Fetal MRI in management of complicated meconium ileus: Prenatal and surgical imaging

Objective To review fetal MRI cases surgically proven to have meconium ileus (MI) and obstruction, describe the common fetal MRI findings that distinguish cases of complicated MI, and to compare these findings with surgical images and perinatal outcomes. Method We performed a retrospective review of all fetal MRI examinations and the corresponding medical record from our tertiary care children's hospital over an 18‐month period. Postnatal management and outcomes were reviewed for these patients, and those patients with surgical or postmortem diagnosis of complicated MI were included in the study. Results Our analysis revealed 7 cases. In this cohort, 3 imaging features of the fetal bowel were repeatedly seen: gradient appearance of intraluminal bowel contents, abnormally localized meconium signal, and collapsed appearance of the colon on MRI. Surgical diagnoses confirmed MI. All live‐born infants underwent surgical repair. Conclusion Fetal MRI should be included in the diagnostic algorithm of any pregnancy where fetal bowel obstruction is suspected to better risk stratify patients

Malaria treatment-seeking behaviour and recovery from malaria in a highland area of Kenya

<p>Abstract</p> <p>Background</p> <p>Malaria epidemics in highland areas of Kenya cause significant morbidity and mortality.</p> <p>Methods</p> <p>To assess treatment-seeking behaviour for malaria in these areas, a questionnaire was administered to 117 randomly selected households in the highland area of Kipsamoite, Kenya. Self-reported episodes of malaria occurred in 100 adults and 66 children.</p> <p>Results</p> <p>The most frequent initial sources of treatment for malaria in adults and children were medical facilities (66.0% and 66.7%) and local shops (19.0% and 30.3%). Adults and children who initially visited a medical facility for treatment were significantly more likely to recover and require no further treatment than those who initially went to a local shop (adults, 84.9% v. 36.8%, <it>P </it>< 0.0001, and children, 79.6% v. 40.0%, <it>P </it>= 0.002, respectively). Individuals who attended medical facilities recalled receiving anti-malarial medication significantly more frequently than those who visited shops (adults, 100% vs. 29.4%, and children, 100% v. 5.0%, respectively, both <it>P </it>< 0.0001).</p> <p>Conclusion</p> <p>A significant proportion of this highland population chooses local shops for initial malaria treatment and receives inappropriate medication at these localshops, reslting in delay of effective treatment. Shopkeeper education has the potential to be a component of prevention or containment strategies for malaria epidemics in highland areas.</p

Different levels of overnutrition and weight gain during pregnancy have differential effects on fetal growth and organ development

<p>Abstract</p> <p>Background</p> <p>Nearly 50% of U.S. women of child-bearing age are overweight or obese, conditions linked to offspring obesity and diabetes.</p> <p>Methods</p> <p>Utilizing the sheep, females were fed a highly palatable diet at two levels of overfeeding designed to induce different levels of maternal body weight increase and adiposity at conception, and from conception to midgestation. Fetal growth and organ development were then evaluated at midgestation in response to these two different levels of overfeeding. Ewes were fed to achieve: 1) normal weight gain (control, C), 2) overweight (125% of National Research Council [NRC] recommendations, OW125) or 3) obesity (150% of NRC recommendations, OB150) beginning 10 wks prior to breeding and through midgestation. Body fat % and insulin sensitivity were assessed at three points during the study: 1) diet initiation, 2) conception and 3) mid-gestation. Ewes were necropsied and fetuses recovered at mid-gestation (day 78).</p> <p>Results</p> <p>OB150 ewes had a higher % body fat than OW125 ewes prior to breeding (P = 0.03), but not at mid-gestation (P = 0.37). Insulin sensitivity decreased from diet initiation to mid-gestation (P = 0.04), and acute insulin response to glucose tended to be greater in OB150 ewes than C ewes (P = 0.09) and was greater than in OW125 ewes (P = 0.02). Fetal crown-rump length, thoracic and abdominal girths, and fetal perirenal fat were increased in the OW125 and OB150 versus C ewes at mid-gestation. However, only fetal heart, pancreas, and liver weights, as well as lipid content of fetal liver, were increased (P < 0.05) in OB150 ewes versus both C and OW125 ewes at midgestation.</p> <p>Conclusions</p> <p>These data demonstrate that different levels of overfeeding, resulting in differing levels of maternal weight gain and adiposity prior to and during pregnancy, lead to differential effects on fetal overgrowth and organ development.</p

To develop evidence-based interventions to support doctors’ wellbeing and promote resilience during COVID-19 (and beyond)

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The Significance of African Lions for the Financial Viability of Trophy Hunting and the Maintenance of Wild Land

