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AMA Research Challenge 2022

Characterization of Salivary Extracellular Vesicles in Preterm Infants

[![](https://assets.underline.io/uploads/markdown_image/1/image/261902fdf187a88bfa74da226ff77186.png)](https://drive.google.com/file/d/1gUViQJJHCSgM38OhwpDoTdN89evCsZ-7/view?usp=sharing)
[![](https://assets.underline.io/uploads/markdown_image/1/image/1605292c232e6f185c7f87ee38e8502a.png)](https://drive.google.com/file/d/1kPkznVX_6cx-n846z_pUtyVDZql9KImc/view?usp=sharing)


### **Welcome Message**

Welcome to the inaugural **Dutch Lung Congress.**  We have all missed our opportunities to network and interact with our colleagues in the last twelve months or more.  While our desire was to meet face to face once again, when it became evident that this would not be possible until much later in 2021 (or even into 2022) the hard working committee organizing the Dutch Lung Congress found, what we hope will be, an excellent alternative to facilitate our annual meeting.

The Dutch Lung Congress aims to bring together everyone interested in research related to pulmonary diseases in the Netherlands.  We hope this event will provide opportunities for multidisciplinary interactions to enhance our approaches for addressing these challenging diseases.  Each session will include input from patients, clinical and basic and/or translational scientists discussing the latest information around the central themes chosen by the organizing committee.  One advantage of holding our congress as a virtual event this year is that we will have the opportunity to hear from world leading experts from all over the globe.  We hope you enjoy the programme the organizing committee have put together and will engage in dynamic discussions with all the speakers.

One highlight of our congress will be the Young Investigator Session.  Remember to join us for this exciting session when we will hear from the presenters who submitted the top scoring abstracts.  This promises to be a session full of exciting science that will display the strengths that constitute the future talent in our field.

When we are not listening to these great presentations we can all meet in Gathertown.  Within this interactive platform you will be able to meet colleagues and friends for networking. Enjoy a private chat over a virtual coffee, visit the booths of our sponsors and other parties, chat with the Young Investigator Board members or take some timeout in the relaxation spaces.  While in Gathertown take the opportunity to visit all the diverse posters on display. Chat live with the presenters or leave them a question on the discussion board for them to engage with you.  Make sure you check for any messages each time you enter Gathertown to make the most of your networking opportunities.

We look forward to seeing you during the DLC and the great scientific (and other) discussions we are anticipating during our 2021 meeting.

On behalf of the DLC organizing Committee
<br>**Janette Burgess
<br>Chair, DLC Organizing Committee**
![](https://assets.underline.io/uploads/markdown_image/1/image/f461fb275d9667fb2a76a30813388e90.png)



### Special Session: Publieksmiddag
![](https://assets.underline.io/uploads/markdown_image/1/image/77e768dd500e6205175e5cafba59abdc.png)






![](https://assets.underline.io/uploads/markdown_image/1/image/f461fb275d9667fb2a76a30813388e90.png)
**More about the committee team:**:
[Barbro N. Melgert, PhD] (https://drive.google.com/file/d/1q_IIH3JvTivumCUzzsZGX7BgD41HxQmk/view?usp=sharing)
// [Bas Holverda, PhD] (https://drive.google.com/file/d/1QKXHmTTQjgs4OZVuM8doXU055S-fu_uU/view?usp=sharing)
// [Frits Franssen, PhD] (https://drive.google.com/file/d/1d7HRUJaqGuRFzkPN3SVgkbBfqFkDkWq2/view?usp=sharing)
// [Janette Burgess, PhD] (https://drive.google.com/file/d/1VHFlrEN6uCQGeeW3Lj4I8aTw7HsB0GFr/view?usp=sharing)
// [Michel van den Heuvel, PhD] (https://drive.google.com/file/d/1JeOEP8MHxiK_4lONr8UM2HaxdxpkAmA2/view?usp=sharing)
// [Patrick Bhairosing] (https://drive.google.com/file/d/1xI8ORq-g1bbVcrlRDviZ9NhAwanc4dFl/view?usp=sharing)
// [Gimano Amatngalim, PhD] (https://drive.google.com/file/d/1fyVDDKARLNjRk_JZk8_GyhGMjmp6DWHp/view?usp=sharing)
// [Peter Kunst, PhD] (https://drive.google.com/file/d/1QhtB4nQezpAjbfUAcBnINc-Bm3Shy2Lf/view?usp=sharing)
// [Dr. Michel van den Heuvel, Prof., MD, PhD] (https://drive.google.com/file/d/1JBdNEBXZCEikEZhJ6MoD5DhQfXMz3bP6/view?usp=sharing)
![](https://assets.underline.io/uploads/markdown_image/1/image/f461fb275d9667fb2a76a30813388e90.png)

