Yoga as a non-pharmacologic therapy to reduce dinutuximab-induced pain in patients with neuroblastoma.

BACKGROUND: Anti-GD2 antibodies are key components of treatment for high-risk neuroblastoma; however, they cause neuropathic pain. Yoga therapy may help reduce pain and distress associated with anti-GD2 therapy. PROCEDURE: Children 3 years of age or older with neuroblastoma participated in individualized yoga therapy while receiving the anti-GD2 antibody dinutuximab (DIN). Yoga therapy was deemed feasible if patients participated during 60% or more of DIN admissions. Patients and caregivers assessed pain/distress before and after yoga therapy with a distress thermometer (DT) and Wong-Baker FACES pain rating scale and completed questionnaires regarding satisfaction with yoga therapy. Therapy was deemed efficacious if there was a ≥1 point pain score change and reduction in distress after yoga. RESULTS: Eighteen patients were enrolled; 52 encounters (admissions for DIN) were evaluable. Ten of 18 were female, three of 18 were Hispanic, and 10/18 were White. Median age at enrollment was 5.5 years (range: 3-11). Yoga therapy was feasible in 39/52 (75%) encounters. Significant reductions in caregiver-reported pain and distress and reductions in patient-reported pain and distress after yoga therapy were reported. Twelve of 18 caregivers completed questionnaires: seven agreed/strongly agreed that yoga was valuable, and nine agreed/strongly agreed to continued participation in yoga. Thirty-four of 36 clinicians reported that they would recommend yoga therapy for other patients receiving DIN. CONCLUSIONS: Yoga therapy was feasible during DIN therapy and may be effective in reducing DIN-associated pain and distress. Future studies are needed to evaluate changes in opioid usage with the addition of yoga therapy during anti-GD2 antibody therapy.

Accuracy and Interobserver Reliability of Magnetic Resonance Imaging for Placenta Accreta Spectrum Disorders.

OBJECTIVE: This study aims to define the accuracy, predictive value, and interobserver reliability of magnetic resonance imaging (MRI) in the diagnosis of placenta accreta spectrum (PAS) disorders. STUDY DESIGN: Two experienced radiologists independently interpreted the MRI studies of patients with possible PAS from two referral centers. Radiologists were blinded to sonographic and clinical information. We calculated diagnostic testing characteristics and kappa statistics of interobserver reliability for MRI findings of PAS. RESULTS: Sixty-eight MRI cases were evaluated. Confirmed PAS and severe PAS were present in 44 (65%) and 20 (29%) cases. For the diagnosis of any PAS, MRI had a sensitivity 66%, specificity 71%, positive predictive value (PPV) 81%, negative predictive value (NPV) 53%, and accuracy 68%. For the diagnosis of severe PAS (percreta), MRI had a sensitivity 85%, specificity 79%, PPV 63%, NPV 93%, and accuracy 81%. The accuracy of individual signs of PAS was lower (44-65%). Interobserver agreement was almost perfect for previa; substantial for myometrial interruptions, PAS, severe PAS, and placental bulging/balling; and moderate to slight for other signs of PAS. CONCLUSION: Although the interobserver reliability of MRI for a diagnosis of PAS is substantial, the accuracy and predictive value are modest and lower than previously reported.

High Altitude Continues to Reduce Birth Weights in Colorado.

Objectives Colorado's relatively high altitudes have been reported to lower birth weight but the most recent studies were conducted 20 years ago. Since then, the accuracy for assigning altitude of residence has been improved with the use of geocoding, and recommendations for pregnancy weight gain have changed. We therefore sought to determine whether currently, residence at high altitude (≥ 2500 m, 8250 ft) lowers birth weight in Colorado. Methods Birth certificate data for all live births (n = 670,017) to Colorado residents from 2007 to 2016 were obtained from the Colorado Department of Public Health and Environment. Geocoded altitude of maternal residence for the current birth was assigned to each birth record. Linear and logistic regression models were used to examine the effects of altitude on birth weight or low birth weight (< 2500 g) while controlling for other factors affecting birth weight, including pregnancy weight gain. Results Compared to low altitude, infants born at high altitude weighed 118 g less and were more often low birth weight (8.8% vs. 11.7%, p < 0.05). After accounting for other factors influencing birth weight, high altitude reduced birth weight by 101 g and increased the risk of low birth weight by 27%. The only factors with larger impacts on birth weight were hypertensive disorders of pregnancy and cigarette use during pregnancy. Conclusions for Practice High altitude remains an important determinant of elevated LBW rates in Colorado, and likely contributes to Colorado's comparative resistance towards meeting the Healthy People 2010/2020 nationwide goal to reduce the low birth weight rate to 7.2% by 2020.

