Beta-adrenergic Blockade Research Articles

SUN-505 Total Thyroidectomy in Severe Hyperthyroidism

Introduction: Patients with hyperthyroidism may be treated with ATDs, RAI therapy or thyroidectomy; in some cases like thyroid storm, plasmapheresis can be used to remove excess hormones prior to surgery. In some cases, such as those with complications derived from ATDs (agranulocytosis, hepatotoxicity), or those with large goiters with l symptomatic compression of surrounding organs within the neck, surgical treatment is considered. Clinical cases: Seven patients were treated with total thyroidectomy for the definitive control of the hyperthyroidism. Six were female, 4 used thionamides, 1 lithium and 2 discontinued treatment. All diffuse goiter (60-160 gr), 2 with autoimmune ophthalmopathy and, 4 had thyroid storm. The thyroid ultrasonography of thyroid evidenced hypoechogenicity and hypervascularity and in 4 cases tracheal compression. All patients had suppressed TSH and free T4 within 2,6-7,76 ng /dl (N: 0.7-1.7). Previous to surgery, six received glucocorticoids and beta-adrenergic blockade, five lugol solution, four thionamides (30-90mg/d), four lithium (3 with agranulocytosis) and two calcium with vitamin D. One patient received plasmapheresis which had a poorly response for thyroid storm treatment.After surgery 2presented hungry bone syndrome, two transient hypoparathyroidism and two permanent hypoparathyroidism. One patient was re-admitted for surgery. Pathological examination reported autoimmunity characteristics (cylindrical thyrocytes, vacuolated colloid, papillae formation and / or lymphocytic infiltrate) in 4 cases. In 3 cases, nodules were found without malignancy signs. Conclusions: Thyroidectomy is a definitive therapeutic option in severe hyperthyroidism with difficult management, particularly in those cases with contraindication to the use of thionamides, large goiters compromising the upper airway, because it leads to faster control of the hyperthyroid state. Hypocalcemia is a frequent postoperative complication that can be attenuated with the pre-operative vitamin D and calcium supplements.

Use of beta-blocker types and risk of incident prostate cancer in a multiethnic population

PurposeIncreased adrenergic innervation is observed in prostate cancer (CaP) and is associated with aggressive disease. Emerging evidence suggests that beta-adrenergic blockade inhibits CaP progression. However, the association between type of beta-blocker use and risk of incident CaP on initial prostate biopsy has not been investigated in multiethnic populations. Materials and methodsA retrospective study of racially/ethnically diverse men (64% African-American and Hispanic), who underwent initial prostate biopsy between 2006 and 2016 in a large healthcare system was performed. Oral use of beta-blocker type was assessed by reviewing active prescriptions within the 5-year period preceding initial biopsy. Patient demographics and clinical factors were collected. ResultsOf 4,607 men who underwent initial prostate biopsy, 4,516 met criteria and 2,128 had a biopsy positive for CaP; 20% high-risk, 41% intermediate-risk, and 39% low or very-low risk (National Comprehensive Cancer Network classification). Overall, 15% of patients were taking a beta-blocker prior to initial biopsy, with Metoprolol, Atenolol, and Carvedilol accounting for the majority. Of beta-blocker types, Atenolol alone was associated with a 38% reduction in odds of incident CaP (P= 0.01), with a 40% and 54% reduction in risks of National Comprehensive Cancer Network intermediate and high-risk CaP (P = 0.03 and P = 0.03, respectively) compared to men not taking a beta-blocker. Furthermore, longer duration of Atenolol use (3–5 years) was associated with a 54% and 72% reduction in intermediate and high-risk disease, (P = 0.03 and P = 0.03, respectively). ConclusionsAmong beta blocker types, long-term Atenolol use is associated with a significant reduction in incident CaP risk on initial prostate biopsy for clinically-significant intermediate and high-risk disease compared to men not taking a beta-blocker.

