Publications by authors named "C Ackerman"

138 Publications

Severe maternal morbidity and mortality during delivery hospitalization of class I, II, III, and super obese women.

Am J Obstet Gynecol MFM 2021 Jun 19;3(5):100420. Epub 2021 Jun 19.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT (Drs Ackerman, Illuzzi, Reddy, Xu, and Lipkind).

Background: Previous studies show that obesity predisposes patients to higher risks of adverse pregnancy outcomes. Data on the relationship between increasing degrees of obesity and risks of severe maternal morbidity, including mortality, are limited.

Objective: We examined the association of increasing classes of obesity, especially super obesity, with the risk of severe maternal morbidity and mortality at the time of delivery hospitalization.

Study Design: Using New York City linked birth certificates and hospital discharge data, we conducted a retrospective cohort study. This study identified delivery hospitalizations for singleton, live births in 2008-2012. Women were classified as having obesity (class I, II, III, or super obesity), as opposed to normal weight or overweight, based on prepregnancy body mass index. Cases of severe maternal morbidity were identified based on International Classification of Diseases, Ninth Revision diagnosis and procedure codes according to Centers for Disease Control and Prevention criteria. Multivariable logistic regression was used to evaluate the association between obesity classes and severe maternal morbidity, adjusting for maternal sociodemographic characteristics.

Results: During 2008-2012, there were 570,997 live singleton births with available information on prepregnancy body mass index that met all inclusion criteria. After adjusting for maternal characteristics, women with class II (adjusted odds ratio, 1.14; 95% confidence interval, 1.05-1.23), class III (adjusted odds ratio, 1.34; 95% confidence interval, 1.21-1.49), and super obesity (adjusted odds ratio, 1.99; 95% confidence interval, 1.57-2.54) were all significantly more likely to have severe maternal morbidity than normal and overweight women. Super obesity was associated with specific severe maternal morbidity indicators, including renal failure, air and thrombotic embolism, blood transfusion, heart failure, and the need for mechanical ventilation.

Conclusion: There is a significant dose-response relationship between increasing obesity class and the risk of severe maternal morbidity at delivery hospitalization. The risks of severe maternal morbidity are highest for women with super obesity. Given that this is a modifiable risk factor, women with prepregnancy obesity should be counseled on the specific risks associated with pregnancy before conception to optimize their pregnancy outcomes.
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http://dx.doi.org/10.1016/j.ajogmf.2021.100420DOI Listing
June 2021

Random access DNA memory using Boolean search in an archival file storage system.

Nat Mater 2021 Jun 10. Epub 2021 Jun 10.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.

DNA is an ultrahigh-density storage medium that could meet exponentially growing worldwide demand for archival data storage if DNA synthesis costs declined sufficiently and if random access of files within exabyte-to-yottabyte-scale DNA data pools were feasible. Here, we demonstrate a path to overcome the second barrier by encapsulating data-encoding DNA file sequences within impervious silica capsules that are surface labelled with single-stranded DNA barcodes. Barcodes are chosen to represent file metadata, enabling selection of sets of files with Boolean logic directly, without use of amplification. We demonstrate random access of image files from a prototypical 2-kilobyte image database using fluorescence sorting with selection sensitivity of one in 10 files, which thereby enables one in 10 selection capability using N optical channels. Our strategy thereby offers a scalable concept for random access of archival files in large-scale molecular datasets.
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http://dx.doi.org/10.1038/s41563-021-01021-3DOI Listing
June 2021

Chemical Inhibition of ENL/AF9 YEATS Domains in Acute Leukemia.

ACS Cent Sci 2021 May 30;7(5):815-830. Epub 2021 Apr 30.

Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.

Transcriptional coregulators, which mediate chromatin-dependent transcriptional signaling, represent tractable targets to modulate tumorigenic gene expression programs with small molecules. Genetic loss-of-function studies have recently implicated the transcriptional coactivator, ENL, as a selective requirement for the survival of acute leukemia and highlighted an essential role for its chromatin reader YEATS domain. Motivated by these discoveries, we executed a screen of nearly 300,000 small molecules and identified an amido-imidazopyridine inhibitor of the ENL YEATS domain (IC = 7 μM). Improvements to the initial screening hit were enabled by adopting and expanding upon a SuFEx-based approach to high-throughput medicinal chemistry, ultimately demonstrating that it is compatible with cell-based drug discovery. Through these efforts, we discovered SR-0813, a potent and selective ENL/AF9 YEATS domain inhibitor (IC = 25 nM). Armed with this tool and a first-in-class ENL PROTAC, SR-1114, we detailed the biological response of AML cells to pharmacological ENL disruption for the first time. Most notably, we discovered that ENL YEATS inhibition is sufficient to selectively suppress ENL target genes, including , , , and a number of other leukemia proto-oncogenes. Cumulatively, our study establishes YEATS domain inhibition as a viable approach to disrupt the pathogenic function of ENL in acute leukemia and provides the first thoroughly characterized chemical probe for the ENL YEATS domain.
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http://dx.doi.org/10.1021/acscentsci.0c01550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161486PMC
May 2021

End of life simulation to improve interprofessional competencies: A mixed methods study.