Magnetic resonance imaging is often misleading when used as an adjunct to ultrasound in the management of placenta accreta spectrum disorders.

BACKGROUND: Magnetic resonance imaging is reported to have good sensitivity and specificity in the diagnosis of placenta accreta spectrum disorders, and is often used as an adjunct to ultrasound. But the additional utility of obtaining magnetic resonance imaging to assist in the clinical management of patients with placenta accreta spectrum disorders, above and beyond the information provided by ultrasound, is unknown. OBJECTIVE: We aimed to determine whether magnetic resonance imaging provides data that may inform clinical management by changing the sonographic diagnosis of placenta accreta spectrum disorders. STUDY DESIGN: In all, 78 patients with sonographic evidence or clinical suspicion of placenta accreta spectrum underwent magnetic resonance imaging of the abdomen and pelvis in orthogonal planes through the uterus utilizing T1- and T2-weighted imaging sequences at the University of Utah and the University of Colorado from 1997 through 2017. The magnetic resonance imaging was interpreted by radiologists with expertise in diagnosis of placenta accreta spectrum who had knowledge of the sonographic interpretation and clinical risk factors for placenta accreta spectrum disorders. The primary outcome was a change in diagnosis from sonographic interpretation that could alter clinical management, which was defined a priori. Diagnostic accuracy was verified by surgical and histopathologic diagnosis at the time of delivery. RESULTS: A change in diagnosis that could potentially alter clinical management occurred in 28 (36%) cases. Magnetic resonance imaging correctly changed the diagnosis in 15 (19%), and correctly confirmed the diagnosis in 34 (44%), but resulted in an incorrect change in diagnosis in 13 (17%), and an incorrect confirmation of ultrasound diagnosis in 15 (21%). Magnetic resonance imaging was not more likely to change a diagnosis in the 24 cases of posterior and lateral placental location compared to anterior location (33% vs 37%, P = .84). Magnetic resonance imaging resulted in overdiagnosis in 23% and in underdiagnosis in 14% of all cases. When ultrasound suspected severe disease (percreta) in 14 cases, magnetic resonance imaging changed the diagnosis in only 2 cases. Lastly, the proportion of accurate diagnosis with magnetic resonance imaging did not improve over time (61-65%, P = .96 for trend) despite increasing volume and increasing numbers of changed diagnoses. CONCLUSION: Magnetic resonance imaging resulted in a change in diagnosis that could alter clinical management of placenta accreta spectrum disorders in more than one third of cases, but when changed, the diagnosis was often incorrect. Given its high cost and limited clinical value, magnetic resonance imaging should not be used routinely as an adjunct to ultrasound in the diagnosis of placenta accreta spectrum until evidence for utility is clearly demonstrated by more definitive prospective studies.

Do Obese Women Receive the Necessary Interventions to Achieve Vaginal Birth after Cesarean?

Objective We aimed to determine if obese women undergoing trial of labor after cesarean (TOLAC) were more likely to undergo repeat cesarean for arrest disorders prior to active labor, and whether this was due to decreased use of standard interventions to achieve vaginal birth. Study Design This was a secondary analysis of a prospective registry. Women undergoing TOLAC with one prior cesarean and a singleton, term gestation who had a repeat cesarean for an arrest disorder were included. The primary outcome was repeat cesarean prior to active labor (cervical dilation < 6 cm). Obese (body mass index ≥30 kg/m(2)) and nonobese women were compared. Multivariable logistic regression was used to estimate the association between obesity and repeat cesarean prior to active labor. Clinical interventions were compared between groups using t-test and χ (2) test. Results Among 2,098 women undergoing TOLAC, 1,454 (69%) were obese. Obese women were more likely to undergo repeat cesarean for an arrest disorder prior to active labor (odds ratio, 1.4; 95% confidence interval, 1.1-1.7) despite being allowed longer labors and receiving higher maximum doses of oxytocin for a longer duration than nonobese women. Conclusion Obese women were more likely to undergo repeat cesarean prior to active labor despite more clinical interventions to achieve vaginal birth.

Inflammatory predictors of neurologic disability after preterm premature rupture of membranes.

