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Dronabinol, a synthetic form of delta-9-tetrahydrocannabinol (THC), holds a significant and expanding role in the medical field. Its approval for various medical conditions, such as alleviating chemotherapy-induced nausea and stimulating appetite in HIV-associated cachexia, is well-documented (Ahmedzai, 2004; Beal, 1995). However, its relevance is now extending into pain management and perioperative care.

Recent research, as indicated by Abrams (2011), suggests that Dronabinol possesses potential as both an antiemetic and analgesic agent, particularly in situations where conventional treatments have limitations. This is particularly significant in the context of the opioid crisis, as Dronabinol offers pain relief without the same associated risks as opioids.

As the medical community seeks alternative solutions to opioid-based pain management, Dronabinol&#39;s multifaceted relevance becomes increasingly evident. Supported by a body of clinical trials and research reviews, Dronabinol emerges as a valuable tool in addressing various medical challenges.

The reduction in opioid requirements post-surgery, as seen in the case presented, underscores the potential of Dronabinol in the perioperative setting, and this paper aims to explore its medical, social, economic, and legal aspects comprehensively.

AMA Research Challenge 2024 

Beyond Opioids: Exploring Dronabinol in Enhanced Recovery After Surgery (ERAS)

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Dronabinol, a synthetic form of delta-9-tetrahydrocannabinol (THC), holds a significant and expanding role in the medical field. Its approval for various medical conditions, such as alleviating chemotherapy-induced nausea and stimulating appetite in HIV-associated cachexia, is well-documented (Ahmedzai, 2004; Beal, 1995). However, its relevance is now extending into pain management and perioperative care.

Recent research, as indicated by Abrams (2011), suggests that Dronabinol possesses potential as both an antiemetic and analgesic agent, particularly in situations where conventional treatments have limitations. This is particularly significant in the context of the opioid crisis, as Dronabinol offers pain relief without the same associated risks as opioids.

As the medical community seeks alternative solutions to opioid-based pain management, Dronabinol's multifaceted relevance becomes increasingly evident. Supported by a body of clinical trials and research reviews, Dronabinol emerges as a valuable tool in addressing various medical challenges.

The reduction in opioid requirements post-surgery, as seen in the case presented, underscores the potential of Dronabinol in the perioperative setting, and this paper aims to explore its medical, social, economic, and legal aspects comprehensively.

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Methylene blue is controversially used in the management of refractory vasoplegia and septic shock due to its mechanism of inhibiting guanylate cyclase and decreasing cGMP levels to improve vascular tone. In recent meta-analysis, methylene blue use in septic shock resulted in improvement of hypotension, blood pressure, and cardiac function, while significantly reducing mortality and ICU/hospital stays. Further usage of methylene blue may benefit anaphylactic and drug-induced shock by reducing vasopressor requirements. Administered intravenously, methylene blue peaks at 30 minutes, with effects lasting 48–72 hours, making it a valuable treatment for various shock conditions.


Methylene Blue Use for Refractory Hypotension in Setting of Necrotizing Pancreatitis 

Abstract Title
Postoperative Opioid Use for Regional vs. General Anesthesia in Hip Arthroplasty
Background
Total hip arthroplasty is a commonly performed surgical procedure, especially among elderly patients. Effective anesthesia management significantly influences outcomes and reduces complications. The choice between regional anesthesia (RA) and general anesthesia (GA) remains a subject of ongoing debate. This comprehensive database study aims to compare long-term postoperative opioid usage for pain management between patients who received general anesthesia versus regional anesthesia.
Methods
The study utilized the TriNetX database, comprising deidentified patient information for over 124 million individuals. Subjects with at least two years of follow-up electronic health data were included in the regional (Bupivacaine) and general (Propofol) anesthesia groups. The study focused on patients who underwent total hip arthroplasty (THA) under anesthesia from 2015 to 2021. Propensity score matching was employed in a 1:1 ratio to balance outcome-affecting variables between the two cohorts. Postoperative opioid use was compared across 90 days, 1 year, and 2 years. Statistical analysis, including odds ratios (ORs) and 95% confidence intervals (CIs), was conducted using the TriNetX database.
Results
A total of 253,827 patients underwent THA under anesthesia, with 112,206 under regional anesthesia and 150,930 under general anesthesia. Propensity score matching resulted in 112,205 patients in both the regional and general anesthesia groups. Following matching, statistical analysis revealed no significant differences in opioid use between regional and general anesthesia groups at 90 days [(OR (95% CI), 1.17 (0.96, 1.425)], 1 year [OR (95% CI), 1.123 (0.983, 1.284)], and 2 years [OR (95% CI), 1.105 (0.991, 1.232)].
Conclusion
The findings suggest that regional anesthesia does not provide superior postoperative pain control with reduced opioid consumption compared to general anesthesia. However, regional anesthesia may lead to shorter hospital stays for these patients. Clinicians should consider these results when customizing anesthesia strategies for individual patients, aiming to achieve the most suitable plan based on each patient's specific needs.

