Impact of fetal trisomy 21 on umbilical artery Doppler indices

Objectives - Umbilical artery (UA) Doppler indices are surrogate measures of placental function, most commonly used to assess fetal wellbeing in pregnancies with fetal growth restriction. Fetuses with trisomy 21 (t21) are reported to have elevated UA Doppler indices, but reference percentiles are currently lacking for this population. We hypothesized that gestational age-specific values of UA Doppler indices in pregnancies complicated by t21 will be elevated compared to established percentiles based on euploid pregnancies. We aimed to assess UA Doppler indices longitudinally in fetuses with t21 in order to demonstrate Doppler patterns across gestation in this population, compare them with euploid fetuses, and investigate their association with pregnancy outcomes. Methods - We conducted a retrospective cohort study of singleton pregnancies with confirmed fetal t21 who underwent UA Doppler surveillance antenatally from January 2012 to August 2019. UA Doppler indices, including systolic/diastolic (S/D) ratio, pulsatility index (PI), and resistance index (RI) were extracted from ultrasound reports or directly from ultrasound images. UA S/D, PI, and RI percentiles by gestational week were created from available observations from our cohort via a data-driven approach using a generalized additive model. A secondary analysis was run to statistically compare t21 values to established percentiles based on observations from a historical population of euploid fetuses. Results - UA Doppler measurements from 86 t21 fetuses and 130 euploid fetuses were included in our analysis. Median (IQR) maternal age in t21 pregnancies and euploid pregnancies were 35 years (29–38) and 30 years (27–33), respectively. As in euploid fetuses, we found a negative association between Doppler indices and gestational age in the t21 fetuses. Maternal tobacco use, obesity, or chronic hypertension had no significant effect on UA Doppler indices. As hypothesized, values for UA S/D ratio, PI, and RI at the 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97.5th percentiles by gestational week were significantly higher in t21 fetuses compared to euploid fetuses (p Conclusions - At each week of gestation, UA Doppler indices in t21 fetuses were significantly higher than established percentiles from a euploid population. Reference intervals based on euploid fetuses may therefore not be appropriate for antenatal surveillance of fetuses with t21. Prospective studies are needed to investigate the role and impact of serial UA Doppler velocimetry in the surveillance of pregnancies complicated by fetal t21

Impact of fetal trisomy 21 on umbilical artery Doppler indices

Umbilical artery (UA) Doppler indices are surrogate measures of placental function, most commonly used to assess fetal wellbeing in pregnancies with fetal growth restriction. Fetuses with trisomy 21 (t21) are reported to have elevated UA Doppler indices, but reference percentiles are currently lacking for this population. We hypothesized that gestational age-specific values of UA Doppler indices in pregnancies complicated by t21 will be elevated compared to established percentiles based on euploid pregnancies. We aimed to assess UA Doppler indices longitudinally in fetuses with t21 in order to demonstrate Doppler patterns across gestation in this population, compare them with euploid fetuses, and investigate their association with pregnancy outcomes. We conducted a retrospective cohort study of singleton pregnancies with confirmed fetal t21 who underwent UA Doppler surveillance antenatally from January 2012 to August 2019. UA Doppler indices, including systolic/diastolic (S/D) ratio, pulsatility index (PI), and resistance index (RI) were extracted from ultrasound reports or directly from ultrasound images. UA S/D, PI, and RI percentiles by gestational week were created from available observations from our cohort via a data-driven approach using a generalized additive model. A secondary analysis was run to statistically compare t21 values to established percentiles based on observations from a historical population of euploid fetuses. UA Doppler measurements from 86 t21 fetuses and 130 euploid fetuses were included in our analysis. Median (IQR) maternal age in t21 pregnancies and euploid pregnancies were 35 years (29–38) and 30 years (27–33), respectively. As in euploid fetuses, we found a negative association between Doppler indices and gestational age in the t21 fetuses. Maternal tobacco use, obesity, or chronic hypertension had no significant effect on UA Doppler indices. As hypothesized, values for UA S/D ratio, PI, and RI at the 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97.5th percentiles by gestational week were significantly higher in t21 fetuses compared to euploid fetuses (pp  At each week of gestation, UA Doppler indices in t21 fetuses were significantly higher than established percentiles from a euploid population. Reference intervals based on euploid fetuses may therefore not be appropriate for antenatal surveillance of fetuses with t21. Prospective studies are needed to investigate the role and impact of serial UA Doppler velocimetry in the surveillance of pregnancies complicated by fetal t21.</p

Cerebrospinal Fluid Alterations Following Endoscopic Third Ventriculostomy With Choroid Plexus Cauterization: A Retrospective Laboratory Analysis of Two Tertiary Care Centers

Purpose: This study sought to determine the previously undescribed cytologic and metabolic alterations that accompany endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC). Methods: Cerebrospinal fluid (CSF) samples were collected from infant patients with hydrocephalus at the time of index ETV/CPC and again at each reintervention for persistent hydrocephalus. Basic CSF parameters, including glucose, protein, and cell counts, were documented. A multivariable regression model, incorporating known predictors of ETV/CPC outcome, was constructed for each parameter to inform time-dependent normative values. Results: A total of 187 infants were treated via ETV/CPC for hydrocephalus; initial laboratory values were available for 164 patients. Etiology of hydrocephalus included myelomeningocele (53, 32%), intraventricular hemorrhage of prematurity (43, 26%), aqueductal stenosis (24, 15%), and others (44, 27%). CSF parameters did not differ significantly with age or etiology. Glucose levels initially drop below population average (36 to 32 mg/dL) post-operatively before slowly rising to normal levels (42 mg/dL) by 3 months. Dramatically elevated protein levels post-ETV/CPC (baseline of 59 mg/dL up to roughly 200 mg/dL at 1 month) also normalized over 3 months. No significant changes were appreciated in WBC. RBC counts were very elevated following ETV/CPC and quickly declined over the subsequent month. Conclusion: CSF glucose and protein deviate significantly from normal ranges following ETV/CPC before normalizing over 3 months. High RBC values immediately post-ETV/CPC decline rapidly. Age at time of procedure and etiology have little influence on common clinical CSF laboratory parameters. Of note, the retrospective study design necessitates ETV/CPC failure, which could introduce bias in the results

Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme.

Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%), and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P<0.001 by the log-rank test, hazard ratio = 10.75 for overall survival]. The median survival time for patients with low tumor CcO activity was 14.3 months, compared with 6.3 months for patients with high tumor CcO activity. High CcO activity occurs in a significant subset of high-grade glioma patients and is an independent predictor of poor outcome. Thus, CcO activity may serve as a useful molecular marker for the categorization and targeted therapy of GBMs

Interrater Reliability in Pediatric Urodynamic Tracings: A Pilot Study

© 2017 American Urological Association Education and Research, Inc. Purpose Urodynamic studies are crucial to neuropathic bladder management and they often determine surgical intervention. However, current evidence indicates that interpretations show poor agreement across physicians. We sought to determine the interrater reliability of urodynamic interpretation in our practice. We hypothesized that there would be strong correlation among pediatric urologists of similar training in a single academic practice. Materials and Methods We retrospectively identified patients with neuropathic bladder who underwent urodynamics at our institution between 2014 and 2015. An anonymous electronic survey (phase I) was developed with 20 clinical scenarios, each containing a brief history, a single urodynamic tracing and an accompanying fluoroscopic image. Faculty members assessed each tracing by an online instrument developed using urodynamic reports and published literature. The primary outcome was statistical correlation across raters as measured by the Spearman correlation coefficient. In a followup study (phase II) we investigated the sources of variability in urodynamic interpretations. Results Six faculty members completed the study with a response rate of 100%. In comparing urodynamic interpretation across raters, the faculty demonstrated a weak to strong correlation (r s 0.39–0.61, p \u3c0.001). A strong correlation was found for fluoroscopic and clinical decision making variables, while electromyography synergy and detrusor overactivity demonstrated weaker correlation across physicians. Conclusions Faculty interpretations of urodynamic tracings showed only moderate agreement despite a close working relationship and similar training at a single institution. Variability in interpretation can strongly impact patient treatment. Therefore, further work is needed to standardize the reporting and interpretation of urodynamic studies to optimize patient care

Multivariate Analysis of Survival for the Cohorts with High and Low CcO Activity.

<p><b>Panel A</b> shows the Kaplan-Meier estimate of the probability of overall survival, according to CcO activity, in all 84 patients combined from the training and validation tissue cohorts (P<0.0001 by the log-rank test; hazard ratio for death in patients with high CcO activity, 24.20; 95% CI, 9.12 to 34.20). Red denotes tumors with low CcO activity and blue denotes tumors with high CcO activity. <b>Panel B, C, D, and E</b> show the probability of survival in patients with high (left) and low (right) CcO activity with respect to age (Panel B; hazard ratio, 0.24; P = 0.14), gender (Panel C; hazard ratio, 0.58; P = 0.42), treatment administered (Panel D; hazard ratio, 0.39; P = 0.05) and MGMT promoter methylation status (Panel E; hazard ratio, 0.9; P = 0.83). Black circles denote censored points, and the numbers between brackets indicate the median survival for each group. CcO denotes cytochrome c oxidase, F denotes female, M denotes male, TMZ denotes temozolomide, and Rad denotes radiotherapy.</p

Kaplan–Meier Estimates of Overall Survival and Progression Free Survival.

<p><b>Panel A</b> shows the probability of overall survival and <b>Panel B</b> shows the probability of progression-free survival for the 58 patients with grade IV primary glioblastoma in the training set. <b>Panel C</b> shows the difference in the probability of overall survival for patients with high and low tumor CcO activity (P<0.0001 by the log-rank test; hazard ratio for death in patients with high tumor CcO activity, 10.75; 95% CI, 3.79 to 30.51). <b>Panel D</b> shows the difference in the probability of progression-free survival for patients with high and low tumor CcO activity (P = 0.0087 by the log-rank test; hazard ratio for death in patients with high tumor CcO activity, 3.57; 95% CI, 1.38 to 9.22). Black circles denote censored points, and the numbers between brackets indicate the median survival for each group. CcO denotes cytochrome c oxidase.</p

Determination of CcO Activity Levels.

<p><b>Panel A</b> shows the representative time course curves of CcO activity (top) and CS activity (bottom). CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome <i>c</i>, as indicated by the decrease of absorbance at 550 nm. CS activity was determined by measuring spectrophotometric thionitrobenzoic acid (TNB) production, as indicated by the increase of absorbance at 412 nm. For each tissue sample, activities were measured at least twice at protein concentrations that ensured the linearity of the reaction. CcO-specific and CS-specific activities were calculated using the slopes of the curves, and activities were expressed as nanomoles of cytochrome <i>c</i> oxidized per minute per milligram of protein. Red and black lines denote duplicate determinations of a representative tissue. <b>Panel B</b> shows representative CcO/CS ratios from normal brain (epilepsy patients, gray bars) and from primary glioma tissue samples (red bars). Bars represent the average of at least two independent determinations ± SEM.</p