Stem Cell–Derived Cardiomyocytes and Beta-Adrenergic Receptor Blockade in Duchenne Muscular Dystrophy Cardiomyopathy

BackgroundAlthough cardiomyopathy has emerged as a leading cause of death in Duchenne muscular dystrophy (DMD), limited studies and therapies have emerged for dystrophic heart failure. ObjectivesThe purpose of this study was to model DMD cardiomyopathy using DMD patient-specific human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and to identify physiological changes and future drug therapies. MethodsTo explore and define therapies for DMD cardiomyopathy, the authors used DMD patient-specific hiPSC-derived cardiomyocytes to examine the physiological response to adrenergic agonists and β-blocker treatment. The authors further examined these agents in vivo using wild-type and mdx mouse models. ResultsAt baseline and following adrenergic stimulation, DMD hiPSC-derived cardiomyocytes had a significant increase in arrhythmic calcium traces compared to isogenic controls. Furthermore, these arrhythmias were significantly decreased with propranolol treatment. Using telemetry monitoring, the authors observed that mdx mice, which lack dystrophin, had an arrhythmic death when stimulated with isoproterenol; the lethal arrhythmias were rescued, in part, by propranolol pre-treatment. Using single-cell and bulk RNA sequencing (RNA-seq), the authors compared DMD and control hiPSC-derived cardiomyocytes, mdx mice, and control mice (in the presence or absence of propranolol and isoproterenol) and defined pathways that were perturbed under baseline conditions and pathways that were normalized after propranolol treatment in the mdx model. The authors also undertook transcriptome analysis of human DMD left ventricle samples and found that DMD hiPSC-derived cardiomyocytes have dysregulated pathways similar to the human DMD heart. The authors further determined that relatively few patients with DMD see a cardiovascular specialist or receive β-blocker therapy. ConclusionsThe results highlight mechanisms and therapeutic interventions from human to animal and back to human in the dystrophic heart. These results may serve as a prelude for an adequately powered clinical study that examines the impact of β-blocker therapy in patients with dystrophinopathies.

Complex Interaction Between Low-Frequency APD Oscillations and Beat-to-Beat APD Variability in Humans Is Governed by the Sympathetic Nervous System.

BackgroundRecent clinical, experimental and modeling studies link oscillations of ventricular repolarization in the low frequency (LF) (approx. 0.1 Hz) to arrhythmogenesis. Sympathetic provocation has been shown to enhance both LF oscillations of action potential duration (APD) and beat-to-beat variability (BVR) in humans. We hypothesized that beta-adrenergic blockade would reduce LF oscillations of APD and BVR of APD in humans and that the two processes might be linked.Methods and ResultsTwelve patients with normal ventricles were studied during routine electrophysiological procedures. Activation-recovery intervals (ARI) as a conventional surrogate for APD were recorded from 10 left and 10 right ventricular endocardial sites before and after acute beta-adrenergic adrenergic blockade. Cycle length was maintained constant with right ventricular pacing. Oscillatory behavior of ARI was quantified by spectral analysis and BVR as the short-term variability. Beta-adrenergic blockade reduced LF ARI oscillations (8.6 ± 4.5 ms2 vs. 5.5 ± 3.5 ms2, p = 0.027). A significant correlation was present between the initial control values and reduction seen following beta-adrenergic blockade in LF ARI (rs = 0.62, p = 0.037) such that when initial values are high the effect is greater. A similar relationship was also seen in the beat-to beat variability of ARI (rs = 0.74, p = 0.008). There was a significant correlation between the beta-adrenergic blockade induced reduction in LF power of ARI and the witnessed reduction of beat-to-beat variability of ARI (rs = 0.74, p = 0.01). These clinical results accord with recent computational modeling studies which provide mechanistic insight into the interactions of LF oscillations and beat-to-beat variability of APD at the cellular level.ConclusionBeta-adrenergic blockade reduces LF oscillatory behavior of APD (ARI) in humans in vivo. Our results support the importance of LF oscillations in modulating the response of BVR to beta-adrenergic blockers, suggesting that LF oscillations may play role in modulating beta-adrenergic mechanisms underlying BVR.

A Personalized Low Intensity Exercise Prescription based on an Index of Non-Linear Heart Rate Variability: A Case Report

The potential of an index of cardiac interbeat fractal complexity (DFA a1) to demarcate low intensity training was undertaken in a recreational athlete. The influence of absolute heart rate elevation versus work rate as factors responsible for loss of interbeat complexity was also examined via the usage of beta adrenergic blockade. Incremental cycling ramps were performed with and without the beta adrenergic blocking agent Atenolol 25 mg measuring DFA a1 during the last 2 minutes of each stage. No difference was seen between control and Atenolol trials for lactate thresholds, ventilation rates, rectus femoris muscle O2 desaturation and DFA a1 despite a 15 to 20 beat decrease in heart rate across all stages in the Atenolol trial. In both studies, DFA a1 progressively declined with cycling power reaching a value consistent with white noise at 25 Watts above the first ventilatory threshold. In conclusion, DFA a1 transition to an uncorrelated low complexity state occurred just above the VT1. In addition, the complexity index was related to cycling power, ventilation and presumably VO2 rather than the absolute heart rate. Longer constant power intervals near VT1 did not show additional or progressive complexity loss. DFA a1 may be a promising guide for low intensity training zone demarcation.