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Dutch Lung Congress

technical paper

Welcome to the largest national, multi-specialty research event **featuring research from 750 medical students, residents and fellows, and international medical graduates.**


#### Event Details
The 2022 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. Log in at any time throughout the event to:
* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges and compete to win a $10,000 grand prize sponsored by Laurel Road.
<br>

#### Attend Live Forums
**Oct. 20, 6 — 7 p.m. Central**
<br>**How to plan a career in academic medicine** 
<br>Learn how to plan a career in academic medicine and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
<br>
<br>**Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/d5adb133dfc58eb0a6d469e9cedcd5d4.jpg)
Ricardo Correa, MD, EdD
![](https://assets.underline.io/uploads/markdown_image/1/image/5f9437ab87861538bf02b9ca7c0d926e.jpg)
Stuart M. Greenstein, MD
![](https://assets.underline.io/uploads/markdown_image/1/image/05b1b637c99286d558c371f8e8b185ce.jpg)
Stephanie Strohbeen, MD
<br>
<br>**Oct. 22, 11 a.m. — Noon Central**
<br>**How to get published**
<br>Learn tips to get your research published and get your questions answered. [Access Here](https://underline.io/events/363/lounge)
<br>
<br>**Speakers**
![](https://assets.underline.io/uploads/markdown_image/1/image/8ce6235e957d31cb5e6f9097cc6f6972.jpg)
Jessica Li, MD/PhD Candidate
![](https://assets.underline.io/uploads/markdown_image/1/image/9950ef2e0237f54cb3d8280334d42491.jpg)
Charles Lopresto, DO

### Sponsor
AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in the judging or scoring process to select the winner. The winner will be announced on Dec. 7 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)

<br>

**There is no registration fee for this event! **

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals.

**Please use the link below to register for free if you have not already done so:**

https://www.ama-assn.org/about/events/ama-research-challenge

Registration Is Required

Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Mosaic Chromosomal Alterations Increase Risk of MGUS and Multiple Myeloma

The aim of this study was to create an accurate risk stratification tool for Covid-19 admissions. We looked at data from 1093 patients admitted to a regional hospital in Michigan with the primary diagnosis of Covid-19. Through various statistical approaches we analyzed factors that lead to worse outcomes. We then combined our analysis to determine which predictive factor had a stronger influence on Covid-19 mortality. Our end goal is to use this data to drive clinical decision making by identifying patients at greater risk of worse outcomes.

Multifaceted, Data-Driven Approach for Characterization and Prediction of Covid-19 Morbidity and Mortality in Rural Health Care Facilities

Background: The purpose of this study was to define the prevalence of orthopaedic knee scooter (OKS)-related injuries, describe the patient perceptions of OKS safety and identify potential risk factors.
Methods: This single-surgeon prospective study enrolled 134 patients at a community-based orthopaedic clinic from 6/2020 to 4/2021. Our primary outcome informed an a priori power analysis. The prevalence of OKS-related injury, patient perceptions, and riskfactors were analyzed.
Results: The prevalence of patient falls was 37% (44/118, 95CI 29-46%), and the prevalence of patient injury was 15% (18/118, 95CI 10-23%). Sedentary lifestyle increased odds (OR = 4.67, 1.52-14.35 95CI) of OKS-related injury.
Conclusion: Despite a high prevalence of patient falls (37%), there is a low prevalence of injury (15%) and a favorable perception of OKS safety. Sedentary lifestyles may be a risk factor for OKS-related injury.

Orthopaedic Knee Scooter-Related Injury: Prevalence and Patient Safety Perception in a Prospective Cohort with Exploratory Risk Factor Analysis

Orthopaedic surgery, the NFL's biggest gateway drug: a case study

Background
Colorectal adenomas are precursors of colorectal cancer (CRC). Pro-inflammatory states associated with colorectal adenomas significantly predispose for colorectal tumorigenesis via upregulation of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis. The PGE2/COX-2 axis allows cancer cells to progress and evade attack from immune cells via increasing immunosuppressive cell activity, disrupting antigen-presenting and T-cell functions, and interrupting innate leukocyte responses. The purpose of this study was to demonstrate that PGE2 can upregulate expression of PD-1, an immunosuppressive signaling receptor, on THP-1-derived macrophages and CD8+ T-cells. 

