Effect of docosahexaenoic acid and olive oil supplementation on pup weight in alcohol-exposed pregnant rats.

Background: Low birth weight has been observed in offspring of alcoholic mothers due likely to unresolved inflammation and oxidative injury. Dietary lipids play a role in inflammation and its resolution. The primary objective was to investigate the effect of DHA and olive oil on the birth weight of pups born to alcohol-exposed dams. Methods: Pregnant rats were randomized to the control or three treatment (alcohol) groups. From gestational days (GD) 8-19, the control group received daily olive oil and malto/dextrose, whereas groups 2 and 3 received olive oil and low-dose alcohol or high-dose alcohol, respectively. Group 4 received daily DHA and high-dose alcohol. The dam's blood was collected on GD 15 and 20 for cytokine analysis. Dams were sacrificed on GD 20. The mean birth weight of pups was compared by one-way ANOVA with post hoc Duncan's test. Results: There was a significant increase in the pups' mean birth weight in the high-dose alcohol/DHA and high-dose alcohol/olive oil. Higher pro-inflammatory cytokines (IL-1ß and IL-12p70) were noted in the alcohol-exposed dams. Conclusions: DHA and olive oil supplementation in alcohol-exposed pregnant rats significantly increased their pups' birth weight despite having high pro-inflammatory cytokines. The mechanism of this effect remains to be determined.

Clinical Trial Enrollment is Associated With Improved Follow-up Rates Among Survivors of Childhood Cancer.

Fortunately >80% of children diagnosed with cancer become long-term survivors; however, this population is at a significantly increased risk of morbidity and mortality as a result of their previous cancer therapy, and long-term follow-up (LTFU) is critical. Multiple barriers to receiving adequate LTFU care have been studied. We investigated whether lack of enrollment in a therapeutic clinical trial may be a barrier to receiving LTFU care. We conducted a review of 353 patient records at the Children's Hospital of Michigan enrolled in our Children's Oncology Group registry between January 1, 2005 and December 31, 2010. In total, 71 patients were excluded (death before follow-up, n=61; currently receiving therapy, n=5; known transfer of care, n=4; insufficient information, n=1). In total, 158 (56%) patients were enrolled in a therapeutic clinical trial. Follow-up rates at 1-, 2- and 5-years following completion of therapy for patients enrolled in a therapeutic clinical trial were 96.8% (153/158), 93.7% (148/158), and 81.7% (103/126), respectively, compared with 83.1% (103/124; P<0.001), 74.2% (92/124; P<0.001), and 66.7% (72/108; P=0.001) for patients not enrolled. Our findings suggest patients enrolled in a therapeutic clinical trial have better LTFU rates and supports the importance of patient enrollment in therapeutic clinical trials when possible. Additional resources may be warranted to improve LTFU for patients not enrolled.

Outcomes of tracheostomy in the neonatal intensive care unit: is there an optimal time?

OBJECTIVE: To compare short-term outcomes of infants who underwent early versus late tracheostomy during their initial hospitalization after birth and determine the association, if any, between tracheostomy timing and outcomes. STUDY DESIGN: Retrospective chart review of infants who underwent a tracheostomy during their initial hospitalization at a single site. RESULTS: The median (range) gestational age of our cohort (n = 127) was 28 (23-42) weeks and birth weight was 988 (390-4030) g. Tracheostomy indications included airway lesions (47%), bronchopulmonary dysplasia (25%), both (22%) and others (6%). Median postmenstrual age (PMA) at tracheostomy was 45 (35-75) weeks. Death occurred in 27 (21%) infants and 65 (51%) infants were mechanically ventilated. G-tube was present at discharge in 42 (33%) infants. Infants who underwent early tracheostomy (<45 weeks PMA) (n = 66) had significantly lower gestational ages, weights and respiratory support than the late (≥45 weeks PMA) (n = 61) group. Death (29.5% versus 14%), home ventilation (41% versus 21%) and G tube (44% versus 14%) were significantly more frequent in the late tracheostomy group. On bivariate regression, outcomes were not independently associated with tracheostomy timing, after adjustment for gestational age and respiratory support. CONCLUSIONS: Of infants who underwent tracheostomy during the initial hospitalization after birth, 21% died. On adjusted analysis, tracheostomy timing was not independently associated with outcomes.

