was drawn up as a guideline and advocacy tool for professionals treating patients with this disease., Competing Interests: The authors declare no conflict of interest. Research involving human participants and/or animals Not applicable to this type of consensus document. Informed consent Not applicable to this type of consensus document.

Dehydrohalogenation and dehydration reactions of gas-phase i-C3H7Br and i-C3H7OH molecules induced by collision with Na(+), all participants being in their electronic ground state, were studied experimentally in our laboratory using a radiofrequency-guided ion beam apparatus and covering the 0.10-10.00 eV center of mass (CM) energy range. In Na(+) + i-C3H7Br collisions the formation of [C3H6-Na](+) and [HBr-Na](+) by dehydrohalogenation was observed and quantified, as well as that of the ion-molecule adduct [Na-i-C3H7Br](+) together with its decomposition products C3H7(+) and NaBr. In Na(+) + i-C3H7OH collisions the dehydration product [H2O-Na](+) was also found, while [C3H6-Na](+) was hardly detected. Moreover, the [Na-i-C3H7OH](+) adduct formation as well as its decomposition into C3H7(+) and NaOH were also quantified. For all these processes, absolute reaction cross sections were measured as a function of the CM collision energy. From measured excitation functions, rate constants for the formation of [C3H6-Na](+), [HBr-Na](+), and [H2O-Na](+) at 303 K were obtained. Complementing the experiments, exhaustive ab initio structure calculations at the MP2 level of theory were performed, giving information on the most relevant features of the potential energy surfaces (PESs) where the dehydrohalogenation, dehydration, and decomposition reactions take place adiabatically for both collision systems. On these PESs different stationary points associated with potential energy minima and transition state barriers were characterized, and their connectivity was ensured using the intrinsic-reaction-coordinate method. The main topology features of the ab initio calculated PESs allowed a qualitative interpretation of the experimental data also exposing the role of the sodium ion as a catalyst in elimination reactions.

Objective: Using noninvasive bedside impedance cardiography (ICG), we compared the effectiveness and the hemodynamic impact of intravenous labetalol versus hydralazine for the reduction of acute-onset severe hypertension to ACOG-recommended blood pressure levels (ACOG Committee Opinion 514)., Study Design: In this prospective randomized pilot study of acutely severe systolic hypertension (≥160 mmHg), pregnant women received either labetalol (L) or hydralazine (H) intravenously and underwent thoracic ICG before and after treatment. Data analysis were performed using STATA software (StataCorp LP, College Station, TX); data are expressed as mean ± SD., Results: About 29 patients completed the study. There was no significant difference in mean arterial pressure (MAP) between groups [H = 119.4 mmHg, L = 117.7 mmHg, mean difference (MD) = 1.73); the estimated MD between baseline and follow-up ICG was -9.17 (p = 0.001, 95% CI: -14.39 to -3.95). There were no significant differences in total peripheral resistance (TPR) between groups (H = 1771.3, L = 1976.97, MD = 205.62) or cardiac output (CO) between groups (H = 5.7, L = 5.1, MD = 0.64) or a significant MD between these at baseline and follow-up., Conclusion: Both drugs performed similarly to achieve ACOG-recommended initial blood pressure reduction safely without side effects or excessive acute hemodynamic profile correction toward normal pregnancy values.

Objectives: To evaluate if the estimation of the maximal oxygen consumption (MO2C) in METs (metabolic equivalents) by means of the table proposed in the guidelines of the Spanish Society of Cardiology is a sufficiently reliable method when applied to the bicycle exercise test., Material and Methods: The MO2C in METs was obtained by gas-exchange analysis on bicycle ergometer tests in 97 healthy subjects (group i). It was compared with the estimate of METs using the table in which only watts and patient's weight were included. A better-adjusted formula was validated in 289 subjects with normal exercise myocardial perfusion gated-SPECT (group ii) using the introduction of clinical and ergometric variables., Results: In group i individuals a good correlation between METs estimated with the table and those obtained through gas-exchange analysis (CCI: 0.93) was observed. However, the best adjusted formula to estimate METs in group ii subjects included watts, body mass index (BMI), age and gender (METS=11.820-0.054×age-0.189×BMI+1.031×gender+0.020×watts) (women: 0, men: 1). This formula allowed the reclassification of 46.9% of group ii subjects into the category <5METs versus the estimation by table., Conclusions: Estimating the METs with the conventional table is reliable. However, the best adjustment in subjects with normal bicycle exercise SPECT was obtained when, in addition to watts and BMI, age and gender were also considered., (Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.)

