Publications by authors named "Grace Huang"

206 Publications

A Resident-as-Leader Curriculum for Managing Inpatient Teams.

Teach Learn Med 2022 Jan 13:1-10. Epub 2022 Jan 13.

Carl J. Shapiro Institute for Education and Research, Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Problem: Leading inpatient teams is a foundational clinical responsibility of resident physicians and leadership is a core competency for inpatient physicians, yet few training programs have formal leadership curricula to realize this clinical skill.

Intervention: We implemented a 4-module curriculum for PGY1 internal medicine residents. The program focused on the managerial skills necessary for daily clinical leadership, followed by clinical coaching. Interns were first introduced to foundational concepts and then given the opportunity to apply those concepts to real-world practice followed by clinical coaching.

Context: Using direct-observations and a previously published checklist for rounds leadership, this study sought to evaluate the workplace behavior change for novice residents leading inpatient teams for the first time. We conducted a prospective cohort study (March 2016 and August 2018) of internal medicine residents at a large tertiary academic medical center in Boston, MA. Trained faculty raters performed direct observations of clinical rounding experiences using the checklist and compared the findings to historical and internal controls. Questionnaires were distributed pre- and post- curriculum to assess satisfaction and readiness to lead a team.

Impact: We trained 65 PGY1 residents and raters conducted 140 direct observations - 36 in the intervention group and 104 among historical controls. The unadjusted mean score in rounds leadership skills for the intervention group was 19.0 ( = 5.1) compared to 16.2 ( = 6.2) for historical controls. Adjusting for repeated measures, we found significant improvement in mean scores for behaviors linked to the curricular objectives (p = 0.008) but not for general behaviors not covered by the curriculum (p = 0.2).

Lessons Learned: A formal curriculum to train residents as leaders led to behavior change in the workplace in domains essential to rounds leadership. We also found that the curriculum was highly regarded in that all interns indicated they would recommend the curriculum to a peer. Moreover, the program may have assuaged some anxiety during the transition to junior year as 90% of interns surveyed felt more ready to start PGY2 year than historical trainings. We learned that while a robust, multi-faceted modular curriculum and clinical coaching successfully resulted in behavior change, the resources required to manage this program are significant and difficult to sustain. Future iterations could include asynchronous material and potentially peer-observation of rounds leadership to reduce the burden on faculty and program curricular time.
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http://dx.doi.org/10.1080/10401334.2021.2009347DOI Listing
January 2022

Clinical Considerations in Orthodontically Forced Eruption for Restorative Purposes.

J Clin Med 2021 Dec 18;10(24). Epub 2021 Dec 18.

Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

For restorations on teeth involving invasion of the supracrestal tissue attachment (biological width), as well as for lack of ferrule effect, crown lengthening is required for long-term periodontal health and success of the restoration. In the same fashion, site development is often necessary prior to implant placement in order to provide optimal peri-implant soft and hard tissue architecture conducive to future esthetics and function. Orthodontic extrusion, also known as forced eruption, has been developed and employed clinically to serve the purposes of increasing the clinical crown length, correcting the periodontal defect, and developing the implant site. In order to provide comprehensive guidance on the clinical usage of this technique and maximize the outcome for patients who receive the dental restoration, the currently available literatures were summarized and discussed in the current review. Compared to traditional crown lengthening surgery, forced eruption holds advantages of preserving supporting bone, providing improved esthetics, limiting the involvement of adjacent teeth, and decreasing the negative impact on crown-to-root ratio compared to the traditional resective approach. As a non-invasive and natural technique capable of increasing the available volume of bone and soft tissue, forced eruption is also an attractive and promising option for implant site development. Both fixed and removable appliances can be used to achieve the desired extrusion, but patient compliance is a primary limiting factor for the utilization of removable appliances. In summary, forced eruption is a valuable treatment adjunct for patients requiring crown lengthening or implant restorations. Nonetheless, comprehensive evaluation and treatment planning are required for appropriate case selection based upon the known indications and contraindications for each purpose; major contraindications include inflammation, ankylosis, hypercementosis, vertical root fracture, and root proximity. Further studies are necessary to elucidate the long-term stability of orthodontically extruded teeth and the supporting bone and soft tissue that followed them.
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http://dx.doi.org/10.3390/jcm10245950DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706734PMC
December 2021

Anti-Bias and Inclusive Language in Scholarly Writing: A Primer for Authors.

Acad Med 2021 Dec 21. Epub 2021 Dec 21.

dean for faculty affairs and associate professor of medicine, Harvard Medical School; editor-in-chief, MedEdPORTAL assistant professor of medicine, Departments of Pediatrics and Medical Education, Icahn School of Medicine at Mount Sinai; associate editor, MedEdPORTAL professor of medicine, Harvard Medical School; associate editor, MedEdPORTAL associate professor of obstetrics and gynecology, University of North Carolina School of Medicine; associate editor, MedEdPORTAL managing editor, MedEdPORTAL.

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http://dx.doi.org/10.1097/ACM.0000000000004571DOI Listing
December 2021

An Inside Look: Qualitative Study of Underrepresented in Medicine Recruitment Strategies used by OB-GYN Program Directors.