Postoperative Opioid Use for Regional vs. General Anesthesia in Hip Arthroplasty

Background: A hemodynamically significant patent ductus arteriosus (HSPDA) is a common concern in the care of premature infants, but its definition remains a challenge and its preferred treatment remains controversial. 

Methods: We sent an electronic survey to the members of the AAP Sections on Neonatal and Perinatal Medicine, Cardiology and Cardiac Surgery and the PediHeartNet online community regarding their diagnosis and treatment of the HSPDA in premature infants.

Results: 382 neonatologists and 124 pediatric cardiologists completed the survey. Formal echocardiographic and clinical scoring systems for PDA were used infrequently (22.1% and 15.5%). Neonatologists and pediatric cardiologists had significantly different (P<0.001) perceptions of the importance in 11 of 14 echocardiographic parameters used to determine a HSPDA. Surgical ligation was less frequently recommended than catheter closure.

Conclusion: This survey reflects the current best practice in the care of HSPDA and suggests an emphasis on imaging based on clinical condition with formal scoring systems used infrequently.. The difference in perceived value of various echocardiographic parameters between neonatologists and cardiologists may contribute to uncertainty in the determination of HSPDA. Despite being a relatively new technology, catheter occlusion of the HSPDA is recommended more frequently than surgical ligation by this cohort.


A Survey Regarding the Care of the Hemodynamically Significant Patent Ductus Arteriosus (HSPDA)

Background
Bicuspid aortic valve (BAV) is the most common congenital heart condition. BAV complications include aortic valve surgery, aortic surgery, infective endocarditis, and aortic dissection. Due to its 10% chance of transmission to offspring and lifetime morbidity burden of >80%, screening of first-degree relatives is recommended for early detection. Several barriers to echocardiographic screening for BAV have been identified, therefore, a cheap and fast “rule-out” BAV tool is appealing. The objective of our study is to create an artificial intelligence (AI)-enabled electrocardiogram (ECG) model to aid the detection of BAV in suspected individuals.
Methods
Between January 1, 1990, and June 30, 2023, 13,066 adults [mean age 58.3±17 years, 46.6% women] with both an ECG and an echocardiographic study within 6 months of each other, were identified from the Mayo Clinic database. Cases were selected as patients with a confirmed BAV diagnosis either by echocardiographic or pathologic report. Controls were selected as patients with an ECG indication of abnormal auscultation, rule out, suspected, or family history of BAV. Patients were excluded if they displayed any of the following criteria: a previous heart surgery or procedure, potential cardiac remodeling conditions(cardiomyopathies, history of chemotherapy or radiation, autoimmune disease, previous known congenital heart disease, heart failure, myxomas, history of endocarditis, rheumatic heart disease, heart transplant and pacemaker). ECGs by patient were randomly shuffled into mutually exclusive training (80%), internal validation (10%), and test (10%) data sets. A convolutional neural network was built using the Keras Framework under Tensorflow backend (Google;Mountain View,CA,USA).
Results
BAV prevalence in the model’s development was 45%. In the test group, the AI-enabled ECG model achieved an area under the curve (AUC) of 0.704 with the following values: sensitivity 65%, specificity 64.8%, accuracy 64.9%, positive predictive value (PPV) 60.1%, and negative predictive value (NPV) 69.4%.
Conclusion
An AI-enabled ECG model has shown modest diagnostic performance in detecting BAV. When assuming a prevalence of 10% (chance of transmission to offspring), the NPV increases to 94.3% with decreased PPV of 17%. This approach could save a major number of echocardiograms for “ruling-out” BAV, but needs external validation.

