Reed E Pyeritz

University of Pennsylvania, Philadelphia, Pennsylvania, United States

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Publications (161)1557.61 Total impact

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    ABSTRACT: -ACTA2 mutations are the major cause of familial thoracic aortic aneurysms and dissections. We sought to characterize these aortic diseases in a large case series of individuals with ACTA2 mutations. -Aortic disease, management, and outcome associated with the first aortic event (aortic dissection or aneurysm repair) were abstracted from the medical records of 277 individuals with 41 various ACTA2 mutations. Aortic events occurred in 48% of these individuals, with the vast majority presenting with thoracic aortic dissections (88%) associated with 25% mortality. Type A dissections were more common than type B dissections (54% versus 21%), but the median age of onset of type B dissections was significantly younger than type A dissections (27 years, IQR 18-41 versus 36 years, IQR 26-45). Only 12% of aortic events were repair of ascending aortic aneurysms, which variably involved the aortic root, ascending aorta and aortic arch. Overall cumulative risk of an aortic event at age 85 years was 0.76 (95% CI 0.64, 0.86). After adjustment for intra-familial correlation, gender and race, mutations disrupting p.R179 and p.R258 were associated with significantly increased risk for aortic events, whereas p.R185Q and p.R118Q mutations showed significantly lower risk of aortic events compared to other mutations. -ACTA2 mutations are associated with high risk of presentation with an acute aortic dissection. The lifetime risk for an aortic event is only 76%, suggesting that additional environmental or genetic factors play a role in expression of aortic disease in individuals with ACTA2 mutations.
    Circulation Cardiovascular Genetics 03/2015; DOI:10.1161/CIRCGENETICS.114.000943 · 5.34 Impact Factor
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    ABSTRACT: Background Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. Methods We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. Results From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change (±SE) in the aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the degree of aortic-root dilatation relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. Conclusions Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; number, NCT00429364 .).
    New England Journal of Medicine 11/2014; DOI:10.1056/NEJMoa1404731 · 54.42 Impact Factor
  • Reed E. Pyeritz
    Journal of Pediatrics 09/2014; 165(5). DOI:10.1016/j.jpeds.2014.08.002 · 3.74 Impact Factor
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    ABSTRACT: BACKGROUND: Acute aortic dissection associated with cocaine use is rare and has been reported predominantly as single cases or in small patient cohorts. METHODS: Our study analyzed 3584 patients enrolled in the International Registry of Acute Aortic Dissection from 1996 to 2012. We divided the population on the basis of documented cocaine use (C+) versus noncocaine use (C-) and further stratified the cohorts into type A (33 C+/2332, 1.4%) and type B (30 C+/1252, 2.4%) dissection. RESULTS: C+ patients presented at a younger age and were more likely to be male and black. Type B dissections were more common among C+ patients than in C-patients. Cocaine-related acute aortic dissection was reported more often at US sites than at European sites (86.4%, 51/63 vs 13.6%, 8/63; P < .001). Tobacco use was more prevalent in the C+ cohort. No differences were seen in history of hypertension, known atherosclerosis, or time from symptom onset to presentation. Type B C+ patients were more likely to be hypertensive at presentation. C+ patients had significantly smaller ascending aortic diameters at presentation. Acute renal failure was more common in type A C+ patients; however, mortality was significantly lower in type A C+ patients. CONCLUSIONS: Cocaine use is implicated in 1.8% of patients with acute aortic dissection. The typical patient is relatively young and has the additional risk factors of hypertension and tobacco use. In-hospital mortality for those with cocaine-related type A dissection is lower than for those with noncocaine-related dissection, likely due to the younger age at presentation.
    The American Journal of Medicine 05/2014; 127(9). DOI:10.1016/j.amjmed.2014.05.005 · 5.30 Impact Factor
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    ABSTRACT: Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.