Methods
THP-1 cells were differentiated into macrophages via phorbol 12-myristate-13-acetate (PMA) administration. Following serum starvation and incubation with three different concentrations of PGE2 (0.1μM, 0.3μM, and 1μM), the cells were analyzed with western blot and qRT-PCR. CD8+ T-cells were isolated from mice spleens using biotin-antibody cocktail and anti-biotin microbeads and then stimulated with rIL-2 and CD3/CD28 Dynabeads. The cells were serum starved, incubated with two different concentrations of PGE2 (0.1μM and 0.3μM), and analyzed utilizing flow cytometry and qRT-PCR.

Results
Western blot analysis of THP-1-derived macrophages incubated in 0.1μM, 0.3μM, and 1.0μM PGE2 demonstrated increased PD-1 expression. qRT-PCR analysis of THP-1-derived macrophages incubated in 0.1μM, 0.3μM, and 1.0μM PGE2 demonstrated 3.030-fold, 5.712-fold, and 2.683-fold increased PD-1 mRNA expression, respectively. qRT-PCR of mouse CD8+ T-cells incubated in 0.1μM and 0.3μM PGE2 demonstrated 1.874-fold and 9.594-fold increased PD-1 mRNA expression, respectively. Flow cytometry demonstrated that 9.14% and 9.35% of mouse CD8+ T-cells incubated in 0.1μM and 0.3μM PGE2 expressed PD-1, respectively, while 4.65% of control cells expressed PD-1. 

Conclusion
Our in vitro data shows PGE2 inducing PD-1 expression in THP-1-derived macrophages and mouse CD8+ T-cells. Greater PD-1 expression would allow cancer cells to progress safe from the host immune system. These data demonstrate that PGE2 produced in the colorectal tumor microenvironment promotes immune evasion by suppressing tumor-infiltrating CD8+ T-cell cytotoxicity and macrophage phagocytosis via induction of PD-1. Because of PGE2’s immunosuppressive effects, NSAIDs and COXIBs are effective at preventing and treating CRC by inhibiting PGE2 synthesis via COX-2 blockade.

PGE2 Promotes Colorectal Tumorigenesis via Increased PD-1 Expression on Macrophages and CD8+ T-Cells

Background: Pulmonary Artery Pulsatility index (PAPi) is calculated by pulmonary artery pulse pressure divided by central venous pressure and is directly proportional to right ventricular contractility and stroke volume, and inversely related to pulmonary artery afterload and filling pressures. While PAPi as a prognostic hemodynamic measure has been studied in various adult populations, including to predict right ventricular (RV) failure following left ventricular assist device (LVAD) implantation and to predict renal outcomes following heart transplant (HTx), it has not been evaluated in children post HTx. We hypothesize that PAPi will correlate with known hemodynamic parameters and predict acute kidney injury (AKI) following pediatric HTx.

Methods: Medical records and hemodynamic data were retrospectively reviewed for patients ≤18 years old undergoing HTx at a single center between 1/2007-9/2021. Subgroups by HTx indication were myopathy or congenital heart disease (CHD). PAPi was calculated at routine cardiac catheterizations initially following HTx, and at 6 months, 1 year, and 5 years post HTx, with normal being PAPi ≥2.0. Correlations between PAPi and established hemodynamic measures collected at post HTx catheterizations including right ventricular end diastolic pressure (RVEDp), thermodilution cardiac index (TDCI), and central venous pressure to pulmonary capillary wedge pressure ratio (CVP-to-PCWP ratio) were analyzed using linear regressions. Correlation between PAPi and AKI was analyzed using a Fischer’s Exact test. 

Results: Fifty-three children underwent HTx in myopathy (n=27) or CHD (n=26) subgroups. PAPi correlated with RVEDp (p<0.001), TDCI (p=0.004), and CVP-to-PCWP ratio (p<0.001). At 6 months post HTx, PAPi <2.0 was associated with increased incidence of AKI (n=12/53, p=0.047). In analyzing 5-year trends, the myopathy subgroup had a normal early PAPi with no significant change at any time point. However, the CHD subgroup had a normal early (2.12 ± 0.18) and 6 month (2.45 ± 0.25) PAPi, but had a decline to an abnormal PAPi at 1 year (1.98 ± 0.13) and 5 years post HTx (1.67 ± 0.16). This decline between the 6 month and 5-year catheterizations was statistically significant (p=0.048).

