Vitamin B12 supplementation during pregnancy for maternal and child health outcomes.

BACKGROUND: Vitamin B12 deficiency is a major public health problem worldwide, with the highest burden in elderly people, pregnant women, and young children. Due to its role in DNA synthesis and methylation, folate metabolism, and erythropoiesis, vitamin B12 supplementation during pregnancy may confer longer-term benefits to maternal and child health outcomes. OBJECTIVES: To evaluate the benefits and harms of oral vitamin B12 supplementation during pregnancy on maternal and child health outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP) on 2 June 2023, and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs, or cluster-RCTs evaluating the effects of oral vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation during pregnancy. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Four review authors independently assessed trial eligibility. Two review authors independently extracted data from included studies and conducted checks for accuracy. Three review authors independently assessed the risk of bias of the included studies using the Cochrane RoB 1 tool. We used GRADE to evaluate the certainty of evidence for primary outcomes. MAIN RESULTS: The review included five trials with 984 pregnant women. All trials were conducted in low- and middle-income countries, including India, Bangladesh, South Africa, and Croatia. At enrolment, 26% to 51% of pregnant women had vitamin B12 deficiency (less than 150 pmol/L), and the prevalence of anaemia (haemoglobin less than 11.0 g/dL) ranged from 30% to 46%. The dosage of vitamin B12 supplementation varied from 5 µg/day to 250 µg/day, with administration beginning at 8 to 28 weeks' gestation through to delivery or three months' postpartum, and the duration of supplementation ranged from 8 to 16 weeks to 32 to 38 weeks. Three trials, involving 609 pregnant women, contributed data for meta-analyses of the effects of vitamin B12 supplementation compared to placebo or no vitamin B12 supplementation. Maternal anaemia: there may be little to no difference for maternal anaemia by intervention group, but the evidence is very uncertain (70.9% versus 65.0%; risk ratio (RR) 1.08, 95% confidence interval (CI) 0.93 to 1.26; 2 trials, 284 women; very low-certainty evidence). Maternal vitamin B12 status: vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain (25.9% versus 67.9%; RR 0.38, 95% CI 0.28 to 0.51; 2 trials, 272 women; very low-certainty evidence). Women who received vitamin B12 supplements during pregnancy may have higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (mean difference (MD) 60.89 pmol/L, 95% CI 40.86 to 80.92; 3 trials, 412 women). However, there was substantial heterogeneity (I2 = 85%). Adverse pregnancy outcomes: the evidence is uncertain about the effect on adverse pregnancy outcomes, including preterm birth (RR 0.97, 95% CI 0.55 to 1.74; 2 trials, 340 women; low-certainty evidence), and low birthweight (RR 1.50, 95% CI 0.93 to 2.43; 2 trials, 344 women; low-certainty evidence). Two trials reported data on spontaneous abortion (or miscarriage); however, the trials did not report quantitative data for meta-analysis and there was no clear definition of spontaneous abortion in the study reports. No trials evaluated the effects of vitamin B12 supplementation during pregnancy on neural tube defects. Infant vitamin B12 status: children born to women who received vitamin B12 supplementation had higher total vitamin B12 concentrations compared to placebo or no vitamin B12 supplementation (MD 71.89 pmol/L, 95% CI 20.23 to 123.54; 2 trials, 144 children). Child cognitive outcomes: three ancillary analyses of one trial reported child cognitive outcomes; however, data were not reported in a format that could be included in quantitative meta-analyses. In one study, maternal vitamin B12 supplementation did not improve neurodevelopment status (e.g. cognitive, language (receptive and expressive), motor (fine and gross), social-emotional, or adaptive (conceptual, social, practical) domains) in children compared to placebo (9 months, Bayley Scales of Infant and Toddler Development Third Edition (BSID-III); 1 trial; low-certainty evidence) or neurophysiological outcomes (72 months, event-related potential measures; 1 trial; low-certainty evidence), though children born to women who received vitamin B12 supplementation had improved expressive language domain compared to placebo (30 months, BSID-III; 1 trial; low-certainty evidence). AUTHORS' CONCLUSIONS: Oral vitamin B12 supplementation during pregnancy may reduce the risk of maternal vitamin B12 deficiency and may improve maternal vitamin B12 concentrations during pregnancy or postpartum compared to placebo or no vitamin B12 supplementation, but the evidence is very uncertain. The effects of vitamin B12 supplementation on other primary outcomes assessed in this review were not reported, or were not reported in a format for inclusion in quantitative analyses. Vitamin B12 supplementation during pregnancy may improve maternal and infant vitamin B12 status, but the potential impact on longer-term clinical and functional maternal and child health outcomes has not yet been established.