Collisions between potassium ions and neutral i-C3H7Br and i-C3H7OH, all in their electronic ground state, have been studied in the 0.10-10.00 eV center of mass (CM) collision energy range, using the radiofrequency-guided ion beam technique. In K(+) + i-C3H7Br collisions KHBr(+) formation was observed and quantified, while the analogous KH2O(+) formation in K(+) + i-C3H7OH was hardly detected. Moreover, formation of the ion-molecule adducts and their decomposition leading to C3H7(+) and either KBr or KOH, respectively, have been observed. For all these processes, absolute cross-sections were measured as a function of the CM collision energy. Ab initio structure calculations at the MP2 level have given information about the potential energy surfaces (PESs) involved. In these, different stationary points have been characterized using the reaction coordinate method, their connectivity being ensured by using the intrinsic-reaction-coordinate method. From the measured excitation function for KHBr(+) formation the corresponding thermal rate constant at 303 K has been calculated. The topology of the calculated PESs allows an interpretation of the main features of the reaction dynamics of both systems, and in particular evidence the important role played by the potential energy wells in controlling the reactivity for the different reaction channels.

Purpose: Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established., Patients and Methods: Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival., Results: After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%)., Conclusion: For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.

Inelastic electronically non-adiabatic reactions between Na(+) ions and neutral ZnBr(2) molecules, both in their electronic ground state, have been studied using crossed beams techniques and measuring the decaying emission radiation of the excited species produced. The fluorescent emission corresponding to Na(3 (2)P) produced by a charge transfer reaction was observed, as well as that corresponding to the decay of Zn(4s 5s (3)S), generated by dissociation of the neutral target molecule, to Zn(4s 4p (3)P). The phosphorescent decaying emission of Zn*(4s 4p (3)P) to the zinc ground state was also observed. For each emission process, the cross section energy dependences have been measured in the 0.10-3.50 keV energy range in the laboratory system. The ground electronic state of the (NaZnBr(2))(+) collision system has been characterized by ab initio chemical structure calculations at the second order Möller-Plesset perturbation level of theory using pseudo-potentials. By performing restricted open shell Hartree-Fock calculations for C(2v) geometries, four singlet and four triplet potential energy surfaces of the system have been calculated and used to interpret qualitatively the observed reactions. A simple two-state dynamical model is presented that allows an estimation of the maximum values for measured cross sections at high collision energies to be made.

The association reactions of benzene molecules with alkali ions M(+) (Li(+), Na(+) and K(+)) under single collision conditions have been studied using a radiofrequency-guided-ion-beam apparatus and mass spectrometry characterization of the different adducts. Cross-section energy dependences for [M-C(6)H(6)](+) adduct formation have been measured at collision energies up to 1.20 eV in the center of mass frame. All excitation functions decrease when collision energy increases, showing the expected behaviour for barrierless reactions. From ab initio chemical structure calculations at the MP2(full) level, the formation of the adducts makes evident the alkali ion-benzene non-covalent chemical bond. The cross-section energy dependence and the role of radiative cooling rates and unimolecular decomposition on the stabilization of the energized collision complex are also discussed.