OBJECTIVE: The maternal-fetal inflammatory response contributes to both preterm premature rupture of membranes (PPROM) and adverse neurological outcomes. Additionally, cytokines associated with fetal placental inflammation can be detrimental to brain development regardless of inciting infection. We investigated whether differential patterns of cytokine markers in maternal and fetal plasma samples reflect subtypes of placental inflammation and neurological outcomes at 6 months in infants born to mothers with PPROM. STUDY DESIGN: Within a prospective cohort study of 25 women with PPROM, plasma cytokines (interleukin [IL]-1ß, IL-6, IL-8, and tumor necrosis factor-α) were measured by enzyme-linked immunosorbent assay from maternal blood samples at rupture and delivery, and from fetal umbilical cord blood samples. Patterns of cytokine expression were correlated with specific placenta pathologies. Infants underwent cranial ultrasound after birth and standardized neurological examinations at 6 months' corrected gestational age. Predictors of inflammation and adverse neurological outcome were assessed by logistic regression, adjusting for gestational age at birth. RESULTS: Inflammation of the fetal side of the placenta was associated with elevated maternal IL-6 and IL-8 at delivery and fetal IL-1ß, IL-6, IL-8, and tumor necrosis factor-α. Worse neurological outcome at 6 months was associated with inflammation of the fetal side of the placenta and shorter duration from rupture of membrane to delivery, independent of gestational age at birth or cranial ultrasound results. CONCLUSION: Our findings support the connection between fetal inflammation with adverse neurological outcome with PPROM, regardless of cranial ultrasound results. Further longitudinal studies are needed to adequately examine these patterns, and will aid in risk assessment and intervention strategies.

Adolescent mental distress in the wake of climate disasters.

Objective: Retrospective exposure to a higher number and prolonged duration of climate-related disasters could be positively associated with adolescent mental distress. Methods: Person-level data came from 38,616 high-school students residing in 22 urban public-school districts in 14 states (U.S. Youth Risk Behavior Survey, 2019). Each district's federally declared climate-related catastrophes (severe storms, floods, wildfire, etc.) came from the Federal Emergency Management Agency. Logistic regression models estimated the adjusted odds ratios (aOR) of adolescent mental distress (MD, using survey responses feeling prolonged sadness/ hopelessness and short sleep duration) according to disaster events and days during three exposure periods (past 2-, 5-, 10-years); adjusted for age, gender, race/ethnicity, socio-economic disadvantage, feeling unsafe at school, district area size, district poverty, and region. Results: Over 10 years, the median number of disaster events was 3 and total disaster days was 64. Adolescents experiencing the highest number of disaster days (top quartile vs. less) had 25% higher odds of MD when exposed within the past 2-years (aOR 1.25 [95% CI 1.14, 1.38]), and 20% higher odds of MD when exposed within the past 5-years (aOR 1.20 95% CI 1.07, 1.35). The odds of MD were not statistically associated with exposure periods that extended to 10 years, nor disaster events (instead of disaster days, all p-values > 0.1). Conclusions: Severe weather will become more frequent and last longer with human-induced climate warming. More studies like this are needed to understand the broad range of adverse effects and enhance planning and preparedness including preparing for worsening mental health among adolescents.

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease.

Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6­0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm.

High Altitude Reduces NO-Dependent Myometrial Artery Vasodilator Response During Pregnancy.

The chronic hypoxia of high-altitude (HA) residence reduces uterine artery blood flow during pregnancy, likely contributing to an increased frequency of preeclampsia and intrauterine growth restriction. We hypothesized that this lesser pregnancy blood flow rise was due, in part, to reduced vasodilation of myometrial arteries (MAs). Here, we assessed MA vasoreactivity in healthy residents of high (2902±39 m) or low altitude (LA; 1669±10 m). MA contractile responses to potassium chloride, phenylephrine, or the thromboxane A2 agonist U46619 did not differ between LA and HA women. Acetylcholine vasodilated phenylephrine or U466119 preconstricted MAs at LA, yet had no effect on HA MAs. In contrast, another vasodilator, bradykinin, relaxed MAs from both altitudes similarly. At LA, the NO synthase inhibitor L-NG-nitroarginine methyl ester decreased both acetylcholine and bradykinin vasodilation by 56% and 33%, respectively. L-NG-nitroarginine methyl ester plus the COX (cyclooxygenase) inhibitor indomethacin had similar effects on acetylcholine and bradykinin vasodilation (68% and 42% reduction, respectively) as did removing the endothelium (78% and 50% decrease, respectively), suggesting a predominantly NO-dependent vasodilation at LA. However, at HA, L-NG-nitroarginine methyl ester did not change bradykinin vasodilation, whereas indomethacin or endothelium removal decreased it by 28% and 72%, respectively, indicating impaired NO signaling at HA. Suggesting that the impairment was downstream of eNOS (endothelial NO synthase), HA attenuated the vasodilation elicited by the NO donor sodium nitroprusside. We concluded that reduced NO-dependent MA vasodilation likely contributes to diminished uteroplacental perfusion in HA pregnancies.