Folic Acid and the Prevention of Birth Defects: 30 Years of Opportunity and Controversies.

For three decades, the US Public Health Service has recommended that all persons capable of becoming pregnant consume 400 µg/day of folic acid (FA) to prevent neural tube defects (NTDs). The neural tube forms by 28 days after conception. Fortification can be an effective NTD prevention strategy in populations with limited access to folic acid foods and/or supplements. This review describes the status of mandatory FA fortification among countries that fortify (n = 71) and the research describing the impact of those programs on NTD rates (up to 78% reduction), blood folate concentrations [red blood cell folate concentrations increased ∼1.47-fold (95% CI, 1.27, 1.70) following fortification], and other health outcomes. Across settings, high-quality studies such as those with randomized exposures (e.g., randomized controlled trials, Mendelian randomization studies) are needed to elucidate interactions of FA with vitamin B12 as well as expanded biomarker testing.

Comparison of Anemia Screening Methods Using Paired Venous Samples in Women of Reproductive Age in Southern India.

BACKGROUND: Anemia is an important public health problem, and accurate estimates may inform policy and programs. Although hemoglobin (Hb) assessment of venous blood via automated hematology analyzers (AHAs) is recommended, most population-based surveys estimate anemia prevalence based on analysis of capillary blood via portable hemoglobinometers. OBJECTIVES: We aimed to evaluate screening methods for hemoglobin and anemia assessment using paired venous samples. METHODS: Participants were women 15-40 y who were not pregnant or lactating. Paired venous whole blood samples (n = 896) were analyzed for hemoglobin (Hb) via portable hemoglobinometer (HemoCue 301) and Coulter Counter AHA. Anemia and severe anemia were defined as Hb <12.0g/dL and <8.0 g/dL, respectively. Bland-Altman methods were used to assess the level of agreement for Hb results (mean difference, SD of differences, limits of agreement). Diagnostic accuracy parameters (sensitivity, specificity, positive predictive value, negative predictive value, accuracy) were calculated to evaluate HemoCue performance compared to the AHA reference, overall and by sociodemographic, nutritional, and metabolic characteristics. RESULTS: The estimated anemia prevalence was significantly lower via HemoCue vs. AHA (36.3% compared with 41.6%; P value < 0.0001). The HemoCue had 84.4% accuracy for anemia screening and 98.8% for severe anemia, compared to the AHA reference. The HemoCue had 74.8% sensitivity and 91.2% specificity, compared to AHA. HemoCue sensitivity was higher in women with iron deficiency [serum ferritin (SF) <15.0 µg/L: 81.6% compared with SF ≥15.0 µg/L: 41.3%], and lower in women with metabolic risk factors, including overweight [BMI ≥25.0 kg/m2: 63.9% vs. BMI <25.0 kg/m2: 78.8%], or elevated CRP (>1.0 mg/L: 67.2% vs. ≤1.0 mg/L: 82.9%), trunk fat (>35%: 62.7% vs. ≤35%: 80.1%), or whole-body fat (>35%: 63.9% vs. ≤35%: 80.3%). CONCLUSIONS: Findings suggest that women with anemia may be incorrectly identified as not anemic via portable hemoglobinometer, and anemia prevalence may be underestimated at the population level.This study was registered at clinicaltrials.gov as NCT04048330.