The association reactions between Li(+), K(+), and Rb(+) (M) and butanone and cyclohexanone molecules under single collision conditions have been studied using a radiofrequency-guided ion-beam apparatus, characterizing the adducts by mass spectrometry. The excitation function for the [M-(molecule)](+) adducts (in arbitrary units) has been obtained at low collision energies in the 0.10 eV up to a few eV range in the center of mass frame. The measured relative cross sections decrease when collision energy increases, showing the expected energy dependence for adduct formation. The energetics and structure of the different adducts have been calculated ab initio at the MP2(full) level, showing that the M(+)-molecule interaction takes place through the carbonyl oxygen atom, as an example of a nontypical covalent chemical bond. The cross-section energy dependence and the role of radiative cooling rates allowing the stabilization of the collision complexes are also discussed.

Background: The purposes of this study were to determine: 1) if periodontal treatment in pregnant women before 21 weeks of gestation alters levels of inflammatory mediators in serum; and 2) if changes in these mediators are associated with birth outcomes., Methods: A total of 823 pregnant women with periodontitis were randomly assigned to receive scaling and root planing before 21 weeks of gestation or after delivery. Serum obtained between 13 and 16 weeks, 6 days (study baseline) and 29 to 32 weeks of gestation was analyzed for C-reactive protein; prostaglandin E(2); matrix metalloproteinase-9; fibrinogen; endotoxin; interleukin (IL)-1 beta, -6, and -8, and tumor necrosis factor-alpha. Cox regression, multiple linear regression, and the t, chi(2), and Fisher exact tests were used to examine associations among the biomarkers, periodontal treatment, and gestational age at delivery and birth weight., Results: A total of 796 women had baseline serum data, and 620 women had baseline and follow-up serum and birth data. Periodontal treatment did not significantly alter the level of any biomarker (P >0.05). Neither baseline levels nor the change from baseline in any biomarker were significantly associated with preterm birth or infant birth weight (P >0.05). In treatment subjects, the change in endotoxin was negatively associated with the change in probing depth (P <0.05)., Conclusions: Non-surgical mechanical periodontal treatment in pregnant women, delivered before 21 weeks of gestation, did not reduce systemic (serum) markers of inflammation. In pregnant women with periodontitis, levels of these markers at 13 to 17 weeks and 29 to 32 weeks of gestation were not associated with infant birth weight or a risk for preterm birth.

Reactive collisions between Li(+) ions and i-C(3)H(7)Cl molecules have been studied in the 0.20-12.00 eV center-of-mass energy range using an octopole radio frequency guided-ion beam apparatus recently developed in our laboratory. At low collision energies, dehydrohalogenation reactions giving rise to Li(C(3)H(6))(+) and Li(HCl)(+) are the main reaction channels, while at higher ones C(3)H(7)(+) and C(2)H(3)(+) become dominant, all their reactive cross sections having been measured as a function of the collision energy. To obtain information about the potential energy surfaces (PESs) on which the reactive processes take place, ab initio calculations at the MP2 level have been performed. For dehydrohalogenations, the reactive ground singlet PES shows ion-molecule adduct formation in both the reactant and product sides of the surface. Following the minimum energy path connecting both minima, an unstable intermediate and the corresponding barriers, both lying below the reactant's energy, have been characterized. The entrance channel ion-molecule adduct is also involved in the formation of C(3)H(7)(+), which then generates C(2)H(3)(+) via an CH(4) unimolecular elimination. A qualitative interpretation of the experimental results based on ab initio calculations is also included.

Aim: Determine whether periodontitis progression during pregnancy is associated with adverse birth outcomes., Methods: We used clinical data and birth outcomes from the Obstetrics and Periodontal Therapy Study, in which randomly selected women received periodontal treatment before 21 weeks of gestation (N=413) or after delivery (410). Birth outcomes were available for 812 women and follow-up periodontal data for 722, including 75 whose pregnancies ended <37 weeks. Periodontitis progression was defined as >or=3 mm loss of clinical attachment. Birth outcomes were compared between non-progressing and progressing groups using the log rank and t tests, separately in all women and in untreated controls., Results: The distribution of gestational age at the end of pregnancy (p>0.1) and mean birthweight (3295 versus 3184 g, p=0.11) did not differ significantly between women with and without disease progression. Gestational age and birthweight were not associated with change from baseline in percentage of tooth sites with bleeding on probing or between those who did versus did not progress according to a published definition of disease progression (p>0.05)., Conclusions: In these women with periodontitis and within this study's limitations, disease progression was not associated with an increased risk for delivering a pre-term or a low birthweight infant.