J Surg Educ 2021 Dec 9. Epub 2021 Dec 9.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

Introduction: Since 2019, the Accreditation Council for Graduate Medical Education has mandated that all residency programs develop initiatives to recruit underrepresented in medicine (URiM) applicants to increase diversity among physicians. The literature has described a variety of recruitment strategies, but the underlying viewpoints of leaders most responsible for these efforts have not been characterized. We aimed to describe the experience and perspective of program directors around URiM recruitment.

Methods: We conducted a qualitative analysis of 14 semi-structured interviews with OB-GYN program directors recruited electronically about their perspectives on URiM recruitment between August 2018 and October 2019. We coded audio transcripts from these interviews in an independent and iterative fashion. Using inductive content analysis, we derived several themes.

Results: Fourteen OB-GYN program directors participated. Themes arising from data included an acknowledgement of the contextual nature of diversity, which included not just race but also other forms of self-identity; the visual nature of recruitment efforts; the lack of consistent support for programs despite shared goals in workforce diversity; the imperative of upending traditional approaches to recruitment (e.g., undue emphasis on Step 1 scores); and finally, the prerequisites of a critical mass of URiM residents, faculty diversity and supportive culture for successful URiM recruitment.

Discussion: Our findings shed light on the motivations and obstacles that program directors face in URiM recruitment, underscoring a need for more broad-based initiatives to ensure that society is served by a healthcare workforce reflecting the diversity of our patients.
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http://dx.doi.org/10.1016/j.jsurg.2021.10.013DOI Listing
December 2021

Invasive bacterial diseases in northern Canada, 1999 to 2018.

Can Commun Dis Rep 2021 Nov 10;47(11):491-499. Epub 2021 Nov 10.

Infectious Disease Programs Branch, Public Health Agency of Canada, Ottawa, ON.

Background: The International Circumpolar Surveillance (ICS) program conducts surveillance on five invasive bacterial diseases: pneumococcal disease (IPD), group A streptococcus (iGAS), (Hi), meningococcal disease (IMD) and group B streptococcus (GBS). Invasive bacterial diseases have a higher burden of disease in northern populations than the rest of Canada.

Methods: To describe the epidemiology of invasive bacterial diseases in northern Canada from 1999 to 2018, data for IPD, iGAS, Hi, IMD and GBS were extracted from the ICS program and the Canadian Notifiable Diseases Surveillance System (CNDSS) and analyzed.

Results: The annualized incidence rates for IPD, iGAS, Hi, GBS and IMD were 23.3, 10.5, 8.9, 1.9 and 1.1 per 100,000 population, respectively. The incidence of IPD, iGAS and Hi serotype b were 2.8, 3.2 and 8.8 times higher, respectively, in northern Canada than in the rest of Canada. Rates of disease decreased statistically significantly for IPD (β=-0.02) and increased statistically for iGAS (β=0.08) and Hi serotype a (β=0.04) during the study period. In Northern Canada, the annualized incidence rates for IPD, iGAS and Hi were statistically higher for Indigenous residents than for non-Indigenous residents. The highest incidence rates were among the very young and older age groups.

Conclusion: Invasive bacterial diseases represent a high burden of disease in Canada's northern populations. Indigenous peoples, children and seniors are particularly at risk.
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http://dx.doi.org/10.14745/ccdr.v47i11a09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601277PMC
November 2021

The Infinity Mirror: Conducting an Interactive Workshop on How to Develop an Educational Summary Report for .

MedEdPORTAL 2021 22;17:11197. Epub 2021 Oct 22.

Dean for Faculty Affairs, Harvard Medical School.

Introduction: is an open-access journal for health professions educators to publish their educational activities. The Educational Summary Report (ESR) is the manuscript that represents scholarly expression of those activities, aligned with Glassick's criteria for scholarship; however, prospective authors face challenges in writing ESRs, which can lead to rejection.

Methods: We developed a conference workshop to teach health professions educators how to write an ESR by reviewing a sample ESR in small groups. The workshop began with a didactic on best practices in crafting each section of an ESR. We then divided participants into small groups to review an assigned section of a sample ESR using a reviewer's checklist and completing a templated flip chart. Each small group then reported out in a large-group discussion. A conference evaluation was distributed online to solicit perceptions of the workshop's effectiveness.

Results: The 90-minute workshop was presented by separate teams of two facilitators at three national conferences. Approximately 35 participants attended the first workshop, and 50 attended the second and third workshops. Survey feedback from 19 respondents (38%) to the evaluation survey at the third workshop was representative of the previous two iterations and demonstrated that workshop content and materials were helpful.

Discussion: A workshop enabling educators to serve as group peer reviewers of a sample ESR for a submission was well received. Associate editors, faculty mentors, and other experienced faculty development leaders can use these materials to support future authors in submitting to while providing opportunities for national presentations.
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http://dx.doi.org/10.15766/mep_2374-8265.11197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8552417PMC
October 2021

How to ACTFAST But Think Deliberately: An Intervention to Teach Critical Thinking in the Pediatric Clerkship.

J Pediatr 2020 11 22;226:5-8.e2. Epub 2020 Oct 22.

Department of Medicine, Harvard Medical School, Boston, MA; Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Carl J. Shapiro Institute for Education and Research, Boston, MA.