Experimental evolution of dispersal: Unifying theory, experiments and natural systems.

Dispersal is a central life history trait that affects the ecological and evolutionary dynamics of populations and communities. The recent use of experimental evolution for the study of dispersal is a promising avenue for demonstrating valuable proofs of concept, bringing insight into alternative dispersal strategies and trade-offs, and testing the repeatability of evolutionary outcomes. Practical constraints restrict experimental evolution studies of dispersal to a set of typically small, short-lived organisms reared in artificial laboratory conditions. Here, we argue that despite these restrictions, inferences from these studies can reinforce links between theoretical predictions and empirical observations and advance our understanding of the eco-evolutionary consequences of dispersal. We illustrate how applying an integrative framework of theory, experimental evolution and natural systems can improve our understanding of dispersal evolution under more complex and realistic biological scenarios, such as the role of biotic interactions and complex dispersal syndromes.

Strengthening capacity of health workers to diagnose birth defects in Ugandan hospitals from 2015 to 2021.

BACKGROUND: Limited diagnostic capabilities, resources and health worker skills have deterred the advancement of birth defects surveillance systems in most low- and middle-income countries (LMICs). Empowering health workers to identify and diagnose major external birth defects (BDs) is crucial to establishing effective hospital-based BD surveillance. Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration BD Surveillance System consists of three diagnostic levels: (1) surveillance midwives, (2) MU-JHU clinical team, and (3) U.S. Centers for Disease Control and Prevention (CDC) birth defects subject matter experts (SMEs) who provide confirmatory diagnosis. The diagnostic concordance of major external BDs by surveillance midwives or MU-JHU clinical team with CDC birth defects SMEs were estimated. METHODS: Study staff went through a series of trainings, including birth defects identification and confirmation, before surveillance activities were implemented. To assess the diagnostic concordance, we analyzed surveillance data from 2015 to 2021 for major external BDs: anencephaly, iniencephaly, encephalocele, spina bifida, craniorachischisis, microcephaly, anophthalmia/microphthalmia, anotia/microtia, cleft palate alone, cleft lip alone, cleft lip with cleft palate, imperforate anus, hypospadias, talipes equinovarus, limb reduction, gastroschisis, and omphalocele. Positive predictive value (PPV) as the proportion of BDs diagnosed by surveillance midwives or MU-JHU clinical team that were confirmed by CDC birth defects SMEs was computed. PPVs between 2015 and 2018 and 2019-2021 were compared to assess the accuracy of case diagnosis over time. RESULTS: Of the 204,332 infants examined during 2015-2021, 870 infants had a BD. Among the 1,245 BDs identified, 1,232 (99.0%) were confirmed by CDC birth defects SMEs. For surveillance midwives, PPV for 7 of 17 BDs was > 80%. For the MU-JHU clinical team, PPV for 13 of 17 BDs was > 80%. Among surveillance midwives, PPV improved significantly from 2015 to 2018 to 2019-2021, for microcephaly (+ 50.0%), cleft lip with cleft palate (+ 17.0%), imperforate anus (+ 30.0%), and talipes equinovarus (+ 10.8%). Improvements in PPV were also observed among MU-JHU clinical team; however, none were significant. CONCLUSION: The diagnostic accuracy of the midwives and clinical team increased, highlighting that BD surveillance, by front-line health care workers (midwives) in LMICs is possible when midwives receive comprehensive training, technical support, funding and continuous professional development.

