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AMA Research Challenge 2022

Variability in Researcher Dependent Data Collection, Rat Behavioral Testing

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Ricardo Correa, MD, EdD
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Jessica Li, MD/PhD Candidate
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Charles Lopresto, DO

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Welcome to the largest national, multi-specialty research event featuring research from 750 medical students, residents and fellows, and international medical graduates.


Title: Association and predictors of secondary pulmonary hypertension amongst patients suffering from Takayasu’s arteritis - a nationwide study.
Introduction: Most previous studies on patients with Takayasu’s arteritis (TA) along with PHTN have focused on clinical symptoms and imaging characteristics. Data on the predictors of secondary PHTN amongst patients suffering from takayasu’s arteritis are scarce.
Aims: Primary aim of our study was to identify predictors of developing secondary pulmonary hypertension amongst patients suffering from takayasu’s arteritis.
Methods: A population-based cross-sectional study was performed in adult US hospitalizations from the nationwide inpatient sample (NIS-2016-2018). We identified patients with TA and subgrouped them into patients with and without PHTN using ICD-10 codes. Univariate analysis was performed using unpaired student's t test and chi-square test to identify prevalence of comorbidities amongst Takayasu’s arteritis patients with secondary pulmonary hypertension. Mix effects multivariate survey logistic regression analyses weighted for variables were performed to identify comorbidities (adjusted odds ratio [aOR] and 95% confidence interval [95%CI]) associated with PTHN amongst TA. p <0.05 was considered as significant.
Results: Out of 3560 patients with TA, prevalence of PHTN was 6.04%. The odds of developing secondary PHTN among TA patients is 1.56 times more than the patients who do not have TA (aOR 1.56, 95%CI 1.09-2.23). We noticed higher prevalence odds of secondary PHTN among patients with TA in age group of 50-75 years (aOR 1.23, 95% CI 1.21-1.25), age group of more than 75 years (1.14, 1.11-1.17), black race (1.35, 1.34-1.36), and female sex (1.33, 1.32-1.34). The odds of developing PHTN in patients with takayasu arteritis was seen to be 6.53 higher (6.53, 6.48-6.58) in the presence of CHF as a comorbidity than in the absence of it . Other comorbidities associated with PHTN among patients with Takayasu arteritis were essential HTN (1.23, 1.22-1.24), IHD (1.21, 1.20-1.22), atrial fibrillation (1.5, 1.49-1.51), AIDS (1.36, 1.28-1.44), renal failure (1.42, 1.42-1.43) and obesity (1.54, 1.53-1.55). 
Conclusion: Predictors of developing secondary PHTN in patients with TA are advanced age, black race, female sex, CHF, essential HTN, IHD, atrial fibrillation, AIDS, renal failure, and obesity. Early identification of these risk factors helps to mitigate the burden associated with pulmonary hypertension. Our findings are limited due to missing data on PHTN severity and long-term followup.

Association and Predictors of secondary pulmonary hypertension amongst patients suffering from Takayasu’s Arteritis - a Nationwide Study

Association and predictors of secondary pulmonary hypertension amongst patients suffering from Takayasu’s arteritis - a nationwide study

Characterizing chest radiographic patterns of small opacities in New Mexico coal miners

Mueez Rehman, Nour Assad, Charles Pollard, Orrin Myers, Xin Wang Shore, Linda Cook, and Akshay Sood

Abstract:
Rationale: Previous literature cites chest radiograph pneumoconiosis opacities to be different for Coal Miners vs other mineral miners. Our objective was to characterize chest radiograph patterns and compare the findings with other resource miners. Methods: Our chest radiographs and B- Reads were taken from a small cohort of coal miners in rural New Mexico, who had opacities consistent with pneumoconiosis. The chest radiograph patterns were characterized and compared to chest radiographs of non-coal miners diagnosed with pneumoconiosis. The primary study outcome was the chest radiographic pattern, determined by factors such as: shape, size, zonal development, and profusion score. The study predictor was the mining status with coal miners classified as 1. exclusively coal miners and 2. mixed coal and non-coal miners, and 3. Never coal miners (Control) Results: Our data showed no difference in chest radiograph patterns of opacities between coal miners and other resource miners. Furthermore, we found 95% of pneumoconiosis patterns to be the same between coal miners and other mineral miners. Conclusions: According to our data, the patterns for pneumoconiosis are the same amongst coal and non-coal miners. 