Objective: To describe fetal macrocrania including prenatal diagnosis, delivery considerations and clinical outcomes., Study Design: A retrospective case series was developed by reviewing 26 885 ultrasounds performed between 1 March 2003 and 30 June 2007 for the prenatal diagnosis of macrocrania. Medical records of each mother/infant pair were reviewed for demographic information, ultrasound findings, obstetric management and outcomes., Result: Twenty-three fetuses were diagnosed with macrocrania. Median gestational age at diagnosis was 31.1 weeks (range 18.3-38.1) and at delivery was 36.9 weeks (range 30.7-39.9). Fifteen patients (65%) underwent amniocentesis for karyotype; none were aneuploid but one had a duplication on chromosome 7. All the 23 infants were liveborn. Twenty-one deliveries were by Cesarean (91%), with thirteen of these by classical incision (62%). Of the infants, 5 (22%) died shortly after birth, 16 (70%) were stabilized in the neonatal intensive care unit and were discharged alive and 2 (8%) were transferred to another center and subsequently died. Eighteen babies required ventriculoperitoneal shunting (78%)., Conclusion: Macrocrania is a diagnosis usually made in children but can also be made prenatally. Fetal macrocrania is usually a result of ventriculomegaly due to an obstructive process to cerebrospinal fluid flow. Abdominal delivery is usually required, often necessitating a classical uterine incision. Targeted ultrasonography, extensive counseling of parents and delivery at a tertiary care center with availability of neurosurgery is recommended.

Background: Although clinicians generally consider it safe to provide dental care for pregnant women, supporting clinical trial evidence is lacking. This study compares safety outcomes from a trial in which pregnant women received scaling and root planing and other dental treatments., Methods: The authors randomly assigned 823 women with periodontitis to receive scaling and root planing, either at 13 to 21 weeks' gestation or up to three months after delivery. They evaluated all subjects for essential dental treatment (EDT) needs, defined as the presence of moderate-to-severe caries or fractured or abscessed teeth; 351 women received complete EDT at 13 to 21 weeks' gestation. The authors used Fisher exact test and a propensity-score adjustment to compare rates of serious adverse events, spontaneous abortions/stillbirths, fetal/congenital anomalies and preterm deliveries (<37 weeks' gestation) between groups, according to the provision of periodontal treatment and EDT., Results: Rates of adverse outcomes did not differ significantly (P> .05) between women who received EDT and those who did not require this treatment, or between groups that received both EDT and periodontal treatment, either EDT or periodontal treatment alone, or no treatment. Use of topical or local anesthetics during root planing also was not associated with an increased risk of experiencing adverse outcomes., Conclusions: EDT in pregnant women at 13 to 21 weeks' gestation was not associated with an increased risk of experiencing serious medical adverse events or adverse pregnancy outcomes. Data from larger studies and from groups with other treatment needs are needed to confirm the safety of dental care in pregnant women., Clinical Implications: This study provides evidence that EDT and use of topical and local anesthetics are safe in pregnant women at 13 to 21 weeks' gestation.