Clinician perspectives on strategies to improve patient maternal immunization acceptability in obstetrics and gynecology practice settings.

Pregnancy is an ideal time to communicate with women about vaccines for themselves and their infants, yet maternal immunization rates remain suboptimal. This study aimed to identify clinic, provider, and staff-related attributes and facilitators to be utilized for a comprehensive vaccine intervention in ob-gyn clinical settings. We conducted in-depth interviews with 24 providers, both healthcare providers (e.g., physicians, nurse practitioners, midwives) and practice managers, from urban and suburban ob-gyn practices in Georgia and Colorado about their immunization attitudes, practices, and patient experiences. Qualitative analyses included Pearson correlation tests to evaluate patterns and relationships within the data to determine themes. Six major themes emerged: 1) strong provider "buy in" for maternal immunization; 2) the supporting role of clinical/interpersonal cues for vaccine promotion; 3) varying provider-patient communication approaches and its influence on maternal and pediatric uptake; 4) an urgent need for a designated office immunization champion; 5) reimbursement and practice implementation challenges; and 6) region differences in attitudes and values toward maternal immunization. Although providers expressed strong support for maternal immunization practices and offered environmental cues for vaccine promotion, practices often lacked a designated, structured role for an immunization champion equipped to manage delicate conversations with patients. The findings reflect needs for immunization champion identification, training, and support, along with best practices guidelines to improve coordination of vaccine promotion and delivery efforts in ob-gyn provider offices. Additionally, provider training on communication approaches to enhance acceptance and uptake of maternal vaccines is warranted.

Early severe fetal Graves disease in a mother after thyroid ablation and thyroidectomy.

BACKGROUND: Fetal Graves disease rarely presents before 26 weeks of gestation. We report a case of severe fetal Graves disease at 18 weeks of gestation in a mother who had very elevated Graves disease antibodies despite being several years post-thyroid ablative therapy and thyroidectomy. CASE: A 36-year-old woman, gravida 1 para 0, with severe Graves disease post-radioiodine ablation followed by thyroidectomy on levothyroxine presented at 18 weeks of gestation for ultrasound examination. Her fetus was found to be severely tachycardic with a goiter. Propylthiouracil was initiated for fetal therapy. Delivery at 34 weeks of gestation was undertaken as a result of preterm premature rupture of membranes. The neonate experienced heart failure and pulmonary hypertension at birth but recovered with appropriate medical therapy. CONCLUSION: It is possible for fetal Graves disease to develop as early as 18 weeks of gestation, and women who have had thyroid ablation and postsurgical hypothyroidism remain at risk for this serious pregnancy complication.

Influenza and Pertussis Vaccination Among Pregnant Women and Their Infants' Close Contacts: Reported Practices and Attitudes.

BACKGROUND: Our objectives were to describe the receipt of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines among postpartum women and their close contacts and the factors associated with cocooning. METHODS: A survey between February 2013 and April 2013 of 613 postpartum women from 9 obstetrics practices assessed vaccine receipt among respondents and close contacts, demographics and 5 domains of health beliefs (benefits, barriers, susceptibility, severity and social norms). Multivariable models assessed the association of these factors with Tdap or influenza "cocooning," defined as the mother plus at least 1 close contact of her newborn receiving the vaccine. RESULTS: The response rate was 45%; 61% of mothers reported that they and at least 1 close contact of their newborn had received influenza vaccine, and 67% reported this for Tdap. Infants whose mothers received influenza vaccine had a mean of 2.8 close contacts who also received influenza vaccine versus a mean of 0.9 contacts for infants whose mothers did not receive influenza vaccine (P < 0.0001). Infants whose mothers received Tdap vaccine had an average of 2.4 contacts who also received it versus 0.8 for infants whose mothers did not receive Tdap (P < 0.0001). Factors associated with influenza and Tdap cocooning included obstetrician recommendation, high perceived benefits, low perceived barriers and perceived susceptibility to disease. For Tdap, race/ethnicity was associated with cocooning (Hispanic/Latino, adjusted odds ratio 0.26, 95% confidence interval: 0.10-0.64 referent to White). CONCLUSION: Maternal vaccination and obstetrician recommendation are associated with infant cocooning. Interventions to increase cocooning of infants should focus on encouraging strong provider recommendations, increasing maternal knowledge of disease risk and addressing identified barriers. Reasons for possible racial/ethnic differences should be further explored.

A Hertzian contact mechanics based formulation to improve ultrasound elastography assessment of uterine cervical tissue stiffness.