Conclusions: PAPi in children post HTx correlates with established hemodynamic parameters routinely collected post HTx and may serve as a marker predicting renal dysfunction 6 months post HTx. Following HTx, PAPi declined significantly for the CHD subgroup. These findings suggest that incorporating PAPi into existing risk models may substantially improve earlier implementation for advanced therapies, thus improving clinical outcomes. PAPi as a comprehensive prognostic hemodynamic measure post pediatric HTx should be investigated in a larger multi-center study.


Pulmonary Artery Pulsatility Index After Pediatric Heart Transplant

Background
Rett Syndrome (RTT) is a pervasive neurodevelopmental disorder affecting females. RTT results from loss of function mutations in the X-linked gene Methyl CpG Binding Protein 2 (MeCP2*). MeCP2 encodes for the eponymously named protein, a ubiquitously expressed transcription factor critical for neuronal development and mature synapse maintenance. However, this pathogenesis is complicated by unequal mutation distribution; heterozygous mosaicism, one X-chromosome in each cell in lionized, results in a patchwork pattern of protein expression. Differences in the number, type, and location of MeCP2-deficient cells likely underlies the phenotype spectrum among the RTT patients. Whether some cells are more dependent on MeCP2, and therefore contribute more to clinical symptomatology or severity, is unknown. Here we explore that hypothesis in the context of impaired perceptive communication. 

Methods
We used Cre-lox genetic mouse lines to examine the consequences of cell-type restricted Mecp2 mutation to perception of naturally produced ultrasonic vocalizations (USVs). We employed infant pup retrieval behavior as a learned and ecologically relevant readout of auditory perception. Adult rodents naturally learn this behavior in response to pup USVs. We collected electrophysiology recordings and conducted calcium imaging to identify single neuron firing and neuronal population activity patterns in the auditory cortex during retrieval behavior and during passive playback of USVs. 

Results
Cortical cell type identity dictated MeCP2 dependence for supporting auditory processing. Mecp2 mutation restricted to parvalbumin positive (PV) inhibitory interneurons (IN) impaired pup retrieval behavior. However, mutation restricted to somatostatin- or vasoactive-intestinal-peptide- positive IN had no such effect. The inability of PV-Mecp2 mutants to response behaviorally to USVs resulted from degraded stimulus-driven neuronal activity in the auditory cortex, both at the single unit and population levels. That is, PV-restricted Mecp2 mutation impaired inhibitory cortical plasticity.

Conclusion
Our findings demonstrate a disproportionate dependence among cortical cell populations on MeCP2. This argues for cell-type specific pharmacological or genetic therapies, and a personalized medicine approach to the treatment of mosaic genetic disorders, including RTT. Moreover, these findings expand our understanding of neurotypical processes of audition and the contributions of various cortical subtype populations to those processes.

Rett Syndrome Mutation in Select Cortical Cell Populations Disrupts Auditory Processing

Background
Disease modifying antirheumatic drugs (DMARDs) are used to treat Rheumatoid Arthritis (RA).
The rates of total shoulder arthroplasty (TSA) in RA patients since the implementation of
DMARDs therapy is unknown. Furthermore, the utilization rates of TSA among various age
cohorts as well as by procedure type (anatomic (ATSA) and reverse (RTSA) total shoulder
arthroplasty) are not well defined in this patient population. The primary aim of this study was to
assess TSA trends from 2011-2019 for RA patients with and without filled DMARD
prescriptions.
Methods
A retrospective trends analysis utilizing a national claims database was performed investigating
the trends of TSA in RA patients with and without DMARD from 2011-2019. Patients were
identified using International Classification of Diseases codes and database-specific drug codes
were used to identify DMARD prescriptions. Patients were divided into two cohorts: RA patients
who underwent a TSA with or without DMARD prescription claims. Patients were also stratified
by age groups and procedure type for analysis. Linear regression and compound annual growth
rate (CAGR) were performed to compare trends of surgical utilization. Significant changes
between trends were determined using an interaction term between the trend and calendar year
within the regression. Statistical analysis were performed with Stata version 17.0.
 2018 American Medical Association. All rights reserved.
2
Results
From 2011-2019, incidence of TSA in RA patients without filled DMARD prescriptions
increased significantly more than RA patients with filled prescriptions (CAGR = 9.43% vs -
0.54%; linear regression P<0.001; quadratic P<0.001). Among the age groups, incidence of TSA
in RA patients with and without filled DMARD prescriptions significantly increased among all
age groups (P<0.001). The rate of change of TSA incidence in RA patients was significantly
higher increased in patients without filled DMARD prescription for all age groups compared to
RA patients with filled prescriptions (P<0.001). By procedure type, the incidence of RTSA were
significantly increasing while incidences of ATSA were significantly decreasing in both groups
(P<0.001).
Conclusion
Our findings show a greater increase in TSA surgeries among patients younger than 59 without
prescription claims suggesting that DMARD therapy may play a beneficial role in preventing or
delaying the need for TSA in RA patients.