Background: Maternal periodontal disease has been associated with an increased risk of preterm birth and low birth weight. We studied the effect of nonsurgical periodontal treatment on preterm birth., Methods: We randomly assigned women between 13 and 17 weeks of gestation to undergo scaling and root planing either before 21 weeks (413 patients in the treatment group) or after delivery (410 patients in the control group). Patients in the treatment group also underwent monthly tooth polishing and received instruction in oral hygiene. The gestational age at the end of pregnancy was the prespecified primary outcome. Secondary outcomes were birth weight and the proportion of infants who were small for gestational age., Results: In the follow-up analysis, preterm birth (before 37 weeks of gestation) occurred in 49 of 407 women (12.0%) in the treatment group (resulting in 44 live births) and in 52 of 405 women (12.8%) in the control group (resulting in 38 live births). Although periodontal treatment improved periodontitis measures (P<0.001), it did not significantly alter the risk of preterm delivery (P=0.70; hazard ratio for treatment group vs. control group, 0.93; 95% confidence interval [CI], 0.63 to 1.37). There were no significant differences between the treatment and control groups in birth weight (3239 g vs. 3258 g, P=0.64) or in the rate of delivery of infants that were small for gestational age (12.7% vs. 12.3%; odds ratio, 1.04; 95% CI, 0.68 to 1.58). There were 5 spontaneous abortions or stillbirths in the treatment group, as compared with 14 in the control group (P=0.08)., Conclusions: Treatment of periodontitis in pregnant women improves periodontal disease and is safe but does not significantly alter rates of preterm birth, low birth weight, or fetal growth restriction. (ClinicalTrials.gov number, NCT00066131 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

Inelastic and charge-transfer excitation processes in collisions between ground-state neutral Mg atoms and K+ ions have been studied by means of a crossed molecular-beam technique. Decay fluorescent emissions from Mg(3 1P1),Mg(4 3S1), and Mg(3s(1)3d(1), 3(3)D3,2,1) as well as the phosphorescent emission due to Mg(3 3P1) have been observed from excited Mg atoms and the charge-transfer emission decays from K(4 2P 3/2,1/2), K(5 2P 3/2, 1/2), K(6 2S 1/2), and K(4 2D 5/2, 3/2) for excited K atoms. The corresponding absolute cross-sections values versus collision energy functions were determined in the 0.10-3.80 keV laboratory energy range. In order to interpret the experimental results, accurate ab initio full configuration-interaction calculations using pseudopotentials have been performed for the (Mg-K)+ system, giving a manifold of adiabatic singlet and triplet potential-energy curves correlating with the different collision channels, which allow a qualitative interpretation of the emission excitation functions measured for the different processes studied. A comparative study with other Mg-alkali ion systems previously studied is also included.

Objective: The purpose of this prospective study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal/neonatal infectious morbidity., Study Design: In this double-blind placebo-controlled trial, cefazolin was given at skin incision (group A) or at cord clamping (group B). Patients were eligible for the trial if they had labored and required a cesarean delivery., Results: Over a 30-month period 303 patients with singleton pregnancies entered the trial; 153-group A, 149-group B. Demographics, indication for cesarean delivery (P = .54), and operative time (P = .999), as well as rates of endometritis (RR 0.67, 95% CI 0.42-1.07), wound infection (RR 0.84, 95% CI 0.45-1.55), neonatal sepis (RR 1.28, 95% CI 0.91-1.79), and NICU admissions (RR 1.28, 95% CI 0.91-1.79) were similar between the 2 groups., Conclusion: There was no difference in maternal infectious morbidity whether antibiotics were given before skin incision or at cord clamping.

Inelastic collision processes between neutral Mg atoms and Rb(+) ions, both in their ground states, have been studied by means of a crossed molecular beam technique measuring the decay fluorescence of the excited species formed. Emissions corresponding to Mg(3 (1)P(1)), Mg(3 (3)D(3,2,1)), and Mg(4 (3)S(1)), formed by direct target excitation, Rb(5 (2)P(3/2,1/2)), Rb(6 (2)P(3/2,1/2)) produced by electron capture and also the phosphorescent emission due to decay of Mg(3 (3)P(1)), have been detected and the corresponding absolute cross-section values measured both as total values and resolved into their J states. No polarization measurements could be made. Ab initio calculations using pseudopotentials have been performed and from these a manifold of adiabatic energy curves correlating with the different entry and exit channels have been obtained, allowing to propose a qualitative interpretation of the results, such as the shape of the cross section vs energy for different transitions and the oscillating nature of the branching ratios due to interference effects.