    Journal of Clinical Investigation 02/2014; DOI:10.1172/JCI71059 · 13.77 Impact Factor
  • Urologic Oncology 02/2014; 32(2):198-201. DOI:10.1016/j.urolonc.2013.09.016 · 3.36 Impact Factor
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    ABSTRACT: Little is known about the relation between type A acute aortic dissection (TAAAD) and pulse pressure (PP), defined as the difference between systolic and diastolic blood pressure. In this study, we explored the association between PP and presentation, complications, and outcomes of patients with TAAAD. PP at hospital presentation was used to divide 1,960 patients with noniatrogenic TAAAD into quartiles: narrowed (≤39 mm Hg, n = 430), normal (40 to 56 mm Hg, n = 554), mildly elevated (57 to 75 mm Hg, n = 490), and markedly elevated (≥76 mm Hg, n = 486). Variables relating to index presentation and in-hospital outcomes were analyzed. Patients with TAAAD in the narrowed PP quartiles were frequently older and Caucasian, whereas patients with markedly elevated PPs tended to be male and have a history of hypertension. Patients who demonstrated abdominal vessel involvement more commonly demonstrated elevated PPs, whereas patients with narrowed PPs were more likely to have periaortic hematoma and/or pericardial effusion. Narrowed PPs were also correlated with greater incidences of hypotension, cardiac tamponade, and mortality. Patients with TAAAD who were managed with endovascular and hybrid procedures and those with renal failure tended to have markedly elevated PPs. No difference in aortic regurgitation at presentation was noted among groups. In conclusion, patients with TAAAD in the third PP quartile had better in-hospital outcomes than patients in the lowest quartile. Patients with narrowed PPs experienced more cardiac complications, particularly cardiac tamponade, whereas those with markedly elevated PPs were more likely to have abdominal aortic involvement. Presenting PP offers a clue to different manifestations of acute aortic dissection that may facilitate initial triage and care.
    The American journal of cardiology 01/2014; DOI:10.1016/j.amjcard.2013.12.037 · 3.58 Impact Factor
  • Reed E Pyeritz
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    ABSTRACT: Disease of the wall of the thoracic aorta has many causes: inflammation, infection and atherosclerosis are the most common 'acquired' causes, but even these have genetic predispositions. This article deals with aortic disease due to mutations in specific genes. The conditions can affect tissues and organs other than the aorta (syndromic) or be limited to the aorta (nonsyndromic). A classification scheme based on the gene is emerging, those that affect primarily the extracellular matrix (e.g., FBN1, COL3A1), TGF-β signaling (e.g., TGFBR1, TGFB2), or vascular smooth muscle cell contractility (e.g., ACTA2, MYH11). Understanding pathogenesis is driving the development of novel therapies, such as angiotensin receptor blockade, which is in clinical trial. However, recurrent imaging, restriction of exercise, β-adrenergic blockade, and prophylactic surgery remain effective in preventing dissection and sudden death.
    Current opinion in cardiology 11/2013; DOI:10.1097/HCO.0000000000000023 · 2.59 Impact Factor
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    ABSTRACT: To examine community pharmacists' attitudes towards pharmacogenetic (PGx) testing, including their views of the clinical utility of PGx and the ethical, social, legal and practical implications of PGx testing. A web-based survey administered to 5600 licensed community pharmacists in the states of Ohio and Pennsylvania (USA). Of 580 respondents, 78% had a Bachelor of Science degree in pharmacy and 58% worked in a chain drug store. Doctors of pharmacy-trained pharmacists had a significantly higher knowledge score than those with a Bachelor of Science in pharmacy (3.2 ± 0.9 vs 2.6 ± 0.6; p < 0.0001). All pharmacists had positive attitudes towards PGx and most (87%) felt it would decrease the number of adverse events, and optimize drug dosing. More than half (57%) of pharmacists felt that it was their role to counsel patients regarding PGx information. Many (65%) were concerned that PGx test results may be used to deny health insurance. Regardless of the type of education, all pharmacists had positive attitudes towards PGx. There is still a concern among pharmacists that PGx test results may be used to deny health insurance and, thus, there is a need to educate pharmacists about legal protections prohibiting certain forms of unfair discrimination based on genotype.
