Philadelphia University
  • Philadelphia, United States
Recent publications
Mutations found in AML such as DNMT3A, TET2 and ASXL1 can be found in the peripheral blood of healthy adults - a phenomenon termed clonal hematopoiesis (CH). These mutations are thought to represent the earliest genetic events in the evolution of AML. Genomic studies on samples acquired at diagnosis, remission, and at relapse have demonstrated significant stability of CH mutations following induction chemotherapy. Meanwhile, later mutations in genes such as NPM1 and FLT3, have been shown to contract at remission and in the case of FLT3 often are absent at relapse. We sought to understand how early CH mutations influence subsequent evolutionary trajectories throughout remission and relapse in response to induction chemotherapy. We assembled a retrospective cohort of patients diagnosed with de novo AML at our institution that underwent genomic sequencing at diagnosis, remission and/or relapse (total n=182 patients). FLT3 and NPM1 mutations were generally eliminated at complete remission but subsequently reemerged upon relapse, whereas DNMT3A, TET2 and ASXL1 mutations often persisted through remission. CH-related mutations exhibited distinct constellations of co-occurring genetic alterations, with NPM1 and FLT3 mutations enriched in DNMT3Amut AML, while CBL and SRSF2 mutations were enriched in TET2mut and ASXL1mut AML, respectively. In the case of NPM1 and FLT3 mutations, these differences vanished at the time of complete remission yet readily reemerged upon relapse, indicating the reproducible nature of these genetic interactions. Thus, CH-associated mutations that likely precede malignant transformation subsequently shape the evolutionary trajectories of AML through diagnosis, therapy, and relapse.
Registry data and randomized controlled trials have demonstrated high mortality of cardiogenic shock which unfortunately has not changed in the past several decades. The definition of cardiogenic shock is sustained hypotension with systolic blood pressure <90 mm Hg for 30 min accompanied with symptoms of decreased end organ perfusion. Mechanical circulatory support offers an opportunity to save lives but there is paucity of literature on device specific recommendations in cardiogenic shock state. There is a concept of a tailored approach to acute cardiogenic shock and the selection of mechanical circulatory support. It is alarming that despite a growing armamentarium of mechanical circulatory support devices and sophisticated skill sets, the outlook has remained grim for cardiogenic shock. A multifaceted approach including timely intervention, an individualized approach focusing on tailored device selection of mechanical circulatory support deployed by a shock team that is capable of early and efficient execution of protocols holds promise in improving mortality and making a substantial difference in existing outcomes. Clinical trials which are not only focused on the etiologic subgroups but also on the hemodynamic trajectory of the patient may very well provide the guidance needed for acute mechanical circulatory support device selection in cardiogenic shock.
Plain Language Summary Geological materials are viscoelastic solids, exhibiting elastic and viscous behavior as they deform. Quantifying the viscoelastic behavior of rocks and minerals through experimentation is important for constraining geodynamical models and for extrapolating these models to make useful predictions. Measuring the viscoelastic deformation of these materials is, however, challenging due to the relatively extreme experimental conditions required to activate various mechanisms of deformation. We present a new method for measuring the dissipation of elastic strain energy, or attenuation, of quartz, halite and olivine using nanoindentation. The method is easy to implement and allows for testing with high spatial resolution. We apply a sinusoidal load to the indenter's diamond tip which causes it to penetrate into and emerge out of the tested specimen. We measure the phase shift between the imposed sinusoidal load and the resulting sinusoidal displacement of the tip and use it to calculate the attenuation. To test the validity of our method we also measure the attenuation spectrum of indium and an acrylic plastic, PMMA, and compare these data to reported attenuation values for these materials from other apparatuses. Our results are in excellent agreement with reported attenuation data for indium and PMMA, showing the robustness of our method.
In this narrative medicine essay, the memories of joyfully preparing meals with her parents that must shift to learning how to prepare low-glycemic foods fills a medical student’s mind when a patient during clinic learns they must stop their weekly indulgence.