Shoulder Arthroplasty Trends in Patients with Rheumatoid Arthritis Receiving DMARD Therapy

Background and Purpose: Deep burns and wounds remain difficult to treat effectively. Recent advances in tissue engineering and biotechnology have led to the advent of several skin substitutes (SS) including xenografts, bioscaffolds, and tissue-engineered dermal templates, though no product has been proven superior to current standards of care (SOC) for burns or wounds. We aim provide a systematic review and meta-analysis on clinical trials (CT) and randomized controlled trials (RCT) investigating the available skin substitute options for burn and wound treatment.

Methods: A systematic review of the PubMed, Scopus, and CINAHL databases was performed using PRISMA guidelines for CTs and RCTs published between 2017 and 2022. Articles were screened for relevance using Covidence®. Studies were then grouped by indication for use in burn or wound treatment. Meta-analysis was performed using RevMan v.5® on burn studies that assessed mean time to complete re-epithelialization and wound studies that assessed the proportion of wounds completely closed at 12 months. 

Results: 48 studies (39 RCT; 9 CT) were included and stratified by indication: burns (20 studies) or wounds (28 studies). For burns, 4 studies compared SS to SOC silver sulfadiazine cream as assessed by mean time to complete re-epithelialization (190 burns) and were included in meta-analyses. Fish skin xenografts (FSX) significantly outperformed SOC (p=0.0003) with burn depths ranging from superficial partial thickness to deep 2nd degree. For wounds, 13 studies compared SS to SOC alginate dressings assessed by the proportion of wounds completely healed at 12 weeks (2529 wounds) and were included in meta-analysis. Dehydrated human amnion and chorion allografts (dHACA; p=0.01) and human reticular acellular dermal matrices (HR-ADM, p<0.00001) all significantly outperformed SOC.

Conclusions: FSXs were superior to SOC in the treatment of burns and both dHACAs and HR-ADMs were superior to SOC for wound treatment.


State-of-the-art Skin Substitute and Scaffold Designs for Burns and Wounds: A Systematic Review and Meta-Analysis

Background: Despite the significant advances in detecting pulmonary nodules, the management plan of small tumors with malignant potential remains controversial. The objective of this study was to evaluate the overall survival of patients with ≤8 mm non-small cell lung cancer (NSCLC) who undergo stereotactic body radiation therapy (SBRT) versus wedge resection.

Methods: Kaplan-Meier analysis, multivariable Cox proportional hazards modeling, and propensity score-matched analysis were performed to evaluate the overall survival of patients with ≤8 mm NSCLC in the National Cancer Database (NCDB) from 2004-2017 who underwent SBRT versus patients who underwent wedge resection. The above-mentioned matched analyses were repeated for patients with no comorbidities. Patients who were coded in the NCDB as having undergone radiation because surgery was contraindicated due to patient risk factors (e.g., comorbid conditions, advance age, etc.) and those with a history of prior malignancy were excluded from analysis.

Results: Of the 1,505 patients who had NSCLC ≤8 mm during the study period, 1,339 (89%) patients underwent wedge resection, and 166 (11%) patients underwent SBRT. In both unadjusted analysis and in multivariable Cox modeling and propensity score-matched analysis, wedge resection was associated with improved survival when compared to SBRT. These results were consistent in a sensitivity analysis limited to patients with no comorbidities.

Conclusion: In this national analysis, patients with NSCLC ≤8 mm undergoing wedge resection experienced improved survival when compared to SBRT. This finding can be used to help inform the treatment decision-making process for tumors that are being discovered incidentally or through lung cancer screening. 





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Characterization of Salivary Extracellular Vesicles in Preterm Infants

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Mosaic Chromosomal Alterations Increase Risk of MGUS and Multiple Myeloma

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