Peripheral blood marker of residual acute leukemia after hematopoietic cell transplantation using multi-plex digital droplet PCR.

Background: Relapse remains the primary cause of death after hematopoietic cell transplantation (HCT) for acute leukemia. The ability to identify minimal/measurable residual disease (MRD) via the blood could identify patients earlier when immunologic interventions may be more successful. We evaluated a new test that could quantify blood tumor mRNA as leukemia MRD surveillance using droplet digital PCR (ddPCR). Methods: The multiplex ddPCR assay was developed using tumor cell lines positive for the tumor associated antigens (TAA: WT1, PRAME, BIRC5), with homeostatic ABL1. On IRB-approved protocols, RNA was isolated from mononuclear cells from acute leukemia patients after HCT (n = 31 subjects; n = 91 specimens) and healthy donors (n = 20). ddPCR simultaneously quantitated mRNA expression of WT1, PRAME, BIRC5, and ABL1 and the TAA/ABL1 blood ratio was measured in patients with and without active leukemia after HCT. Results: Tumor cell lines confirmed quantitation of TAAs. In patients with active acute leukemia after HCT (MRD+ or relapse; n=19), the blood levels of WT1/ABL1, PRAME/ABL1, and BIRC5/ABL1 exceeded healthy donors (p<0.0001, p=0.0286, and p=0.0064 respectively). Active disease status was associated with TAA positivity (1+ TAA vs 0 TAA) with an odds ratio=10.67, (p=0.0070, 95% confidence interval 1.91 - 59.62). The area under the curve is 0.7544. Changes in ddPCR correlated with disease response captured on standard of care tests, accurately denoting positive or negative disease burden in 15/16 (95%). Of patients with MRD+ or relapsed leukemia after HCT, 84% were positive for at least one TAA/ABL1 in the peripheral blood. In summary, we have developed a new method for blood MRD monitoring of leukemia after HCT and present preliminary data that the TAA/ABL1 ratio may may serve as a novel surrogate biomarker for relapse of acute leukemia after HCT.

Neuroimaging Wisely.

Diagnostic imaging is the most rapidly growing physician service in the Medicare and privately insured population. The growing share of medical costs devoted to imaging procedures has led to increasing concerns among the key federal agencies and private payers. In an attempt to educate health care providers, patients, and families on the importance of making optimal clinical decisions, the American Board of Internal Medicine Foundation organized the Choosing Wisely initiative with strong collaboration from specialty societies representing nearly all medical disciplines. Among 45 tests and treatments listed on the Choosing Wisely Web site, 24 are directly related to imaging. Eleven of the 24 are associated with neuroimaging. The listing of imaging tests in the Choosing Wisely program by multiple medical societies other than the radiology societies acknowledges that appropriate use of medical imaging is a shared responsibility between radiologists and referring physicians. In this article, we highlight why radiologists are uniquely positioned to support the appropriate use of imaging. We review some of the strategies that radiologists can use to help their referring physicians with appropriate ordering of neuroimaging in real-world practice and address some the challenges and pitfalls in implementing patient-centered imaging decision-making and shifting to a value-based focus in radiology.

CT and MRI of pulmonary valvular abnormalities.

Pulmonary valve disease constitutes a wide spectrum of conditions. Traditionally, echocardiography has been the technique of choice for the evaluation of pulmonary and other valvular disease. However, with advances in technology, computed tomography (CT) and magnetic resonance imaging (MRI) are playing increasingly important roles in the evaluation of these disorders. In this article, we review the normal appearance of the pulmonary valve and then illustrate various variants and pathological entities of the pulmonary valve.

Molecular characterization of Pegarn: a Drosophila homolog of UNC-51 kinase.

We have isolated and characterized the gene encoding a Drosophila melanogaster homolog of Caenorhabditis elegans UNC-51 (uncoordinated movement-51): Pegarn. Developmental Northern blot shows the Pegarn gene is expressed at all stages of development. The protein is detected throughout the Drosophila third instar larval central nervous system (CNS) in axons projecting out from the ventral ganglion and in the optic anlagen of the optic lobe. Heterozygous Pegarn mutant embryos show defects in larval axonal neuronal patterning, but survive to adulthood. Homozygous mutants have an even more deformed pattern of neuronal development and do not survive through the larval stages. The data from this research suggest the critical roles of Pegarn in CNS and PNS axonal formation in Drosophila melanogaster and indicates its similar role in other multicellular species.

A comprehensive cognitive-behavioral/educational program for schizophrenic patients.

Modern treatment of schizophrenia emphasizes pharmacology and nonspecific rehabilitative strategies, but there is renewed interest in psychologically oriented treatments as well. Borrowing from dynamic, cognitive-behavioral, and psychoeducational traditions, the authors describe a program aimed at teaching patients with schizophrenia about their illness and at addressing key cognitive, social, and emotional areas of difficulty from which they generally suffer. The authors document the enthusiasm of the patients for such an approach and provide a case example.

Pleurectomy through the triangle of auscultation for treatment of recurrent pneumothorax in younger patients. Evaluation of 60 consecutive cases.

Sixty patients, aged 14 to 35 years, with recurrent pneumothorax were treated with pleurectomy through the triangle of auscultation, with no chest wall muscle transection. The advantages of this approach over a full thoracotomy are that with no muscle transection, a shorter postoperative recovery is expected and, subsequently, early return to normal activity is achieved. The scar may also be more cosmetically acceptable. There was no postoperative mortality, and only one patient required reoperation because of bleeding. The technique is simple, and exposure is adequate. If necessary, this limited thoracotomy can be converted to a full thoracotomy with no difficulty.

Which neurotransmitters modulate corneal sensitivity?

Corneal sensitivity was assessed before and after applying atropine (0.5, 0.05, 0.005% w/v), pilocarpine (1.0, 0.1%), eserine (0.1, 0.01%) and potassium chloride (171mM). Atropine (0.5 - 0.005%) significantly depressed corneal sensitivity; parasympathomimetics, taken together, significantly increased sensitivity. Exposure to potassium chloride for 2 min had no effect on sensitivity, nor did it affect corneal sensation. These results are consistent with the hypothesis that epithelial acetylcholine is a neurotransmitter to the corneal nerves. We conclude, however, that the nerves may have only weak muscarinic properties.

Corneal sensitivity in myasthenia gravis.

Corneal touch thresholds were measured in 11 people suffering from myasthenia gravis (MG) and in a control group of 20 subjects. The mean threshold in MG was 75.6 mg (SD 52) and in the control group 18.9 mg (SD 7.3); thresholds were thus significantly (p less than 0.01) raised in MG. Although it is not possible to say whether the sensory deficit is due to MG or to the treatment, the results implicate acetylcholine in sensory transduction in the cornea.

Marfanoid hypermobility syndrome associated with coarctation of the aorta.

There are intimate interrelations between various elements of connective tissue, viz. collagen, elastin, and glycoproteins. It is not unexpected that Marfan and Ehlers-Danlos syndromes share common features. The condition is labelled as Marfanoid hypermobility syndrome. In the patient described here, the Marfanoid hypermobility syndrome was associated with coarctation of the aorta which was corrected surgically.