Artificial Intelligence-Enabled Electrocardiogram Model for Screening of Bicuspid Aortic Valve

Single ventricle surgical palliation with a Glenn surgery universally leads to unintended pulmonary vascular remodeling with pulmonary arteriovenous malformations (PAVMs) and aortopulmonary collaterals (APCs). The pathogenesis of PAVMs and APCs after Glenn is poorly understood, and published literature is limited. Our research team identified increased macrophages in lung biopsies from patients prior chronic Glenn circulation. Most recently we also identified increased lung macrophages and decreased lung lymphocytes in a surgical animal of Glenn circulation. Because lung macrophages and lymphocytes can originate from the bone marrow and circulate in peripheral blood as monocytes and lymphocytes, we hypothesized that peripheral blood samples from patients with chronic Glenn circulation would demonstrate increased monocytes and decreased lymphocytes compared to age-matched controls. We conducted a retrospective cohort study of patients 0-17 years old who underwent cardiac surgery between 1/1/2012 - 1/1/2024. To assess peripheral blood leukocyte counts, we recorded cell counts from pre-operative complete blood counts (CBC) from patients prior to single ventricle palliation (pre-Glenn and pre-Fontan). We also included age-matched control groups (pre-tetralogy of Fallot surgery and pre-atrial septal defect surgery) because normal leukocyte counts are known to change with age. Patient cohorts were identified through an institutional surgical database and CBCs were recorded through manual chart review immediately prior to the date of surgery. We identified a total of 736 pre-surgical CBCs, including 420 single ventricle CBCs (208 [28.3%] pre-Glenn, 212 [28.8%] pre-Fontan) and 316 control CBCs (156 [21.2%] pre-ASD, 160 [21.7%] pre-TOF). There was no difference in years of age at surgery between our age-matched groups (pre-Glenn 0.35 [0.28, 0.45] vs pre-TOF 0.35 [0.21, 0.50]; p>0.99) (pre-Fontan 3.5 [3.0, 4.1] vs pre-ASD 4.3 [3.0, 7.1]; p=0.19). Compared to their respective age-matched control groups, the pre-Fontan group had increased absolute monocytes (p<0.0001), whereas the pre-Glenn group was not different (p=0.57). Surprisingly, both single ventricle groups had decreased absolute lymphocyte counts (both p<0.0001) and increased absolute neutrophil counts (both p=0.01) compared to their respective control groups. In our single institutional study, chronic Glenn circulation is associated with increased monocytes and decreased lymphocytes in peripheral blood compared to an age-matched control group with an isolated ASD. Further investigation is needed to determine whether peripheral blood leukocyte counts may serve as a biomarker to predict clinical outcomes.

Assessment of leukocyte dysregulation in single ventricle congenital
heart disease

Association Between Pulmonary Artery Catheterization (PAC) Mortality, Length of Stay, and Cost utilizing a National Electronic Health Record Database in 2020


Samuel Y Huang1
1 Icahn School of Medicine At Mount Sinai and Mount Sinai South Nassau, Oceanside, NY, United States of America


Abstract

Importance
Pulmonary artery catheters (PACs) play a pivotal role in managing acute hemodynamic decompensation, allowing for the assessment of right and left ventricular hemodynamic parameters and can allow for determination of SVO2 over echocardiogram. However, because of their invasive nature, increased understanding of their overall benefits is important. In certain populations with decrease compliance such as in patients with ischemia, information from PACs may be hard to utilize.

Aim
This study focuses on evaluating the impact of Pulmonary Artery Catheterizations (PAC) in patients with heart failure and ischemia admitted to the inpatient setting to discern whether PAC usage is associated with increased in hospital mortality rates, prolonged length of stay, costs, and complications. A subgroup analysis will be performed to see if there is a change in outcomes in individuals with and without cardiogenic shock as well as in individuals with mechanical circulatory support devices such as Intra-aortic balloon pumps (IABP), intraoperative Extracorporeal mechanical oxygenation (ECMO), mechanical ventilation, and renal dialysis. 

Objective
The utilization of pulmonary artery catheters (PACs) in guiding decision-making for the management of cardiogenic shock is a common practice. However, despite their widespread use, there is a paucity of robust evidence delineating the optimal application of PACs in the context of cardiogenic shock. The existing literature lacks conclusive support for the efficacy and benefits of obtaining hemodynamic data through early PAC placement in patients experiencing CS. This study seeks to address this gap by rigorously examining the association between early PAC placement and pertinent clinical outcomes, aiming to contribute evidence that can inform and optimize the management of cardiogenic shock.


