WAPM-World Association of Perinatal Medicine Practice Guidelines: Fetal central nervous system examination

These practice guidelines follow the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation, bringing together groups and individuals throughout the world, with the goal of improving the ultrasound assessment of the fetal Central Nervous System (CNS) anatomy. In fact, this document provides further guidance for healthcare practitioners for the evaluation of the fetal CNS during the mid-trimester ultrasound scan with the aim to increase the ability in evaluating normal fetal anatomy. Therefore, it is not intended to establish a legal standard of care. This document is based on consensus among perinatal experts throughout the world, and serves as a guideline for use in clinical practice

The clinical diagnosis of pelvic inflammatory disease – reuse of electronic medical record data from 189 patients visiting a Swedish university hospital emergency department

BACKGROUND: The pelvic inflammatory disease (PID) diagnosis is mostly based on clinical findings. However, few studies have examined the clinical basis for the diagnostics of PID, which was the aim of this study. METHODS: A retrospective study was performed of 189 out-patients diagnosed as having PID at the obstetric and gynecological emergency department of a Swedish university hospital. Data on symptoms, signs, pelvic examination and laboratory tests were extracted from the electronic medical records in comparison with the diagnostic criteria of the PID Guideline of the US Center of Disease Control from 2002 (CDC 2002 Guidelines). RESULTS: Eight symptoms in varying combinations were associated with the PID diagnosis. Most of them are mentioned in the CDC 2002 Guidelines. Detected rates of C. Trachomatis (CT) and N. Gonorrhoeae (NG) were 5% and 0%, respectively, among the tested patients (CT = 52% and NG = 12%). The C-reactive protein was normal in the majority of tested patients. CONCLUSION: The clinical basis for the diagnostics of PID was largely in accordance with the criteria in the CDC 2002 Guidelines. The limited number of CT tests performed is somewhat disappointing, considering the fact that effective disease prevention includes widespread CT screening. Further studies in different settings are needed in order to analyze how the testing rate for CT can be improved in clinical praxis

Integration of first-trimester assessment in the ultrasound staging of placenta accreta spectrum disorders.

OBJECTIVE: To explore the role of early first trimester ultrasound at 5-7 postmenstrual weeks of gestation in predicting sonographic staging of placenta accreta spectrum (PAS) and to elucidate whether integrating first trimester assessment with ultrasound staging of PAS can predict surgical outcome in women at risk for PAS. METHODS: Secondary analysis of prospectively collected data of women who had at least one previous caesarean delivery (CD) or uterine surgery and placenta previa for whom early (5-7 weeks of gestation) ultrasound images could be retrieved. The relationship between gestational sac position and prior CD scar was assessed using classifications by Cali et al. (cross-over COS), Kaelin Agten et al. ("on the scar" vs "in the niche" implantation) and Timor-Tritsch et al. ("above the line" vs "below the line" implantation) by two different examiners blinded to the final diagnosis and clinical outcome. Primary aim of the study was to explore the strength of association and predictive accuracy of first trimester ultrasound in predicting PAS stage. Secondary aim was to elucidate whether integration of first trimester ultrasound with PAS staging can predict surgical outcome. Logistic regression and area under the curve analyses were used to analyse the data. RESULTS: One hundred and eighty-seven women were included. Of these ,79.6% (95% CI 67.1-88.2) had COS1, 94.4% (95% CI 84.9-98.1) "in the niche" and 92.6% (95% CI 82.4-97.1) "below the line" implantation confirmed to be affected by PAS3 in the third trimester of pregnancy. On multivariate logistic regression analysis, COS1 (OR: 7.9 (95% CI 4.0-15.5; p<0.001), "in the niche" (OR: 29.1, 95% CI 8.1-104; p<0.001) and "below the line" (OR: 38.1, 95% CI 12.1-121; p<0.001) implantations, however, neither parity (p= 0.4), nor the number of prior CDs (p= 0.5) were independently associated with PAS3. When translating these figures in a diagnostic model, either COS1 (AUC: 0.94, 95% CI 0.91-0.97), or implantation "in the niche" (AUC: 0.92, 95% CI 0.89-0.96) or "below the line" (AUC: 0.92, 95% CI 0.88-0.96) had a high predictive accuracy for PAS3. Adverse surgical outcome was more common in women with COS1 (p<0.001), implantation "in the niche" (p<0.001) and "below the line" (p<0.001) then those without them.) On multivariate logistic regression analysis, ultrasound diagnosis of PAS3 (OR: 4.3, 95% CI 2.1-17.3), COS1 (OR: 7.9, 95% CI 4.0-15.5; p<0.001), "in the niche" (OR: 29.1, 95% CI 8.1-104; p<0.001) and "below the line" (OR: 7.9, 95% CI 4.0-15.5; p<0.001) implantations were independently associated with adverse surgical outcome. When combining the three imaging methods, we identified, an area we call "high-risk-for-PAS Triangle" which may enable an easy visual perception and application of the three methods to prognosticate the risk for CSP and PAS, although it requires validation in further large prospective studies. CONCLUSION: Early first trimester sonographic assessment of pregnancies after CDs can reliably predict ultrasound staging of possible PAS. Integrating first with second and third trimester ultrasound can stratify surgical risk of women affected by PAS. This article is protected by copyright. All rights reserved