1. Laney, A. Scott, and Edward L. Petsonk. “Small Pneumoconiotic Opacities on U.S. Coal Worker Surveillance Chest Radiographs Are Not Predominantly in the Upper Lung Zones.” American Journal of Industrial Medicine 55, no. 9 (September 2012): 793–98. https://doi.org/10.1002/ajim.22049.




Characterizing Chest Radiographic Patterns of Regular, Primary, & Small Pneumoconiotic Opacities in New Mexico Coal Miners

Introduction: Insufficient sleep results in a pro-inflammatory state (marked by elevated IL-6 and C-reactive protein), autonomic dysfunction (marked by decreased heart rate variability [HRV] and increased mean arterial pressure [MAP]) and is prospectively associated with increased disease risks, in particular cardiovascular disease (CVD). While studies suggest that the observed pro-inflammatory state and autonomic dysfunction following sleep loss may be a mechanism driving the increased CVD risk, this remains unclear. It is clear, however, that sleep loss presents an inflammatory and cardiovascular challenge to the body’s homeostatic functioning, and individuals respond with great variability to such challenges (i.e., some have increased inflammation and autonomic dysfunction after sleep loss while others are resilient). This variability represents a barrier to understanding the relationship between inadequate sleep and disease risk. The purpose of this study was to provide novel insight into factors that explain the variability in responses to prolonged experimental sleep disturbance as experienced by about 20% of the general population. We hypothesized that baseline levels of inflammatory markers (i.e., IL-6) and behavioral markers (i.e., habitual sleep duration) predict inflammatory and autonomic responses to a prolonged experimentally induced sleep loss challenge.

Methods: 23 healthy participants (ages between 18 and 42 years, 11 females) completed two 19-day stays in the Clinical Research Center, separated by at least 2 months. This included a control stay with an 8-hour sleep opportunity per night, and a sleep disturbance stay with three cycles of disturbed sleep for 3 nights (20-minute awakenings per hour; 4-hour sleep opportunity per night) followed by one night of recovery sleep (undisturbed sleep for 8 hours). Participants’ blood was drawn at baseline as well as every other day, and tested for levels of inflammatory markers (IL-6 and cortisol). Brachial blood pressure measurements were taken three times a day. HRV (tracked by the calculated HFnu) was measured every other day. Prior to enrollment in the study, subjects reported their sleep duration daily for 14 days using an online software. A multiple linear regression model (SPSS 27) was used to test if baseline plasma IL-6, cortisol, and habitual sleep duration significantly predicted the response of plasma IL-6 levels, HFnu, or MAP following exposure to sleep disturbance.

Results: Higher baseline plasma IL-6 levels predicted reduced HFnu following sleep disturbance (β = -.603, p = 0.019). Higher baseline plasma IL-6 levels predicted increased MAP following sleep disturbance (β = 0.401, p = 0.003). Also, higher baseline habitual sleep duration predicted reduced plasma cortisol levels by week three (β = -0.447, p = 0.024).

Conclusion: Findings suggest that individuals with higher levels of baseline IL-6 respond to sleep disturbance with increased inflammation and autonomic dysfunction, while those who habitually sleep for longer periods of time respond with less inflammation. Findings have the potential to be used clinically to identify individuals with increased cardiovascular disease vulnerability to sleep loss using their baseline inflammatory state and habitual sleep duration. 

Acknowledgment: A special thanks to the BIDMC Sleep and Inflammatory Systems Laboratory for their support. This work was supported by the Carmen Pettapiece Student Research Fellowship (to KO) and R01 NIH/NINDS NS091177 (to MH). IRB approval was granted by the Beth Israel Deaconess Medical Center IRB committee (protocol 2014P-000354).

Predicting Inflammatory and Autonomic Responses to Sleep Disturbance: The Role of Baseline IL-6 and Habitual Sleep Duration

Role of inhalational epoprostenol in mechanically ventilated COVID-19 patients
– Literature Review

Background
Strategies in management of COVID-19 revolved around redirection of available drugs, with no large-scale clinical trials supporting their repurpose. Inhalational epoprostenol (iEPO) is a pulmonary vasodilator used off-label in the management of acute respiratory distress syndrome (ARDS). Although the role of iEPO and inhaled nitric oxide (iNO) as rescue strategy has been extensively studied in ARDS, the current recommendations by the Surviving Sepsis Campaign on COVID-19 management on their utilization in mechanically ventilated adults with COVID-
19, severe ARDS and hypoxemia were weak.

