Doses Of Propranolol Research Articles

The effect of propranolol on gastrointestinal motility and permeability in patients with cirrhosis and significant portal hypertension

BackgroundPatients with cirrhosis and portal hypertension may have alterations in intestinal barrier resulting in increased susceptibility for infections. We investigated the effect of propranolol in gastrointestinal motility, permeability and bacterial overgrowth in cirrhosis.MethodsPatients with cirrhosis and esophageal varices were studied before and after a build-up dose of propranolol according to standard guidelines. Serum TNF-a, IL-6, IL-1b, LPS and bacterial DNA were measured before and during propranolol therapy. Oro-caecal transit time (OCTT) and bacterial overgrowth (BO) have been evaluated with H2 breath testing. Intestinal paracellular (IP), cellular passive non-carrier (ICNC), cellular passive carrier-mediated (ICCM), and gastric permeability (GP) were evaluated by measurement of lactulose, mannitol, D-xylose and sucrose respectively in urine, with high performance liquid chromatography (HPLC).Results35 patients with cirrhosis and portal hypertension with median age was 59.6 years (range 42–86) were included in the study. Twenty one had viral hepatitis and 25 were classified as having advanced cirrhosis (Child-Pugh B: 14 or C: 11). Median dose of administrated propranolol was 40 mg/day. After 7 days propranolol treatment BO was resolved in 15 out of 16 patients (93.7%, p = 0.0001) and OCTT was reduced significantly from 180 min to 139 min (SD 58.5, difference − 4 1 min, p = 0.0001). Serum IL-6 levels were reduced in 21/35 (60%) patients from 41.1 to 19 pg/ml (p = 0.01), TNF-a in 10/35 (28.5%) patients from 10.7 to 5.6 pg/ml (p = 0.007) and LPS in 20/35 (57%) from 7.1 to 5.2 mg/L (p = 0.1). No bacterial DNA was detected in serum of all patients either baseline or under propranolol treatment. IP was significantly reduced (0.2 to 0.16, p = 0.04) whereas ICNC (p = 0.9), ICCM (p = 0.4) and GP (p = 0.7) were not affected significantly. Intestinal Permeability (PI) index (Lactulose to Mannitol ratio) was significantly reduced (0.027 to 0.02, p = 0.03).ConclusionIn patients with cirrhosis and portal hypertension, propranolol use is associated with reduction in BO, increase in intestinal motility and amelioration in intestinal permeability. Moreover IL-6 and LPS levels are being decreased in the majority of patients under propranolol.

High‐dose propranolol decreases aggression in young people with autism

As many as two‐thirds of individuals with autism spectrum disorder (ASD) experience challenging symptoms of irritability, including aggression and self‐injury. The antipsychotics risperidone and aripiprazole are approved for the treatment of irritability associated with ASD; however, their adverse effects can compromise long‐term use in many patients. Based on longstanding case reports showing promising results for the beta‐blocker propranolol in reducing challenging symptoms in ASD, investigators conducted a randomized, double‐blind, placebo‐controlled crossover trial to evaluate the feasibility of high‐dose propranolol for treating aggression in patients with ASD. The investigators recruited youths and young adults aged 12 to 30 with ASD and a history of severe and chronic aggression, self‐injury, and disruptive behaviors that interfere with daily activities. Participants were required to have had an inadequate trial of at least two psychotropic medications, including at least one antipsychotic. Dosing of propranolol started at 10 mg three times a day and could be increased until adequate therapeutic response was achieved, to a maximum dose of 200 mg three times a day. Most study visits were conducted via telehealth in order to minimize patient schedule disruption. The primary outcomes were change in scores on the Clinical Global Impression‐Improvement (CGI‐I) and Aberrant Behavior Checklist‐Community (ABC‐C) scales from baseline to study endpoint. Six participants with a mean age of 16 years were enrolled. The investigators found that propranolol resulted in mean reductions of 50% in scores on the CGI‐I and 37% in scores on the ABC‐C. Effect sizes were large for both measures: –0.74 for the CGI‐I and –0.64 for the ABC‐C. “As this was a feasibility pilot study, we had a small sample that limits the generalization of our results to a wider population, and therefore, until a placebo‐controlled, double‐blind study with an adequate number of subjects is conducted, the clinical value of this report is limited,” the study's authors wrote. [London, E., et al. (2024). J Clin Psychopharmacol. https://doi.org/10.1097/JCP.0000000000001895]

50855 TID Dosing of Propranolol Leads to Improvement in Sleep Patterns in Patients Being Treated for Infantile Hemangiomas

50855 TID Dosing of Propranolol Leads to Improvement in Sleep Patterns in Patients Being Treated for Infantile Hemangiomas

Comparison of Different Doses of Oral and Ocular Propranolol for Retinopathy of Prematurity: A Network Meta-Analysis.