    Personalized Medicine 11/2013; 10(8). DOI:10.2217/pme.13.85 · 1.13 Impact Factor
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    ABSTRACT: The utilization of genome-wide chromosomal microarray analysis (CMA) in pediatric clinical practice provides an opportunity to consider how genetic diagnostics is evolving, and to prepare for the clinical integration of genome-wide sequencing technologies. We conducted semi-structured interviews with 15 healthcare providers (7 genetic counselors, 4 medical geneticists, and 4 non-genetics providers) to investigate the impact of CMA on clinical practice, and implications for providers, patients and families. Interviews were analyzed qualitatively using content analysis. Most providers reported that genomic testing enhanced their professional experience and was beneficial to patients, primarily due to the improved diagnostic rate compared with earlier chromosomal studies. Other effects on practice included moving towards genotype-first diagnosis and broadening indications for chromosomal testing. Opinions varied concerning informed consent and disclosure of results. The duty to disclose incidental findings (IFs) was noted; however concerns were raised about potential psychosocial harms of disclosing pre-symptomatic findings. Tensions were revealed between the need for comprehensive informed consent for all families and the challenges of communicating time-consuming and potentially anxiety-provoking information regarding uncertain and incidental findings that may be relevant only in rare cases. Genetic counselors can play an important role in liaising with families, health professionals and testing laboratories, providing education and guidance to non-genetics providers, and enabling families to receive adequate pre-and post-test information and follow-up care.
    Journal of Genetic Counseling 09/2013; 23(4). DOI:10.1007/s10897-013-9653-8 · 1.75 Impact Factor
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    ABSTRACT: Few data exist on race-related differences in acute aortic dissection patients. We evaluated black (n = 189, 14%) or white (n = 1165, 86%) patients (mean age 62.8 ± 15.3 years; 36.4% women) enrolled in 13 US centers participating in the International Registry of Acute Aortic Dissection. We excluded patients of other racial descent. Type B acute aortic dissection was more frequent in the black cohort (52.4% vs 39.3%, P = .001). Black patients were younger (mean age 54.6 ± 12.8 years vs 64.2 ± 15.2 years, P <.001) and more likely to have a history of cocaine abuse (12% vs 1.6%, P <.001), hypertension (89.7% vs 73.9%, P <.001), and diabetes (13.2% vs 6.4%, P = .001). Conversely, they were less likely to have bicuspid aortic valve (1.8% vs 5.8%, P = .029), iatrogenic dissection (0.5% vs 4.5%, P = .010), and prior aortic dissection repair (7.7% vs 12.8%, P = .047). Presenting features were similar except for more abdominal pain (44.6% vs 30.6%, P <.001) and left ventricular hypertrophy on echocardiogram (44.2% vs 20.1%, P <.001) in blacks. Management was similar. Hypotension/shock/tamponade was less common (7.6% vs 20.1%, P <.001), whereas acute kidney failure was more common (41.0% vs 21.7%, P <.001) in blacks. Mortality was similar in-hospital (14.3% vs 19.1%, P = .110, odds ratio 0.704, 95% confidence interval 0.457-1.085) and at 3 years postdischarge, as evaluated by Kaplan-Meier survival analysis (22.0% vs 14.3%, P = .224, SE = 0.062 and 0.018). Our study shows differences in type, etiology, and presentation of blacks and whites with acute aortic dissection, yet similar mortality for these cohorts.
    The American journal of medicine 08/2013; 126(10). DOI:10.1016/j.amjmed.2013.04.020 · 5.30 Impact Factor
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    ABSTRACT: Purpose:To determine the relative frequencies of persistence patterns in treated pulmonary arteriovenous malformations (PAVMs) and to assess whether there is a difference in retreatment outcomes between PAVMs persisting via recanalization and those persisting via reperfusion.Materials and Methods:Between May 2003 and May 2011, 23 patients (10 male, 13 female; mean age, 44 years ± 18 [standard deviation]; age range, 12-72 years) who had PAVM embolization, persistence by computed tomography (CT), and a follow-up pulmonary arteriogram were included. This retrospective study was approved by the institutional review board and was fully HIPAA