Postoperative pain management after spinal fusion surgery: an analysis of the efficacy of continuous infusion of local anesthetics.

Spinal fusion surgery is a major surgery that results in severe postoperative pain, therefore pain reduction is a primary concern. New strategies for pain management are currently under investigation and include multimodal treatment. A 3-year retrospective analysis of patients with idiopathic scoliosis undergoing spinal fusion surgery was performed at our hospital, assessing patient pain scores, opioid use, and recovery. We evaluated the effect of adding continuous infusion of local anesthetics (CILA) to a postoperative pain management protocol that includes intraoperative intrathecal morphine, as well as postoperative patient-controlled analgesia and oral opioid/acetaminophen combination. The study compared 25 patients treated according to the standard protocol, with 62 patients treated with CILA in addition to the pain management protocol. Patients in the CILA group used nearly 0.5 mg/kg less opioid analgesics during the first 24 hours after surgery.

An epidemiologic study comparing fetal exposure to tobacco smoke in three Southeast Asian countries.

The high prevalence of smoking in Southeast Asia (SEA) means pregnant women face exposure to tobacco smoke that may affect the health of their fetus. This study determined fetal exposure to tobacco smoke by meconium analysis for cotinine in 3 locations in SEA: Bulacan Province, Philippines (N=316), Bangkok, Thailand (N=106) and Singapore City (N=61). Maternal exposure to tobacco smoke was 71.1% (1.3% active; 69.8% passive) in Bulacan, 57.5% (0.9% active; 58.6% passive) in Bangkok and 54.1% (11.5% active; 42.0% passive) in Singapore. Fetal exposure to tobacco smoke (by meconium analysis) was 1.3% (Bulacan), 4.7% (Bangkok) and 13.1% (Singapore); however, a large proportion of infants who tested positive for cotinine (65%) were born to mothers who gave no history of either active or passive exposure to environmental tobacco smoke. Fetal exposure to tobacco smoke is a major health problem.

Chorioamnionitis and ontogeny of circulating prostaglandin and thromboxane in preterm infants.

Our objective was to determine the effect of chorioamnionitis on plasma prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) during the first week in preterm infants. Plasma PGE2 and TxB2 were measured at 1, 3, and 7 days of age in preterm infants (birth weights 501 to 1500 g), with ( N = 26) and without ( N = 22) chorioamnionitis. Infants with maternal chorioamnionitis had significantly lower mean gestational age ( P = 0.0001) and birth weight ( P = 0.03) and a marginally higher rate of bronchopulmonary dysplasia (37% versus 12.5, P = 0.05), a result that may be related to the lower mean gestational age. Plasma PGE2 and TxB2 varied widely, more so on the first day but did not significantly differ between the two groups. TxB2 was lower among infants who died or developed morbidities. Circulating PGE2 and TxB2 concentrations in preterm infants in the first week vary considerably, are relatively unaltered by chorioamnionitis, and are lower in association with mortality and clinical morbidities. Further research on their role in the causation of adverse neonatal outcomes is necessary.

Technique of single-stage repair of coarctation of the aorta with ventricular septal defect.

The results of single-stage and two-stage repair of coarctation of the aorta (CoA) with ventricular septal defect (VSD) have improved, but the optimal treatment strategy remains controversial. This article emphasizes the technical details for performing the single-stage repair of CoA with VSD and compares the results of this technique with the two-stage approach. A retrospective analysis of 46 patients who underwent completed surgical repair of CoA with VSD at Children's Hospital of Michigan, either using the single-stage (N=23) or the two-stage (N=23) techniques, was performed. The postoperative complications, hospital mortality, freedom from cardiac re-interventions, and actuarial survival were the same in both groups. The advantages of single-stage over two-stage repair include an earlier age at completion of repair, fewer operations, and fewer incisions. The one disadvantage of a single-stage repair was the increased need for delayed sternal closure compared with the two-stage approach, but this disadvantage has been neutralized in the recent era.

Single-stage versus 2-stage repair of coarctation of the aorta with ventricular septal defect.

