Prediction of intrapartum caesarean section in vaginal breech birth: development of models for nulliparous and multiparous women.

OBJECTIVES: To develop prediction models for intrapartum caesarean section in vaginal breech birth. METHODS: This single-center cohort-study included 262 nulliparous and 230 multiparous women attempting vaginal breech birth. For both groups, we developed and (internally) validated three models for the prediction of intrapartum cesarean section. RESULTS: The prediction model for nulliparous women (AUC: 0.67) included epidural analgesia (aOR 2.14; p=0.01), maternal height (aOR 0.64 per 10 cm; p=0.08), birthweight ≥3.8 kg (aOR 2.45; p=0.03) and an interaction term describing the effect of OC if birthweight is ≥3.8 kg (aOR 0.24; p=0.04). An alternative model for nulliparous women which, instead of birthweight, included fetal abdominal circumference with a cut-off at 34 cm (aOR 1.93; p=0.04), showed similar performance (AUC: 0.68). The prediction model for multiparous women (AUC: 0.77) included prelabor rupture of membranes (aOR 0.31; p=0.03), epidural analgesia (aOR 2.42; p=0.07), maternal BMI (aOR 2.92 per 10 kg/m2; p=0.01) and maternal age (aOR 3.17 per decade; p=0.06). CONCLUSIONS: Our prediction models show the most relevant risk factors associated with intrapartum cesarean section in vaginal breech birth for both nulliparous and multiparous women. Importantly, this study clarifies the role of the OC by showing that this parameter is only associated with intrapartum cesarean section if birthweight is above 3.8 kg (or abdominal circumference is above 34 cm). Conversely, knowing the OC when the birthweight is less than 3.8 kg (or abdominal circumference is less than 34 cm) did not improve prediction of this surgical outcome.

Mechanics of vaginal breech birth: Factors influencing obstetric maneuver rate, duration of active second stage of labor, and neonatal outcome.

BACKGROUND: We investigated possible parameters that could predict the need for obstetric maneuvers, the duration of the active second stage of labor (i.e., the duration of active pushing), and short-term neonatal outcome in vaginal breech births. MATERIALS AND METHODS: We performed a retrospective analysis of 268 successful singleton vaginal breech births in women without previous vaginal births from January 2015 to August 2022. Multivariable regression was used to investigate associations between maternal and fetal characteristics (including antepartum magnetic resonance (MR) pelvimetry) with obstetric maneuvers, the duration of active second stage of labor, pH values, and admission to the neonatal unit. Models for the prediction of obstetric maneuvers were built and internally validated. RESULTS: Obstetric maneuvers were performed in a total of 130 women (48.5%). A total of 32 neonates (11.9%) had to be admitted to the neonatal unit. The intertuberous distance (ITD) (p < 0.001), epidural analgesia (p < 0.001), and birthweight (p = 0.026) were associated with the duration of active second stage of labor. ITD (p = 0.028) and birthweight (p = 0.011) were also independently associated with admission to the neonatal unit, while pH values below 7.10 dropped significantly (p = 0.0034) if ITD was ≥13 cm. Furthermore, ITD (p < 0.001) and biparietal diameter (p = 0.002) were independent predictors for obstetric maneuvers. CONCLUSIONS: ITD is independently associated with the duration of active second stage of labor. Thus, it can predict suboptimal birth mechanics in the last stage of birth, which may lead to the need for obstetric maneuvers, lower arterial pH values, and admission to the neonatal unit. Consequently, MR pelvimetry gives additional information for practitioners and birthing people preferring a vaginal breech birth.

Novel Three-Dimensional Body Scan Anthropometry versus MR-Pelvimetry for Vaginal Breech Delivery Assessment.

In this prospective, monocentric study, we investigated the potency of a novel three-dimensional (3D) body scanner for external pelvic assessment in birth planning for intended vaginal breech delivery. Between April 2021 and June 2022, 73 singleton pregnancies with intended vaginal birth from breech presentation (>36.0 weeks of gestation) were measured using a pelvimeter by Martin, a three-dimensional body scanner, and MR-pelvimetry. Measures were related to vaginal birth and intrapartum cesarean section. A total of 26 outer pelvic dimensions and 7 inner pelvic measurements were determined. The rate of successful vaginal breech delivery was 56.9%. The AUC (area under the curve) of the obstetric conjugate (OC) measured by MRI for predicting the primary outcome was 0.62 (OR 0.63; p = 0.22), adjusted for neonatal birth weight 0.66 (OR 0.60; p = 0.19). Of the 22 measured 3D body scanner values, the ratio of waist girth to maternal height showed the best prediction (AUC = 0.71; OR 1.27; p = 0.015). The best predictive pelvimeter value was the distantia spinarum with an AUC of 0.65 (OR = 0.80). The 3D body scanner technique is at least equal to predict successful vaginal breech delivery compared to MRI diagnostics. Further large-scale, prospective studies are needed to verify these results.