Complete atrioventricular block due to timolol eye drops: a case report and literature review

BackgroundTimolol Maleate is a non-selective beta-adrenergic blocker that is commonly used to treat open-angle glaucoma. Despite its topical administration, ophthalmic timolol enters systemic circulation and produces a systemic beta-adrenergic blockade. We report a case of long-term timolol use that uncovered and worsened an underlying cardiac conduction defect demonstrated as a third degree atrioventricular (AV) block.Case presentationA 62-year old male with a 13-year history of glaucoma was hospitalized due to shortness of breath, dizziness, and amaurosis. Electrocardiography indicated a heart rate (HR) of 29 bpm with complete atrioventricular (AV) block, and the HR was significantly increased with the treatment of isoprenaline. However, the patient experienced bradycardic episodes (− 20 Δbpm) immediately after self-administration of timolol eye drops. The AV block and bradycardia resolved 48-h after timolol cessation. The man was discharged 1 week later with an asymptomatic first-degree A-V block. However, he presented with a worsened A-V block at his one-year checkup.ConclusionWe conclude that chronic topical timolol administration may aggravate a cardiac conduction defect leading to an AV block that is only temporarily resolved by timolol cessation. Patients taking timolol should be routinely monitored for cardiovascular aberrations and if any detected, immediately discontinue timolol therapy. Individuals experiencing timolol induced cardiovascular side effects should receive long term follow-up even if symptoms resolve, as they may be indicative of an underlying conduction defect.

Haemodynamic Balance in Acute and Advanced Heart Failure: An Expert Perspective on the Role of Levosimendan.

Acute and advanced heart failure are associated with substantial adverse short- and longer-term prognosis. Both conditions necessitate complex treatment choices to restore haemodynamic stability and organ perfusion, relieve congestion, improve symptoms and allow the patient to leave the hospital and achieve an adequate quality of life. Among the available intravenous vasoactive therapies, inotropes constitute an option when an increase in cardiac contractility is needed to reverse a low output state. Within the inotrope category, levosimendan is well suited to the needs of both sets of patients since, in contrast to conventional adrenergic inotropes, it has not been linked in clinical trials or wider clinical usage with increased mortality risk and retains its efficacy in the presence of beta-adrenergic receptor blockade; it is further believed to possess beneficial renal effects. The overall haemodynamic profile and clinical tolerability of levosimendan, combined with its extended duration of action, have encouraged its intermittent use in patients with advanced heart failure. This paper summarises the key messages derived from a series of 12 tutorials held at the Heart Failure 2019 congress organised in Athens, Greece, by the Heart Failure Association of the European Society of Cardiology.

Heart Failure with Preserved Ejection Fraction - To beta-Block or Not to beta-Block