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http://dx.doi.org/10.1016/j.jpeds.2020.02.073DOI Listing
November 2020

Women sidelined in pandemic research.

BMJ 2021 10 6;375:n2381. Epub 2021 Oct 6.

Harvard Medical School, Boston, MA, USA

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http://dx.doi.org/10.1136/bmj.n2381DOI Listing
October 2021

A Call for Reform: Variability and Insufficiency in Radiation Oncology Resident Didactics-a Brief Report and National Survey of Program Directors.

J Cancer Educ 2021 Aug 18. Epub 2021 Aug 18.

Harvard Medical School, Boston, MA, USA.

An informal needs assessment and lack of a national standardized curriculum suggest that there is tremendous variability in the formal teaching of radiation oncology resident throughout the USA. The goal of this study was to characterize formal radiation oncology resident education, in order to identify knowledge gaps and areas for improvement. We developed a 14-item survey consisting of the following domains: program characteristics, teaching faculty, formal teaching time, instructional approaches for formal teaching, curricular topics, and satisfaction with didactics. All 91 accredited US-based radiation oncology program directors received an invitation to complete the survey anonymously by email. Twenty-four (26% response rate) program directors responded. Programs used a variety of instructional methods; all programs reported using lecture-based teaching and only a minority using simulation (38%) or flipped classroom techniques (17%). Other than PowerPoint, the most common electronic resource utilized was quizzing/polling (67%), webinar (33%), and econtour.org (13%). The lack of a national, standardized, radiation oncology residency didactic curriculum promotes variability and insufficiency in resident training. Themes for improvement were diversity in didactic topics, incorporation of evidence-based teaching practices, increased faculty involvement, and sharing of resources across programs. Development of a national curriculum and increased electronic resource sharing may help address some of these areas of improvement.
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http://dx.doi.org/10.1007/s13187-021-02080-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373291PMC
August 2021

Age-Related Changes in the Anatomy of the Triangle of Koch: Implications for Catheter Ablation of Atrioventricular Nodal Re-entry Tachycardia.

CJC Open 2021 Jul 6;3(7):924-928. Epub 2021 Apr 6.

Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

Background: Atrioventricular nodal re-entrant tachycardia is the most common type of paroxysmal supraventricular tachycardia. We sought to assess whether important anatomic factors, such as the location of the slow pathway, proximity to the bundle of His, and coronary sinus ostium dimensions, varied with patient age, and whether these factors had an impact on procedural duration, acute success, and complications.

Methods: Baseline demographic and procedural data were collected, and the maps were analyzed. Linear regression models were performed to evaluate the associations between age and these anatomic variations. Associations were also assessed, with age categorized as being ≥ 60 years or < 60 years.

Results: The slow pathway was more commonly located in a superior location relative to the coronary sinus ostium in older patients. The location of the slow pathway moved in a superior direction by 1 mm for every increase in 2 years from the mean estimate of age. Additionally the slow pathway tended to be closer to the coronary sinus ostium in older patients, and the diameter of the ostium was larger in older patients. This resulted in longer procedure time, longer ablation times, and a greater need for long sheaths for stability.

Conclusions: The location of the slow pathway becomes more superior and closer to the coronary sinus ostium with increasing age. Additionally, the coronary sinus diameter increases with age. These factors result in longer ablation and procedural times in older patients.
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http://dx.doi.org/10.1016/j.cjco.2021.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348584PMC
July 2021

Cohort study of hospitalists' procedural skills: baseline competence and durability after simulation-based training.

BMJ Open 2021 08 16;11(8):e045600. Epub 2021 Aug 16.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Objectives: Hospitalists are expected to be competent in performing bedside procedures, which are associated with significant morbidity and mortality. A national decline in procedures performed by hospitalists has prompted questions about their procedural competency. Additionally, though simulation-based mastery learning (SBML) has been shown to be effective among trainees whether this approach has enduring benefits for independent practitioners who already have experience is unknown. We aimed to assess the baseline procedural skill of hospitalists already credentialed to perform procedures. We hypothesised that simulation-based training of hospitalists would result in durable skill gains after several months.

Design: Prospective cohort study with pretraining and post-training measurements.

Setting: Single, large, urban academic medical centre in the USA.

Participants: Twenty-two out of 38 eligible participants defined as hospitalists working on teaching services where they would supervise trainees performing procedures.

Interventions: One-on-one, 60 min SBML of lumbar puncture (LP) and abdominal paracentesis (AP).

Primary And Secondary Outcome Measures: Our primary outcome was the percentage of hospitalists obtaining minimum passing scores (MPS) on LP and AP checklists; our secondary outcomes were average checklist scores and self-reported confidence.

Results: At baseline, only 16% hospitalists met or exceeded the MPS for LP and 32% for AP. Immediately after SBML, 100% of hospitalists reached this threshold. Reassessment an average of 7 months later revealed that only 40% of hospitalists achieved the MPS. Confidence increased initially after training but declined over time.

Conclusions: Hospitalists may be performing invasive bedside procedures without demonstration of adequate skill. A single evidence-based training intervention was insufficient to sustain skills for the majority of hospitalists over a short period of time. More stringent practices for certifying hospitalists who perform risky procedures are warranted, as well as mechanisms to support skill maintenance, such as periodic simulation-based training and assessment.
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http://dx.doi.org/10.1136/bmjopen-2020-045600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370503PMC
August 2021

How do we measure attention? Using factor analysis to establish construct validity of neuropsychological tests.