Recent studies indicate that trophy hunting is impacting negatively on some lion populations, notably in Tanzania. In 2004 there was a proposal to list lions on CITES Appendix I and in 2011 animal-welfare groups petitioned the United States government to list lions as endangered under their Endangered Species Act. Such listings would likely curtail the trophy hunting of lions by limiting the import of lion trophies. Concurrent efforts are underway to encourage the European Union to ban lion trophy imports. We assessed the significance of lions to the financial viability of trophy hunting across five countries to help determine the financial impact and advisability of the proposed trade restrictions. Lion hunts attract the highest mean prices (US$24,000–US$71,000) of all trophy species. Lions generate 5–17% of gross trophy hunting income on national levels, the proportional significance highest in Mozambique, Tanzania, and Zambia. If lion hunting was effectively precluded, trophy hunting could potentially become financially unviable across at least 59,538 km2 that could result in a concomitant loss of habitat. However, the loss of lion hunting could have other potentially broader negative impacts including reduction of competitiveness of wildlife-based land uses relative to ecologically unfavourable alternatives. Restrictions on lion hunting may also reduce tolerance for the species among communities where local people benefit from trophy hunting, and may reduce funds available for anti-poaching. If lion off-takes were reduced to recommended maximums (0.5/1000 km2), the loss of viability and reduction in profitability would be much lower than if lion hunting was stopped altogether (7,005 km2). We recommend that interventions focus on reducing off-takes to sustainable levels, implementing age-based regulations and improving governance of trophy hunting. Such measures could ensure sustainability, while retaining incentives for the conservation of lions and their habitat from hunting

Sacral nerve stimulation allows for decreased antegrade continence enema use in children with severe constipation.

BackgroundSacral nerve stimulation (SNS) can be beneficial for children with constipation, but no studies have focused on children with constipation severe enough to require antegrade continence enemas (ACEs). Our objective was to evaluate the efficacy of SNS in children with constipation treated with ACE.MethodsUsing a prospective patient registry, we identified patients &lt;21years old who were receiving ACE prior to SNS placement. We compared ACE/laxative usage, PedsQL Gastrointestinal Symptom Scale (GSS), Fecal Incontinence Quality of Life Scale (FIQL), Fecal Incontinence Severity Index (FISI), and Vancouver Dysfunctional Elimination Syndrome Score (DES) at baseline and progressive follow-up time intervals.ResultsTwenty-two patients (55% male, median 12years) were included. Median ACE frequency decreased from 7 per week at baseline to 1 per week at 12months (p&lt;0.0001). Ten children (45%) had their cecostomy/appendicostomy closed. Laxative use, GSS, FIQL, and DES did not change. FISI improved over the first 12months with statistical significance reached only at 6months (p=0.02). Six (27%) children experienced complications after SNS that required further surgery.ConclusionsIn children with severe constipation dependent on ACE, SNS led to a steady decrease in ACE usage with nearly half of patients receiving cecostomy/appendicostomy closure within 2years.Level of evidenceIV

Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI

Antenatal Determinants of Bronchopulmonary Dysplasia and Late Respiratory Disease in Preterm Infants

RATIONALE: Mechanisms contributing to chronic lung disease after preterm birth are incompletely understood. OBJECTIVES: To identify antenatal risk factors associated with increased risk for bronchopulmonary dysplasia (BPD) and respiratory disease during early childhood after preterm birth, we performed a prospective, longitudinal study of 587 preterm infants with gestational age less than 34 weeks and birth weights between 500 and 1,250 g. METHODS: Data collected included perinatal information and assessments during the neonatal intensive care unit admission and longitudinal follow-up by questionnaire until 2 years of age. MEASUREMENTS AND MAIN RESULTS: After adjusting for covariates, we found that maternal smoking prior to preterm birth increased the odds of having an infant with BPD by twofold (P = 0.02). Maternal smoking was associated with prolonged mechanical ventilation and respiratory support during the neonatal intensive care unit admission. Preexisting hypertension was associated with a twofold (P = 0.04) increase in odds for BPD. Lower gestational age and birth weight z-scores were associated with BPD. Preterm infants who were exposed to maternal smoking had higher rates of late respiratory disease during childhood. Twenty-two percent of infants diagnosed with BPD and 34% of preterm infants without BPD had no clinical signs of late respiratory disease during early childhood. CONCLUSIONS: We conclude that maternal smoking and hypertension increase the odds for developing BPD after preterm birth, and that maternal smoking is strongly associated with increased odds for late respiratory morbidities during early childhood. These findings suggest that in addition to the BPD diagnosis at 36 weeks, other factors modulate late respiratory outcomes during childhood. We speculate that measures to reduce maternal smoking not only will lower the risk for preterm birth but also will improve late respiratory morbidities after preterm birth

Urine cell-free DNA multi-omics to detect MRD and predict survival in bladder cancer patients

Circulating tumor DNA (ctDNA) sensitivity remains subpar for molecular residual disease (MRD) detection in bladder cancer patients. To remedy this problem, we focused on the biofluid most proximal to the disease, urine, and analyzed urine tumor DNA in 74 localized bladder cancer patients. We integrated ultra-low-pass whole genome sequencing (ULP-WGS) with urine cancer personalized profiling by deep sequencing (uCAPP-Seq) to achieve sensitive MRD detection and predict overall survival. Variant allele frequency, inferred tumor mutational burden, and copy number-derived tumor fraction levels in urine cell-free DNA (cfDNA) significantly predicted pathologic complete response status, far better than plasma ctDNA was able to. A random forest model incorporating these urine cfDNA-derived factors with leave-one-out cross-validation was 87% sensitive for predicting residual disease in reference to gold-standard surgical pathology. Both progression-free survival (HR = 3.00, p = 0.01) and overall survival (HR = 4.81, p = 0.009) were dramatically worse by Kaplan-Meier analysis for patients predicted by the model to have MRD, which was corroborated by Cox regression analysis. Additional survival analyses performed on muscle-invasive, neoadjuvant chemotherapy, and held-out validation subgroups corroborated these findings. In summary, we profiled urine samples from 74 patients with localized bladder cancer and used urine cfDNA multi-omics to detect MRD sensitively and predict survival accurately