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored. We performed a comprehensive pharmacological inhibition screen of the protein kinome and found that replication stress response (RSR) inhibitors were synthetically lethal with chloroquine (CQ) in PDAC cells. CQ treatment reduced de novo nucleotide biosynthesis and induced replication stress. We found that CQ treatment caused mitochondrial dysfunction and depletion of aspartate, an essential precursor for de novo nucleotide synthesis, as an underlying mechanism. Supplementation with aspartate partially rescued the phenotypes induced by CQ. The synergy of CQ and the RSR inhibitor VE-822 was comprehensively validated in both 2D and 3D cultures of PDAC cell lines, a heterotypic spheroid culture with cancer-associated fibroblasts, and in vivo xenograft and syngeneic PDAC mouse models. These results indicate a codependency on functional lysosomes and RSR in PDAC and support the translational potential of the combination of CQ and RSR inhibitors.

Outcomes in pediatric patients with documented delays between ileocolic intussusception diagnosis and therapeutic enema attempt: evaluation of reduction efficacy and complication rate.

BACKGROUND: Ileocolic intussusception is considered a pediatric emergency, with concerns for risk of significant morbidity in children with a prolonged intussusception state. Emergent therapy is standard of care, as prior studies have shown poor outcomes in patients with long delays (> 24 h) before intervention. Various factors can result in shorter delays, and there are limited studies evaluating outcomes in these patients. This study aimed to determine if there were differences in reduction success rates associated with short in-hospital time delays. OBJECTIVE: This study is to determine enema success rate and morbidity in patients with documented time delays between intussusception diagnosis and therapeutic enema. MATERIALS AND METHODS: A retrospective evaluation of pediatric patients with intussusception at a single children's hospital between 2007 and 2019 was performed. Patient's records were reviewed for time of symptom onset, radiologic diagnosis, and attempted enema. Ultrasounds and radiographs were reviewed for bowel obstruction, free peritoneal fluid, trapped fluid around the intussusceptum, and absent bowel wall perfusion. Patients were evaluated for efficacy of reduction attempt, requirement for surgical reduction, and complications including bowel resection and bowel perforation. RESULTS: There were 175 cases of ileocolic intussusception requiring enema reduction. Successful reduction occurred in 72.2% (13/18) of cases performed within 1 h of diagnosis; 74.3% (78/105) between 1 and3 h; 73.2% (30/41) between 3 and 6 h; and 81.2% (9/11) with greater than 6 h. Need for bowel resection was not associated with short delays between diagnosis and reduction attempts (p = .07). CONCLUSIONS: There was no difference in intussusception reduction efficacy or complication rate in patients with increasing time between imaging diagnosis of ileocolic intussusception and reduction attempt, including delay intervals up to 8 h.

Life history variation in an invasive plant is associated with climate and recent colonization of a specialist herbivore.

PREMISE: Spatial variation in selective pressures can lead to intraspecific variation in life history, favoring some life histories and constraining others depending on the vulnerability of life stages. We examined how spatial variation in herbivory and climate influences flowering size and the occurrence of semelparity (reproducing once) versus iteroparity (reproducing multiple times) in the introduced range of an invasive plant, houndstongue (Cynoglossum officinale). Houndstongue is a short-lived, semelparous perennial in its native range. In its introduced range, we previously documented increased rates of iteroparity and a higher median threshold flowering size compared to the native range. We hypothesized that the recent introduction of a specialist biocontrol insect (a root-boring weevil, Mogulones crucifer) would decrease threshold flowering size and reduce the proportion of iteroparous plants because M. crucifer preferentially attacks large individuals and may reduce overwinter survival. METHODS: We surveyed 24 sites across the northwestern United States to quantify the frequency of semelparity versus iteroparity and to estimate weevil abundance and used demographic data collected from six sites to estimate median threshold flowering size. RESULTS: We found that sites with greater winter precipitation and no weevils had a greater proportion of iteroparous plants. Sites with higher weevil attack had a lower median threshold flowering size. CONCLUSIONS: The variation in frequency of flowering and threshold flowering size that we documented in North American houndstongue populations, and the relationships between this variation and herbivory and climate, provide evidence for how selective pressures covary with the life histories of invasive plants.