The mechanism of the gas-phase reaction of *CH2OH+O2 to form CH2O+HO2* was studied theoretically by means of high-level quantum-chemical electronic structure methods (CASSCF and CCSD(T)). The calculations indicate that the oxidation of *CH2OH by O2 is a two-step process that goes through the peroxy radical intermediate *OOCH2OH (1), formed by the barrier-free radical addition of *CH2OH to O2. The concerted elimination of HO2* from 1 is predicted to occur via a five-membered ringlike transition structure of Cs symmetry, TS1, which lies 19.6 kcalmol(-1) below the sum of the energies of the reactants at 0 K. A four-membered ringlike transition structure TS2 of Cs symmetry, which lies 13.9 kcalmol(-1) above the energy of the separated reactants at 0 K, was also found for the concerted HO2* elimination from 1. An analysis of the electronic structures of TS1 and TS2 indicates that both modes of concerted HO2* elimination from 1 are better described as internal proton transfers than as intramolecular free-radical H-atom abstractions. The intramolecular 1,4-H-atom transfer in 1, which yields the alkoxy radical intermediate HOOCH2O*, takes place via a puckered ringlike transition structure TS3 that lies 13.7 kcalmol(-1) above the energy of the reactants at 0 K. In contrast with earlier studies suggesting that a direct H-atom abstraction mechanism might occur at high temperatures, we could not find any transition structure for direct H-atom transfer from the OH group of *CH2OH to the O2. The observed non-Arrhenius behavior of the temperature dependence of the rate constant for the gas-phase oxidation of *CH2OH is ascribed to the combined effect of the initial barrier-free formation of the *OO-CH2OH adduct with a substantial energy release and the existence of a low-barrier and two high-barrier pathways for its decomposition into CH2O and HO2*.

The application of the exciton coupling model to interacting porphyrin chromophores is discussed. Covalently bonded systems and ionic or electrostatically bonded homoassociates require different orientations of the transition dipole moments in order to explain the experimental results: according to the symmetry of the assembly for covalently bonded porphyrins, and assuming isolated chromophores for ionic bonded porphyrins. Further, for covalently bonded systems, an extended exciton coupling has been demonstrated, but the ionic systems are in agreement with non-extended couplings. The relation of these facts to a molecular description of solid-state Wannier-Mott or Frenkel excitons is briefly discussed.

We have carried out a theoretical investigation of the gas-phase reaction mechanism of the H2COO+ H2O reaction, which is interesting for atmospheric purposes. The B3LYP method with the 6-31G(d,p) and 6-311 + G(2d,2p) basis sets was employed for the geometry optimization of the stationary points. Additionally, single-point CCSD(T)/6-311 + G(2d,2p) energy calculations have been done for the B3LYP/6-311 + G(2d,2p) optimized structures. The reaction begins with the formation of a hydrogen-bond complex that we have calculated to be 6 kcalmol(-1) more stable than the reactants. Then, the reaction follows two different channels. The first one leads to the formation of hydroxymethyl hydroperoxide (HMHP), for which we have calculated an activation barrier of deltaGa(298) = 11.3 kcalmol(-1), while the second one gives HCO + OH + H2O, with a calculated activation barrier of deltaGa(298) = 20.9 kcalmol(-1). This process corresponds to the water-catalyzed decomposition of H2COO, and its unimolecular decomposition has been previously reported in the literature. Additionally, we have also investigated the HMHP decomposition. We have found two reaction modes that yield HCOOH+H2O; one reaction mode leads to H2CO + H2O2 and a homolytic cleavage, which produces H2COOH + OH radicals. Furthermore, we have also investigated the water-assisted HMHP decomposition, which produces a catalytic effect of about 14 kcalmol(-1) in the process that leads to H2CO + H2O2.

Background: Risk factors for and management of intrauterine fetal demise (IUFD) have been investigated, but the maternal morbidity has not been evaluated., Methods: Over a 60-month interval, all cases of IUFD after 20 weeks' gestation were reviewed for maternal trauma and maternal postpartum complications., Results: In this retrospective analysis, 498 singleton and 24 twin pregnancies with an IUFD were identified. A cervical or perineal laceration requiring surgical repair complicated 9.4% of pregnancies. One uterine dehiscence and one uterine rupture occurred. Endometritis, the most common postpartum complication, occurred in 63 of 522 patients (12%). One maternal death occurred. Total mean hospital stay was 4.9 +/- 5.7 days., Conclusion: Maternal morbidity and rarely mortality can follow IUFD, but this morbidity is similar to that observed without IUFD.

