Angle of progression measured using transperineal ultrasound for prediction of uncomplicated operative vaginal delivery: systematic review and meta-analysis.

OBJECTIVE: To determine whether intrapartum transperineal ultrasound measurement of the angle of progression (AoP) during the second stage of labor can predict uncomplicated operative vaginal delivery (OVD) using vacuum or forceps extraction. METHODS: A systematic search in PubMed, EMBASE, Scopus, Web of Science and Google Scholar was performed from inception to February 2021. Studies assessing the predictive accuracy of AoP, measured using intrapartum transperineal ultrasound, for uncomplicated OVD, defined as successful vaginal delivery within three pulls using forceps or no more than two detachments of the vacuum extractor cup, were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Summary receiver-operating-characteristics (ROC) curves, pooled sensitivity and specificity, area under the ROC curve (AUC) and summary likelihood ratios (LRs) were calculated. RESULTS: Seven studies reporting on a total of 782 patients undergoing OVD were included in this systematic review and meta-analysis. Second-stage AoP measured during maternal rest had a pooled sensitivity of 80% (95% CI, 59-92%) and specificity of 89% (95% CI, 76-95%), with a LR+ of 7.3 (95% CI, 3.1-15.8) for uncomplicated OVD. AoP measured during active pushing had a sensitivity of 91% (95% CI, 85-94%) and specificity of 83% (95% CI, 69-92%), with a LR+ of 5.4 (95% CI, 2.7-10.6) for uncomplicated OVD. The performance of AoP measured at rest was particularly high in nulliparous women, with a sensitivity of 87% (95% CI, 75-94%) and specificity of 90% (95% CI, 82-94%) for uncomplicated OVD. CONCLUSION: AoP may be a reliable predictor for uncomplicated OVD when measured during the second stage of labor, especially in nulliparous women. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal heart rate mirrors maternal temperature during posterior fossa craniotomy: a case report.

While it is well known that maternal temperature affects fetal heart rate, the exact relationship is not well described. The circumstances accompanying most cases of maternal hypothermia and rewarming (e.g. a drowning event) have precluded a precise quantitative description of this relationship. We describe hypothermia and controlled rewarming during resection of a maternal brain stem tumor in the early third trimester. Continuous electronic fetal heart rate and core temperature monitoring demonstrated a near linear relationship during the development of hypothermia and rewarming. Recognition of the close relationship between maternal temperature and fetal heart rate can help safeguard maternal and fetal health, and prevent unnecessary delivery during non-obstetric surgery in pregnancy.

Airway management for cesarean delivery performed under general anesthesia.

BACKGROUND: With the increasing popularity of neuraxial anesthesia, there has been a decline in the use of general anesthesia for cesarean delivery. We sought to examine the incidence, outcome and characteristics associated with a failed airway in patients undergoing cesarean delivery under general anesthesia. METHODS: A retrospective review of airway management in women undergoing cesarean delivery under general anesthesia over an eight-year period from 2006-2013 at an academic medical center was conducted. RESULTS: During the study period, 10 077 cesarean deliveries were performed. Neuraxial anesthesia was used in 9382 (93%) women while general anesthesia was used in 695 (7%). Emergent cesarean delivery was the most common indication for general anesthesia. Failed intubation was encountered in only three (0.4%) women, who were successfully managed with a laryngeal mask airway. The overall incidence of failed intubation was 1 in 232 (95% CI 1:83 to 1:666) and general anesthesia was continued in all cases. There were no adverse maternal or fetal outcomes directly related to failed intubation. CONCLUSION: Advances in adjunct airway equipment, availability of an experienced anesthesiologist and simulation-based teaching of failed airway management in obstetrics may have contributed to our improved maternal outcomes in patients undergoing cesarean delivery under general anesthesia.

Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization.

Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In this study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine (MA)-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate, FDR <0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent MA levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization.

Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D.

Affecting about 1 in 12 Americans annually, depression is a leading cause of the global disease burden. While a range of effective antidepressants are now available, failure and relapse rates remain substantial, with intolerable side effect burden the most commonly cited reason for discontinuation. Thus, understanding individual differences in susceptibility to antidepressant therapy side effects will be essential to optimize depression treatment. Here we perform genome-wide association studies (GWAS) to identify genetic variation influencing susceptibility to citalopram-induced side effects. The analysis sample consisted of 1762 depression patients, successfully genotyped for 421K single-nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study. Outcomes included five indicators of citalopram side effects: general side effect burden, overall tolerability, sexual side effects, dizziness and vision/hearing side effects. Two SNPs met our genome-wide significance criterion (q<0.1), ensuring that, on average, only 10% of significant findings are false discoveries. In total, 12 additional SNPs demonstrated suggestive associations (q<0.5). The top finding was rs17135437, an intronic SNP within EMID2, mediating the effects of citalopram on vision/hearing side effects (P=3.27 × 10(-8), q=0.026). The second genome-wide significant finding, representing a haplotype spanning ∼30 kb and eight genotyped SNPs in a gene desert on chromosome 13, was associated with general side effect burden (P=3.22 × 10(-7), q=0.096). Suggestive findings were also found for SNPs at LAMA1, AOX2P, EGFLAM, FHIT and RTP2. Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that potentially mediate adverse effects of antidepressant medications.

Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.

BACKGROUND: Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression. METHOD: We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries. RESULTS: Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p = 4.98 × 10(-7), q = 0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1. CONCLUSIONS: Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

A report on dental anxiety levels in children undergoing nitrous oxide inhalation sedation and propofol target controlled infusion intravenous sedation.

AIM: To report on two separate child sedation cohorts; one undergoing propofol intravenous sedation (IVS) and the other, nitrous oxide inhalation sedation (IS) in respect to changes in dental anxiety and subject characteristics. STUDY DESIGN: The age, gender, level of social deprivation and amount of treatment performed and observed patient behaviour during treatment, using the Frankl and a VAS scale, were recorded for each subject. Anxiety questionnaires were completed before and after treatment. These were: - Modified Child Dental Anxiety Scale (MCDAS); Children's Fear Survey Schedule- Dental Subscale (CFSS-DS) and two Visual Analogue Scales (VAS). RESULTS AND STATISTICS: Participants (36) attended for treatment under IS and 40 attended for treatment under propofol IVS. The IVS cohort was older (p<0.01), by between 1.9 and 4.1 years and had more treatment [p = 0.015, 95% confidence interval for the difference between the cohort medians was (0, 3) units]. The two cohorts were closely matched in respect to pre-operative anxiety as measured by the MCDAS and CFSS-DS scales. There were significant anxiety reductions within each cohort as measured by three of the scales: - MCDAS, CFSS-DS and VAS (1) (p< or = 0.001) but no significant change in the VAS (2) scores. When the two cohorts were compared, there was no significant difference in the reduction of the self-reported anxiety for any of the four scales (p>0.05). The observed behaviour was good for both cohorts. CONCLUSION: Propofol target-controlled intravenous sedation and nitrous oxide inhalation sedation were similarly efficacious at anxiety reduction in referred dentally anxious children. Subjects undergoing propofol IVS were older than those undergoing IS. Propofol TCI may offer the opportunity for more treatment at each visit. Further propofol TCI conscious sedation studies are required.

Induction of intestinal rotavirus-specific antibodies in respiratory, but not gut, lymphoid tissues following mucosal immunization of mice with inactivated rotavirus.

Intranasal (i.n.), but not oral, immunization of mice with inactivated rotavirus induces protection against challenge. To understand the mechanisms by which i.n. immunization with inactivated rotavirus evokes protective immunity, we examined the site of rotavirus-specific B cell activation and the origins of intestinal IgA-secreting B cells following i.n. inoculation of mice with inactivated rhesus rotavirus. We found that (1) i.n., but not oral, inoculation induced partial protection after challenge; (2) i.n., but not oral, inoculation induced production of rotavirus-specific IgM, IgA, and IgG by intestinal lymphoid tissues; and (3) after i.n. inoculation, nasal-associated lymphoid tissues (NALT) and bronchial lymph nodes (BLN) were the sites of initial production of rotavirus-specific antibodies. These studies indicate that after inoculation with inactivated rotavirus, virus-specific effector B cells may be more easily activated in respiratory, compared to intestinal, lymphoid tissues. Additional studies are needed to determine if these observations are due to fundamental differences in the microenvironment of NALT and BLN compared to Peyer's patches or are a function of the anatomic differences between the respiratory and the gastrointestinal tracts.

Coumarin derivatives and breast-feeding.

Coumarin derivatives are the anticoagulants most widely used in the United States. These agents are relatively contraindicated during pregnancy, and the use of these drugs in breast-feeding women remains controversial. Much of the confusion regarding the passage of these agents into breast milk might stem from the fact that different agents possess significantly different chemical properties. A review of the chemical structure of different coumarin derivatives, as well as available clinical evidence, suggests that warfarin sodium is not excreted into breast milk, and can be safely given to women requiring therapeutic anticoagulation postpartum. For the rare patient who cannot tolerate warfarin sodium, the use of dicumarol, rather than anisindione, is preferred.

Is vaginal birth after cesarean less expensive than repeat cesarean delivery?