Cogn Res Princ Implic 2021 07 22;6(1):51. Epub 2021 Jul 22.

Basic Biobehavioral and Psychological Sciences Branch, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD, 20850, USA.

We investigated whether standardized neuropsychological tests and experimental cognitive paradigms measure the same cognitive faculties. Specifically, do neuropsychological tests commonly used to assess attention measure the same construct as attention paradigms used in cognitive psychology and neuroscience? We built on the "general attention factor", comprising several widely used experimental paradigms (Huang et al., 2012). Participants (n = 636) completed an on-line battery (TestMyBrain.org) of six experimental tests [Multiple Object Tracking, Flanker Interference, Visual Working Memory, Approximate Number Sense, Spatial Configuration Visual Search, and Gradual Onset Continuous Performance Task (Grad CPT)] and eight neuropsychological tests [Trail Making Test versions A & B (TMT-A, TMT-B), Digit Symbol Coding, Forward and Backward Digit Span, Letter Cancellation, Spatial Span, and Arithmetic]. Exploratory factor analysis in a subset of 357 participants identified a five-factor structure: (1) attentional capacity (Multiple Object Tracking, Visual Working Memory, Digit Symbol Coding, Spatial Span), (2) search (Visual Search, TMT-A, TMT-B, Letter Cancellation); (3) Digit Span; (4) Arithmetic; and (5) Sustained Attention (GradCPT). Confirmatory analysis in 279 held-out participants showed that this model fit better than competing models. A hierarchical model where a general cognitive factor was imposed above the five specific factors fit as well as the model without the general factor. We conclude that Digit Span and Arithmetic tests should not be classified as attention tests. Digit Symbol Coding and Spatial Span tap attentional capacity, while TMT-A, TMT-B, and Letter Cancellation tap search (or attention-shifting) ability. These five tests can be classified as attention tests.
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http://dx.doi.org/10.1186/s41235-021-00313-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298746PMC
July 2021

Measuring Trainee Duty Hours: The Times They Are a-Changin'.

J Hosp Med 2021 07;16(7):447

Section of Hospital Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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http://dx.doi.org/10.12788/jhm.10.12788/jhm.3614DOI Listing
July 2021

A Selective Androgen Receptor Modulator (OPK-88004) in Prostate Cancer Survivors: A Randomized Trial.

J Clin Endocrinol Metab 2021 07;106(8):2171-2186

Research Program in Men's Health: Aging and Metabolism, Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital, Boston, MA, USA.

Background: Androgen deficiency is common among prostate cancer survivors, but many guidelines consider history of prostate cancer a contraindication for testosterone replacement. We determined the safety and efficacy of a selective androgen receptor modulator (OPK-88004) in symptomatic, testosterone-deficient men who had undergone radical prostatectomy for low-grade, organ-confined prostate cancer.

Methods: In this placebo-controlled, randomized, double-blind trial, 114 men, ≥19 years of age, who had undergone radical prostatectomy for low-grade, organ-localized prostate cancer, undetectable PSA (<0.1 ng/mL) for ≥2 years after radical prostatectomy and testosterone deficiency were randomized in stages to placebo or 1, 5, or 15 mg OPK-88004 daily for 12 weeks. Outcomes included PSA recurrence, sexual activity, sexual desire, erectile function, body composition, muscle strength and physical function measures, mood, fatigue, and bone markers.

Results: Participants were on average 67.5 years of age and had severe sexual dysfunction (mean erectile function and sexual desire domain scores 7.3 and 14.6, respectively). No participant experienced PSA recurrence or erythrocytosis. OPK-88004 was associated with a dose-related increase in whole-body (P < 0.001) and appendicular (P < 0.001) lean mass and a significantly greater decrease in percent body fat (P < 0.001) and serum alkaline phosphatase (P < 0.001) than placebo. Changes in sexual activity, sexual desire, erectile function, mood, fatigue, physical performance, and bone markers did not differ among groups (P = 0.73).

Conclusions: Administration of OPK-88004 was safe and not associated with PSA recurrence in androgen-deficient men who had undergone radical prostatectomy for organ-confined prostate cancer. OPK-88004 increased lean body mass and decreased fat mass but did not improve sexual symptoms or physical performance.
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http://dx.doi.org/10.1210/clinem/dgab361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277210PMC
July 2021

The use of minimal fluoroscopy for cardiac electrophysiology procedures: A meta-analysis and review of the literature.

Clin Cardiol 2021 Jun 17;44(6):814-823. Epub 2021 May 17.

Division of Cardiology, University of Toronto, Toronto, Ontario, Canada.

Background: Conventional catheter ablation involves prolonged exposure to ionizing radiation, potentially leading to detrimental health effects. Minimal fluoroscopy (MF) represents a safer alternative, which should be explored. Data on the safety and efficacy of this technique are limited.

Hypothesis: Our hypothesis is that MF is of equal efficacy and safety to conventional catheter ablation with the use of fluoroscopy by performing a meta-analysis of both randomized controlled trials (RCTs) and real-world registry studies.