DWI of the Breast - Possibilities and Limitations. / Diffusionsbildgebung der Mamma ­ Möglichkeiten und Limitationen der DWI.

BACKGROUND: The MRI of the breast is of great importance in the diagnosis of disorders of the breast. This can be stated for the primary diagnosis as well as the follow up. Of special interest is diffusion weighted imaging (DWI), which has an increasingly important role. The present review provides results regarding the diagnostic and prognostic relevance of DWI for disorders of the breast. METHODS: Under consideration of the recently published literature, the clinical value of DWI of the breast is discussed. Several diagnostic applications are shown, especially for the primary diagnosis of unclear tumors of the breast, the prediction of the axillary lymph node status and the possibility of a native screening. Moreover, correlations between DWI and histopathology features and treatment prediction with DWI are provided. RESULTS: Many studies have shown the diagnostic value of DWI for the primary diagnosis of intramammary lesions. Benign lesions of the breast have significantly higher apparent diffusion coefficients (ADC values) compared to malignant tumors. This can be clinically used to reduce unnecessary biopsies in clinical routine. However, there are inconclusive results for the prediction of the histological subtype of the breast cancer. DWI can aid in the prediction of treatment to neoadjuvant chemotherapy. CONCLUSION: DWI is a very promising imaging modality, which should be included in the standard protocol of the MRI of the breast. DWI can provide clinically value in the diagnosis as well as for prognosis in breast cancer. KEY POINTS: · DWI can aid in the discrimination between benign and malignant tumors of the breast and therefore avoiding unnecessary biopsies.. · The ADC value cannot discriminate between immunhistochemical subtypes of the breast cancer. · The ADC value of breast cancer increases under neoadjuvant chemotherapy and can by this aid in treatment prediction.. · There is definite need of standardisation for clinical translation. CITATION FORMAT: · Meyer HJ, Martin M, Denecke T. DWI of the Breast - Possibilities and Limitations. Fortschr Röntgenstr 2022; 194: 966 - 973.

The Importance of Clinical Examination under General Anesthesia: Improving Parametrial Assessment in Cervical Cancer Patients.

BACKGROUND: Parametrial tumor involvement is an important prognostic factor in cervical cancer and is used to guide management. Here, we investigate the diagnostic value of clinical examination under general anesthesia (EUA) and magnetic resonance imaging (MRI) in determining parametrial tumor spread. METHODS: Post-operative pathological findings of 400 patients with primary cervical cancer were compared to the respective MRI data and the results from EUA. The gynecological oncologist had access to the MR images during clinical assessment (augmented EUA, aEUA). RESULTS: Pathologically proven parametrial tumor invasion was present in 165 (41%) patients. aEUA exhibited a higher accuracy than MRI alone (83% vs. 76%; McNemar's odds ratio [OR] = 2.0, 95%CI 1.25-3.27, p = 0.003). Although accuracy was not affected by tumor size in aEUA, MRI was associated with a lower accuracy in tumors ≥2.5 cm (OR for a correct diagnosis compared to smaller tumors 0.22, p < 0.001). There was also a decrease in specificity when evaluating parametrial invasion by MRI in tumors ≥2.5 cm in diameter (p < 0.0001) compared to smaller tumors (< 2.5 cm). Body mass index had no influence on performance of either method. CONCLUSIONS: aEUA has the potential to increase the diagnostic accuracy of MRI in determining parametrial tumor involvement in cervical cancer patients.

ERBB2 overexpression triggers transient high mechanoactivity of breast tumor cells.