Experimental evidence that density dependence strongly influences plant invasions through fragmented landscapes.

Populations of range expanding species encounter patches of both favorable and unfavorable habitat as they spread across landscapes. Theory shows that increasing patchiness slows the spread of populations modeled with continuously varying population density when dispersal is not influence by the environment or individual behavior. However, as is found in uniformly favorable landscapes, spread remains driven by fecundity and dispersal from low density individuals at the invasion front. In contrast, when modeled populations are composed of discrete individuals, patchiness causes populations to build up to high density before dispersing past unsuitable habitat, introducing an important influence of density dependence on spread velocity. To test the hypothesized interaction between habitat patchiness and density dependence, we simultaneously manipulated these factors in a greenhouse system of annual plants spreading through replicated experimental landscapes. We found that increasing the size of gaps and amplifying the strength of density dependence both slowed spread velocity, but contrary to predictions, the effect of amplified density dependence was similar across all landscape types. Our results demonstrate that the discrete nature of individuals in spreading populations has a strong influence on how both landscape patchiness and density dependence influence spread through demographic and dispersal stochasticity. Both finiteness and landscape structure should be critical components to theoretical predictions of future spread for range expanding native species or invasive species colonizing new habitat.

Rapid evolution of phenology during range expansion with recent climate change.

Although climate warming is expected to make habitat beyond species' current cold range edge suitable for future colonization, this new habitat may present an array of biotic or abiotic conditions not experienced within the current range. Species' ability to shift their range with climate change may therefore depend on how populations evolve in response to such novel environmental conditions. However, due to the recent nature of thus far observed range expansions, the role of rapid adaptation during climate change migration is only beginning to be understood. Here, we evaluated evolution during the recent native range expansion of the annual plant Dittrichia graveolens, which is spreading northward in Europe from the Mediterranean region. We examined genetically based differentiation between core and edge populations in their phenology, a trait that is likely under selection with shorter growing seasons and greater seasonality at northern latitudes. In parallel common garden experiments at range edges in Switzerland and the Netherlands, we grew plants from Dutch, Swiss, and central and southern French populations. Population genetic analysis following RAD-sequencing of these populations supported the hypothesized central France origins of the Swiss and Dutch range edge populations. We found that in both common gardens, northern plants flowered up to 4 weeks earlier than southern plants. This differentiation in phenology extended from the core of the range to the Netherlands, a region only reached from central France over approximately the last 50 years. Fitness decreased as plants flowered later, supporting the hypothesized benefits of earlier flowering at the range edge. Our results suggest that native range expanding populations can rapidly adapt to novel environmental conditions in the expanded range, potentially promoting their ability to spread.

Juvenile myelomonocytic leukemia presenting as bilateral breast masses.

An 8-year-old girl presented with bilateral breast masses and was subsequently diagnosed with juvenile myelomonocytic leukemia. Juvenile myelomonocytic leukemia is a rare myelodysplastic syndrome that typically presents in boys younger than 3 years of age with splenomegaly, lymphadenopathy and skin findings. Bilateral breast masses in a child are rare and, as such, present a diagnostic dilemma due to the relative paucity of cases in the literature. We present a case of granulocytic sarcoma of the breasts in a patient with juvenile myelomonocytic leukemia. The authors hope that increased reporting and research regarding pediatric breast masses will help create awareness for such cases.

Impact of a mindfulness-based stress reduction program from the perspective of adolescents with serious mental health concerns.