OBJECTIVE: The results of single-stage and 2-stage repair of coarctation of the aorta with ventricular septal defect have improved, but the optimal treatment strategy remains controversial. This study compares our results with these 2 approaches. METHODS: We performed a retrospective analysis of 46 patients, 23 with single-stage repair and 23 with 2-stage repair, who underwent completed surgical treatment of coarctation of the aorta with a ventricular septal defect at the Children's Hospital of Michigan between March 1994 and June 2006. RESULTS: The average number of operations in the single-stage group was 1.5 +/- 0.6, and in the 2-stage group it was 2.2 +/- 0.4 (P < or = .0001). Postoperative complications were similar, except for the number of planned reoperations to perform delayed sternal closure in the single-stage operation (n = 7) compared with the 2-stage operation (n = 1, P = .023). The patient age in the single-stage group at the time of discharge (completed repair time) was a median of 39.0 days (range, 19-250 days) compared with a median of 113.0 days (range, 26-1614 days) in the 2-stage group after stage 2 (P < or = .0001). Freedom from cardiac reintervention was 89.8% in the single-stage group versus 84.9% in the 2-stage group (P = .33). The hospital mortality was 4.4% (1 patient) in each group. The actuarial survival rate was 95.7% in the single-stage group versus 90.6% in the 2-stage group (P = .38). CONCLUSIONS: The advantages of single-stage over 2-stage repair of a ventricular septal defect with coarctation of the aorta include an earlier age at completion of repair, fewer operations, and fewer incisions. Postoperative complications and hospital mortality are similar. The one disadvantage of a single-stage repair was the increased need for delayed sternal closure compared with the 2-stage approach.

Pulmonary synovial sarcoma presenting as a pneumothorax during pregnancy.

BACKGROUND: Synovial sarcoma is a clinically rare, but morphologically well-defined neoplasm, which accounts for approximately 10% of all malignant soft-tissue tumors. The diagnosis can be established with clinical and imaging evaluations together with immunohistochemical, electron microscopy, and molecular genetic studies. CASE: We describe a case of primary pulmonary synovial sarcoma presenting as a pneumothorax in a young woman at 34 weeks of gestation. Her persistent symptomatology ultimately led to a video-assisted thoracoscopy and thorascopic decortication. The diagnosis was established by pathology and immunohistochemistry of the cells, which were consistent with primary pulmonary synovial sarcoma. CONCLUSION: Malignancies, even those as uncommon as primary synovial sarcoma, should be considered in the differential diagnosis of pneumothorax during pregnancy.

Pregnancy outcomes after laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Early reports described adverse perinatal outcomes of pregnancies after weight loss surgery (WLS), which subsequently raised concerns regarding safety. Our objective was to investigate, in a community-based, academic, tertiary care center, the safety of pregnancies after laparoscopic Roux-en-Y gastric bypass (LRYGB) and its potential effect on obesity-related perinatal complications. METHODS: The pregnancy outcomes of patients delivering infants after LRYGB at our institution were compared with those of control subjects (stratified by body mass index) who had not undergone WLS. The charts were retrospectively reviewed for demographics, delivery route, and perinatal complications. RESULTS: A total of 26 patients who delivered after LRYGB and 254 controls were identified. The mean interval from LRYGB to conception was 25.4 +/- 13.0 months. In general, the perinatal complications in the LRYGB patients were similar to those in the nonobese controls and lower than in the obese and severe obese controls, although statistical significance was not noted for all complications. No spontaneous abortions or stillbirths occurred in the LRYGB patients. No LRYGB patients required intravenous nutrition or hydration. The overall incidence of cesarean section in the LRYGB patients was similar to that in the obese and severely obese controls but significantly greater than that in the nonobese controls. The complication rates were similar in pregnancies occurring "early" (<12 mo) versus "late" (>18 mo) after LRYGB. CONCLUSION: The results of our study have shown that pregnancy after LRYGB is safe, with an incidence of perinatal complications similar to that of nonobese patients, and lower than that of obese and severely obese patients, who had not undergone WLS. Larger studies are required to demonstrate statistically significant improvements in outcome in patients treated with WLS.

Improvement in infertility and pregnancy outcomes after weight loss surgery.

