United States

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&#39;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.

2022 AMA Research Challenge

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

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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.


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.

poster

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.

Rocuronium-Induced Anaphylaxis, Systematic review, and current opinion

Background: Surgery provides an excellent opportunity for smokers to quit. Our prior work showed that many smokers scheduled for surgery are willing to “quit for a bit” (from the morning of surgery until at least one week after surgery), even if not ready to contemplate sustained abstinence (“quit for good”). This project aimed to develop, and pilot test an innovative tobacco use intervention to help surgical patients who smoke to maintain at least short-term perioperative abstinence.
Methods: An existing SMS message library used to promote sustained abstinence (“quit for good”) was modified to target “quitting for a bit” by emphasizing the benefits of smoking cessation to surgery. Numerous opportunities for patients to provide responses to queries were provided. Current smokers seen in a preoperative evaluation clinic were stratified according to the intended duration of perioperative abstinence and randomized within each stratum to receive either the “quit for a bit” intervention or the conventional “quit for good” intervention. The primary outcomes were a treatment engagement index calculated as the proportion of response opportunities completed by subjects, and the proportion of subjects who continued using the SMS service at study completion (30 days). Secondary outcomes were self-reported smoking status and satisfaction with the service.
Results: The engagement index did not differ between groups (median [25th, 75th] of 23.7 [8.8, 46.0] for “quit for a bit” group (n=48) and 22.2 [4.8, 46.0] for “quit for good” group (n=50), p= 0.74), nor did the proportion of patients continuing SMS use after study completion (33% and 28%, respectively). Abstinence outcomes on the morning of surgery, 7, and 30 days after surgery did not differ between groups. Satisfaction with the programs was high in both groups and did not differ. There was no significant interaction between intended abstinence duration and any outcome, i.e., alignment of intent with intervention did not affect efficacy.
Conclusion: Tobacco use treatment delivered via SMS was feasible and well-utilized by surgical patients. Tailoring an SMS intervention to focus on the benefits of short-term abstinence in surgical patients did not increase engagement in treatment or perioperative abstinence rates.

SMS 2 QUIT: A randomized clinical trial to promote perioperative smoking cessation using short message services.

Percutaneous electrical nerve field stimulation (PENFS) is a minimally invasive therapy that involves electrodes placed on the ear through needle arrays to stimulate the auricular branches of the cranial nerves. We hypothesize that PENFS can decrease pain in fibromyalgia through stimulation of the auricular branch of the vagus nerve. We previously published data suggesting a neuromodulatory effect of PENFS in fibromyalgia1, and here we seek to further explore the potential vagal mechanisms. This was a randomized, controlled, open label investigation conducted in a government hospital. Twenty-one veterans with fibromyalgia were randomized to receive either standard therapy or ST with auricular PENFS (ST+PENFS). Seed-based connectivity using a vagal nucleus seed was assessed and correlated to pain scores using the CONN toolbox. Functional connectivity between the vagal nucleus and several clusters in the cuneus and lingual gyri predicted greater decreases in pain for the PENFS treatment group, relative to the standard-care control group. Our results further suggest that connectivity to the vagal nucleus may be predictive of treatment response in fibromyalgia. Future directions include extracting heart rate variability data to further assess the potential effects of PENFS on vagal nerve modulation for pain treatment.

Vagal Nucleus Connectivity Predicts Percutaneous Electrical Nerve Field Stimulation Treatment Response in Veterans with Fibromyalgia

Introduction:
Alcoholic cardiomyopathy (AC) results due to the consumption of high levels of alcohol on a long-term basis. Its prevalence varies and ranges from 4 to 40 percent. Although AC makes up approximately 4% of all cardiomyopathies, it is the second most common cause of dilated cardiomyopathy. We herein explore the outcomes of percutaneous coronary intervention (PCI) among patients with AC.

Methods:
This is a cross-sectional study of the National Inpatient Sample (NIS) for hospital discharges in the United States between 2012 to 2014. We identified the number of patients with a primary or secondary diagnosis of AC using the ICD-9 code of 4.255. Using the ICD-9 code for PCI (00.66, 36.01, 36.02, 36.05, 36.06, 36.07, 17.55), we identified patients diagnosed with AC who underwent a PCI (AC/PCI). Hospital length of stay (LOS), death, cost of hospitalization, and cardiovascular outcomes, including atrial fibrillation (AF) and Ventricular fibrillation (VF) were compared between patients with and without AC who underwent a PCI.