Methods: Pubmed and Embase were searched from their inception to July 2020 for RCTs, cohort and observational studies that assessed the outcomes of catheter ablation using a MF technique versus the conventional approach.

Results: Fifteen studies involving 3795 patients were included in this meta-analysis. There was a significant reduction in fluoroscopy and procedural time with no difference in acute success (odds ratio [OR]:0.74, 95% CI: 0.50-1.10, p = .14), long-term success (OR:0.92, 95% CI: 0.65-1.31, p = .38), arrhythmia recurrence (OR:1.24, 95% CI: 0.75-2.06, p = .97) or rate of complications. (OR:0.83, 95% CI: 0.46-1.48, p = .65). Additionally sub-group analysis for those undergoing catheter ablation for atrial fibrillation (AF) did not demonstrate a difference in success or complication rates (OR:0.86, 95% CI: 0.30-2.42, p = .77). Multivariate meta-regression did not identify the presence of moderator variables.

Conclusion: This updated meta-analysis demonstrated an overall reduction in procedural and fluoroscopy time for those undergoing a minimal fluoroscopic approach. There was no significant difference in either acute or chronic success rates or complications between a MF approach and conventional approach for the management of all arrhythmias including those undergoing catheter ablation for AF.
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http://dx.doi.org/10.1002/clc.23609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207968PMC
June 2021

Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.

J Am Heart Assoc 2021 05 14;10(10):e019755. Epub 2021 May 14.

Center for Translational Medicine Lewis Katz School of Medicine Temple University Philadelphia PA.

Background Impaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus-impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus-impaired MVEC function remain unclear. We studied the role of serum-derived small extracellular vesicles (ssEVs) in diabetes mellitus-impaired MVEC function. Methods and Results ssEVs were isolated from 8-week-old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano-sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro-angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2-specific inhibitor significantly reversed diabetic ssEVs-enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs-induced H3K27me3 expression at promoter of pro-angiogenic genes. Conclusions Diabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2-enhanced expression of H3K27me3 and consequent silencing of pro-angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.120.019755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200714PMC
May 2021

More than Meets the Eye: Diagnostic Procedures as Hazards in Clinical Decision-Making.

Am J Med Qual 2021 Sep-Oct 01;36(5):373

Harvard Medical School, Boston, MA Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.

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http://dx.doi.org/10.1097/01.JMQ.0000735492.90156.beDOI Listing
November 2021

The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From Both and Exhibits Potent Phosphatidylinositol-3,4,5-Triphosphate Phosphatase Activity.

Front Cell Infect Microbiol 2021 29;11:664221. Epub 2021 Mar 29.

Department of Basic and Translational Sciences, University of Pennsylvania School of Dental Medicine, Philadelphia, PA, United States.

Human lymphocytes exposed to (Aa) cytolethal distending toxin (Cdt) undergo cell cycle arrest and apoptosis. In previous studies, we demonstrated that the active Cdt subunit, CdtB, is a potent phosphatidylinositol (PI) 3,4,5-triphosphate phosphatase. Moreover, AaCdt-treated cells exhibit evidence of PI-3-kinase (PI-3K) signaling blockade characterized by reduced levels of PIP3, pAkt, and pGSK3β. We have also demonstrated that PI-3K blockade is a requisite of AaCdt-induced toxicity in lymphocytes. In this study, we extended our observations to include assessment of Cdts from (HdCdt) and (CjCdt). We now report that the CdtB subunit from HdCdt and CjCdt, similar to that of AaCdt, exhibit potent PIP3 phosphatase activity and that Jurkat cells treated with these Cdts exhibit PI-3K signaling blockade: reduced levels of pAkt and pGSK3β. Since non-phosphorylated GSK3β is the active form of this kinase, we compared Cdts for dependence on GSK3β activity. Two GSK3β inhibitors were employed, LY2090314 and CHIR99021; both inhibitors blocked the ability of Cdts to induce cell cycle arrest. We have previously demonstrated that AaCdt induces increases in the CDK inhibitor, p21, and, further, that this was a requisite for toxin-induced cell death apoptosis. We now demonstrate that HdCdt and CjCdt also share this requirement. It is also noteworthy that p21 was not involved in the ability of the three Cdts to induce cell cycle arrest. Finally, we demonstrate that, like AaCdt, HdCdt is dependent upon the host cell protein, cellugyrin, for its toxicity (and presumably internalization of CdtB); CjCdt was not dependent upon this protein. The implications of these findings as they relate to Cdt's molecular mode of action are discussed.
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http://dx.doi.org/10.3389/fcimb.2021.664221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039388PMC
July 2021

Small Incision Lenticule Extraction (SMILE): Myths and Realities.

Semin Ophthalmol 2021 May 6;36(4):140-148. Epub 2021 Apr 6.

Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.

The emergence of SMILE in the last decade has provided an alternative to LASIK for patients considering cornea laser refractive surgery. SMILE offers a novel approach using the femtosecond laser to create an intrastromal lenticule that can be removed through a small three to four millimeter incision.The purpose of this study is to review the recent literature on popular SMILE claims - reduced iatrogenic dry eye, better recovery of corneal sensation, and a biomechanically stronger cornea - summarize the published outcomes, and determine which claims are myths versus realities.SMILE is still in its infancy as a refractive technique in the US after recent USFDA approval for its treatment of myopia astigmatism in October 2018. Future randomized controlled studies are needed to compare its outcomes to LASIK, which has well-documented good visual outcomes, rapid postoperative recovery, and good safety profile.
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http://dx.doi.org/10.1080/08820538.2021.1887897DOI Listing
May 2021

Procedural Competency Among Hospitalists: A Literature Review and Future Considerations.