The majority of bariatric surgical procedures are performed in young women. There is a concern about safety and outcomes of pregnancies after weight loss surgery. Pregnancy after weight loss surgery is not only safe, but is associated with more favorable outcomes in comparison to obese populations who do not undergo weight loss surgery. An interval of 2 years is recommended from surgery to pregnancy. This delay helps avoid most of the potential nutritional complications. Optimal patient care is achieved in an experienced, multidisciplinary center. Early involvement of the bariatric surgeon in evaluating abdominal pain is critical because the underlying pathology may relate to the previous weight loss surgery. Although infertility is improved after weight loss surgery, reliable modes of contraception may be limited in this population.

Using quantitative methods to improve the diagnostic workup for abdominal pain in children.

INTRODUCTION: The differential diagnosis of abdominal pain in children can be challenging. We applied quantitative decision-making methods to this process and sought to determine if their use provided measurable benefit. METHODS: After obtaining institutional review board approval, we recorded key elements of the history, physical examination, laboratory, and imaging evaluations along with the cost and the time spent in the emergency department (ED) for children presenting with abdominal pain. Initially, data were collected (group 1, n = 1366 patients) and then presented to the ED pediatricians. For subsequent patients, ED physicians received a sheet specific to that patient's age and sex reporting the most common diagnoses and the elements of the evaluation that had proven most useful (group 2, n = 624 patients). We compared the difference in length of stay and costs before and after intervention, between study groups, by age groups, and separately by sex using a 2-factor analysis of variance. RESULTS: The diagnostic workup cost less in boys aged 2 to 12 years after the intervention. In boys and girls older than 12 years, the cost trended lower. DISCUSSION: This study demonstrates that ED physicians equipped with specific information were able to complete their diagnostic evaluation of children presenting with abdominal pain at a lower cost.

Efficacy of intraluminal pulmonary artery banding.

OBJECTIVE: The extraluminal technique of pulmonary artery banding can be difficult to perform precisely in conjunction with cardiopulmonary bypass and is associated with a significant risk of band-related complications. We analyzed our results with an intraluminal technique of pulmonary artery banding in patients who required cardiopulmonary bypass for the performance of associated cardiac repairs. METHODS: The medical records of 18 neonates and infants who underwent intraluminal pulmonary artery banding were retrospectively reviewed. A circular patch with a 3.0-mm, 3.6-mm, or 4.0-mm diameter fenestration was sutured to the inner circumference of the main pulmonary artery. Preoperative, intraoperative, and postoperative variables were reviewed to assess the efficacy and safety of the intraluminal technique. RESULTS: Intraluminal pulmonary artery banding produced a consistent and significant reduction in the systolic pulmonary artery pressure (64.00 +/- 12.24 to 16.53 +/- 6.33 mm Hg, P < .001), the systolic pulmonary artery pressure/systolic systemic pressure ratio (0.91 +/- 0.10 to 0.19 +/- 0.07, P < .001), and the pulmonary flow/systemic flow ratio (4.32 +/- 3.04 to 0.91 +/- 0.49, P = .015). There were no band-related anatomic complications. Two patients did require percutaneous dilation of the intraluminal pulmonary artery band before debanding to palliate systemic arterial desaturation. CONCLUSIONS: Intraluminal pulmonary artery banding is an effective palliative procedure that can be used in patients who require cardiopulmonary bypass for the performance of cardiac repairs in addition to placement of the pulmonary artery band.

GATA1, cytidine deaminase, and the high cure rate of Down syndrome children with acute megakaryocytic leukemia.