Biomechanical properties of tumor cells play an important role for the metastatic capacity of cancer. Cellular changes of viscoelastic features are prerequisite for cancer progression since they are essential for proliferation and metastasis. However, only little is known about the way how expression of oncogenes influences these biomechanical properties. To address this aspect we used a breast cancer cell line with inducible expression of an oncogenic version of ERBB2. ERBB2 is known to be correlated with bad prognosis in breast cancer. Cell elasticity was determined by the Optical Stretcher, where suspended cells are deformed by two slightly divergent laser beams. We found that induction of ERBB2 caused remarkable biomechanical alterations of the MCF-7 cells after 24 h: the cells actively contracted in response to mechanical stimuli, a phenomenon known as mechanoactivation. After this period, as the cells became senescent, the mechanoactivity returned to control levels. Time-resolved gene array analysis revealed that mechanoactivation was accompanied by temporal upregulation of 46 cytoskeletal genes. A possible role of these genes in tumor progression was investigated by expression analyses of 766 breast cancer patients. This showed an association of 12 out of these 46 genes with increased risk of metastasis. Our results demonstrate that overexpression of ERBB2 causes mechanoactivation of tumor cells, which may enhance tumor cell motility fostering distant metastasis.

Glutamine gluconeogenesis in the small intestine of 72 h-fasted adult rats is undetectable.

Recent reports have indicated that 48-72 h of fasting, Type 1 diabetes and high-protein feeding induce gluconeogenesis in the small intestine of adult rats in vivo. Since this would (i) represent a dramatic revision of the prevailing view that only the liver and the kidneys are gluconeogenic and (ii) have major consequences in the metabolism, nutrition and diabetes fields, we have thoroughly re-examined this question in the situation reported to induce the highest rate of gluconeogenesis. For this, metabolically viable small intestinal segments from 72 h-fasted adult rats were incubated with [3-13C]glutamine as substrate. After incubation, substrate utilization and product accumulation were measured by enzymatic and NMR spectroscopic methods. Although the segments utilized [13C]glutamine at high rates and accumulated 13C-labelled products linearly for 30 min in vitro, no substantial glucose synthesis could be detected. This was not due to the re-utilization of [13C]glucose initially synthesized from [13C]glutamine. Arteriovenous metabolite concentration difference measurements across the portal vein-drained viscera of 72 h-fasted Wistar and Sprague-Dawley rats clearly indicated that glutamine, the main if not the only gluconeogenic precursor taken up, could not give rise to detectable glucose production in vivo. Therefore we challenge the view that the small intestine of the adult rat is a gluconeogenic organ.

Intrinsic gluconeogenesis is enhanced in renal proximal tubules of Zucker diabetic fatty rats.

Recent studies indicate that renal gluconeogenesis is substantially stimulated in patients with type 2 diabetes, but the mechanism that is responsible for such stimulation remains unknown. Therefore, this study tested the hypothesis that renal gluconeogenesis is intrinsically elevated in the Zucker diabetic fatty rat, which is considered to be an excellent model of type 2 diabetes. For this, isolated renal proximal tubules from diabetic rats and from their lean nondiabetic littermates were incubated in the presence of physiologic gluconeogenic precursors. Although there was no increase in substrate removal and despite a reduced cellular ATP level, a marked stimulation of gluconeogenesis was observed in diabetic relative to nondiabetic rats, with near-physiologic concentrations of lactate (38%), glutamine (51%) and glycerol (66%). This stimulation was caused by a change in the fate of the substrate carbon skeletons resulting from an increase in the activities and mRNA levels of the key gluconeogenic enzymes that are common to lactate, glutamine, and glycerol metabolism, i.e., mainly of phosphoenolpyruvate carboxykinase and, to a lesser extent, of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Experimental evidence suggests that glucocorticoids and cAMP were two factors that were responsible for the long-term stimulation of renal gluconeogenesis observed in the diabetic rats. These data provide the first demonstration in an animal model that renal gluconeogenesis is upregulated by a long-term mechanism during type 2 diabetes. Together with the increased renal mass (38%) observed, they lend support to the view so far based only on in vivo studies performed in humans that renal gluconeogenesis may be stimulated by and crucially contribute to the hyperglycemia of type 2 diabetes.

Identification of novel targets of cephaloridine in rabbit renal proximal tubules synthesizing glutamine from alanine.