Clinical practice requires improved techniques to assess human cervical tissue properties, especially at the internal os, or orifice, of the uterine cervix. Ultrasound elastography (UE) holds promise for non-invasively monitoring cervical stiffness throughout pregnancy. However, this technique provides qualitative strain images that cannot be linked to a material property (e.g., Young's modulus) without knowledge of the contact pressure under a rounded transvaginal transducer probe and correction for the resulting non-uniform strain dissipation. One technique to standardize elastogram images incorporates a material of known properties and uses one-dimensional, uniaxial Hooke's law to calculate Young's modulus within the compressed material half-space. However, this method does not account for strain dissipation and the strains that evolve in three-dimensional space. We demonstrate that an analytical approach based on 3D Hertzian contact mechanics provides a reasonable first approximation to correct for UE strain dissipation underneath a round transvaginal transducer probe and thus improves UE-derived estimates of tissue modulus. We validate the proposed analytical solution and evaluate sources of error using a finite element model. As compared to 1D uniaxial Hooke's law, the Hertzian contact-based solution yields significantly improved Young's modulus predictions in three homogeneous gelatin tissue phantoms possessing different moduli. We also demonstrate the feasibility of using this technique to image human cervical tissue, where UE-derived moduli estimations for the uterine cervix anterior lip agreed well with published, experimentally obtained values. Overall, UE with an attached reference standard and a Hertzian contact-based correction holds promise for improving quantitative estimates of cervical tissue modulus.

Contemporary management of human immunodeficiency virus in pregnancy.

Contemporary management of HIV in pregnancy remains a moving target. With the development of newer antiretroviral agents with lower side-effect profiles and laboratory methods for detection and monitoring of HIV, considerable progress has been made. This review examines key concepts in the pathophysiology of HIV and pregnancy with emphasis on perinatal transmission and reviews appropriate screening and diagnostic testing for HIV during pregnancy. Current recommendations for medical, pharmacologic, and obstetric management of women newly diagnosed with HIV during pregnancy and for those women with preexisting infection are discussed. Preconception counseling for HIV+ women as well as postpartum issues are addressed.

Acceptability of a hypothetical group B strep vaccine among pregnant and recently delivered women.

OBJECTIVE: Group B Streptococcus (GBS) causes significant infant morbidity and mortality. Promising GBS vaccines are currently in clinical trials. Because GBS vaccines would be the first to specifically target pregnant women, we sought to assess acceptability of a hypothetical GBS vaccine. STUDY DESIGN: We performed an internet survey among currently pregnant or recently delivered women receiving care at one of 9Ob/Gyn practices in Colorado. Vaccine acceptability was assessed using questions based on constructs from the Health Belief Model. Multivariable analyses assessed the characteristics associated with GBS vaccine acceptability during the current/recent pregnancy. RESULTS: The response rate was 50% (n=231). While 78% agreed that a GBS vaccine would be a good way to protect newborns, 90% and 83% agreed, respectively, that they worried generally about the safety and effectiveness of new vaccines. Moreover, 39% believed it is generally dangerous for pregnant women to get vaccines. Seventy nine percent 'definitely' or 'probably' would have gotten a GBS vaccine in their most recent pregnancy if available. The most influential factors associated with this outcome were a strong belief in the vaccine's benefits (adjusted odds ratio [AOR] 6.37, 95% confidence interval [CI] 2.01-20.16), and low perceived barriers to vaccination (AOR 0.11, 95% CI (0.03-0.37)). CONCLUSION: A GBS vaccine may be acceptable to pregnant women but would benefit from strong provider support and education about the risks and consequences of GBS infection and the benefits to vaccination.

Two nonadjacent regions in enteroaggregative Escherichia coli flagellin are required for activation of toll-like receptor 5.

Flagellin is the major structural protein of the flagella of Gram-negative bacteria. Recent work has demonstrated that flagellin is a potent trigger of innate immune responses in a number of eukaryotic cells and organisms, including both mammals and plants. In several different human epithelial cell lines, this innate immune response involves toll-like receptor 5 (TLR5). The mechanisms by which flagellin activates TLR5 and the importance of this interaction in other model systems of flagellin-induced inflammation remain unknown. In this work, random and site-directed mutagenesis of the inflammatory flagellin from enteroaggregative Escherichia coli identified two regions in the conserved D1 domain that are required for interleukin-8 release and TLR5 activation. In contrast, large regions of the variable domain could be excised without reducing the inflammatory activity. In addition, regions of the protein analogous to epitopes that trigger innate immune responses in plants are not involved in Caco-2 flagellin responses. These results highlight the complexity of the interaction between bacterial flagellin and its eukaryotic recognition partners and provide the basis for further studies to characterize the innate immune response to flagellin.