Introduction: Intracerebral Hemorrhage (ICH) is associated with a high case fatality and survivors of ICH are at increased risk for ICH recurrence. Roughly 20-30% of patients with ICH take a statin at the time of ICH onset. The role of statins, whether protective or deleterious, in the setting of ICH remains unclear. The SPARCL (Stroke Prevention by Aggressive Reduction of Cholesterol Level) study amongst others, have suggested that statin use may increase risk of ICH in those with prior history ICH, due to increased erythrocyte fragility and inhibition of platelet aggregation. However subsequent observational studies refuted these findings citing statins improve endothelial function and reduce oxidative stress thus theoretically. We reviewed relevant studies discussing the relationship between statin use and risk of ICH. Methods: A comprehensive search strategy utilizing the key terms “statin use” and “intracerebral hemorrhage” was performed utilizing four electronic databases: Cochrane, Embase, Google Scholar, PubMed. The search was conducted by two authors (PM and CO). Following the search, articles citing a correlation between statin use and risk of intracerebral hemorrhage were included. Below is a table citing selected studies from our review (Table 1). Discussion: There continues to be mixed evidence regarding statin use and risk of ICH. Current clinical guidelines do not provide a formal recommendation on statin use restriction in those with prior ICH. However, contrary to the SPARCL study, newer studies have suggested there is neither a statistically nor clinically significant relationship between LDL-C and ICH incidence. Our review also uncovered that one’s genetic signature may play a mediating role in this relationship as evidenced namely by the Honolulu Heart study, which analyzed a relatively monogenic study population. This implies a more nuanced relationship and we posit the burgeoning use of polygenic risk scoring may provide more utility here as well. Ultimately consideration of statin therapy should be determined by weighing one’s atherogenicity versus propensity to develop ICH. An optimal LDL-C goal has yet to be determined however many studies suggest targeting between 70-160 mg/dL is optimal. Additional studies should assess the role of other lipid lowering agents in the setting of ICH such as bempedoic acid and PCSK9 inhibitors, as well as discern optimal ranges for newer Apo-B and Lp(a) lipid biomarkers.
Introduction: Cardiomyopathy (CM) can occur in patients hospitalized with acute ischemic stroke (AIS). The epidemiology of AIS and concomitant CM subtypes is not well-described. Methods: Adult hospitalizations in the National Inpatient Sample (NIS) from 2018-2020 with diagnosis of AIS and concomitant CM were characterized by CM etiologies using International Classification of Diseases-10 codes. Demographic characteristics and clinical outcome rates were computed among patients with each CM subtype. The outcomes of interest are detailed in Table 1. Further statistical analyses within CM etiology subgroups were not performed given that the encoded subgroups were not mutually exclusive. Results: Of 1,918,985 weighted AIS hospitalizations, there were 144,875 (7.6%) patients with concomitant CM diagnosis, one-third due to ischemic etiology and two-thirds were non-ischemic (CM etiologies not mutually exclusive, Table 1). Patients with CM etiologies such as ischemic and amyloid-induced CM were older (mean ages 70.5 and 72.3 years, respectively) versus those with peripartum and sarcoidosis-related CM (mean ages 33.5 and 48.5 years, respectively). There were sex differences, as patients with concomitant ischemic CM were more likely to be male (71%) versus those with concomitant stress CM (24.9%). Patients with stress CM (72%) and ischemic CM (68%) identified as White, and those with sarcoid-induced (88%) and peripartum (54%) CM were mostly Black. Intracardiac thrombus was detected in decreasing order by CM subtype: drug-induced (13.6%), alcohol-induced (7.7%), dilated (6.2%), restrictive (5.9%), and ischemic (5.2%). Circulatory support was most common with restrictive CM (2.4% IABP). Thrombolysis use was most frequent in patients with peripartum (18%), dilated (9.3%), drug-induced (8.8%), and ischemic CM (8.2%). EVT rates in decreasing order by CM subtype were: Chagas-associated, wet Beriberi, and sarcoidosis-induced CMs (88-100%), drug-induced (10.1%), and stress-induced (7.7%). Stress-induced CM was associated with highest in-hospital mortality rate (17%) and lowest frequency of routine discharge (18%). Conclusions: We describe the epidemiology of CM subtypes among patients hospitalized with AIS, the cardiac and stroke-related procedures that these patients undergo, and their clinical outcomes. Understanding the demographic and in-hospital outcomes specific to each CM etiology may provide insight into multidisciplinary management of this vulnerable population.
