Donald N. Di Salvo

Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

Cerebral Hemodynamic Changes During Intensive Care of Preterm Infants

OBJECTIVES. The objectives of this study were to examine the circulatory changes experienced by the immature systemic and cerebral circulations during routine events in the critical care of preterm infants and to identify clinical factors that are associated with greater hemodynamic-oxygenation changes during these events. METHODS. We studied 82 infants who weighed <1500 g at birth and required intensive care management and continuous blood pressure monitoring from an umbilical arterial catheter. Continuous recording of cerebral and systemic hemodynamic and oxygenation changes was performed. We studied 6 distinct types of caregiving events during 10-minute epochs: (1) quiet baseline periods; (2) minor manipulation; (3) diaper changes; (4) endotracheal tube suctioning; (5) endotracheal tube repositioning; and (6) complex events. Each event was matched with a preceding baseline. We examined the effect of specific clinical factors and cranial ultrasound abnormalities on the systemic and cerebral hemodynamic oxygenation changes that were associated with the various event types. RESULTS. There were highly significant differences in hemodynamics and oxygenation between events overall and baseline epochs. The magnitude of these circulatory changes was greatest during endotracheal tube repositioning and complex caregiving events. Lower gestational age, higher illness severity, chorioamnionitis, low Apgar scores, and need for pressor-inotropes all were associated with circulatory changes of significantly lower magnitude. Cerebral hemodynamic changes were associated with early parenchymal ultrasound abnormalities. CONCLUSIONS. Routine caregiving procedures in critically ill preterm infants are associated with major circulatory fluctuations that are clinically underappreciated and underdetected by current bedside monitoring. Our data underscore the importance of continuous cerebral hemodynamic monitoring in critically ill preterm infants.

National Ultrasound Curriculum for Medical Students

Abstract Ultrasound (US) is an extremely useful diagnostic imaging modality because of its real-time capability, noninvasiveness, portability, and relatively low cost. It carries none of the potential risks of ionizing radiation exposure or intravenous contrast administration. For these reasons, numerous medical specialties now rely on US not only for diagnosis and guidance for procedures, but also as an extension of the physical examination. In addition, many medical school educators recognize the usefulness of this technique as an aid to teaching anatomy, physiology, pathology, and physical diagnosis. Radiologists are especially interested in teaching medical students the appropriate use of US in clinical practice. Educators who recognize the power of this tool have sought to incorporate it into the medical school curriculum. The basic question that educators should ask themselves is: “What should a student graduating from medical school know about US?” To aid them in answering this question, US specialists from the Society of Radiologists in Ultrasound and the Alliance of Medical School Educators in Radiology have collaborated in the design of a US curriculum for medical students. The implementation of such a curriculum will vary from institution to institution, depending on the resources of the medical school and space in the overall curriculum. Two different examples of how US can be incorporated vertically or horizontally into a curriculum are described, along with an explanation as to how this curriculum satisfies the Accreditation Council for Graduate Medical Education competencies, modified for the education of our future physicians.

Topography of cerebral white-matter disease of prematurity studied prospectively in 1607 very-low-birthweight infants.

The objective of this study was to evaluate to what extent (1) the characteristics of localization, distribution, and size of echodense and echolucent abnormalities enable individuals to be designated as having either periventricular hemorrhagic infarction or periventricular leukomalacia and (2) the characteristics of periventricular hemorrhagic infarction and periventricular leukomalacia are independent occurrences. The population for this study consisted of 1607 infants with birthweights of 500 to 1500 g, born between January 1991 and December 1993, who had at least one cranial ultrasound scan read independently by at least two ultrasonographers. The ultrasound data collection form diagrammed six standard coronal views. The cerebrum was divided into 17 zones in each hemisphere. All abnormalities were described as being echodense or echolucent and were classified on the basis of their size, laterality, location, and evolution. Eight percent (134/1607) of infants had at least one white-matter abnormality. The prevalence of white-matter disease decreased with increasing gestational age. Most abnormalities were small or medium sized and unilateral; only large echodensities tended to be bilateral and asymmetric. Large abnormalities, whether echodense or echolucent, were more likely than smaller abnormalities to be widespread, and the extent of cerebral involvement was independent of whether abnormalities were unilateral or bilateral. Large abnormalities were relatively more likely than small abnormalities to involve anterior planes. Small abnormalities, whether echodense or echolucent, or whether unilateral or bilateral, preferentially occurred near the trigone. Using the characteristics of location, size, and laterality/symmetry, we were able to allocate only 53% of infants with white-matter abnormalities to periventricular hemorrhagic infarction or periventricular leukomalacia. Assuming that periventricular leukomalacia and periventricular hemorrhagic infarction are independent and do not share risk factors, and that each occurs in approximately 5% of infants, we would have expected 0.25%, or about 4 individuals, to have abnormalities with characteristics of both periventricular leukomalacia and periventricular hemorrhagic infarction, whereas we found 63 such infants. Most infants with white-matter disease could not be clearly designated as having periventricular hemorrhagic infarction or periventricular leukomalacia only. Periventricular hemorrhagic infarction contributes to the risk of periventricular leukomalacia occurrence, or the two sorts of abnormalities share common risk antecedent factors. The descriptive term echodense or echolucent and the generic term white-matter disease of prematurity should be used instead of periventricular leukomalacia or periventricular hemorrhagic infarction when referring to sonographically defined white-matter abnormalities. (J Child Neurol 2001;16:401-408).

