Tetralogy of Fallot with right pulmonary artery origin from the ascending aorta: noninvasive diagnosis and surgical correction in a 7-week-old infant

Anomalous origin of one pulmonary artery from the ascending aorta is a rare anomaly which is almost always associated with hypertension in the contralateral pulmonary artery originating from the right ventricle. We report echocardiographic evaluation of an infant with tetralogy of Fallot and aortic origin of the right pulmonary artery. Since all relevant information regarding anatomy and hemodynamics could be obtained by echocardiography, cardiac catheterization and angiography were unnecessary. Surgical correction including transatrial patch closure of the ventricular septal defect, resection of the infundibular stenosis and direct reimplantation of the right pulmonary artery was performed successfully at the age of 7 weeks. The postoperative course was uneventful and persistent pulmonary hypertension was excluded by echocardiography. Our case shows that complete echocardiographic evaluation is possible in infants with this complex cardiac malformation. We recommend reserving cardiac catheterization for those patients with echocardiographic evidence of significant elevation of pulmonary vascular resistance. In order to avoid irreversible pulmonary vascular changes early surgical correction within the first 3 months of life should be performed in all children with aortic origin of a pulmonary artery including those with associated tetralogy of Fallot.     

Prenatal Polybrominated Diphenyl Ether Exposures and Neurodevelopment in U.S. Children through 5 Years of Age: The HOME Study

Background: Polybrominated diphenyl ethers (PBDEs) are persistent chemicals that have been widely used as flame retardants in furniture, carpet padding, car seats, and other consumer products during the past three decades.Objective: We examined whether in utero exposure to PBDEs is associated with child cognitive function and behavior in a U.S. study sample.Methods: In a prospective birth cohort, we measured maternal serum concentrations of BDE-47 and other PBDE congeners in 309 women at 16 weeks of gestation during 2003–2006 and followed their children in Cincinnati, Ohio. We measured cognitive and motor abilities using the Bayley Scales of Infant Development-II at ages 1, 2, and 3 years; intelligence using the Wechsler Preschool and Primary Scale of Intelligence-III at age 5 years; and children’s behaviors using the Behavioral Assessment System for Children-2 annually at ages 2–5 years. We used linear mixed models or generalized estimating equations with adjustment for potential confounders to estimate associations between these outcomes and log₁₀-transformed PBDE concentrations.Results: The geometric mean of BDE-47 in maternal serum (20.1 ng/g lipid) was comparable with U.S. adult national reference values. Prenatal BDE-47 was not significantly associated with Bayley Mental or Psychomotor Development Indices at 1–3 years, but a 10-fold increase in prenatal BDE-47 was associated with a 4.5-point decrease (95% CI: –8.8, –0.1) in Full-Scale IQ and a 3.3-point increase (95% CI: 0.3, 6.3) in the hyperactivity score at age 5 years.Conclusions: Prenatal exposure to PBDEs was associated with lower IQ and higher hyperactivity scores in children.Citation: Chen A, Yolton K, Rauch SA, Webster GM, Hornung R, Sjödin A, Dietrich KN, Lanphear BP. 2014. Prenatal polybrominated diphenyl ether exposures and neurodevelopment in U.S. children through 5 years of age: the HOME study. Environ Health Perspect 122:856–862; http://dx.doi.org/10.1289/ehp.1307562     

Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome

To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. Conclusion: In patients with short stature—especially when clinical features are accompanied by vascular complications—MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.     