Functional Refinement in the Projection from Ventral Cochlear Nucleus to Lateral Superior Olive Precedes Hearing Onset in Rat

Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds. To perform this computation, the LSO requires precisely tuned, converging excitatory and inhibitory inputs that are driven by the two ears and that are matched for stimulus frequency. In rodents, the inhibitory inputs, which arise from the medial nucleus of the trapezoid body (MNTB), undergo extensive functional refinement during the first postnatal week. Similar functional refinement of the ascending excitatory pathway, which arises in the anteroventral cochlear nucleus (AVCN), has been assumed but has not been well studied. Using whole-cell voltage clamp in acute brainstem slices of neonatal rats, we examined developmental changes in input strength and pre- and post-synaptic properties of the VCN-LSO pathway. A key question was whether functional refinement in one of the two major input pathways might precede and then guide refinement in the opposite pathway. We find that elimination and strengthening of VCN inputs to the LSO occurs over a similar period to that seen for the ascending inhibitory (MNTB-LSO) pathway. During this period, the fractional contribution provided by NMDA receptors (NMDARs) declines while the contribution from AMPA receptors (AMPARs) increases. In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter. Finally, the progressive decrease in paired-pulse depression between birth and hearing onset allows these synapses to follow progressively higher frequencies. Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway

First-trimester cesarean scar pregnancy: a comparative analysis of treatment options from the international registry

Background: A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous cesarean delivery, and this carries a substantial risk for major maternal complications. The aim of this study was to report, analyze, and compare the effectiveness and safety of different treatments options for cesarean scar pregnancies managed in the first trimester through a registry. Objective: This study aimed to evaluated the ultrasound findings, disease behavior, and management of first-trimester cesarean scar pregnancies. Study design: We created an international registry of cesarean scar pregnancy cases to study the ultrasound findings, disease behavior, and management of cesarean scar pregnancies. The Cesarean Scar Pregnancy Registry collects anonymized ultrasound and clinical data of individual patients with a cesarean scar pregnancy on a secure, digital information platform. Cases were uploaded by 31 participating centers across 19 countries. In this study, we only included live and failing cesarean scar pregnancies (with or without a positive fetal heart beat) that received active treatment (medical or surgical) before 12+6 weeks' gestation to evaluate the effectiveness and safety of the different management options. Patients managed expectantly were not included in this study and will be reported separately. Treatment was classified as successful if it led to a complete resolution of the pregnancy without the need for any additional medical interventions. Results: Between August 29, 2018, and February 28, 2023, we recorded 460 patients with cesarean scar pregnancies (281 live, 179 failing cesarean scar pregnancy) who fulfilled the inclusion criteria and were registered. A total of 270 of 460 (58.7%) patients were managed surgically, 123 of 460 (26.7%) patients underwent medical management, 46 of 460 (10%) patients underwent balloon management, and 21 of 460 (4.6%) patients received other, less frequently used treatment options. Suction evacuation was very effective with a success rate of 202 of 221 (91.5%; 95% confidence interval, 87.8-95.2), whereas systemic methotrexate was least effective with only 38 of 64 (59.4%; 95% confidence interval, 48.4-70.4) patients not requiring additional treatment. Overall, surgical treatment of cesarean scar pregnancies was successful in 236 of 258 (91.5%, 95% confidence interval, 88.4-94.5) patients and complications were observed in 24 of 258 patients (9.3%; 95% confidence interval, 6.6-11.9). Conclusion: A cesarean scar pregnancy can be managed effectively in the first trimester of pregnancy in more than 90% of cases with either suction evacuation, balloon treatment, or surgical excision. The effectiveness of all treatment options decreases with advancing gestational age, and cesarean scar pregnancies should be treated as early as possible after confirmation of the diagnosis. Local medical treatment with potassium chloride or methotrexate is less efficient and has higher rates of complications than the other treatment options. Systemic methotrexate has a substantial risk of failing and a higher complication rate and should not be recommended as first-line treatment

Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth: A Cohort Study

In an analysis of a cohort of pregnant women, Radek Bukowski and colleagues describe an association between taking folic acid supplements and a reduction in the risk of preterm birth