Design, setting, and participants
This retrospective study utilized the National Inpatient Sample (NIS) data for the year 2020, focusing on patients with heart failure and diagnosis of ST elevation myocardial infarction (STEMI) with description of those experiencing cardiogenic shock, individuals receiving intra-aortic balloon pumps (IABPs), undergoing mechanical interventions, and those treated with extracorporeal membrane oxygenation (ECMO). Additionally, the study included patients who underwent Pulmonary Artery Catheterization (PAC).
Methods
ICD-10 codes lung cancers were identified from the American Medical Association Complete Official Handbook. Heart failure, Ischemia, and pulmonary artery catheterizationss ICD-10 codes. Multivariable linear regression and logistic regression models were employed, incorporating Charlson comorbidity, age, gender, race, and cardiogenic shock, to assess the impact of catheterization on length of stay, healthcare costs, and mortality in patients with heart failure, ischemia, and cardiogenic shock. Additionally, a Kaplan-Meier analysis was conducted to evaluate the time to 30-day discharge for patients who underwent catheterization, considering demographic variables and cardiogenic shock as potential influencing factors. 

Results
The final minimal dataset comprised a total of 114,647 individuals who had both congestive heart failure and ischemia, with a mean age of 70.66 years (SD = 13.37). Among these patients, 11.47% (13,147 individuals) experienced mortality. Females constituted 42.19% of the cohort. The mean length of hospital stay (LOS) for this population was 7.16 days (SD = 8.64). Notably, 5.52% of patients received pulmonary artery catheterization (PAC). Upon multivariable analysis pulmonary catheterization was associated with a 18% decreased mortality (95% CI: 0.76 – 0.89, pvalue < 0.001), increase length of stay of 2.1 days (95% CI 1.88 to 2.32, p<0.001), and increased cost of $20,150.37 (95% CI $19,109.28 to $21,191.46, pvalue < 0.001).

Conclusion
Using a nationally representative sample and a large dataset, pulmonary artery catheterizations in patients with congestive heart failure and a diagnosis of STEMI who received a PAC was associated with decreased mortality, increased length of stay and increased cost. Further studies are needed to characterize causation and to apply for each specific region and population of interest. 



Association Between Pulmonary Artery Catheterization (PAC) Mortality, Length of Stay, and Cost utilizing a National Electronic Health Record Database in 2020

Background
Mobile low-dose computed tomography (LDCT) lung cancer screenings (LCS) are part of an outreach program in rural Appalachia to detect early malignancy in areas with limited healthcare access. While the primary goal is to screen for lung cancer, LDCT LCS can identify calcium deposits in coronary arteries and can prompt risk modification strategies for prevention of cardiovascular disease (CVD) events. There is no clear guidance for follow-up regarding CAC or prevention of associated CVD risk in patients undergoing LDCT LCS. The aim of this study was to determine how many patients with no known CVD had the presence of CAC on LDCT LCS. Secondary objectives were to determine if patients with CAC scores ≥100 received appropriate CVD risk reduction follow-up, and if initiation of statin or aspirin therapy occurred within 3 months after LDCT LCS. 

Methods
A retrospective review of mobile LDCT LCS from September 2021 to December 2022 was conducted in one large, tertiary health-system. Adult patients with no previous CVD history were included. CT images were obtained at 100 kVp with a slice thickness of 3 mm. Agatston CAC scoring was completed retroactively. Descriptive statistics and chi-square analyses were utilized.

Results
A total of 526 LDCT LCS were included. Over 54% of patients had coronary calcification on LDCT lung screening. 161 patients (30.6%) had a CAC score of ≥100 and 75 patients (14.3%) had a CAC score ≥400. Of patients with a CAC score ≥100, only 7.5% received referrals for follow-up and 9.3% had additional cardiac testing. Of those with a CAC score ≥100 not already on a statin (45.3%), only 8.2% were initiated on statin therapy within 3 months after LDCT LCS. Of those with a CAC score ≥100 not already on aspirin therapy (63.3%), only 5.9% were initiated on aspirin therapy within 3 months after LDCT LCS. Aspirin and statin initiations were dependent on calcium score (p<0.01).