BACKGROUND: While studies on mindfulness-based stress reduction (MBSR) for youth have recently emerged, there is a shortage of research on how adolescents from clinical populations experience MBSR. The purpose of this qualitative study was to explore the impact of MBSR from the subjective perspective of adolescents with serious mental health concerns. METHOD: Adolescents (n = 28) from a residential treatment center participated in an adapted 8-week MBSR program in which they learned a range of mindfulness skills and were encouraged to apply the skills to their everyday lives. At the end of the program and at a 3-month follow-up, the youth participated in semistructured interviews in which they were asked to describe the impact of the program from their perspectives. Basic interpretive qualitative analysis methods were used to code the data and to group the codes into higher level themes. RESULTS: Six main themes were found, including improved mood, enhanced relationship to self, increased self-control, improved problem-solving, awareness of the present, and enhanced interpersonal relationships. DISCUSSION: Results from this study suggest that the MBSR program was perceived as beneficial both in the short-term and follow-up in several aspects of emotional, cognitive, and interpersonal functioning.

The Influence of Evolution on Population Spread through Patchy Landscapes.

Predicting the spatial advance of biological invasions and range-shifting native species under climate change requires understanding how evolutionary processes influence the velocity of spread. Although landscape heterogeneity and the finite nature of individuals are known to influence the ecological dynamics of spreading populations, their effect on evolutionary dynamics influencing spread is poorly understood. We used adaptive dynamics and simulation approaches to evaluate the direction of selection on demographic and competitive traits in annual plant populations spreading through linear landscapes. In contrast to models in homogeneous environments where low-density fecundity is selectively favored, we found that large gaps between suitable habitat could favor the rise of competitively tolerant individuals at the invasion front, even when this ability to tolerate competitors came at the cost of reduced fecundity when rare. Simulations of the same processes incorporating finite individuals revealed a spatial priority effect; the long-term outcome of evolution strongly depended on which strategy initially got ahead. Finally, we found that although evolutionary change in demographic and competitive traits could increase the spread velocity, this increase could be insignificant in patchy landscapes, where competitive traits were favored in both spreading and nonspreading populations.

Spaces between home and school: The effect of eating location on adolescent nutrition.

Using interview and self-administered survey data, this article examines how homes, schools, and the community spaces between these two locations affect adolescent nutrition in a low-income, urban setting. Results from this research show that eating location can play a significant role in the foods that adolescents consume. Food acquisition data provided by adolescents reveal that homes and schools provide spaces for the consumption of healthy foods while shops, restaurants, takeouts, and community centers contribute unhealthy snack foods to adolescent diets in a traditionally low-income, urban neighborhood in Northern Ireland. The results of this research show that eating location can provide a starting point for designing healthy eating interventions in low-income places to avoid overlap with spaces that already provide healthy foods to young people.

Revisiting outcomes of right congenital diaphragmatic hernia.

BACKGROUND: Studies comparing outcomes of right- and left-sided congenital diaphragmatic hernia (R-CDH and L-CDH) have yielded conflicting results. We hypothesized that R-CDH is associated with higher short-term pulmonary morbidity than L-CDH. METHODS: We reviewed all CDH patients at a tertiary children's hospital over 10 y. In prenatally diagnosed CDH, the observed-to-expected total fetal lung volume and percentage liver herniation (%LH) were calculated using fetal magnetic resonance imaging-based measurements. Outcomes were compared in patients with isolated CDH. Patients were subsequently matched by %LH to compare outcomes. RESULTS: Of 189 CDH patients, 37 (20.1 %) were R-CDH and 147 (79.9%) were L-CDH. Those with R-CDH were prenatally diagnosed at a significantly lower rate (40.5% versus 73.5%; P < 0.001) and later gestational age (26.5 ± 7.7 versus 22.6 ± 5.65 wk; P = 0.062). There was no difference in observed-to-expected total fetal lung volume between those with R-CDH and L-CDH (30.2 ± 11.1% versus 33.1 ± 14.2%; P = 0.471). Fetuses with R-CDH had a higher %LH than those with L-CDH (37.5 ± 14.1% versus 18.6 ± 12.2%; P < 0.001). Patients with isolated R-CDH had a higher need for extracorporeal membrane oxygenation than L-CDH (48% versus 27%; P = 0.055). There was no difference in duration of tracheal intubation, hospital stay, need for supplemental oxygen at 30-d of life or 6-mo mortality between groups. There was no difference in mortality and pulmonary morbidity when patients were matched by %LH. CONCLUSIONS: Compared to those with L-CDH, fetuses with R-CDH are less likely to be diagnosed prenatally and have a higher need for extracorporeal membrane oxygenation. The sidedness of the hernia defect was not associated with differences in short-term pulmonary morbidity in this large, contemporary single-institution experience of neonates with CDH.

