United States

Background: Wound healing is a complex balance of cascading events orchestrated by dynamic autocrine/paracrine signaling of heterogenous factors. An imbalanced composition of bioactive compounds results in a cycle of sustained, inappropriate cellular signaling, and progression towards chronic wounds. The diverse and complex nature of chronic wounds has resulted in a lack of development of focused and effective therapeutic interventions. Therefore, there remains a critical need for a system that can generate customizable therapies for chronic wounds that can aid in reestablishing proper balance in wound healing signaling. Recent investigations have demonstrated that the diverse milieu of secreted factors from Adipose-derived Mesenchymal Stem Cells (ASCs) could offer a unique approach to treating chronic wounds that circumvents the limitations of other autologous cell therapies. Objective: Investigate the ability to tailor ASC biologics with “wound stimuli” priming.

Methods: A novel 3D-printed tissue-mimetic hydrogel system was utilized as a customizable in vitro bioreactor system to generate ASC-derived acellular biologics. ASCs were exposed to a variety of different native “wound stimuli”, including exposure to collagen peptides and fibrin(ogen). The “wound stimuli” were assessed for their ability to modulate the secretory composition of the ASC secretome and to enhance the wound healing activity of keratinocytes, fibroblasts, and endothelial cells.

Results: Our novel 3D system enhanced the regenerative activity of ASCs. Proteomic evaluation demonstrated ~15% increase in protein secretion, including a number of pro-wound healing growth factors and immunomodulatory compounds. Similarly, ASCs exhibited enhanced production of antioxidants (~25%) and EV/Exosomes (~4-5x). Treatment of keratinocytes, fibroblasts, and endothelial cells with the ASC-derived biologics resulted in enhanced wound healing activity, including increases in metabolic, proliferative, and migratory activity. Furthermore, introduction of “wound stimuli” to the 3D system resulted in modulation of the ASC secretome composition and further enhancement of its wound healing capacity. 

Conclusion: Together, this data demonstrates the potential of a novel 3D system to enhance the regenerative capacity of ASCs and permit the priming of ASCs to tailor secreted biologics. Thus, these studies provide insight towards advancing the development of tailored acellular biologics for future regenerative therapeutics for a variety of soft tissue application, including wound healing.

2022 AMA Research Challenge

Tailoring Stem Cell Biologics to Enhance Regenerative Wound Healing

ENDO 2021

ENDO is the leading meeting for endocrinology research and clinical care worldwide. 

poster

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
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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.
 

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 **Speakers**
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Ricardo Correa, MD, EdD
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Stuart M. Greenstein, MD
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Stephanie Strohbeen, MD
 
 **Oct. 22, 11 a.m. — Noon Central**
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Jessica Li, MD/PhD Candidate
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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.

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**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.


Objective:
The main objective of this article is to study the efficacy and safety of vedolizumab in the management of moderate to severe Ulcerative Colitis (UC) patients.
Methods:
We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (
guidelines, conducted a literature search in PubMed, Google Scholar, and Science Direct, and nine studies were included in the systematic review.
Results:
At week six, vedolizumab showed a significant clinical response At week 52 vedolizumab showed significant mucosal healing and clinical remission The
most commonly associated adverse effects are nasopharyngitis, oropharyngeal infection, and gastrointestinal infection.
Conclusions:
Most of the included studies showed a significant clinical response and clinical remission of the disease Additionally, vedolizumab is well tolerated with
fewer side effects and is safe to use in UC patients.

Vedolizumab Therapy For Management OF Moderate to Severe Ulcerative Colitis

Background: Alzheimer's Disease (AD), related diseases (ADRD), and Multiple Cognitive Impairments (MCI) portend cognitive decline in the elderly, causing significant time course-dependent deficits in language, memory, comprehension, attention, judgment, and reasoning. There is a relative paucity of literature that characterizes sociodemographic implications of these diseases and even fewer systematic reviews that assess the disease burden. The Cleveland Alzheimer’s Disease Research Center (CADRC) is a collaborative effort to establish a National Institute on Aging (NIA) funded Alzheimer’s disease research center; our aim is to determine if people with AD and MCI due to AD who live in rural communities demonstrate greater utilization of healthcare resources compared to those living in non-rural settings.