Methods
Trip, Cochrane, and Pubmed databases were searched using keywords COVID-19, Coronavirus-2019, epoprostenol, and ARDS. Of the 11 identified studies, 3 were specific for the role of iEPO in mechanically ventilated COVID-19 patients with ARDS and refractory hypoxemia. These included 2 retrospective single-center and 1 retrospective two-center study involving 38, 43, and 80 patients respectively. The interventions were utilization of iEPO followed by introduction of iNO in the first, iEPO and prone position individually and in combination in the second, and
iEPO with and without prone position in the third study.

Results
No variables were available for comparison. In the first study, 41% patients responded to iEPO with < 10% increase in PaO2/FiO2 (PF) ratio. In the second study, 63% patients had > 20% improvement in the PF ratio with the combination of iEPO and prone position (p < 0.001), with resultant lower mortality in responders (p = 0.025). The third study demonstrated a 10% increase in PF ratio in 50% patients with iEPO alone (p-value < 0.01) and a 16-17% increase in PF ratio noted in patients with iEPO, prone position, and severe ARDS (p = 0.03).

Conclusion
The level of evidence on the role of iEPO in mechanically ventilated COVID-19 patients with refractory hypoxemia is weak. Studies are small, retrospective, and lack outcomes such as time for extubation, duration of ventilation, mortality outcomes. Large-scale randomized clinical trials are warranted to assess the role of iEPO alone and in combination with prone positioning in this patient population.

Role of inhalational epoprostenol in mechanically ventilated COVID-19 patients:Literature review

3D Printed Anatomic Models for Removal of Complex IVC Filters


Background
The use of Millimeter Wave (MMW) to Terahertz (THz) sensors in the diagnosis of thermal burn injury, radiation dermatitis, and other complications associated with tissue injury secondary to thermal, chemical, or radiation burns has not been previously seen. This ex-vivo investigation of pigskin utilizes MMW sensors to view the underlying skin damage caused by high-temperature internal and external thermal burns.

Methods
Fresh porcine skin is sectioned into 5 cm by 5 cm squares, and the subdermal adipose is removed revealing the dermis. A triangle brand is heated to 300ºC and placed on the underside of the porcine skin for 10 seconds inducing a thermal burn. Another sample group is burned on the epidermis at both 100ºC and 300ºC. The samples are then placed under the 94 GHz and 30 GHz MM-wave sensors, that generate 2D images of the epidermis. Punch biopsies are taken from the samples and sent to dermatopathology for analysis of thermal burn injury depth.

Results
The 94 GHz radiation penetrates the epidermis and upper dermis showing sensitivity to various changes in hydration and surface roughness. The triangle-shaped burn on the underside of the porcine skin was not visible from the epidermal side; however, the MMW-generated image revealed the presence of a triangular structure with lower reflectivity readings in deeper skin layers. The triangular 300ºC and 100ºC burns on the epidermis were clearly shown on the MMW images as areas of low and high reflectance, respectively. Punch biopsies are currently being analyzed to correlate differences in reflectance with the depth of burn to differentiate between second and third-degree burns. 30-GHz MMW sensor imaging studies show an increase in penetration depth of the waves at the expense of image resolution, indicating its use for deeper or thicker skin.

Conclusion
The use of MMW sensors may be used to view changes in skin hydration that are not directly visible to the clinician. Integration of this device with current imaging methods may yield valuable information about skin injury. This tool may aid in prompt clinical diagnosis between second and third-degree burns and subcutaneous thermal burn injuries caused by interventional procedures.


A Novel Method for Non-Invasive Medical Imaging of Thermal Burn Injuries Utilizing Millimeter Wave and Terahertz Technology

Purpose 
Growing evidence suggests sarcopenia, body mass index (BMI), and the inflammatory marker neutrophil-lymphocyte ratio (NLR) correlate with outcomes among patients undergoing radiotherapy (RT). Maintaining nutritional status and BMI among head and neck cancer patients can be difficult— especially among those undergoing RT. We evaluated whether pre-RT sarcopenia, BMI, and NLR were associated with treatment outcomes among patients with oropharyngeal cancer. 