Pancreatic cancer patients with lymph node involvement by direct tumor extension have similar survival to those with node-negative disease.

BACKGROUND: Lymph node (LN) involvement is a well-known poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC). However, there have been conflicting results on the significance of the mechanism of LN involvement, "direct" tumor invasion versus "metastatic," disease on patient survival. METHODS: Clinicopathologic records from all patients who underwent resection for PDAC from 1990 to 2014 at a single-institution were reviewed. RESULTS: Of the 385 total patients, there was tumor invasion outside of the pancreas in 289 (75.1%) patients. Overall, 239 (62.1%) had node-positive disease: 220 (92.0%) by "metastatic" involvement, 14 (5.9%) by "direct" tumor extension, and five (2.1%) by a mix of "metastatic" and "direct". There were no significant differences in clinicopathologic factors associated with PDAC survival between "metastatic" and "direct" LN patients. The median overall survival for the whole cohort was 31.1 months. Compared to overall survival in patients with LN-negative disease (median 40.7 months), those with LNs involved by "metastatic" spread was significantly shorter (median 25.7 months, P < 0.001), yet "direct" LN extension was similar (median 48.1 months, P = 0.719). CONCLUSIONS: The mechanism of LN involvement affects PDAC prognosis. Patients with LNs involved by direct extension have similar survival to those with node-negative disease.

Qualitative FDG PET Image Assessment Using Automated Three-Segment MR Attenuation Correction Versus CT Attenuation Correction in a Tertiary Pediatric Hospital: A Prospective Study.

OBJECTIVE: The purpose of this study was to systematically evaluate the diagnostic quality of (18)F-FDG PET images generated using MR attenuation correction (MRAC) compared with those images generated using CT attenuation correction (CTAC) in a pediatric population. SUBJECTS AND METHODS: Forty-two patients (mean age, 12.8 years; percentage who were male, 57%) who were referred for 62 indicated whole-body PET/CT studies were prospectively recruited to undergo PET/MRI examinations during the same clinic visit in which PET/CT was performed. MRAC was performed using an automatic three-segment model. Three nuclear radiologists scored the diagnostic quality of the PET images generated by MRAC and CTAC using a Likert scale (range of scores, 1-5). Images graded with a score of 1-3 were considered clinically unacceptable, whereas images with a score of 4-5 were considered clinically acceptable. A Wilcoxon signed-rank test was used to compare differences in the grading of PET/MRI and PET/CT images. The Fisher exact test was used to evaluate potential differences in clinically acceptable image quality and the presence of artifact. Fleiss kappa statistics were used to examine interobserver agreement. RESULTS: There was no statistically significant difference in the proportion of PET images generated with MRAC and CTAC for which image quality was considered clinically acceptable. A total of 3.9% of PET assessments generated with MRAC were of unacceptable image quality, compared with 2.2% of PET images generated with CTAC. Two of the three radiologists who reviewed the PET images reported the presence of artifacts more often on MRAC-derived images, and they graded the mean quality of these images 0.48 and 0.29 points lower on the 5-point Likert scale than they graded the mean quality of CTAC-derived images (p < 0.0001). Interobserver agreement was fair (κ = 0.39). CONCLUSION: The diagnostic quality of PET images obtained from a pediatric population with the use of an automatic three-segmentation MRAC method was comparable to that of PET images obtained with the use of CTAC.