Methods: Traditional methods of large-scale systematic review are laborious, inefficient, and circuitous for first-pass filtering. Alternatively, our utilization of the machine learning-based method known as Rayyan QCRI allows the first pass researcher to quickly screen with predefined inclusion and exclusion criteria. Repeated screening reinforces the neural network to prefer literature similar to those that have been included, deduplicates imported publications, and provides quality of life features that traditional methods cannot offer.

Results: Of 2239 publications selected for review, 107 were marked as potential “Include,” 290 were marked as “Maybe,” and the remaining 1802 as “Exclude” in a span of 30 hours of in-software time. “Include” and “Maybe” articles were passed into second-pass analysis for data extraction with machine-learning ratings in mind. In comparison, 35 publications were reviewed by traditional methods, yielding 2 potential “Include”, and 5 “Maybe” in a span of 10 hours. 

Conclusion: Rayyan is an effective method for first-pass systematic review and has distinct qualities that make it a preferential alternative to traditional methods.

A Modern Procedure for Systematic Review: Comparing Classic Methodology to a Machine Learning–Based Technique

Background

Shared Decision-Making (SDM) is a collaborative process where patients and clinicians work together to determine a treatment plan, balancing evidence-based medicine with patient values. Little is known about how SDM is documented by clinicians in the Electronic Medical Record (EMR). Understanding how patient preferences are reflected in clinical documentation is important as clinicians strive to make care more patient-centered. This study seeks to evaluate whether clinical documentation is reflective of verbal communication in pediatric clinical encounters.

Methods

This Mixed Methods Sequential Exploratory Analysis included 109 pediatric surgical consultations. For each encounter, the transcript of the verbal clinician-family communication was descriptively evaluated for elements of SDM: discussion of risks/benefits/alternatives, parental preferences, and expression of parental concern. Next, the corresponding EMR documentation was evaluated for these elements. Qualitative methods were used to describe similarities and differences of these elements in both types of communication. A basic descriptive quantitative analysis was conducted to further describe the similarities/differences between these two types of communication describing the same clinical encounter.

Results

In the discussion of risks/benefits/alternatives, the EMR documentation for 48% of encounters used a standard dot phrase, which often differed from what was discussed verbally. Common discrepancies also included a parental preference being documented in the EMR when no preference was verbally expressed by the parent, occurring in 12% of consultations. The opposite was also seen: in 14% of consultations, a parental preference was expressed but was not documented. Overall, expression of parental concern was infrequent, occurring in 30% of the consultations. Of the 34 parental concerns that were expressed, only 21% were documented. 

Conclusion

In conclusion, there are substantial discrepancies between what is verbally communicated in pediatric surgical encounters and what is subsequently documented in EMR documentation. As clinicians evolve in delivering patient-centered care, understanding how patient perspectives are reflected in medical documentation could significantly impact clinical practice, informing interventions to make documentation more inclusive of patient values. This research is particularly significant as patient care is becoming more transparent with increased patient access to their EMR, emphasizing the importance of understanding whether SDM is accurately reflected in clinical documentation.


Is Documentation Reflective of Parent-Clinician Communication in Pediatric Surgical Consultations?


Abstract Title:
The Bystander effect: Impact of rural hospital closures on the health of surrounding institutions
Background
Abstract: 
There is presently a rural hospital shortage in the United States with 180 closures since 2005 and hundreds of institutions in financial peril. Although the hospital closure phenomenon is well-established, less is known about the spillover impact on the operations and financial wellbeing of surrounding hospitals. This preliminary study quantified how discrete rural hospital closures impact institutions in their regional proximity, finding a significant increase in inpatient admissions and emergency department visits for these “bystander hospitals”. 

Methods
Using a repository of rural hospital closures collected by the UNC Sheps Center for Health Services Research, we identified closures over the past 15 years. Criteria for inclusion were hospitals that had been fully closed between 2005-2016 and with >25-bed capacity. We then designated surrounding hospitals within a 30-mile radius of each closed hospital as “bystander hospitals.” We examined the average rate-of-change for inpatient admissions and emergency department visits in surrounding hospitals both two years before and after relevant hospital closures. 


Results
We identified 53 hospital closures and 93 bystander hospitals meeting our criteria during the study period. With respect to geographic distribution, 66% of closures were in the Southern US, including 21% in Appalachia. Average emergency department visits increased by 3.59% two years prior to a hospital’s closure; however, at two years post-closure the average rate of increase rose to 10.22% (F(4,47)=2.77, p=0.0375). Average bystander hospital admissions fell by 5.73% in the two years preceding the hospital closure but increased 1.17% in the two years after (F(4,46)=3.05, p=0.0259). 