J Hosp Med 2021 04;16(4):230-235

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts.

Background: As general internists practicing in the inpatient setting, hospitalists at many institutions are expected to perform invasive bedside procedures, as defined by professional standards. In reality, hospitalists are doing fewer procedures and increasingly are referring to specialists, which threatens their ability to maintain procedural skills. The discrepancy between expectations and reality, especially when hospitalists may be fully credentialed to perform procedures, poses significant risks to patients because of morbidity and mortality associated with complications, some of which derive from practitioner inexperience.

Methods: We performed a structured search of the peer-reviewed literature to identify articles focused on hospitalists performing procedures.

Results: Our synthesis of the literature characterizes contributors to hospitalists' procedural competency and discusses: (1) temporal trends for procedures performed by hospitalists and their associated referral patterns, (2) data comparing use and clinical outcomes of procedures performed by hospitalists compared with specialists, (3) the lack of nationwide standardization of hospitalist procedural training and credentialing, and (4) the role of medical procedure services, although limited in supportive evidence, in concentrating procedural skill and mitigating risk in the hands of a few well-trained hospitalists.

Conclusion: We conclude with recommendations for hospital medicine groups to ensure the safety of hospitalized patients undergoing bedside procedures.
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http://dx.doi.org/10.12788/jhm.3590DOI Listing
April 2021

Partnering with healthcare facilities to understand psychosocial distress screening practices among cancer survivors: pilot study implications for study design, recruitment, and data collection.

BMC Health Serv Res 2021 Mar 17;21(1):238. Epub 2021 Mar 17.

Centers for Disease Control and Prevention, Division of Cancer Prevention and Control, Atlanta, GA, USA.

Background: We sought to understand barriers and facilitators to implementing distress screening (DS) of cancer patients to inform and promote uptake in cancer treatment facilities. We describe the recruitment and data collection challenges and recommendations for assessing DS in oncology treatment facilities.

Methods: We recruited CoC-accredited facilities and collected data from each facility's electronic health record (EHR). Collected data included cancer diagnosis and demographics, details on DS, and other relevant patient health data. Data were collected by external study staff who were given access to the facility's EHR system, or by facility staff working locally within their own EHR system. Analyses are based on a pilot study of 9 facilities.

Results: Challenges stemmed from being a multi-facility-based study and local institutional review board (IRB) approval, facility review and approval processes, and issues associated with EHR systems and the lack of DS data standards. Facilities that provided study staff remote-access took longer for recruitment; facilities that performed their own extraction/abstraction took longer to complete data collection.

Conclusion: Examining DS practices and follow-up among cancer survivors necessitated recruiting and working directly with multiple healthcare systems and facilities. There were a number of lessons learned related to recruitment, enrollment, and data collection. Using the facilitators described in this manuscript offers increased potential for working successfully with various cancer centers and insight into partnering with facilities collecting non-standardized DS clinical data.
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http://dx.doi.org/10.1186/s12913-021-06250-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968218PMC
March 2021

Striving for Diversity: National Survey of OB-GYN Program Directors Reporting Residency Recruitment Strategies for Underrepresented Minorities.

J Surg Educ 2021 Sep-Oct;78(5):1476-1482. Epub 2021 Mar 13.

Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts. Electronic address:

Objective: To characterize strategies among OB-GYN residency programs to recruit underrepresented minorities in medicine, the relative effectiveness of these approaches, and the associated barriers to recruitment.

Design: We conducted a survey to solicit strategies from OB-GYN PDs at 253 United States (U.S.) accredited programs for recruiting underrepresented minorities in medicine (URiM) applicants. We also sought their relative effectiveness and barriers to recruitment.

Setting: A national survey of U.S. accredited residency programs in OB-GYN in 2017-2018.

Results: A total of 56 (22% response rate) PDs responded. Programs reported either "some" or "significant emphasis" on URiM recruitment (77%), with only 32% employing specific recruitment strategies. Fifteen (83%) reported using race and/or ethnicity data in the U.S.'s centralized electronic residency application service, 10 (56%) recruiting applicants from URiM association events, 9 (50%) meeting with potential URiMs prior to official interviews, and 5 (28%) offering a second visit. Efforts perceived to be most effective were second visits (39%), identifying race/ethnicity in electronic residency application service (33%), URiM recruitment events (28%), and individual phone calls (22%). Barriers included the lack of applicant pool (32%), lack of department diversity (29%) and lack of institutional diversity (30%).

Conclusions: This systematic collation of URiM recruitment practices and perceptions of their effectiveness represents a toolbox of options for residency programs to consider in diversifying their workforce.
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http://dx.doi.org/10.1016/j.jsurg.2021.02.007DOI Listing
November 2021

Three-dimensional unity of engineered heart tissue mimics the heart better than two-dimensional cellular diversity.