Introduction Heart failure with reduced ejection fraction (HFrEF) enjoys the luxury of well- established clinical guideline-directed medical therapy (GDMT). However, heart failure with preserved ejection fraction (HFpEF) remains an orphan disease with no clear guidelines. Beta- adrenergic blockade has garnered the most interest owing to previous meta-analyses studies. We undertook a retrospective observational study to measure the effect of beta-blockade in such a population. Methods This was a retrospective observational study from January 1, 2012 to December 31, 2017. We included patients that underwent transthoracic echocardiogram (TTE) at our center either in the inpatient or outpatient settings and which demonstrated a left ventricular ejection fraction (LVEF) of over 50% as well as evidence of diastolic dysfunction. Additionally, patients must have had at least 3 outpatient visits during this time frame. Variables collected included age, gender, ethnicity, LVEF, grade of diastolic dysfunction on TTE, use of beta-adrenergic blocker if any, presence of any baseline arrhythmias, heart rate during three outpatient clinic visits, hospital admissions due to heart failure (HF), complications if any during the admissions and finally death attributable to HF. Results After a review of over 1500 patients, 625 met the criteria to be included in the study. Approximately 55% were Hispanic, 39% Black, 5% Caucasian and the remaining 1.8% Asian. 90% of the study population had grade 1-2 diastolic dysfunction and 15% had baseline arrhythmias. We found that 27% of the population had a heart rate under 70 bpm at baseline. 62% of the population were treated with beta-adrenergic blockers. When patients were stratified based on beta-adrenergic blockade usage, it was found that the inpatient admission rates for cardiac reasons between the two groups did not differ. The likelihood of requiring critical care services between the two groups was similarly insignificant. Furthermore, the likelihood of death due to cardiovascular causes between the two groups did not differ. Conclusions Multiple meta-analyses studies have demonstrated a reduction in cardiovascular as well as all-cause mortality in HFpEF. However, observational studies are unable to reproduce similar success. We propose that the use of beta-adrenergic blockade is still up for debate. Undertaking a large multi-center study along the lines proposed by us would settle the debate once and for all.

The Role of Cardioselective versus Non-Cardioselective Beta-Adrenergic Blockade in the Acute Phase of Takotsubo Cardiomyopathy

Background Takotsubo cardiomyopathy (TC) has been associated with hyperactivation of sympathetic nervous system leading to transient left ventricular (LV) dysfunction following acute emotional or physical stress. There are no controlled studies or guidelines on how to treat TC and its therapy remains empirical. We aim to study the effects of cardioselective versus non-cardioselective beta-adrenergic blockade on LV recovery in follow-up transthoracic echocardiographic studies in patients with newly diagnosed TC. Methods We performed retrospective chart review analysis of all patients who were admitted to Bronx-Care Health System from January 1, 2007 through December 31, 2017 with the diagnosis of TC. All cases of TC who presented with acute coronary syndrome and angiogram showing apical ballooning with preserved base of the heart were included. We excluded significant coronary artery disease, prior known cardiomyopathy, suspicion of any myocarditis and recent head trauma or intracranial hemorrhage. Primary outcome variables included improvement in LV end-diastolic and end-systolic volumes, LV ejection fraction as well as degree of LV wall motion abnormalities improvement from the baseline transthoracic echocardiography with use of either cardioselective or non-cardioselective beta-adrenergic antagonists. The secondary outcomes included morbidity and mortality including all-cause and HF readmission in 30 days as well as mortality at 6 and 12 months. Results Of the 2010 patients admitted with acute coronary syndrome and underwent coronary angiogram, 60 patients (2.98%) were found to have TC. The mean age for TC patients was 62 (±16) years with more females (75%) than males. Urine drug screen was positive in 38% of our population and 6% had HIV disease. The average BMI in our study subject was 23.54 KG/M2 which was observed 19.45 KG/M2 in subjects with positive drug screen (p value= 0.0213). Beta-blocker was used in 83% of the cases with 63% were on cardioselective beta-adrenergic blockade and 27% were on non-cardioselective beta-adrenergic blockade. The relationship observed between echocardiographic parameters and type of beta-adrenergic blockade did not differ. The 30-day readmission rate and all-cause mortality were found to be similar in both groups. Positive urine drug screen was not associated with 30-day readmission and all-cause mortality in TC. (p value= 0.262) Conclusions Use of Beta-adrenergic blockers did not show any improvement in echocardiographic parameters in TC. It was not associated with improved adverse outcomes such as 30-day readmission rate and all-cause mortality in TC. The study challenges the proposed role of beta-blockers in improving outcomes in patients with TC.

Prospective pilot trial with combination of propranolol with chemotherapy in patients with epithelial ovarian cancer and evaluation on circulating immune cell gene expression

ObjectiveTo determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. MethodsPatients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. ResultsMedian age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53–81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. ConclusionUse of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.

Pathogenesis and pathophysiology of heart failure with reduced ejection fraction: translation to human studies.