Results:
A total of 2,488,293 PCIs were performed between 2012 to 2014. Of these, there were a total of 161 admissions for alcoholic cardiomyopathy. The patients with AC/PCI were likely to stay longer in the hospital, with an average stay of 6.6 days (SD = 6.2) compared to patients without AC undergoing PCI -3.7 days (SD = 5.0) (p=0.0001). The mean hospital charge for patients with AC/PCI was $120,225 (SD=101,044), while that of those without AC who underwent PCI was $87,936 (SD=83,947) (p=0.0001). A higher death rate during hospitalization, 3.7%, was recorded in the AC/PCI category vs. 2.3% in patients without AC who underwent PCI (p=0.0001). Patients with AC/PCI had a higher prevalence of AF (30.4%) than VF (7.5%).

Conclusion:
Alcohol abuse increases the disease burden and continues to be a public health concern. Despite the decreased prevalence compared to their non-AC/PCI counterparts, the AC/PCI group had poorer hospital outcomes. Further studies are needed to explore the burden of long-term alcohol consumption on cardiovascular disease treatment outcomes.

Alcohol and Heart Health; A Public Health Concern

Assessing Time in Therapeutic Range (TTR): Is remote anticoagulation management as effective as in-person care?

Abstract Title: Catheter ablation for atrial fibrillation: a national study of demographics & socioeconomic factors.

Background: Atrial fibrillation(AF) is the most commonly diagnosed cardiac arrhythmia. With a worldwide prevalence of >33 million, it poses a significant economic burden and serious cardiovascular morbidity and mortality. Catheter ablation(CA) has proven to be an important curative treatment for paroxysmal, persistent, and permanent AF.

Methods: This retrospective study acquired data from the NIS between January,2007 and December,2017. Primary and secondary diagnosis of non-valvular atrial fibrillation were identified using ICD-9 and 10-CM codes. Chi square and unpaired t test were used to evaluate socio-demographic disparities.

Results: From 35,906,946 patients with NVAF, 343641(0.96%) underwent catheter ablation. Patients who underwent CA were mostly in the age group of 50-75 years(63.67%) vs <50 years(8.63%) vs >75 years(27.71%). The majority of patients undergoing CA were men(61.6%) and was more common amongst White race(86.17%) vs Native American(0.58%) vs Black(7.31%). Patients with a median household income falling in 76th-100th percentile(28%) were the majority to have the procedure. Most of the patients had medicare insurance(59.5%) vs Medicaid(4.06%) vs private insurance(32.71%). CA was performed more often during weekdays(89.54%) vs weekends(10.46%) and frequently done as a non-elective procedure(51.41%) vs elective(48.59%). It was more frequent in urban teaching hospitals(73.14%) vs urban non teaching(24.1%) and was more common in the South region(39.57%) vs West region(19.33%). Co-morbidity comparison between the cohorts with vs without CA include hypertension(67.4% vs 75.52%), diabetes(24.53% vs 33.8%), CHF(33.4%
vs 42.45%), alcohol use(2.12% vs 3.17%), tobacco use(7.38% vs 7.72%), and drug abuse(1.02% vs 1.37%). p value was noted to be <0.0001 for above comparisons. In regression analysis, age>50 years(OR-1.59,1.52-1.66,P<0.0001), native-Americans (OR1.39,1.24-1.55,p<0.0001), patients with private insurance(OR-1.307,1.28-1.33,p<0.0001) and high income group(OR-1.154,1.12-1.18,p<0.0001) were associated with higher odds of utilization of catheter ablation.

Conclusion: There is a significant racial and sex disparity in patients undergoing CA for NVAF that mandates further investigation. These results are important when interpreting the characteristics of the patients, so future trials can be made to decrease the high burden of NVAF through CA. Study’s limitation is insufficient data on disease severity and cardiovascular
diagnostic test variables for accurately predicting the factors associated with under utilization.

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

Next from 2022 AMA Research Challenge

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

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Risk Factors for Perioperative Thrombosis in Neonates Undergoing Congenital Cardiac Surgery

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