Most cardiovascular diseases can be prevented by addressing behavioral risk factors (i.e., tobacco use, unhealthy diet, body weight management, physical inactivity, and excess alcohol intake) through self-care. In low- and middle-income countries, barriers can make these self-care behaviors challenging. In this chapter, we define and describe self-care, focusing on individual-level behavioral risk factors and cultural influences on beliefs about self-care within the broader context of healthcare and system factors enabling self-care in under-resourced countries. Finally, we explore the self-care interventions studied in low- and middle-income countries.
Background Within the last decade, system and policy-level changes have driven substantial shifts in heart failure (HF) care from hospital to home, requiring greater support from informal care partners. What has not been examined is the state of the care partner science by person and system-level domains using qualitative studies to understand impact across multiple person and system levels. Objectives (1) Identify by person and system levels and domain what is known about informal care partners and (2) Identify gaps in the caregiving science and suggest ways to move forward. Methods This secondary analysis of a large HF systematic review is guided by the National Institute on Minority Health and Health Disparities and MIRACLE frameworks and uses meta-synthesis techniques with critical realist approaches to synthesize and interpret the themes across papers. Results Using data from 46 papers and 1695 care partners, we identified patterns occurring across 6 domains (biological, behavioral, affective, physical/built environment, sociocultural environment, and healthcare system) and on 4 levels (individual, interpersonal, community, and societal). Existing research predominantly addressed affective and behavioral domains, followed by health system and sociocultural domains. Few studies focused on biological and physical/built environment domains, leaving large gaps in what is known about caregiving at the cellular (biological) and societal (community and societal) levels. Conclusions HF caregiving continues to be studied at a very rudimentary level. This synthesis also reveals critical gaps in what is known about caregiving within the physical/built environment domain and at the community and societal levels.
Objectives Recent studies have challenged the assumption that families are invariable sources of support for cancer caregivers, noting that relationships with family members can have both positive and negative effects on caregiver well-being. This study expands upon prior literature to examine the relationship between cancer caregivers’ perceptions of the quality of their family interactions and their symptoms of anxiety. Methods We employed secondary analysis of baseline data from a multisite randomized clinical trial of an intervention for cancer caregivers conducted at 3 large academic palliative care clinics. We performed linear regression analyses to analyze the relationship between caregivers’ perceptions of the quality of their family interactions and their symptoms of anxiety; additional models were estimated to further characterize this relationship with the addition of relevant covariates: race, ethnicity, sex, marital/relationship status, relationship to patient, employment status, household income, and perceived social support received from friends and significant others. We also conducted a sub-analysis of data provided by caregivers who were married or partnered to examine the relationship between their perceptions of the quality of their family interactions and their symptoms of anxiety with relationship satisfaction as a covariate. Results Among our analytic sample ( n = 244), we identified a significant negative relationship between cancer caregivers’ perceptions of the quality of their family interactions and their symptoms of anxiety; this relationship remained statistically significant with the addition of covariates. Relationship satisfaction was not found to be a statistically significant covariate in our sub-analysis of married or partnered caregivers. Significance of results Study results provide strong support for the development, testing, and implementation of interventions to improve family interactions as a strategy to reduce caregiver anxiety.
Early childhood education teachers often feel underprepared for addressing behavior challenges in the classroom. This can limit a teacher’s ability to teach academic and social skills and lead to interruptions in their educational experience such as suspensions or expulsions. Effective planning can help teachers create and manage positive learning environments. In this article, we describe how to effectively write behavior intervention plan goals for early childhood settings. Resources are shared to support early childhood behavioral goal creation.
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Michael A Rackover
  • College of Science, Health and the Liberal Arts
Jeffrey Ashley
  • College of Science, Health and the Liberal Arts
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