Sonographic Imaging of Maternal Complications of Pregnancy

Objective. To show the role of diagnostic sonography in delineating pathologic conditions occurring during and immediately after pregnancy. Methods. Cases illustrative of a broad range of pathologic conditions were collected primarily from personal experience in a busy ultrasound clinic serving high‐ and low‐risk pregnancies over the past 15 years, with supplemental cases drawn from departmental teaching files. Sonography was the primary diagnostic tool, with confirmation obtained from other imaging modalities in select instances. Results. Cases were organized on an anatomic and time‐of‐onset basis. For conditions occurring during pregnancy, the following anatomic areas are considered: the liver and biliary tree, urinary tract, bowel, ovary, and uterus and placenta. For postpartum complications, the following conditions are discussed: subfascial and bladder flap hematomas, retained products of conception, and ovarian vein thrombophlebitis. Although the main imaging modality in these conditions was sonography, correlation with computed tomography and magnetic resonance imaging was also made in several cases. Conclusions. A broad variety of conditions can affect the pregnant patient, both during and immediately after pregnancy. Sonography can show many of these disease processes, with computed tomography and magnetic resonance imaging useful selectively as supplementary tools.

Sonographic and Doppler characteristics of the corpus luteum: can they predict pregnancy outcome?

To determine whether there is a relationship between gray scale or Doppler characteristics of the corpus luteum and first‐trimester pregnancy outcome.

Imaging presentation of venous thrombosis in patients with cancer.

OBJECTIVE The purpose of this article is to review the imaging of venous thrombosis in patients with cancer. CONCLUSION Multiple imaging techniques have the capacity to display thrombosis accurately. The optimal choice is dictated by the location and duration of symptoms and by the availability of imaging techniques. Peripheral and superficial thrombi are best managed with ultrasound, whereas central thrombi require CT or MRI. If CT and MRI are contraindicated, flow studies are appropriate. FDG PET/CT appropriately shows venous thrombosis and might play a prominent role in the future.

Lithium Nephropathy Unique Sonographic Findings

This case series describes a unique sonographic appearance consisting of numerous microcysts and punctate echogenic foci seen on renal sonograms of 10 adult patients receiving chronic lithium therapy. Clinically, chronic renal insufficiency was present in 6 and nephrogenic diabetes insipidus in 2. Sonography showed numerous microcysts and punctate echogenic foci. Computed tomography in 5 patients confirmed microcysts and microcalcifications, which were fewer in number than on sonography. Magnetic resonance imaging in 2 patients confirmed microcysts in each case. Renal biopsy in 1 patient showed chronic interstitial nephritis, microcysts, and tubular dilatation. The diagnosis of lithium nephropathy should be considered when sonography shows these findings.

Redesign and Implementation of the Radiology Clerkship: From Traditional to Longitudinal and Integrative

PURPOSE The authors discuss the evolution and application of 3 radiology teaching methods-a fundamentals-of-imaging course, a combined clinical-radiology case conference, and a radiology objective structured clinical examination-to medical education at the Brigham and Womens Hospital site of Harvard Medical School. METHODS The evolution of the medical student radiology teaching program from content needs assessment to blueprint creation, through implementation, is outlined. RESULTS The 3 components of the teaching program are described. The changes in format in response to feedback and challenges faced in deploying this new curriculum are detailed. Results from student surveys and the radiology objective structured clinical examination scores from recent years are also presented. CONCLUSIONS As radiology assumes an increasingly central role in patient care and diagnosis, the need for effective integration of radiology teaching into medical education becomes more critical. The concepts presented here have been deemed to be successful by students and faculty members and may be applicable to other institutions.

Sonographic Features of Pectoralis Muscle Necrosis Secondary to Gemcitabine-Induced Radiation Recall Case Report and Review of Current Literature

Radiation recall is defined as an inflammatory reaction within a previously treated radiation field during chemotherapy treatment. 1 Gemcitabine is one of the most common cytotoxic agents implicated in the development of this condition, and for the most part it manifests clinically as a skin reaction (radiation recall dermatitis [RRD]). 2 Radiation recall can however manifest in other tissues such as the central nervous system and the gastrointestinal tract, 3 and rare cases of gemcitabine-induced radiation recall muscle necrosis have been described. 4-7 We present a case of bilateral pectoralis muscle necrosis secondary to radiation recall in a patient treated with gemcitabine in which sonography and computed tomography (CT) provided substantial clinical assistance.