Heart failure represents the end result of different pathophysiologic processes, which culminate in functional impairment. Regardless of its aetiology, the presentation of heart failure usually involves symptoms of pump failure and congestion, which forms the basis for clinical diagnosis. Pathophysiologic descriptions of heart failure with reduced ejection fraction (HFrEF) are being established. Most commonly, HFrEF is centred on a reactive model where a significant initial insult leads to reduced cardiac output, further triggering a cascade of maladaptive processes. Predisposing factors include myocardial injury of any cause, chronically abnormal loading due to hypertension, valvular disease, or tachyarrhythmias. The pathophysiologic processes behind remodelling in heart failure are complex and reflect systemic neurohormonal activation, peripheral vascular effects and localised changes affecting the cardiac substrate. These abnormalities have been the subject of intense research. Much of the translational successes in HFrEF have come from targeting neurohormonal responses to reduced cardiac output, with blockade of the renin-angiotensin-aldosterone system (RAAS) and beta-adrenergic blockade being particularly fruitful. However, mortality and morbidity associated with heart failure remains high. Although systemic neurohormonal blockade slows disease progression, localised ventricular remodelling still adversely affects contractile function. Novel therapy targeted at improving cardiac contractile mechanics in HFrEF hold the promise of alleviating heart failure at its source, yet so far none has found success. Nevertheless, there are increasing calls for a proximal, 'cardiocentric' approach to therapy. In this review, we examine HFrEF therapy aimed at improving cardiac function with a focus on recent trials and emerging targets.

Beta blockade as adjunctive breast cancer therapy: A review.

Pre-clinical data has shown that beta adrenergic stimulation can affect the development and progression of many types of cancer. The use of beta blockers as an anti-neoplastic therapy has been studied in retrospective trials and observational trials, but no definitive conclusions about efficacy have been made. Within the realm of breast cancer, significant advances in therapy have led to improved survival outcomes, yet there is room for improvement. Beta adrenergic blockade may prove an effective adjunct to standard breast cancer therapy, with little associated toxicity. This article provides a review of the published literature on beta blockade as an adjunctive cancer therapy, with a focus on breast cancer.

SAT-316 MAX-Related Bilateral Pheochromocytoma Associated with Subclinical Adrenal Insufficiency: A Case Report

INTRODUCTION: Loss-of-function mutation in the MYC-associated factor X (MAX) gene causes hereditary pheochromocytoma (PCC) that are frequently bilateral or multifocal1. Adrenal insufficiency (AI) associated with unresected bilateral PCC has not been previously described. We hereby present a case of subclinical AI in a patient with bilateral PCC. CLINICAL CASE: An otherwise healthy 30-year-old woman was found to have a pathogenic MAX gene mutation (c.228delG) after undergoing genetic testing for a significant family history of PCC in 3 relatives. She participated in high-intensity interval training 5 times per week and denied episodes of palpitations, flushing, diaphoresis, or dizziness, but endorsed frequent pulsatile tinnitus and morning headaches. She had a history of hypertension in late pregnancy which had been presumed gestational. Exam was notable only for manual BP 152/110 mmHg, HR 110 bpm, and a faint resting tremor. Lab work was consistent with PCC: plasma norepinephrine 12417 pg/mL (ref <874) and normetanephrine 26 nmol/L (ref <0.9); urine norepinephrine 3378 mcg/24h (ref <135) and normetanephrine 16620 mcg/24h (ref <500). AM cortisol was 10.9 mcg/dL (ref 5-20) with a high normal ACTH of 46 pg/mL (ref 0-46) and low DHEA-S of 23 mcg/dL (ref 75-530). She had no prior history of glucocorticoid exposure, and thyroid studies were normal. CT imaging revealed bilateral contrast-enhancing heterogeneous adrenal masses (R: 3.5 x 2.2 cm; L: 4.6 x 4.5 cm). She was treated with alpha- then beta-adrenergic blockade and subsequently underwent surgical removal of both adrenal tumors with sparing of the superior adrenal cortices bilaterally. Plasma and urine catecholamines and metanephrines normalized a week post-operatively, and she began to report fatigue and dizziness. Two weeks post-operatively, midday plasma levels of cortisol, DHEA-S, and ACTH were 6.3 mcg/dL, <15 mcg/dL, and 118 pg/mL, respectively. Standard-dose 250mcg ACTH stimulation test confirmed AI with peak cortisol of 15.1 mcg/dL. Replacement hydrocortisone was initiated with prompt resolution of symptoms. CONCLUSIONS: Individuals with a pathogenic MAX mutation require prompt screening for PCC as symptoms may be subtle despite significant biochemical abnormalities. Large PCCs may also impact hormone synthesis by the adjacent adrenal cortex. Even prior to surgery, this patient had subclinical AI as evidenced by a high-normal plasma ACTH and clearly low DHEA-S. The latter is the earliest adrenal steroid to decline in patients with primary or central AI2. It is unclear whether her worsening adrenal function after surgery was a surgical complication or due to dramatic decline in circulating catecholamines. Regardless, loss of adrenal androgen production warrants close follow-up for development of AI. REFERENCES: (1) Burnichon N et al. Clin Cancer Res 2012;18:2828 (2) Sayyed Kassem L et al. JCEM 2012;97:3655

Arterial Hemodynamics in Prehypertensives.