Down syndrome children with acute megakaryocytic leukemia (AMkL) have higher cure rates than non-Down syndrome acute myeloid leukemia (AML) patients treated with cytosine arabinoside (ara-C). Megakaryoblasts from Down syndrome AML patients are more sensitive in vitro to ara-C than cells from non-Down syndrome AML patients. Somatic mutations in the GATA1 transcription factor have been detected exclusively and almost uniformly in Down syndrome AMkL patients, suggesting a potential linkage to the chemotherapy sensitivity of Down syndrome megakaryoblasts. Stable transfection of wild-type GATA1 cDNA into the Down syndrome AMkL cell line CMK resulted in decreased (8- to 17-fold) ara-C sensitivity and a threefold-lower generation of the active ara-C metabolite ara-CTP compared with that for mock-transfected CMK cells. High intracellular levels of uridine arabinoside (ara-U) (an inactive ara-C catabolite generated by cytidine deaminase) and cytidine deaminase transcripts were detected in GATA1-transfected CMK sublines, whereas no ara-U was detected in mock-transfected cells. Cytidine deaminase transcripts were a median 5.1-fold (P = .002) lower in Down syndrome megakaryoblasts (n = 16) than in blast cells from non-Down syndrome patients (n = 56). These results suggest that GATA1 transcriptionally upregulates cytidine deaminase and that the presence or absence of GATA1 mutations in AML blasts likely confers differences in ara-C sensitivities due to effects on cytidine deaminase gene expression, which, in turn, contributes to the high cure rate of Down syndrome AMkL patients.

Abrupt aortic root dilation after the Ross procedure--is this a progressive phenomenon?

This study provides evidence of aortic root dilation in children, adolescents, and young adults who have undergone the Ross procedure. Several mechanisms are described.

Femoral artery pseudoaneurysms: risk factors, prevalence, and treatment options.

Femoral artery pseudoaneurysms (PSA or false aneurysm) develop in about 1% of patients undergoing procedures that require femoral artery cannulation. PSA prolong hospitalization, consuming health-care resources, and result in significant morbidity. We designed a study to review the prevalence, risk factors, and treatment of PSA. We performed a retrospective, case-controlled study of patients diagnosed with PSA at a large, urban, tertiary-care teaching hospital. We reviewed 48 patients with PSA for our study. The estimated prevalence of PSA was 0.28%, with identical rates found for procedures done in the interventional radiology department and in the cardiac catheterization suite. Logistic regression identified three independent risk factors for developing PSA: being female (odds ratio 2.62), having an intervention performed (odds ratio 3.22), and not having a closure device used (odds ratio 10.2). Patients with PSA had longer hospital length of stay than that of patients without PSA. We found no statistically significant difference in failure or complication rates for the four treatment options and that spontaneous resolution of PSA does not correlate with its size. Thrombin injection and observation are effective, low-complication treatment options.

Fetal human hematopoietic stem cells can differentiate sequentially into neural stem cells and then astrocytes in vitro.

In some rodent models, there is evidence that hematopoietic stem cells (HSC) can differentiate into neural cells. However, it is not known whether humans share this potential, and, if so, what conditions are sufficient for this transdifferentiation to occur. We addressed this question by assessing the ability of fetal human liver CD34(+)/CD133(+)/CD3(-) hematopoietic stem cells to generate neural cells and astrocytes in culture. We cultured fetal liver-derived hematopoietic stem cells in human astrocyte culture-conditioned medium or using a method wherein growing human astrocytes were separated from cultured, nonadherent hematopoietic stem cells by a semipermeable membrane in a double-chamber co-culture system. Hematopoietic stem cell cultures were probed for neural progenitor cell marker expression (nestin and bone morphogenic protein-2 [BMP-2]) during growth in both culture conditions. RT-PCR, western blotting, and immunocytochemistry assays showed that cells cultured in either condition expressed nestin mRNA and protein and BMP-2 mRNA. HSC similarly cultured in nonconditioned medium or in the absence of astrocytes did not express either marker. Cells expressing these neural markers were transferred and cultured on poly-D-lysine-coated dishes with nonconditioned growth medium for further study. Immunocytochemistry demonstrated that these cells differentiated into astrocytes after 8 days in culture as indicated by their morphology and expression of the astrocytic markers glial fibrillary acidic protein (GFAP) and S100, as well as by their rate of proliferation, which was identical to that of freshly isolated fetal brain astrocytes. These findings demonstrate that neural precursor gene expression can be induced when human hematopoietic stem cells are exposed to a suitable microenvironment. Furthermore, the neural stem cells generated in this environment can then differentiate into astrocytes. Therefore, human hematopoietic stem cells may be an alternative resource for generation of neural stem cells for therapy of central nervous system defects resulting from disease or trauma.