Cephaloridine, which accumulates in the renal proximal tubule, is a model compound used for studying the toxicity of antibiotics towards this nephron segment. Several studies have demonstrated that cephaloridine alters renal intermediary and energy metabolism, but the mechanism by which this compound interferes with renal metabolic pathways remains incompletely understood. In an attempt to improve our knowledge in this field, we have studied the influence of cephaloridine on the synthesis of glutamine, which represents a key metabolic process involving several important enzymatic steps in the rabbit kidney. For this, suspensions of rabbit renal proximal tubules were incubated for 90 and 180 min in the presence of 5 mM alanine, an important glutamine precursor, both in the absence and the presence of 10 mM cephaloridine. Glutamate accumulation and glutamine synthesis were found to be inhibited by cephaloridine after 90 and 180 min of incubation, and cephaloridine accumulation in the renal proximal cells occurred in a time-dependent manner. The renal proximal tubule activities of alanine aminotransferase and glutamate dehydrogenase, which initiates alanine removal and releases the ammonia needed for glutamine synthesis, respectively, were inhibited to a significant degree and in a concentration-dependent manner by cephaloridine concentrations in the range found to accumulate in the renal proximal cells. Citrate synthase and glutamine synthetase activities were also inhibited by cephaloridine, but to a much lesser extent. The above enzymatic activities were not found to be inhibited when they were measured after successive dilutions of renal proximal tubules incubated for 180 min in the presence of 5 mM alanine and 10 mM cephaloridine. When microdissected segments (S1-S3) of rabbit renal proximal tubules were incubated for 180 min with 5 mM alanine with and without 5 and 10 mM cephaloridine, glutamate accumulation and glutamine synthesis were also inhibited in the three renal proximal segments studied; the latter cephaloridine-induced inhibitions observed were concentration-dependent except for glutamine in the S3 segment. These results are consistent with the view that cephaloridine accumulates and is toxic along the entire rabbit renal proximal tubule. They also demonstrate that cephaloridine interferes in a concentration-dependent and reversible manner mainly with alanine aminotransferase and glutamate dehydrogenase, which are therefore newly-identified targets of the toxic effects of cephaloridine in the rabbit renal proximal tubule.

Inhibition of glutamine synthetase in the mouse kidney: a novel mechanism of adaptation to metabolic acidosis.

As part of a study on the regulation of renal ammoniagenesis in the mouse kidney, we investigated the effect of chronic metabolic acidosis on glutamine synthesis by isolated mouse renal proximal tubules. The results obtained reveal that, in tubules from control mice, glutamine synthesis occurred at high rates from glutamate and proline and, to a lesser extent, from ornithine, alanine, and aspartate. A 48 h, metabolic acidosis caused a marked inhibition of glutamine synthesis from near-physiological concentrations of both alanine and proline that were avidly metabolized by the tubules; metabolic acidosis also greatly stimulated glutamine utilization and metabolism. These effects were accompanied by a large increase (i) in alanine, proline, and glutamine gluconeogenesis and (ii) in ammonia accumulation from proline and glutamine. In the renal cortex of acidotic mice, the activity of phosphoenolpyruvate carboxykinase increased 4-fold, but that of glutamate dehydrogenase did not change; in contrast with what is known in the rat renal cortex, metabolic acidosis markedly diminished the glutamine synthetase activity and protein level, but not the glutamine synthetase mRNA level in the mouse renal cortex. These results strongly suggest that, in the mouse kidney, glutamine synthetase is an important regulatory component of the availability of the ammonium ions to be excreted for defending systemic acid-base balance. Furthermore, they show that, in rodents, the regulation of renal glutamine synthetase is species-specific.

Effect of starvation on glutamine ammoniagenesis and gluconeogenesis in isolated mouse kidney tubules.

It has been shown recently that glutamine is taken up by the mouse kidney in vivo. However, knowledge about the fate of this amino acid and the regulation of its metabolism in the mouse kidney remains poor. Given the physiological and pathophysiological importance of renal glutamine metabolism and the increasing use of genetically modified mice in biological research, we have conducted a study to characterize glutamine metabolism in the mouse kidney. Proximal tubules isolated from fed and 48 h-starved mice and then incubated with a physiological concentration of glutamine, removed this amino acid and produced ammonium ions at similar rates. In agreement with this observation, activities of the ammoniagenic enzymes, glutaminase and glutamate dehydrogenase, were not different in the renal cortex of fed and starved mice, but the glutamate dehydrogenase mRNA level was elevated 4.5-fold in the renal cortex from starved mice. In contrast, glucose production from glutamine was greatly stimulated whereas the glutamine carbon removed, that was presumably completely oxidized in tubules from fed mice, was virtually suppressed in tubules from starved animals. In accordance with the starvation-induced stimulation of glutamine gluconeogenesis, the activities and mRNA levels of glucose-6-phosphatase, and especially of phosphoenolpyruvate carboxykinase, but not of fructose-1,6-bisphosphatase, were increased in the renal cortex of starved mice. On the basis of our in vitro results, the elevated urinary excretion of ammonium ions observed in starved mice probably reflected an increased transport of these ions into the urine at the expense of those released into the renal veins rather than a stimulation of renal ammoniagenesis.