Curr Pharm Teach Learn 2021 Apr 16;13(4):423-428. Epub 2020 Dec 16.

Pharmacotherapy Education and Research Center, College of Pharmacy, The University of Texas at Austin, and University Health - Department of Pharmacotherapy and Pharmacy Services; 7703 Floyd Curl Drive MC 6220, San Antonio, TX 78229-3900, United States. Electronic address:

Background: The Accreditation Council for Pharmacy Education "Standards 2016" require that pharmacy student education include training in the management of patients "across the lifespan" (Standard 12). Standards 2016 also require that students are practice-ready to participate as a contributing member of an interprofessional (IP) team (Standard 11). Didactic and experiential education in palliative or end-of-life (EOL) care is limited. Palliative care represents unique patient and team challenges in providing patients with empathetic and holistic care.

Interprofessional Education Activity: This study describes an IP, palliative care simulation that achieved both IP and "across the lifespan" educational standards. The goals of the activity included increasing communication skills, recognizing roles and responsibilities, and enhancing the value of various healthcare providers' perspectives and expertise when caring for patients at the EOL. Pharmacy, physical therapy, nursing, and counseling students participated in a low fidelity palliative care simulation. The event consisted of a presentation on anticipatory grief and active listening followed by a role-playing simulation and group debrief. The Interprofessional Socialization and Value Scale were administered to assess student perceptions of IP skills.

Discussion: Quantitative and qualitative data demonstrated achievement of the goals of the activity. Reflections revealed students felt the simulation improved teamwork and communication skills and that using humility and listening in team-based palliative care transformed wisdom for future practice.

Implications: This activity used a cost-effective, low fidelity, role-play simulation to achieve IP education competencies and demonstrated the value of multiple professions in EOL care.
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http://dx.doi.org/10.1016/j.cptl.2020.11.017DOI Listing
April 2021

Outcome of clinical and subclinical myocardial injury in systemic lupus erythematosus - A prospective cohort study.

Lupus 2021 Feb 1;30(2):256-268. Epub 2020 Dec 1.

Division of Cardiology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Academic Hospital, Cape Town, South Africa.

Objectives: To determine the outcome of subclinical lupus myocarditis (LM) over twelve months with regards to: mortality; incidence of clinical LM and change in imaging parameters (echocardiography and cardiac magnetic resonance [CMR]). To evaluate the impact of immunosuppression on CMR evidence of myocardial tissue injury.

Methods: SLE patients with and without CMR evidence of myocardial injury (as per 2009 Lake Louise criteria [LLC]) were included. Analysis at baseline and follow-up included: clinical evaluation, laboratory and imaging analyses (echocardiography and CMR). Clinical LM was defined as clinical features of LM supported by echocardiographic and/or biochemical evidence of myocardial dysfunction. Subclinical LM was defined as CMR myocardial injury without clinical LM.

Results: Forty-nine SLE patients were included with follow-up analyses (after 12 months) available in 36 patients. Twenty-five patients (51%) received intensified immunosuppressive therapy during follow-up for indications related to SLE. Disease activity (SLEDAI-2K) improved (p < 0.001) from 13 (median;IQR:9-20) to 7 (3-11). One patient without initial CMR evidence of myocardial injury developed clinical LM. Mortality (n = 10) and SLE clinical features were similar between patients with and without initial CMR myocardial injury. Echocardiographic left ventricular ejection fraction (LVEF) (p = 0.014), right ventricular function (p = 0.001) and wall motion abnormalities (p = 0.056) improved significantly but not strain analyses nor the left LV internal diameter index. CMR mass index (p = 0.011) and LVEF (p < 0.001) improved with follow-up but not parameters identifying myocardial tissue injury (LLC). A trend towards a reduction in the presence of CMR criteria was counterbalanced by persistence (n = 7) /development of new criteria (n = 11) in patients. Change in CMR mass index correlated with change in T2-weighted signal (myocardial oedema) (r = 386;p = 0.024). Intensified immunosuppressive therapy had no significant effect on CMR parameters.

Conclusion: CMR evidence of subclinical LM persisted despite improved SLEDAI-2K, serological markers, cardiac function and CMR mass index. Subclinical LM did not progress to clinical LM and had no significant prognostic implications over 12 months. Immunosuppressive therapy did not have any significant effect on the presence of CMR evidence of myocardial tissue injury. Improvement in CMR mass index correlated with reduction in myocardial oedema and may be used to monitor SLE myocardial injury.
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http://dx.doi.org/10.1177/0961203320976960DOI Listing
February 2021
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