An fMRI investigation of working memory and sadness in females with bipolar disorder: a brief report

Objective: Functional magnetic resonance imaging (fMRI) studies have documented abnormalities in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex in bipolar disorder in the context of working memory tasks. It is increasingly recognized that DLPFC regions play a role in mood regulation and the integration of emotion and cognition. The purpose of the present study was to investigate with fMRI the interaction between acute sadness and working memory functioning in individuals with bipolar disorder. Methods: Nine depressed individuals with DSM‐IV bipolar I disorder (BP‐I) and 17 healthy control participants matched for age, gender, education, and IQ completed a 2‐back working memory paradigm under no mood induction, neutral state, or acute sadness conditions while undergoing fMRI scanning. Functional MRI data were analyzed with SPM2 using a random‐effects model. Results: Behaviorally, BP‐I subjects performed equally well as control participants on the 2‐back working memory paradigm. Compared to control participants, individuals with BP‐I were characterized by more sadness‐specific activation increases in the left DLPFC (BA 9/46) and left dorsal anterior cingulate (dACC). Conclusions: Our study documents sadness‐specific abnormalities in the left DLPFC and dACC in bipolar disorder that suggest difficulties in the integration of emotion (sadness) and cognition. These preliminary findings require further corroboration with larger sample sizes of medication‐free subjects.     

Type I interferons have opposing effects during the emergence and recovery phases of colitis

The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN‐Is) protect from IBD. In contrast, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN‐Is. Here, we present data suggesting that IFN‐Is play dual roles as regulators of intestinal inflammation in dextran sodium sulfate (DSS)‐treated C57BL/6 mice. Though IFN‐Is reduced acute intestinal damage and the abundance of colitis‐associated intestinal bacteria caused by treatment with a high dose of DSS, they also inhibited the resolution of inflammation after DSS treatment. IFN‐Is played an anti‐inflammatory role by suppressing the release of IL‐1β from the colon MHC class II⁺ cells. Consistently, IL‐1 receptor blockade reduced the severity of inflammation in IFN‐I receptor‐deficient mice and myeloid cell‐restricted ablation of the IFN‐I receptor was detrimental. The proinflammatory role of IFN‐Is during recovery from DSS treatment was caused by IFN‐I‐dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Thus, IFN‐Is play opposing roles in specific phases of intestinal injury and inflammation, which may be important for guiding treatment strategies in patients.     

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.     

Targeted Sequencing of a Pediatric Metabolic Bone Gene Panel Using a Desktop Semiconductor Next-Generation Sequencer

Metabolic bone disorders in children frequently are heritable, but the expanding number of genes associated with these conditions makes it difficult to perform molecular diagnosis. In the present study, we therefore evaluated a semiconductor (SC)-based sequencing system for this purpose. A total of 65 DNA samples were analyzed comprising 24 samples from patients with 27 known pathogenic mutations, 6 samples from patients with prior negative Sanger sequencing, and 35 consecutive samples from patients with suspected heritable metabolic bone disorders who had not had prior molecular diagnosis. In the samples with known pathogenic mutations, 26 of 27 mutations were identified by SC sequencing. All single nucleotide variants were correctly identified, but a 7-nucleotide duplication in CYP27B1 was not detected. SC sequencing revealed two pathogenic mutations in the six samples where prior Sanger sequencing had failed to identify a mutation. Finally, pathogenic mutations were found in 27 samples of patients with unknown mutation status (15 in COL1A1, 9 in COL1A2, 1 in LEPRE1, 1 in LRP5, 1 in PHEX). Subsequent Sanger sequencing confirmed the mutations in all 27 samples. In conclusion, we found that SC sequencing is suitable for the diagnosis of heritable metabolic bone disorders in children.     

What makes a biostatistician?

Biostatisticians play an important role in medical research. They are co-responsible for an appropriate and efficient study design, they are involved in monitoring the study conduct, they plan and perform the data analysis, and they are involved in interpreting and publishing the results. However, how are the biostatisticians prepared for their tasks and responsibilities? Graduate programs in biostatistics are being offered, but some practicing biostatisticians completed their studies in a mathematical or epidemiological program, or obtained their degree in subject-specific fields (such as medicine or biology). Therefore, the expertise and the competencies can vary widely between the individual biostatisticians, also depending on the application field. In this article, focusing on European and US practices, we discuss the required professional expertise for the main areas of applications in the medical field as well as the necessary soft skill competencies of a biostatistician.