We sought to ascertain whether the routine use of instruments, forceps or vacuum, at the time of elective repeat cesarean delivery, permits a delivery that is as safe for mother and infant and as easy for mother and physician as traditional manual delivery of the fetal head. In this prospective study 44 women undergoing elective repeat cesarean were randomized to deliver by Vacuum (V), Forceps (F), or by Manual (M) means. Groups were compared with regard to demographic variables and maternal and neonatal outcomes. Deliveries were timed from entry into the uterus until full delivery of the infant. Maternal pain scores were assessed using a 10-cm visual analog scale. There were no differences in demographic variables except that the M group had fewer women with up to two cesareans. A large percentage of women in each group were delivered with the randomized instrument. Use of the V did not demonstrate fewer extensions of the uterine incision or lesser amounts of blood loss as measured by serial hemoglobin determinations. There was a trend for the F group to require a longer period of time for delivery (p = 0.061). Women in the V group reported significantly lower pain scores (p = 0.015). There were no serious neonatal injuries. The routine use of instruments at the time of elective repeat cesarean delivery appears safe and effective.

Objective: To determine if maternal hypoglycemia is associated with adverse perinatal outcome, particularly low birth weight., Study Design: In this prospective study, all patients after 24 weeks' gestation were screened for gestational diabetes using 50 gm of glucola (oral) followed by a 1-hour plasma glucose measurement and hypoglycemia was defined as < or = 88 mg/dl., Results: In these 426 women the mean (+/- SD) 1-hour plasma glucose value was 99.8 +/- 22.7 mg/dl. Of these, 16 were diagnosed with gestational diabetes and 46 were lost to follow-up leaving 364 patients; 116 with hypoglycemia and 248 with euglycemia. Women with hypoglycemia weighed less at the beginning of pregnancy and at delivery, but total weight gain during pregnancy was similar between both groups. There was no difference between groups in maternal symptomatology, birth weight, or the rate of fetal growth restriction., Conclusion: Hypoglycemia on the 1-hour glucola screen is not predictive of fetal growth restriction or other adverse perinatal consequence.

Objective: To determine the diagnostic accuracy of a DNA probe for beta-hemolytic group B Streptococcus (GBS) in women with threatened preterm labor., Study Design: Two identical vaginal/perianal samples were collected from 75 pregnant women who were being evaluated for threatened preterm labor. One sample was managed in the traditional manner, with direct plating onto blood agar followed by plating after 8 and 24 hours of LIM broth enhancement. The "gold standard" was 24 hours of LIM broth enhancement followed by blood agar plating. The second sample was placed in LIM broth, and DNA probe testing was performed after incubation for 8 and 24 hours., Results: The prevalence of GBS colonization by the gold standard culture was 32%. After 8 hours of incubation in LIM broth, the DNA probe had poor sensitivity (79%); however, after 24 hours of incubation in LIM broth the DNA probe sensitivity rose to 96%. The DNA probe demonstrated only one false negative result after 24 hours of LIM broth enhancement. All DNA probe results were known 25 hours after sample collection., Conclusion: This DNA probe gave results nearly identical to those of standard cultures and allowed a substantial saving of time.

Objective: Our purpose was to examine maternal and neonatal outcomes in a cohort of women who underwent delivery with the sequential use of instruments., Study Design: This retrospective case-control study included deliveries from May 1996 through March 1998. Charts of women who underwent delivery with the sequential use of instruments (vacuum first, then forceps, or vice versa) were identified. Two control groups (1 forceps group, 1 vacuum group) were randomly selected and matched for each case. Maternal and neonatal outcomes were abstracted and compared., Results: There were 34 patients in each group. There were no significant demographic differences. The vacuum group had lower rates of episiotomy (P =.01) and deep perineal lacerations (P =.014), whereas these outcomes were similar in the sequential and forceps groups. All other maternal outcomes were equivalent. There were no differences in any neonatal parameter except for superficial scalp trauma, which was more common in the vacuum group (P =.002)., Conclusion: We conclude that the prudent use of sequential instruments at operative vaginal delivery did not engender higher rates of maternal or neonatal morbidity.