Cardiovasc Res 2021 07;117(9):1995-1997

Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, 3500 N Broad Street, Philadelphia, PA 19140, USA.

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http://dx.doi.org/10.1093/cvr/cvab052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318098PMC
July 2021

Sex Differences in Hemoglobin A1c Levels Related to the Comorbidity of Obesity and Depression.

J Womens Health (Larchmt) 2021 09 2;30(9):1303-1312. Epub 2021 Feb 2.

Division of Women's Health, Department of Medicine, Boston, Massachusetts, USA.

Obesity (OB) and major depressive disorder (MDD) are chronic conditions associated with disease burden, and their comorbidity appears more common among women. Mechanisms linking these conditions may involve inflammatory and metabolic pathways. The goal of this study was to evaluate the impact of MDD on relationships between OB and cardiometabolic function, and sex differences therein. Adult offspring from the New England Family Studies (NEFS) were assessed at ages 39-50, including anthropometry, cardiometabolic profile assays, and metabolic syndrome. Individuals were grouped by body mass index (BMI) and MDD status: healthy weight with ( = 50) or without MDD ( = 95) and obese with ( = 79) or without MDD ( = 131). The interaction of (recurrent) MDD and BMI on cardiometabolic markers was tested using quantile regression models. Participants with MDD exhibited significantly higher hemoglobin A1c (HbA1c) than those without MDD (5.60% vs. 5.35%,  < 0.05). Women with comorbid recurrent MDD and OB had higher HbA1c levels compared to obese women without MDD (5.75% vs. 5.44%,  < 0.05); an interaction between MDD and BMI status was not observed among men. We demonstrated sex differences in the interaction between BMI and recurrent MDD status on a primary biomarker for diabetes risk, suggesting a common metabolic pathway predisposing women to these comorbid conditions. Further investigation is needed to identify mechanisms that may lead to more effective, sex-dependent screening and therapies.
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http://dx.doi.org/10.1089/jwh.2020.8467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558065PMC
September 2021

Effect of Protein Intake on Visceral Abdominal Fat and Metabolic Biomarkers in Older Men With Functional Limitations: Results From a Randomized Clinical Trial.

J Gerontol A Biol Sci Med Sci 2021 05;76(6):1084-1089

Department of Medicine, Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center for Function Promoting Therapies, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: It remains controversial whether high protein diets improve cardiometabolic profile. We investigated whether increasing protein intake to 1.3 g/kg/day in functionally limited older adults with usual protein intake ≤RDA (0.8 g/kg/day) improves visceral fat accumulation and serum cardiovascular risk markers more than the recommended daily allowance (RDA).

Methods: The Optimizing Protein Intake in Older Men Trial was a placebo-controlled, randomized trial in which 92 functionally limited men, ≥65 years, with usual protein intake ≤RDA were randomized for 6 months to: 0.8 g/kg/day protein plus placebo; 1.3 g/kg/day protein plus placebo; 0.8 g/kg/day protein plus testosterone enanthate 100 mg weekly; or 1.3 g/kg/day protein plus testosterone enanthate 100 mg weekly. In this substudy, metabolic and inflammatory serum markers were measured in 77 men, and visceral adipose tissue (VAT) was assessed using dual-energy x-ray absorptiometry in 56 men.

Results: Treatment groups were similar in their baseline characteristics. Randomization to 1.3 g/kg/day protein group was associated with greater reduction in VAT compared to 0.8 g/kg/day group (between-group difference: -17.3 cm2, 95% confidence interval [CI]: -29.7 to -4.8 cm2, p = .008), regardless of whether they received testosterone or placebo. Changes in fasting glucose, fasting insulin, HOMA-IR, leptin, adiponectin, IL-6, and hs-CRP did not differ between the 0.8 versus 1.3 g/kg/day protein groups regardless of testosterone use.

Conclusions: Protein intake >RDA decreased VAT in functionally limited older men but did not improve cardiovascular disease risk markers.

Clinical Trials Registration Number: NCT01275365.
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http://dx.doi.org/10.1093/gerona/glab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140050PMC
May 2021

Associations between Traumatic Brain Injury, Drug Abuse, Alcohol Use, Adverse Childhood Events, and Aggression Levels in Individuals with Foster Care History.

Neurotrauma Rep 2020 10;1(1):241-252. Epub 2020 Dec 10.

Injury Prevention Research Office, Division of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.