Compared to age-matched normotensive adults, those with essential hypertension have been shown to have distinct arterial hemodynamic abnormalities consisting of increased peripheral resistance, pulse wave velocity, and wave reflection magnitude as well as decreased wave reflection time and aortic compliance. These abnormalities are further exacerbated by beta-adrenergic blockade. To see if there are similar hemodynamic abnormalities that antedate the onset of fixed hypertension, we compared age-matched normotensives with prehypertensives selected from patients undergoing diagnostic cardiac catheterization. Ascending aortic pressure and flow were measured with a micromanometer and flow velocity sensor in the baseline state and after beta-adrenergic blockade. In the baseline state the prehypertensive compared to the normotensive group had elevated blood pressure, resistance, left ventricular end-diastolic pressure (LVEDP), and wave reflections. Beta-adrenergic blockade increased resistance, LVEDP, and wave reflections in both groups. Some of these findings are the same as those we previously reported in young persons with established, essential hypertension. The differences in LVEDP and wave reflections, both in the baseline state and after beta-blockade, were still present in subgroups with no differences in blood pressure. Hence, the elevated wave reflections in prehypertensives do not appear to be directly related to the level of blood pressure. These results support the notion that the elevated blood pressure in hypertension may represent a later manifestation of an already abnormal vascular system rather than the vascular abnormalities resulting from hypertension. Consequently, even before blood pressure becomes elevated, early diagnosis and treatment of the vascular abnormalities in prehypertensives may be warranted.

MP48-16 ATENOLOL REDUCES INCIDENT LOW AND INTERMEDIATE RISK PROSTATE CANCER

INTRODUCTION AND OBJECTIVES:Recent evidence from pre-clinical models of prostate cancer (PCa) suggests that disruption of adrenergic signaling by beta-adrenergic receptor blockade inhibits PCa prog...

Abstract # 2055 Beta-adrenergic blockade inhibits stress-related transcriptome profiles associated with worse cancer outcomes: A randomized controlled study of propranolol in hematopoietic cell transplantation recipients

Beta-adrenergic signaling regulates multiple molecular pathways that contribute to cancer progression; beta-adrenergic antagonists efficiently block many of these effects in animals. We previously demonstrated that hematopoietic cell transplant (HCT) patients exposed to socioeconomic stress show activation of a conserved transcriptional response to adversity (CTRA) transcriptome profile, which in turn is associated with increased relapse and decreased disease-free survival. We conducted a randomized controlled trial to evaluate whether the beta-antagonist propranolol is effective in decreasing gene expression of CTRA-related genes of 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for one week prior to transplant and 4 weeks following transplant. Blood was collected at baseline, Day −2, and Day +28. Intention-to-treat analyses assessed effects on the 53-gene CTRA indicator profile and measures of CTRA-related cellular processes. Twelve participants were randomized to the intervention group and 13 to the control arm. Relative to the control group, propranolol-treated patients showed greater decreases from baseline to Day −2 and Day +28 for both CTRA gene expression (p = .017) and bioinformatic measures of CD16- classical monocyte activation (p = .005). Propranolol-treated patients also showed up-regulation of CD34+ hematopoietic progenitor cells (p = .011). Peri-transplant administration of propranolol can down-regulate CTRA gene expression, inhibit myeloid-based cellular dynamics, and up-regulate the CD34+ cells. Ongoing follow-up and future replication studies will be required to assess impacts on clinical outcomes.

Regulation of blood flow in the pulmonary and systemic circuits during submerged swimming in common snapping turtle (Chelydra serpentina).