Conclusion
These findings predict a daunting future for rural healthcare. While previous literature has described the acute effects hospital closures have on communities, this study suggests a significant spillover effect on hospitals within the geographic region and a cyclical process at play in the rural healthcare sector. In the absence of significant public health assistance in regions affected by closures, poor health outcomes, including “diseases of despair,” are likely to continue proliferating, disproportionately affecting the most vulnerable. In the COVID-19 era, it will be especially necessary to focus on hospital closures given increased risk of maintaining solvency due to delayed and deferred care atop already tight margins. 





The Bystander effect: Impact of rural hospital closures on the health of surrounding institutions

Background
Cilia are blood flow sensor organelles found on the surface of vascular endothelial cells (ECs). Cilia loss (deciliation) could result in cellular malfunction, leading to brain- and cardio-vascular stability loss. This observation spurred the possibility that cilium is functionally critical beyond flow sensor. Upon shear stress, deciliation is reported. Thus, the tracking of endothelial cilia could be instrumental in determining the state of cerebro- and cardio-vascular health. 

Sickle cell disease (SCD) is a risk factor for neurologic complications. In SCD, blood flow changes cause sickle cell interaction with ECs promoting vaso-occlusion that could damage the neurovascular unit and cause pain crises. RBCs are in constant contact with EC-cilia. Yet, RBC impact on EC-cilia, and the integrity of brain- and the cardio-vasculature in SCD remains unknown. We hypothesize that disturbed cerebral blood flow promotes sickle RBC adhesion to EC-cilia, triggering cilia shedding, thus resulting in vascular stability/integrity loss. 

Methods
Blood samples from healthy donors, sickle cell trait (SC) patients, and SCD patients were centrifuged to separate plasma and RBCs. RBCs were stained with FITC-conjugated anti-human Arl13b (a cilia protein) antibody and analyzed by flow cytometry. After Arl13b protein levels were quantified on RBCs, SCD patient charts were reviewed to determine the existence of a correlation with the incidence of pain crises with and without cerebrovascular damage.

Results
Preliminary flow cytometry results on circulating RBCs reveal that SCD patients have the highest Arl13b percent positive exposing sickle RBCs at 21.7±3.1% (n=22). Healthy donors have 3.6±0.6% Arl13b positive exposing normal RBCs (n=33), while SC patients have 9±2.7% Arl13b positivity (n=7). A correlation existed between % RBC-exposing cilia and pain crises and neurologic damage score.

Conclusion
Cilia-related proteins have increased presence on sickle RBCs from SCD patients. There was a significant correlation between the percent positive cilia exposing RBCs and pain crises and neurologic complication score. There are currently no effective biomarkers to distinguish SCD patients at high risk for neurologic damage (e.g. stroke) and pain crises from those at low risk. This work suggests that cilia (via measurement of Arl13b) can be used to individually assess an SCD patient's risk for these adverse events. Moving forward, we are interested in exploring the robustness of cilia as a biomarker and the mechanisms by which deciliation destabilizes the neurovascular unit.

Cilia as a biomarker for the neurovascular unit stability and pain crises in sickle cell patients

Background
Patient medication compliance is a common challenge across all medical specialties. Prior studies in anesthesia demonstrate compliance increases with multimodal interventions including standardized EMR generated instructions. However, transitioning from in-person to virtual modalities may narrow the available of interventions patients receive thereby impacting medication compliance. Preoperative telemedicine encounters are associated with high patient satisfaction and cost savings but the effectiveness of preoperative telephone encounters and compliance with medication instructions on the morning of surgery has not been studied at length.
Methods
In this prospective cohort study, anesthesia clinic providers in an academic medical center gave morning of surgery medication (MoSM) instructions during a preoperative anesthetic evaluation, either in-person or via telephone. On the day of surgery, an original questionnaire was administered comparing each patient’s verbal report of their MoSM taken to a record of their MoSM instructions. The percent of compliance for medications taken was calculated and patients who achieved 100% were considered compliant. Questionnaire data was analyzed using Cohort statistics.
Results
Compliance with MoSM taken were 46% and 54% in the in-person and telephone cohorts, respectively. There was no statistically significant association between the compliance and encounter type. (p=0.4681) In the general sample population, those who were 55 or older (RR=1.5085; p=0.0401) or on three or more MoS medications (RR=2.0167; p=0.0001) were associated with a higher likelihood to be non-compliant. There was a statistically significant association between compliance and age among patients younger than 55 years old and patients 55 years old and older (p=0.0431) as well as between compliance and the number of MoSM to take among patients with less than three medications and patients with three or more medications. (p=0.0001)
Conclusion
These findings suggest that implementation of telephone evaluations at an academic medical center achieved a similar level of compliance to in-person visits despite reductions in patient interventions received. However, factors such as older age and high numbers of MoSM may increase the likelihood of patient non-compliance and identify which patients providers should target efforts to achieve greater compliance.