Conclusion
In patients with no CVD history, CAC was frequently identified on mobile LDCT LCS in rural communities. Calcium scoring from LDCT lung screenings allowed for simultaneous assessment of lung cancer and CVD risk. Despite high CAC scores, there was limited initiation of cardiovascular disease prevention measures and follow-up, likely indicating missed opportunities for early intervention. Awareness of CAC score utility, follow-up for identified coronary calcification, and consideration of primary prevention medications when indicated, would be beneficial in patients undergoing LDCT lung cancer screenings, especially in rural areas with limited resources.

Cardiovascular Risk Reduction Strategies After Coronary Artery Calcium Scoring on Mobile CT Lung Screenings in Rural Appalachia

Background
Cardiovascular disease (CVD) is the leading cause of mortality worldwide in both men and women, which is due in part to high prevalence of hypertension. Recent evidence suggests supine, standing, and possibly change in supine to standing blood pressure (BP) may have greater utility to predict future mortality risk compared to the traditionally assessed resting seated BP. We hypothesized that supine, standing and change from supine to standing SBP would have predictive value of all-cause mortality for both men and women.
Methods
The Ball State Adult Fitness Longitudinal Lifestyle (BALL ST) cohort was used for this analysis. The population consisted of 2,116 apparently healthy men and women with no known disease where BP measurements were acquired in the standing and supine positions and the change in supine to standing was calculated. The mean age was 46.2±13.0 yr for men and 44.8±13.2 yr for women. Participants were followed for an average of 18.2±9.0 yr for all-cause mortality. Additionally, measurements of traditional risk factors were obtained. Hazard ratios (95% CIs) were generated for association between BP (supine, standing, change) and all-cause mortality by sex. Multiple Cox proportional hazard models were fit to the following data: 1) BP unadjusted, 2) BP adjusted for age and testing year, 3) BP further adjusted for risk factor (obesity, hypertension, dyslipidemia, diabetes, physical inactivity, and smoking status), 4) BP further adjusted for hypertensive medications.
Results
Two hundred and ten participants died during the follow-up period. Within the whole cohort, the univariate model indicated a positive association between all-cause mortality for supine SBP (HR: 1.030, 95% CI: 1.023-1.038, p<0.05) and standing SBP (HR: 1.023, 95% CI:1.016-1.031, p<0.05). Mortality was associated with the change in SBP (HR: 1.021, 95% CI: 1.007-1.036) in women only (p<0.05). Change in SBP was correlated with all-cause mortality after adjusting for risk factors only in women (HR: 1.025, 95% CI: 1.000-1.051; p≤0.05). Diastolic blood pressure (DBP) in the supine (HR: 1.030, 95% CI: 1.016-1.044), and standing (HR: 1.014, 95% CI: 1.001-1.028) positions in women, and change in DBP (HR: 1.013, 95% CI: 1.013-1.063) in men were correlated with all-cause mortality in the univariate model only (p<0.05, all).
Conclusion
These findings demonstrate the change from supine to standing SBP predicts risk for all-cause mortality in women, but not men after adjusting for risk factors. Assessing positional blood pressure may provide clinicians with additional diagnostic insight and predict all-cause mortality risk in women.

Change in Supine to Standing Systolic Blood Pressure (SBP) Predicts All-Cause Mortality in Women but not Men