Blood flow patterns and heart rate have rarely been investigated in freely swimming turtles and their regulation during swimming is unknown. In this study, we investigated the blood flow patterns and heart rate in surfacing and during graded, submerged swimming activity in common snapping turtles. We further investigated the effects of beta-adrenergic and cholinergic receptor blockade on blood flow and heart rate during these activities. Our findings illustrate that surfacing is accompanied by an increase in heart rate that is primarily due to beta-adrenergic stimulation. During swimming, this mechanism also increases heart rate while vagal withdrawal facilitates a systemic to pulmonary (left to right) shunt. The results indicate there may be important taxonomic effects on the responses of cardiac function to activity in turtle species.

Perioperative Stress, Inflammation, and Cancer Progression: Opportunities for Intervention in Breast and Colorectal Cancer Surgery Utilizing Beta-Adrenergic Blockade and COX-2 Inhibition

Purpose of review This review explores the blockade of cyclooxygenase (COX)-2/prostaglandin and catecholamine/beta(β)-adrenergic signaling as opportunities to enhance the curative potential of surgical excision of breast and colorectal cancer malignancies.

Disparities in the Diagnosis of Hypertrophic Obstructive Cardiomyopathy: A Narrative Review of Current Literature.

Hypertrophic obstructive cardiomyopathy (HOCM) is a disorder of abnormal thickening of the myocardium that affects 0.2% of the population. HOCM is a frequently implicated cause of sudden cardiac death (SCD) in young athletes. In this manner, this condition has the capacity for tremendous emotional, social, financial, and medical burdens for families and communities across the country. Multiple factors including genetics and hormonal elements are believed to play a role in the development of this cardiomyopathy. HOCM is an autosomal dominant trait with variable expressivity. It is associated with several genetic changes in the myosin heavy chain genes. Current treatment includes optimization of cardiac risk factors and medical management with beta-adrenergic blockade with definitive treatment of surgical intervention to reduce cardiac workload. The demographic most likely to be diagnosed with HOCM based upon clinical registry data is Caucasian boys and men. However, a growing body of data supports increased prevalence in African American populations and percentages equal to, if not higher than, Caucasian males in Hispanic populations. Similarly, males of African American ethnicity that participate in basketball are the most likely demographic to be affected by HOCM based on the data available from the National Collegiate Athletic Association (NCAA). Further, though rates of diagnosis may be up to 1.5 times higher in males than in females, an increasing number of studies demonstrate an increased prevalence of HOCM in females, often presenting with worse symptoms and an increased incidence of disease progression. Similarly, data suggest that age of diagnosis is associated with various prognostic factors including annual mortality. In addition, consideration of the social determinants of health undoubtedly impacts the rate of diagnosis, access to care, and HOCM-related complications in underserved populations. Effective screening including auscultation and electrocardiography (EKG) with confirmatory echocardiography in these communities supports equitable surveillance and management of HOCM.

Do Complexity Measures of Frontal EEG Distinguish Loss of Consciousness in Geriatric Patients Under Anesthesia?

While geriatric patients have a high likelihood of requiring anesthesia, they carry an increased risk for adverse cognitive outcomes from its use. Previous work suggests this could be mitigated by better intraoperative monitoring using indexes defined by several processed electroencephalogram (EEG) measures. Unfortunately, inconsistencies between patients and anesthetic agents in current analysis techniques have limited the adoption of EEG as standard of care. In attempts to identify new analyses that discriminate clinically-relevant anesthesia timepoints, we tested 1/f frequency scaling as well as measures of complexity from nonlinear dynamics. Specifically, we tested whether analyses that characterize time-delayed embeddings, correlation dimension (CD), phase-space geometric analysis, and multiscale entropy (MSE) capture loss-of-consciousness changes in EEG activity. We performed these analyses on EEG activity collected from a traditionally hard-to-monitor patient population: geriatric patients on beta-adrenergic blockade who were anesthetized using a combination of fentanyl and propofol. We compared these analyses to traditional frequency-derived measures to test how well they discriminated EEG states before and after loss of response to verbal stimuli. We found spectral changes similar to those reported previously during loss of response. We also found significant changes in 1/f frequency scaling. Additionally, we found that our phase-space geometric characterization of time-delayed embeddings showed significant differences before and after loss of response, as did measures of MSE. Our results suggest that our new spectral and complexity measures are capable of capturing subtle differences in EEG activity with anesthesia administration—differences which future work may reveal to improve geriatric patient monitoring.