Comparison of Telephone and In-Person Preoperative Evaluations on Patient Morning of Surgery Medication Compliance

Background

Congenital vascular malformations cause blood to bypass the capillary bed and directly drain into the venous system. Embolization is one type of treatment and has been used for several decades to treat these malformations. Treatment-related significant pain after the embolization is not uncommon (1), and peripheral nerve blocks could reduce such pain (2). However, there is limited data on the effect of peripheral nerve blocks on postoperative pain in patients undergoing embolization therapy. This study investigates the feasibility of peripheral nerve blocks for pain control following embolization therapy in patients with vascular malformations. We hypothesize that single-injection peripheral nerve blocks can be safely performed to provide perioperative analgesia for patients undergoing embolization therapy. They will reduce morphine milligram equivalents (MME) and postoperative pain scores in patients that receive peripheral nerve blocks.
Methods

We performed a retrospective study of patients that received embolization therapy for a vascular malformation at Children's Hospital of Pittsburgh from 2011 to 2020. Data collected included: demographics, nerve block characteristics, perioperative opioid and non-opioid analgesia, pain scores, and hospital stay.

Results

881 patients aged one day to 61 years old (Mean - 11.6 years) met the inclusion criteria. Peripheral nerve blocks were used in 5.8% of cases, with patients ranging in age from 5 to 49 years old. Out of the 51 patients who received nerve blocks, 33 (65%) received Ropivacaine 0.5%, 27 (53%) received Ropivacaine 0.2%, and 21 (41%) received clonidine. Using a linear regression model, controlling for age, sex, preoperative pain score, and duration of procedure, results showed that patients who received peripheral nerve blocks had significantly lower opioid usage (7.57 vs 12.86, p=0.006) but did not have significantly lower postoperative pain scores (2.53 vs 3.39, p=0.08). One patient from the sclerotherapy group reported sciatic nerve injury unrelated to the block.

Conclusion

The peripheral nerve blocks are feasible and can be used as a multimodal approach for postoperative pain control in patients undergoing embolization therapy. This report is the first study investigating peripheral nerve blocks in patients undergoing embolization therapy.

Feasibility of Nerve Blocks in Patients Undergoing Embolization Therapy for Vascular Malformations

Opioid-free anesthesia versus opioid-based anesthesia in patients undergoing cardiovascular and thoracic surgery: a meta-analysis & systematic review

Background: Children undergoing cardiac surgery have increased rates of thrombosis compared to other hospitalized children. In a retrospective study of infants undergoing cardiac surgery, we found that age < 30 days was associated with increased thrombosis rates. As thrombotic complications are associated with increased morbidity and mortality, we hypothesized that prophylactic heparin could reduce the incidence of perioperative thrombosis in neonates undergoing cardiac surgery.

Methods: We used our institutional Society of Thoracic Surgery (STS) database to identify neonates (age < 30 days) who underwent cardiac surgery between August 1, 2019, and July 31, 2021. Demographics, perioperative factors, and outcomes were collected. Thrombosis was confirmed with imaging studies. The patient’s STS index procedure was used as the primary surgical event. Our primary outcome was the difference in thrombosis rate between the pre-heparin protocol (pre-HP) and post-heparin protocol (post-HP) cohorts. Secondary outcomes included risk factors for thrombosis, hospital, and ICU length of stay (LOS), and adverse events (AE).