compliant. PAVMs were categorized as having recanalization, defined as persistence maintained by flow through a previously placed coil nest; reperfusion, defined as persistence through small feeders from adjacent normal pulmonary arteries; or incomplete treatment. Fifty-three persistent PAVMs were characterized; 38 of which had postretreatment CT data (median follow-up, 1 year). The retreatment success rate, defined by sac shrinkage on CT images, was assessed.Results:Recanalization was the most common pattern, occurring in 91% (n = 48) of 53 PAVMs. Pulmonary-to-pulmonary reperfusion occurred in 24% (n = 13) of 53 PAVMs. Angioarchitecture, coil-sac distance, coil number, and feeder diameter did not significantly differ between recanalized and reperfused PAVMs. There was a significant (P = .014) difference in retreatment success; retreatment was successful in 84% (n = 27) of 32 recanalized PAVMs but only 44% (n = 4) of nine reperfused PAVMs.Conclusion:Recanalization through previously placed coils is the most common pattern of PAVM persistence and responds best to retreatment. Pulmonary-to-pulmonary reperfusion is less common and more difficult to re-treat successfully.© RSNA, 2013Supplemental material:
    Radiology 08/2013; 269(3). DOI:10.1148/radiol.13122153 · 6.21 Impact Factor
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    ABSTRACT: The classification of aortic dissection into acute (<14 days from symptom onset) versus chronic (≥14 days) is based on survival estimates of patients treated decades before modern diagnostic and treatment modalities were available. A new classification of aortic dissection in the current era may provide clinicians with a more precise method of characterizing the interaction of time, dissection location, and treatment type with survival. We developed separate Kaplan-Meier survival curves for Type A and Type B aortic dissection using data from the International Registry of Aortic Dissection (IRAD). Daily survival was stratified based on type of therapy provided: medical therapy alone (medical), nonsurgical intervention plus medical therapy (endovascular), and open surgery plus medical therapy (surgical). The log-rank statistic was used to compare the survival curves of each management type within Type A and Type B aortic dissection. There were 1815 patients included, 67.3% male with mean age 62.0 ± 14.2 years. When survival curves were constructed, 4 distinct time periods were noted: hyperacute (symptom onset to 24 hours), acute (2-7 days), subacute (8-30 days), and chronic (>30 days). Overall survival was progressively lower through the 4 time periods. This IRAD classification system can provide clinicians with a more robust method of characterizing survival after aortic dissection over time than previous methods. This system will be useful for treating patients, counseling patients and families, and studying new diagnostic and treatment methods.
    The American journal of medicine 08/2013; 126(8):730.e19-24. DOI:10.1016/j.amjmed.2013.01.020 · 5.30 Impact Factor
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    ABSTRACT: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by vascular malformations, and many clinical complications are related to pulmonary arteriovenous malformations (PAVMs) because they provide direct right-to-left shunts. Paradoxical emboli through these shunts are a well-recognized cause of transient ischemic attack, stroke, and cerebral abscess. The aim of this study was to determine whether paradoxical emboli through PAVMs could manifest as cardiac ischemic events. The study included a single-center population of 98 patients with PAVMs. Eighty-four had undergone PAVM embolotherapy, and the remaining 14 patients had PAVMs too small to require embolization. Patients were interviewed by telephone and surveyed regarding their cardiopulmonary symptoms and histories of cardiac diagnoses. We found that 6 patients (which is 18% of patients with symptomatic PAVMs, n = 33, and 6% of the total cohort, n = 98) reported that they had experienced typical angina pectoris-like chest pain or had a myocardial infarction before PAVM embolotherapy. Five patients had had a cardiac catheterization, 4 had normal coronary arteries, and 1 had a single artery occlusion. In conclusion, we suggest that in patients with untreated PAVMs, cardiac ischemia can occur because of a paradoxical embolus through PAVMs to a coronary artery.