Renal Ultrasound for Infants Younger Than 2 Months With a Febrile Urinary Tract Infection.

OBJECTIVE: The purpose of this study is to determine the performance of renal ultrasound for detecting vesicoureteral reflux (VUR) and obstructive uropathies in infants younger than 2 months with a febrile urinary tract infection (UTI). MATERIALS AND METHODS: We performed a retrospective cohort study of infants younger than 2 months with fever and culture-proven UTI presenting from July 1, 2008, through December 31, 2011, with renal ultrasound and voiding cystourethrogram (VCUG) performed within 30 days of UTI diagnosis. Two pediatric radiologists independently reviewed the renal ultrasound and VCUG findings. Results of the renal ultrasound were deemed abnormal if collecting system dilation, renal size asymmetry, collecting system duplication, urothelial thickening, ureteral dilation, or bladder anomalies were present. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of renal ultrasound were calculated using VCUG as reference standard. RESULTS: Of the 197 patients included (mean [SD] age, 33 [ 15 ] days; male-to-female ratio, 2:1), 25% (n = 49) had VUR grades I-V, with 16% (n = 31) having VUR grades III-V and 8% (n = 15) having VUR grades IV-V. For grades I-V VUR, sensitivity was 32.7% (95% CI, 20.0-47.5%), specificity was 69.6% (95% CI, 61.5-76.9%), PPV was 26.2% (95% CI, 15.8-39.1%), and NPV was 75.7% (95% CI, 67.6-82.7%). For grades III-V VUR, sensitivity was 51.6% (95% CI, 33.1-69.9%), specificity was 72.9% (95% CI, 65.5-79.5%), PPV was 26.2% (95% CI, 15.8-39.1%), and NPV was 89.0% (95% CI, 82.5-93.7%). For grades IV-V VUR, sensitivity was 86.7% (95% CI, 59.5-98.3%), specificity was 73.6% (95% CI, 66.6-79.9%), PPV was 21.3% (95% CI, 11.9-33.7%), and NPV was 98.5% (95% CI, 94.8-99.8%). No obstructive uropathies were diagnosed by VCUG in patients with normal renal ultrasound findings. CONCLUSION: In infants younger than 2 months, a normal renal ultrasound makes the presence of grades IV and V VUR highly unlikely but does not rule out lower grades of VUR.

Predictive Value of MRI Findings for the Identification of a Hernia Sac in Fetuses With Congenital Diaphragmatic Hernia.

OBJECTIVE: The purpose of this study was to identify MRI features of diaphragmatic hernia sac, as well as to assess the accuracy of diagnosing a sac prenatally. MATERIALS AND METHODS: All fetal MRI examinations performed for intrapleural congenital diaphragmatic hernia (CDH) from 2004 to 2013 were retrospectively reviewed by two pediatric radiologists blinded to the hernia sac status (defined intraoperatively or at autopsy). Reviewers noted whether a sac was present on the basis of identification of the following four MRI findings: 1, meniscus of lung posterior or apical to the hernia contents; 2, encapsulated appearance of hernia contents, exerting less than expected mass effect on the heart and mediastinum; 3, presence of pleural fluid outlining a sac from above; and 4, presence of ascites outlining a sac from below. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each finding and for various combinations. Contingency tables, chi-square testing, and logistic regression were applied to calculate the probability of a sac. RESULTS: Ninety patients were included: 21 with and 69 without a sac. The first three MRI findings correlated with the presence of a sac. Logistic regression yielded high predicted probability of a sac when one finding was identified (finding 1, 94.4%; finding 2, 96.2%). Adding a second and a third finding improved the probability to 99.7% and 99.9%, respectively. Sensitivity and specificity for the presence of a sac were 0.43 and 0.97, respectively. PPV and NPV were 83.8% and 80%, respectively. CONCLUSION: On fetal MRI, presence of a hernia sac in CDH can be diagnosed with high specificity when indicative findings are present.