Nearly 50,000 Canadian children live in foster care. Compared with their peers, foster children experience greater independence and decreased guidance, predisposing them to harmful exposures such as traumatic brain injury (TBI), illicit drugs, and alcohol. Foster children also report a higher level of childhood abuse compared with the general population. This study aimed to: 1) investigate substance/alcohol use disorder, adverse childhood events (ACE), TBI, aggression levels, and the difference between normalized percentages of brain regions of interest (ROIs) in a sample of Canadian youths with and without foster care history; 2) determine the prevalence of substance/alcohol use disorder, ACE, and aggression levels within individuals with foster care history when stratified by likelihood of TBI; and 3) determine the significant correlates of elevated aggression levels within this population. Participants completed standardized questionnaires that measured the prevalence of TBI, substance and alcohol use disorder, ACE, and aggression. Magnetic resonance imaging (MRI) was used to measure differences in brain ROI. Regression and network analysis were used to study interactions between variables. Seventy-four participants (51 individuals with foster care history and 23 age-matched controls from the general population) completed standardized questionnaires. Fifty-five of these individuals (39 foster participants and 16 controls) underwent brain MRI. Foster participants had higher prevalence of substance use disorder ( < 0.001), alcohol use disorder ( = 0.003), ACE ( < 0.001), and elevated aggression levels ( < 0.001) than healthy controls. No significant difference was found among brain ROI. The prevalence of TBI in foster participants was 65%. Foster participants with moderate or high likelihood of TBI exposure had higher levels of drug use and aggression than those with no or low likelihood of exposure. Brain volumes were not associated with substance/alcohol use disorder or ACE. No significant associations were found between aggression levels and the studied variables.
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http://dx.doi.org/10.1089/neur.2020.0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774879PMC
December 2020

Cancer Information-seeking in an Age of COVID-19: Findings from the National Cancer Institute's Cancer Information Service.

Health Commun 2021 Jan 22;36(1):89-97. Epub 2020 Nov 22.

National Cancer Institute, Office of Communications and Public Liaison.

Seeking cancer information is recognized as an important, life-saving behavior under normal circumstances. However, given the significant impact of COVID-19 on society, the healthcare system, and individuals and their families, it is important to understand how the pandemic has affected cancer information needs in a crisis context and, in turn, how public health agencies have responded to meeting the information needs of various audiences. Using data from the National Cancer Institute's Cancer Information Service (CIS) - a long-standing, multi-channel resource for trusted cancer information in English and Spanish - this descriptive analysis explored differences in cancer information-seeking among cancer survivors, caregivers, tobacco users, and members of the general public during the onset and continuation of the COVID-19 pandemic (February - September 2020), specifically comparing interactions that involved a discussion of COVID-19 to those that did not. During the study period, COVID-19 discussions were more likely to involve survivors or caregivers compared to tobacco users and the general public. Specific patterns emerged across the four user types and their respective discussions of COVID-19 related to language of service, point of CIS access, stage on the cancer continuum, subject of interaction, cancer site discussed, and referrals provided by the CIS. These results provide insights that may help public health agencies deliver, prioritize, and tailor their messaging and response to specific audiences based on heightened health information needs during a crisis.
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http://dx.doi.org/10.1080/10410236.2020.1847449DOI Listing
January 2021

A multivariate, quantitative assay that disentangles key kinetic parameters of primary human T cell function in vitro.

PLoS One 2020 9;15(11):e0241421. Epub 2020 Nov 9.

Discovery Research, A2 Biotherapeutics, Inc., Agoura Hills, California, United States of America.

Cell therapy is poised to play a larger role in medicine, most notably for immuno-oncology. Despite the recent success of CAR-T therapeutics in the treatment of blood tumors and the rapid progress toward improved versions of both CAR- and TCR-Ts, important analytical aspects of preclinical development and manufacturing of engineered T cells remain immature. One limiting factor is the absence of robust multivariate assays to disentangle key parameters related to function of engineered effector cells, especially in the peptide-MHC (pMHC) target realm, the natural ligand for TCRs. Here we describe an imaging-based primary T cell assay that addresses several of these limitations. To our knowledge, this assay is the first quantitative, high-content assay that separates the key functional parameters of time- and antigen-dependent T cell proliferation from cytotoxicity. We show that the assay sheds light on relevant biology of CAR- and TCR-T cells, including response kinetics and the influence of effector:target ratio.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241421PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652339PMC
December 2020

Identification and Comparison of Hyperglycemia-Induced Extracellular Vesicle Transcriptome in Different Mouse Stem Cells.

Cells 2020 09 15;9(9). Epub 2020 Sep 15.

Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA.

Extracellular vesicles (EVs) derived from stem /progenitor cells harbor immense potential to promote cardiomyocyte survival and neovascularization, and to mitigate ischemic injury. However, EVs' parental stem/progenitor cells showed modest benefits in clinical trials, suggesting autologous stem cell/EV quality might have been altered by stimuli associated with the co-morbidities such as hyperglycemia associated with diabetes. Hyperglycemia is a characteristic of diabetes and a major driving factor in cardiovascular disease. The functional role of stem/progenitor cell-derived EVs and the molecular signature of their secreted EV cargo under hyperglycemic conditions remain elusive. Therefore, we hypothesized that hyperglycemic stress causes transcriptome changes in stem/progenitor cell-derived EVs that may compromise their reparative function. In this study, we performed an unbiased analysis of EV transcriptome signatures from 3 different stem/progenitor cell types by RNA sequencing. The analysis revealed differential expression of a variety of RNA species in EVs. Specifically, we identified 241 common-dysregulated mRNAs, 21 ncRNAs, and 16 miRNAs in three stem cell-derived EVs. Gene Ontology revealed that potential function of common mRNAs mostly involved in metabolism and transcriptional regulation. This study provides potential candidates for preventing the adverse effects of hyperglycemia-induced stem/progenitor cell-derived EV dysfunction, and reference data for future biological studies and application of stem/progenitor cell-derived EVs.
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http://dx.doi.org/10.3390/cells9092098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564160PMC
September 2020
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