    The American journal of cardiology 05/2013; 112(5). DOI:10.1016/j.amjcard.2013.04.052 · 3.58 Impact Factor
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    ABSTRACT: Previous data suggest women are at increased risk of death from aortic dissection. Therefore, we analyzed data from the GenTAC registry, the NIH-sponsored program that collects information about individuals with genetically triggered thoracic aortic aneurysms and cardiovascular conditions. We performed cross-sectional analyses in adults with Marfan syndrome (MFS), familial thoracic aortic aneurysm or dissection (FTAAD), bicuspid aortic valve (BAV) with thoracic aortic aneurysm or dissection, and subjects under 50 years of age with thoracic aortic aneurysm or dissection (TAAD <50 years). Women comprised 32% of 1,449 subjects and were 21% of subjects with BAV, 34% with FTAAD, 22% with TAAD <50 years, and 47% with MFS. Thoracic aortic dissections occurred with equal gender frequency yet women with BAV had more extensive dissections. Aortic size was smaller in women but was similar after controlling for BSA. Age at operation for aortic valve dysfunction, aneurysm or dissection did not differ by gender. Multivariate analysis (adjusting for age, BSA, hypertension, study site, diabetes, and subgroup diagnoses) showed that women had fewer total aortic surgeries (OR = 0.65, P < 0.01) and were less likely to receive angiotensin converting enzyme inhibitors (ACEi; OR = 0.68, P < 0.05). As in BAV, other genetically triggered aortic diseases such as FTAAD and TAAD <50 are more common in males. In women, decreased prevalence of aortic operations and less treatment with ACEi may be due to their smaller absolute aortic diameters. Longitudinal studies are needed to determine if women are at higher risk for adverse events. © 2013 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 04/2013; 161A(4). DOI:10.1002/ajmg.a.35836 · 2.30 Impact Factor
  • Shana L Merrill, Anjali Vaidya, Reed E Pyeritz
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    ABSTRACT: Genetic testing has been utilized to determine the etiology of some pediatric cardiac conditions for decades. However, new techniques, such as clinical whole exome sequencing, raise ethical challenges that must be addressed for the successful integration of these techniques into routine clinical care. One major ethical concern is the ability of patients to provide meaningful informed consent for this type of complex testing. A case of familial dilated cardiomyopathy with pediatric onset of unknown genetic etiology was utilized to facilitate the discussion of these issues by a panel including cardiologists, a geneticist, and a genetic counselor. Cardiologists and their medical genetics colleagues need to continue to discuss and investigate how to ethically integrate rapidly advancing genetic testing technologies into patient care to optimize potential benefits and minimize potential harms.
    01/2013; 4(1):58-61. DOI:10.1177/2150135112462590
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    ABSTRACT: Chromosomal Micro-array (CMA) testing has improved the diagnostic rate of genomic disorders in pediatric populations, and is used for patients with clinical phenotypes including intellectual disability, developmental delay, congenital anomalies and autism. In addition to detecting known pathogenic mutations, CMA can also lead to uncertain findings, and can present challenges for families and providers. We examined parents' and clinicians' perspectives of CMA testing using mixed methods: semi-structured interviews with 31 parents and 15 health providers; observations of 22 clinical consultations; and an online survey of 40 physicians (11 pediatricians, 24 pediatric specialists, and 5 medical geneticists). Qualitative analyses suggested that parents' understanding of CMA results was impeded by uncertainties deriving from lack of provider knowledge, limitations in scientific knowledge, and personal meanings attributed to the results, including psychosocial implications for individuals tested and their families. Misunderstandings were exacerbated when test results were conveyed by professionals lacking genetics expertise. In the survey, non-geneticists reported a need for more education about interpreting and explaining CMA results. Non-geneticists' main source of information about CMA was informal discussion with colleagues, rather than formal education or professional journals and guidelines, suggesting a lack of systematic education in this area. Genomic tests are ordered increasingly by clinicians lacking adequate genetics training to understand and communicate the meaning and implications of some types of test results. We will examine current health care policies that give rise to this situation, and consider potential ways to alleviate provider burden, and improve patients' and non-genetics providers' understanding of genomic information.
    140st APHA Annual Meeting and Exposition 2012; 10/2012
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    ABSTRACT: Acute aortic intramural hematoma (IMH) is an important subgroup of aortic dissection, and controversy surrounds appropriate management. Patients with acute aortic syndromes in the International Registry of Acute Aortic Dissection (1996-2011) were evaluated to examine differences between patients (based on the initial imaging test) with IMH or classic dissection (AD). Of 2830 patients, 178 had IMH (64 type A [42%], 90 type B [58%], and 24 arch). Patients with IMH were older and presented with similar symptoms, such as severe pain. Patients with type A IMH were less likely to present with aortic regurgitation or pulse deficits and were more likely to have periaortic hematoma and pericardial effusion. Although type A IMH and AD were managed medically infrequently, type B IMH were more frequently treated medically. Overall in-hospital mortality was not statistically different for type A IMH compared to AD (26.6% versus 26.5%; P=0.998); type A IMH managed medically had significant mortality (40.0%), although less than classic AD (61.8%; P=0.195). Patients with type B IMH had a hospital mortality that was less but did not differ significantly (4.4% versus 11.1%; P=0.062) from classic AD. One-year mortality was not significantly different between AD and IMH. Acute IMH has similar presentation to classic AD but is more frequently complicated with pericardial effusions and periaortic hematoma. Patients with IMH have a mortality that does not differ statistically from those with classic AD. A small subgroup of type A IMH patients are managed medically and have a significant in-hospital mortality.