Results: Our populations consisted of 280 neonates (128= preHP; 152 =postHP). The two cohorts were similar except for longer anesthesia times for the postHP group. The incidence of thrombosis was 25% (30% and 19.7% in PreHP and PostHP cohorts, respectively). Patients with thrombosis were more likely to have prematurity, higher STAT scores, circulatory arrest, repeat surgery, surgery with CPB and elevated peak inflammatory markers. A multivariable logistic regression adjusting for statistically significant risk factors in the univariate analysis demonstrated that patients in the preHP were 1.67 times more likely to develop thrombosis than in the PostHP. Thrombosis was associated with increased death, complications, ICU, and hospital length of stay (LOS). 

Conclusion: Prematurity, elevated peak inflammatory markers, STAT scores, and multiple surgeries are associated with thrombosis. After adjusting for risk factors, prophylactic heparin infusions in neonates with central lines reduce thrombosis rates for neonates undergoing cardiac surgery.

Risk Factors for Perioperative Thrombosis in Neonates Undergoing Congenital Cardiac Surgery

Introduction 
Rocuronium-induced anaphylaxis (RIA): 
 Estimated to occur in between 1 in 3,500 & 1 in 20,000 cases.
 90% of cases occur at induction of anesthesia.
 Neuromuscular blocking drugs are thought to be responsible for between 60-70% of anesthesia-induced reactions, with rocuronium being the most implicated.
Sugammadex: 
 Synthetic modified gamma-cyclodextrin derivative.
 The physiological rationale in RIA: Sugammadex incompletely encapsulates rocuronium, preventing the rocuronium epitope from binding IgE. Hence, the Severity of anaphylaxis should be ameliorated. 

Methods: 
Screen process:
We did a systematic review and looked at published case reports. 
We used mesh terms “ anaphylaxis, allergy, or hypersensitivity” and “ Rocuronium, Zemuron, or Esmeron.” 
We looked into Ovid Meline, Embase, and Web of Science. After the screening process, we found 356 published case reports. 
We divided them into two groups, Group A RIA and Group B Sugammdex use in RIA. 
We looked at baseline patient characteristics, ASA severity, the incidence of complications, duration of hypotension, discharge disposition, and mortality. 

Results: 
Baseline patient characteristics: 
All patients of RIA and RIA with sugammadex were ≤60 years old 52% and 73%.
Female sex was more common in the RIA with sugammadex (67%) rather than in RIA alone (58%). 
Almost three-quarters of the RAI group had ASA classification of (1-2) compared to two-thirds of the RIA with the sugammadex group. 
Dose of Sugammadex: 
Dose of sugammdex was ≤4mg kg (25%), >4mg kg (29%), ≤500mg (25%) and >500mg (21%). 
Complications: 
RIA with sugammdex was associated with lower tachycardia (54% vs 78%), rash (39% vs 78%), complications (0% vs 20%) and ICU admission (61% vs 91%) rather than RIA alone (p <0.05). 
However, no differences were detected in bronchospasm or high peak airway pressure, epinephrine infusion, length of hypotension, and mortality (p >0.05). 

Recommendations: 
Early recognition and treatment of anaphylactic shock.
Epinephrine is still the mainstay of treatment. 
Consider using sugammadex in case of suspected RIA.
We recommend a 16 mg/kg dose.
We recommend using sugammadex in case of cardiac arrest or refractory anaphylaxis as evidence of NNT to avoid organ dysfunction is 7 and potential evidence of mortality benefit. 

References: 
Simons FE, Ardusso LR, Bilò MB, El-Gamal YM, Ledford DK, Ring J, et al. World Allergy Organization. World Allergy Organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011;4:13–37. 
Harper NJ, Dixon T, Dugué P, Edgar DM, Fay A, Gooi HC, et al. Working Party of the Association of Anaesthetists of Great Britain and Ireland. Suspected anaphylactic reactions associated with anaesthesia. Anaesthesia. 2009;64:199–211. 
McDonnell NJ, Pavy TJ, Green LK, Platt PR. Sugammadex in the management of rocuronium-induced anaphylaxis. Br J Anaesth. 2011;106:199–201. 
Mertes PM, Laxenaire MC, GERAP [Anaphylactic and anaphylactoid reactions occurring during anaesthesia in France. Seventh epidemiologic survey (January 2001-December 2002)] Ann Fr Anesth Reanim. 2004;23:1133–43. French.

Tailoring Stem Cell Biologics to Enhance Regenerative Wound Healing

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Vedolizumab Therapy For Management OF Moderate to Severe Ulcerative Colitis

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