OBJECTIVE: This study was undertaken to compare total medical costs of trial of labor after cesarean with those of elective repeat cesarean without labor, with both short- and long-term neonatal costs associated with such procedures taken into account. STUDY DESIGN: Costs associated with All Patient Refined diagnosis-related groups and Current Procedural Terminology for a large not-for-profit health care system were applied to an algorithm describing maternal and neonatal outcomes of trial of labor. Perinatal morbidity rates and cost estimates for long-term neurologic damage associated with uterine rupture were derived from published literature. RESULTS: If a 70% vaginal birth rate for women undergoing a trial of labor and delivery in a tertiary center with a mean uterine rupture to delivery time of 13 minutes is assumed, the net cost differential ranged from a saving of $149 to a loss of $217, depending on morbidity assumptions. For vaginal birth after cesarean success rates <70%, trial of labor in the presence of two previous scars, and institutional factors increasing the perinatal morbidity rate by just 4% with respect to that seen in tertiary centers, trial of labor resulted in a net financial loss to the health care system regardless of all other assumptions made. CONCLUSIONS: When costs as opposed to charges are considered and the cost of long-term care for neurologically injured infants is taken into account, trial of labor after previous cesarean is unlikely to be associated with a significant cost saving for the health care system. Recent government-mandated length-of-stay requirements are likely to make the economic benefit of vaginal birth after cesarean even less favorable. Factors other than cost must govern decisions regarding trial of labor or repeat cesarean.

Tissue and cellular alterations in Asian clam (Potamocorbula amurensis) from San Francisco Bay: toxicological indicators of exposure and effect?

The US Geological Survey has reported the presence of a metal contamination gradient in clam tissues, decreased condition indices, and irregular reproductive patterns have been reported in the Asian clam, Potamocorbula amurensis, from San Francisco Bay. If metals are driving the observed patterns in the field, then biomarkers of exposure, and possibly deleterious effect, should show a corresponding gradient. In this study, biomarkers from sub-cellular to tissue levels of biological organization were assessed in P. amurensis collected from the Bay or exposed to cadmium in the laboratory. Cellular and tissue alterations were assessed using histopathology and enzyme histochemistry (EH). Alterations in the ovary, testis, kidney, and gill tissues were most common at the most contaminated station when data were averaged over a 12-month sampling period. EH analysis indicated decreased active transport, energy status, and glucose oxidation in kidney and digestive gland at the most contaminated site which may indicate a decreased potential for growth. Ovarian lesions observed in feral Asian clams were experimentally induced in healthy clams by cadmium exposure in laboratory exposures. Our results suggest a contaminant etiology for tissue alterations.

Vibroacoustic and scalp stimulation.

Both VAS and scalp stimulation are useful in the evaluation of fetal compromise by decreasing the number of falsely abnormal FHR tests and limiting the number of unnecessary interventions, thus improving the efficiency of antepartum and intrapartum FHR monitoring. As is true for all types of fetal assessment using FHR monitoring, VAS and scalp stimulation have limitations, and a lack of response to these methodologies does not necessarily indicate fetal acidemia. When either VAS or scalp stimulation is employed, one must take into consideration their respective predictive values (see Table 1). Fetal VAS or scalp stimulation should be considered as one facet of comprehensive fetal evaluation. When these techniques are used in this manner, the clinician evaluating the fetus in the antepartum or intrapartum period may prevent unnecessary intervention and improve maternal and neonatal outcome.

Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization.

Parenterally administered immunizations have long been used to induce protection from mucosal pathogens such as Bordetella pertussis and influenza virus. We previously found that i.m. inoculation of mice with the intestinal pathogen, rotavirus, induced virus-specific Ab production by intestinal lymphocytes. We have now used adoptive transfer studies to identify the cell types responsible for the generation of virus-specific Ab production by gut-associated lymphoid tissue (GALT) after i.m. immunization. Three days after i.m. immunization with rotavirus, cells obtained from the draining peripheral lymph nodes of donor mice were transferred into naive recipient mice. We found that intestinal lymphocytes produced rotavirus-specific Igs (IgM, IgA, and IgG) 2 wk after transfer of either unfractionated cells, or unfractionated cells rendered incapable of cellular division by mitomycin C treatment. Additional studies demonstrated that rotavirus-specific IgA, but not IgG, was produced by intestinal lymphocytes after transfer of purified B cells. Ig allotype analysis revealed that rotavirus-specific IgA was produced by intestinal B cells of recipient origin, suggesting that migration of Ag-presenting B cells from peripheral lymphoid tissues to GALT may contribute to the generation of mucosal IgA responses after parenteral immunization. Strategies that promote Ag uptake and presentation by B cells may enhance mucosal IgA production following parenteral immunization.