    Circulation 09/2012; 126(11 Suppl 1):S91-6. DOI:10.1161/CIRCULATIONAHA.111.084541 · 14.95 Impact Factor
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    ABSTRACT: Despite predictions of increased clinical applications, little is known about primary care providers' (PCPs') readiness to apply genomics to patient care. The aim was to assess PCPs' current experience with genetic testing, their assessment of the understandability and clinical utility of information in sample direct-to-consumer reports for genomic assessment of disease risk and warfarin dosing and attitudes toward genomic medicine. A web-based survey of PCPs who are members of Knowledge Networks' Physician Consulting Network was conducted. Of the 502 respondents (23.3% response rate), most ordered genetic tests infrequently. When presented with the direct-to-consumer genomic testing reports, most believed the reports were understandable, and would be willing to review results with a patient, and many believed the results would be helpful in patient management. Despite limited experience with genetic tests, PCPs are open to helping patients understand genomic information. However, additional physician education is needed.
    Personalized Medicine 09/2012; 9(7):683-692. DOI:10.2217/pme.12.80 · 1.13 Impact Factor
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    ABSTRACT: Chromosomal microarray analysis (CMA) has improved the diagnostic rate of genomic disorders in pediatric populations, but can produce uncertain and unexpected findings. This paper explores clinicians' perspectives and identifies challenges in effectively interpreting results and communicating with families about CMA. Responses to an online survey were obtained from 40 clinicians who had ordered CMA. Content included practice characteristics and perceptions, and queries about a hypothetical case involving uncertain and incidental findings. Data were analyzed using non-parametric statistical tests. Clinicians' comfort levels differed significantly for explaining uncertain, abnormal, and normal CMA results, with lowest levels for uncertain results. Despite clinical guidelines recommending informed consent, many clinicians did not consider it pertinent to discuss the potential for CMA to reveal information concerning biological parentage or predisposition to late-onset disease, in a hypothetical case. Many non-genetics professionals ordering CMA did not feel equipped to interpret the results for patients, and articulated needs for education and access to genetics professionals. This exploratory study highlights key challenges in the practice of genomic medicine, and identifies needs for education, disseminated practice guidelines, and access to genetics professionals, especially when dealing with uncertain or unexpected findings.
    Clinical Genetics 08/2012; DOI:10.1111/j.1399-0004.2012.12004.x · 3.65 Impact Factor

Publication Stats

7k Citations
1,557.61 Total Impact Points


  • 2004–2014
    • University of Pennsylvania
      • • Penn Center for the Integration of Genetic Healthcare Technologies - Penn CIGHT
      • • Perelman School of Medicine
      • • Department of Medicine
      • • School of Nursing
      Philadelphia, Pennsylvania, United States
  • 2004–2013
    • Hospital of the University of Pennsylvania
      • • Division of Translational Medicine and Human Genetics
      • • Division of General Medicine
      • • Department of Medicine
      Philadelphia, Pennsylvania, United States
  • 2003–2013
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2012
    • University of Rostock
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2010–2011
    • University of Michigan
      • Department of Mechanical Engineering
      Ann Arbor, Michigan, United States
  • 2006
    • Harvard University
      Cambridge, Massachusetts, United States
    • Duke University Medical Center
      • Department of Molecular Genetics and Microbiology
      Durham, North Carolina, United States
  • 2001–2002
    • Allegheny General Hospital
      • Department of Cardiology
      Pittsburgh, Pennsylvania, United States
  • 1982–2000
    • Johns Hopkins Medicine
      • • Department of Orthopaedic Surgery
      • • Division of Cardiac Surgery
      • • Department of Pediatrics
      • • Department of Medicine
      Baltimore, MD, United States
  • 1999
    • Icahn School of Medicine at Mount Sinai
      Manhattan, New York, United States
  • 1984–1997
    • Johns Hopkins University
      • • Department of Orthopaedic Surgery
      • • Department of Pediatrics
      • • Department of Medicine
      • • Department of Otolaryngology - Head and Neck Surgery
      Baltimore, MD, United States
  • 1990
    • Shriners Hospitals for Children
      Tampa, Florida, United States