Materials and Methods 
We retrospectively enrolled 172 patients with oropharyngeal cancer who underwent definitive RT+/-chemo at an academic center from 2013 to 2019. We measured bilateral temporalis muscle thickness (TMT) on CT imaging used for radiation plan design. Sarcopenic patients were defined by a TMT ≤ 25th percentile. We measured pre-RT NLR, with high NLR defined as ≥ 75th percentile. Patients were subdivided into four BMI categories including: underweight (BMI: <18.5), normal weight (BMI: 18.5-24.9), overweight (BMI: 25-29.9), and obese (BMI: ≥ 30). We recorded rates of overall survival, recurrence, and whether a PEG or NG tube was placed during treatment. 



Results 
In our patient cohort, 31%, 43%, 14%, and 10% had stage T1, T2, T3, and T4 primary site tumors by AJCC 8th edition staging, respectively. Furthermore, 6%, 61%, 22%, and 9% had stage N0, N1, N2, and N3 nodal involvement. 86% were HPV+, while 6% were HPV- and 6% were unknown. Sarcopenic patients (n = 43) were found to be older than non-sarcopenic patients (n = 129); (64 vs. 58, p < 0.001). Sarcopenia was associated with lower BMI. Among sarcopenic patients, 2.3%, 30%, 42% and 19% were underweight, normal weight, and obese, respectively. Among non-sarcopenic patients, 1.6%, 16%, 43% and 39% were underweight, normal weight, and obese, respectively (p = .063). No significant differences were found between patients with vs. without sarcopenia with respect to smoking history, p16 status, primary tumor site, chemotherapy exposure, tumor stage, or NLR. At 24-month follow-up, sarcopenia did not significantly impact overall survival (OS) or recurrence-free survival (RFS) (OS 92.6% vs 91.1%, p = 0.790; RFS 69.7% vs 75.1%, p=0.465). PEG/NG tube placement was not significantly different (60% vs 55% with and without sarcopenia, respectively, p=0.378). Age was an independent predictor of poorer OS (hazard ratio [HR], 1.1; 95% CI, 1-1.1; p = 0.0037), whereas greater BMI (HR, 0.57; 95% CI, 0.36-0.9; p = 0.015) predicted improved overall survival. 



Conclusions 
Pre-RT sarcopenia and NLR were not associated with survival and recurrence outcomes. However, pre-RT BMI was found to be of significant prognostic importance. This highlights the value of comprehensive nutritional support for patients undergoing head and neck radiotherapy. Special attention should be paid toward elderly patients as age predicted poorer overall survival.

Association between sarcopenia and overall survival among oropharyngeal cancer patients undergoing radiation therapy

PURPOSE 
This review was undertaken to compare the clinical outcomes of prostate artery embolization (PAE) in patients with >80ml vs <80ml prostatic volume (PV) at 24 month follow up to determine if prostate volume predicted the durability or efficacy of PAE. 
MATERIALS AND METHODS
The PubMed/MEDLINE database was searched for articles published between 2010 and 2022 using the search term “(prostat* artery embolization) AND (long term OR follow-up OR 24-month)”. Articles were included if they discussed PAE for BPH and reported a minimum follow up of 24 months. Articles with fewer than 10 patients were excluded. A subgroup analysis was performed to evaluate for any difference in clinical outcomes at 24 month post-PAE follow-up between studies with mean PV >80ml and those with mean PV <80ml.
RESULTS
17 studies with 2,762 patients were included, all of which demonstrated significant reduction of symptoms at 24 month follow up post-PAE. Four studies were included as part of the >80ml PV subgroup (n=467) and thirteen studies were included as part of the <80ml PV subgroup (n=2,299). There were statistically significant differences between the mean pre-procedural prostatic volume (122.4ml vs 64.0ml, p=0.0052) and mean pre-procedural PSA (7.2 vs 4.0, p=0.027). At 24 month follow up, the only clinical parameter that differed significantly between groups was the PSA (4.9 vs 2.4, p=0.003). The collective incidence of major adverse events reported was <1%.
CONCLUSION
PAE is both safe and durable for patients suffering from BPH, and can be utilized in a wide range of baseline prostate volumes.

Next from AMA Research Challenge 2022

Association and Predictors of secondary pulmonary hypertension amongst patients suffering from Takayasu’s Arteritis - a Nationwide Study

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