Introduction
Hemodynamic gain index (HGI) is a marker of hemodynamic reserve inversely associated with major adverse cardiovascular events in patients undergoing exercise stress testing. HGI and traditional exercise markers, such as metabolic equivalents (METS), are derived from patient data from two to six decades ago. Modern patients have increased comorbidities and cardiac medication use which may affect the applicability of those exercise markers. HGI’s value in comparison to traditional exercise markers in a contemporary population is not well-characterized. 
Methods
This was a retrospective, single-center analysis of patients with exercise stress myocardial perfusion imaging from 2015-2017. Patients with >6 months follow-up and age >18 years were included. HGI was calculated with systolic blood pressure (SBP) and heart rate (HR): (SBPpeak x HRpeak – SBPrest x HRrest) / (SBPrest x HRrest). Other variables were calculated using prior literature: chronotropic incompetence (CI) = (HRpeak – HRrest) / (220 - age - HRrest) <0.8; impaired heart rate recovery (HRR) = HRpeak – HR1, min <12 or HRpeak – HR2, min <22; abnormal blood pressure response (ABPR) = Bruce protocol stage 2 SBP >210 (males), SBP >190 (females), diastolic BP >110, or SBP decrease compared to baseline; abnormal METS = METS <7. Cox proportional hazard analysis modeled subsequent death or nonfatal myocardial infarction (NFMI).
Results
The study included 1582 patients (mean age 62 years, 37% female, 16% non-white) with mean follow-up 4.8 years. Prevalence of coronary artery disease (CAD) and anti-hypertensive medication use was 32% and >50%, respectively. Exercise marker abnormality prevalence was: 24.4% impaired HGI (HGI <1.4), 32.7% CI, 24.2% HRR, 32.3% ABPR, 14.9% METS. Impaired HGI had odds ratio (OR) 1.97 (p<0.001) in multivariable logistic regression accounting for traditional risk factors (sex, tobacco use, diabetes mellitus, hypertension, chronic kidney disease, and CAD), and OR 2.15 (p<0.01) in multivariable modeling with the four other exercise markers. In Cox multivariable modeling, HGI (HR 1.75, p <0.001) outperformed CI (HR 1.63, p=0.001), HRR (HR 1.24, p=0.262), ABPR (HR 1.46, p=0.039), and METS (HR 1.30, p=0.163). Cox model assumptions were verified using Schoenfeld residuals. HGI models were superior to other marker models (likelihood ratio test p<0.01).
Conclusion
In a modern cohort with increased medication use and comorbidities, HGI outperforms established exercise markers in predicting death and NFMI. HGI can be easily calculated using vital signs and provides graded risk assessment beyond other markers. Greater application of this hemodynamic variable in exercise testing can augment ischemic heart disease prognostication.

Comparing the Prognostic Value of Hemodynamic Gain Index to Traditional Assessments of Exercise Hemodynamics in a Modern Cohort

Abstract Title: 

Consanguinity and Atrial Septal Defect: Genetic and Environmental Factors in Global Populations 

Background: 

Atrial septal defect (ASD) accounts for approximately 10 to 15 percent of congenital heart diseases, with a reported birth prevalence of approximately 1 to 2 per 1000 live births. This study aims to explore the relationship between consanguinity and ASD, addressing gaps in understanding both genetic and environmental factors. 

Methods: 

A search of PubMed articles (January 1950 - July 2024) using Medical Subject Headings (MeSH) terms 'congenital heart disease' and 'consanguinity', limited to English language articles, yielded 642 results. The focus was on articles that studied the relationship between consanguinity and ASD across various countries. 

Results: 

A Moroccan study found 3 heterozygous NKX2-5 variants in 9.4% of ASD patients, with 30.8% reporting consanguinity. In Northeast Iran, 85% of ASD patients had secundum ASD, and consanguinity significantly correlated with ASD type (P < 0.001), gender (P < 0.001), and age of onset (P = 0.003). Western Iraq exhibited notably higher consanguinity rates in congenital heart disease cases (78%) compared to controls (43.3%), with first-cousin consanguinity particularly elevated in cases (66.2%) versus controls (35.6%). In South India, consanguinity, including first cousin (44.68%) and uncle-niece marriages (46.81%), significantly increased the risk of ASD. 

Conclusion: 

These findings underscore a significant relationship between consanguinity and ASD prevalence, with consanguinity emerging as a substantial environmental risk factor alongside genetic predispositions such as NKX2-5 variants. The Moroccan cohort study suggests that consanguinity, coupled with a high incidence of maternal miscarriages and sudden sibling deaths, indicates a non-sporadic nature of ASD, potentially influenced by ethnicity. Studies in Western Iraq and South India show that consanguinity significantly increases the risk of ASD, highlighting the role of recessive gene segregation. The elevated prevalence of ASD among consanguineous marriages emphasizes the need for pre-marriage counseling to educate couples about the genetic risks associated with inbreeding. Social education campaigns could raise awareness about these risks and promote healthy family planning practices. Understanding the interplay between genetic and environmental factors is crucial for developing effective prevention and management strategies. Future research should prioritize whole-exome sequencing to identify causative genes of ASD within consanguineous communities.

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