Optimising the use of caesarean section: a generic formative research protocol for implementation preparation

BACKGROUND: Caesarean section rates are rising across all geographical regions. Very high rates for some groups of women co-occur with very low rates for others. Both extremes are associated with short and longer term harms. This is a major public health concern. Making the most effective use of caesarean section is a critical component of good quality, sustainable maternity care. In 2018, the World Health Organization published evidence-based recommendations on non-clinical interventions to reduce unnecessary caesarean section. The guideline identified critical research gaps and called for formative research to be conducted ahead of any interventional research to define locally relevant determinants of caesarean birth and factors that may affect implementation of multifaceted optimisation strategies. This generic formative research protocol is designed as a guide for contextual assessment and understanding for anyone planning to take action to optimise the use of caesarean section. METHODS: This formative protocol has three main components: (1) document review; (2) readiness assessment; and (3) primary qualitative research with women, healthcare providers and administrators. The document review and readiness assessment include tools for local mapping of policies, protocols, practices and organisation of care to describe and assess the service context ahead of implementation. The qualitative research is organized according to twelve identified interventions that may optimise use of caesarean section. Each intervention is designed as a "module" and includes a description of the intervention, supporting evidence, theory of change, and in-depth interview/focus group discussion guides. All study instruments are included in this protocol. DISCUSSION: This generic protocol is designed to underpin the formative stage of implementation research relating to optimal use of caesarean section. We encourage researchers, policy-makers and ministries of health to adapt and adopt this design to their context, and share their findings as a catalyst for rapid uptake of what works

Thyroid hormone action on mitochondria

Measurements of fluorescence at >420 nm and extracted NADPH in mitochondria obtained from the livers of hypothyroid rats show that the addition of Pi, ADP and glutamate rapidly reduces over 90% of the total reducible intrinsic pyridine nucleotides in State 3, compared with 20% in normals. The total fluorescence intensity change and reducible NADP + is about twice normal in hypothyroid mitochondria. Adding 6–30 µM l -thyroxine to hypothyroid mitochondria in vitro decreases and delays the substrate-induced reduction of pyridine nucleotides, and excludes both NADP + from such reduction and NADPH from oxidation by added ADP + Pi, without changing the high NADP(H) content. The correcting actions of the hormone are rapidly reversed by albumin, probably by binding free hormone. Changes in respiration do not appear to account for these observations. There is indirect evidence for decreased phosphorylation of added ADP in hypothyroid mitochondria, and a correction by added hormone. The hormonal actions on NADP(H) redox reactions are not reproduced by 1 to 6 µM dinitrophenol in vitro . l -Thyroxine appears to specifically block the participation of NADP (H) in redox reactions in mitochondria from hypothyroid rats, perhaps by effecting a sequestration of the nucleotide, by inhibiting the pyridine nucleotide transhydrogenase, or by activating an energy-linked process that competes with transhydrogenation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44803/1/10863_2004_Article_BF00761448.pd

ATP-Evoked Intracellular Ca Signaling of Different Supporting Cells in the Hearing Mouse Hemicochlea

Hearing and its protection is regulated by ATP-evoked Ca2+ signaling in the supporting cells of the organ of Corti, however, the unique anatomy of the cochlea hampers observing these mechanisms. For the first time, we have performed functional ratiometric Ca2+ imaging (fura-2) in three different supporting cell types in the hemicochlea preparation of hearing mice to measure purinergic receptor-mediated Ca2+ signaling in pillar, Deiters' and Hensen's cells. Their resting [Ca2+]i was determined and compared in the same type of preparation. ATP evoked reversible, repeatable and dose-dependent Ca2+ transients in all three cell types, showing desensitization. Inhibiting the Ca2+ signaling of the ionotropic P2X (omission of extracellular Ca2+) and metabotropic P2Y purinergic receptors (depletion of intracellular Ca2+ stores) revealed the involvement of both receptor types. Detection of P2X2,3,4,6,7 and P2Y1,2,6,12,14 receptor mRNAs by RT-PCR supported this finding and antagonism by PPADS suggested different functional purinergic receptor population in pillar versus Deiters' and Hensen's cells. The sum of the extra- and intracellular Ca2+-dependent components of the response was about equal with the control ATP response (linear additivity) in pillar cells, and showed supralinearity in Deiters' and Hensen's cells. Calcium-induced calcium release might explain this synergistic interaction. The more pronounced Ca2+ leak from the endoplasmic reticulum in Deiters' and Hensen's cells, unmasked by cyclopiazonic acid, may also suggests the higher activity of the internal stores in Ca2+ signaling in these cells. Differences in Ca2+ homeostasis and ATP-induced Ca2+ signaling might reflect the distinct roles these cells play in cochlear function and pathophysiology