Mandibular aplasia is defined as incomplete development of the mandibular process of the first brachial arch. Its prevalence is less than 1:70,000. It is usually associated with low-set ears, transposition of the viscera, congenital heart defects, and rib abnormalities, and is incompatible with life. In this case report, fetal demise at 26 weeks' gestation in a previous pregnancy revealed the phenotypic features listed. The second pregnancy described here resulted in therapeutic termination of a similar appearing fetus. Because of this recurrence and a positive family history, familial inheritance is postulated.

Background: Diaphragmatic rupture may be easily overlooked at the time of multiple trauma. Occult diaphragmatic rupture may first manifest during pregnancy as severe dyspnea., Case: A parous woman who had sustained multiple traumatic injuries prior to pregnancy presented in midtrimester with abdominal pain and dyspnea. Chest roentgenography and computed tomography revealed bowel in the left hemithorax, compatible with a left-sided diaphragmatic rupture. Surgical correction was indicated secondary to the symptomatic nature of the presentation., Conclusion: Diaphragmatic rupture may be occult and may first present during a subsequent pregnancy. Surgical therapy is the cornerstone of management when a diaphragmatic defect is symptomatic. The route of delivery may be individualized for patients with diaphragmatic repairs in whom there has been sufficient time for healing.

Most patients in the United States have an indication for and receive sonography during pregnancy. The issue of routine sonography for low-risk women continues to be contentious even though the randomized trials have not been able to demonstrate a clear benefit. Clinics that routinely offer sonography for all pregnancies usually schedule such a procedure at 16 to 20 weeks of gestation. Although great progress is being made in the first-trimester diagnoses of congenital anomalies, most targeted studies are performed at 18 to 20 weeks of gestation. Although many private obstetricians perform in-office sonography, the highest rates of detection of congenital anomalies are seen in tertiary care settings such as a university medical center. In difficult or otherwise high-risk cases, a consulting perinatologist is commonly the physician most likely to integrate the ultrasound findings with a rational management plan for the remainder of the pregnancy and for delivery.

Background: Angiotensin II may prove useful in treating regional anesthesia-induced hypotension in obstetric patients, because it causes less uterine vasoconstriction than do other vasoconstrictor drugs (such as phenylephrine). This study compared (1) maternal blood pressure and heart rate and (2) fetal status at delivery in parturients given either prophylactic angiotensin II or ephedrine infusion during spinal anesthesia for elective cesarean delivery., Methods: Fifty-four women were randomized to receive either angiotensin II or ephedrine infusion intravenously during spinal anesthesia for elective cesarean section delivery. Simultaneous with subarachnoid injection, infusion of angiotensin II (2.5 microg/ml) or ephedrine (5 mg/ml) was initiated at 10 ng x kg(-1) x min(-1) and 50 microg x kg(-1) x min(-1), respectively. The rate of each infusion was adjusted to maintain maternal systolic blood pressure at 90-100% of baseline., Results: Cumulative vasopressor doses (mean+/-SD) through 10, 20, and 30 min were 150+/-100, 310+/-180, and 500+/-320 ng/kg in the angiotensin group and 480+/-210, 660+/-390, and 790+/-640 microg/kg in the ephedrine group. Maternal heart rate was significantly higher (P < 0.001) during vasopressor infusion in the ephedrine group than in the angiotensin group. Umbilical arterial and venous blood pH and base excess were all significantly higher (P < 0.05) in the angiotensin group than in the ephedrine group., Conclusions: Angiotensin II infusion maintained maternal systolic blood pressure during spinal anesthesia without increasing maternal heart rate or causing fetal acidosis.