The efficacy and safety of propranolol for retinopathy of prematurity (ROP) remain under debate. This network meta-analysis (NMA) focuses on whether a ranking may be established for different dose levels of propranolol as treatment of ROP in terms of stage progression as the primary outcome, with appearance of plus disease and need for anti-vascular endothelial growth factors (anti-VEGFs) or laser therapy as secondary endpoints. Fourteen studies (10 randomised controlled trials, three single-arm trials and one retrospective observational study) of 474 patients treated with oral or ocular propranolol were retrieved from databases up to April 2024. Meta-insight and model-based NMA were undertaken to evaluate the propranolol dose-response relationship. Studies were evaluated for model fit, risk of bias and Confidence of evidence In Network Meta-Analysis (CINeMA). Effect sizes were determined as odds ratio (OR) with 95% credible interval (CrI). Bayesian analysis showed a trend towards improved effects for propranolol given at late stages (stages 2-3; S23) of ROP progression compared with its administration at earlier stages (stages 0-1; S01). OR values for oral propranolol 1.5 and 2mg/kg/day given at S23 were 0.13 (95% CrI 0.04-0.37) and 0.16 (95% CrI 0.04-0.61), respectively, while given at S01 were 0.28 (95% CrI 0.02-2.96) and 0.78 (95% CrI 0.14-4.43), respectively. Similarly, OR of eye propranolol 0.2% at S23 was 0.37 (95% CrI 0.09-1.00) versus an S01 OR of 0.64 (95% CrI 0.21-2.04). Surface under the cumulative ranking curve (SUCRA) analyses confirmed best probability values for oral propranolol 1.5-2mg/kg followed by eye propranolol 0.2%, all at S23. Model-based NMA showed nonlinearity in the dose-response for oral propranolol with a trend to greater maximal effect for its administration at late versus early stages. For secondary endpoints, lower risk values were found with oral propranolol 1.5mg/kg/day at S23 for progression to plus disease (OR 0.14; 95% CrI 0.02-0.84) and need for anti-VEGFs (OR 0.23; 95% CrI 0.05-0.93) and laser (OR 0.16; 95% CrI 0.02-1.10) therapies also followed by eye propranolol 0.2%, and a similar profile was obtained with SUCRA analysis. Lower doses (0.5-1.0mg/kg/day) of oral propranolol retained efficacy. Threat of adverse events was estimated as risk difference versus control with no difference for eye propranolol 0.2% and oral propranolol 0.5mg/kg/day, modest increases of risk for oral propranolol 1.0 and 1.5mg/kg/day and the highest risk difference for oral propranolol 2.0mg/kg/day (0.06; 95% CI -0.01 to 0.13). A diminished risk of disease progression and need for additional treatment was obtained with propranolol in ROP, but safety is a potential concern. Propranolol eye micro-drops (0.2%) can be as efficacious as oral propranolol. Nonetheless, the evidence is limited due to the paucity and quality of the available studies.

CO168 Association between Initial Propranolol Dose and Blood Pressure Control in 48 to 72 Hours Among Preterm Infants with Hypertension

CO168 Association between Initial Propranolol Dose and Blood Pressure Control in 48 to 72 Hours Among Preterm Infants with Hypertension

Midodrine plus propranolol versus propranolol alone in preventing first bleed in patients with cirrhosis and severe ascites: a randomized controlled trial.

Propranolol, a non-selective beta-blocker, commonly used to prevent variceal bleed, but might precipitate circulatory dysfunction in severe ascites. Midodrine, an alpha-1 adrenergic agonist improves renal perfusion and systemic hemodynamics. Addition of midodrine might facilitate higher maximum tolerated dose (MTD) of propranolol, thereby less risk of variceal bleed in cirrhosis patients with severe ascites. 140 patients with cirrhosis and severe/refractory ascites were randomized- propranolol and midodrine (Gr.A,n = 70) or propranolol alone (Gr.B,n = 70). Primary outcome was incidence of bleed at 1year. Secondary outcomes included ascites control, achievement of target heart rate (THR), HVPG response and adverse effects. Baseline characteristics were comparable between two groups. Cumulative incidence of bleed at 1year was lower in Gr.A than B (8.5%vs.27.1%,p-0.043). The MTD of propranolol was higher in Gr.A (96.67 ± 36.6mg vs. 76.52 ± 24.4mg; p-0.01) and more patients achieved THR (84.2%vs.55.7%,p-0.034). Significantly higher proportion of patients in Gr.A had complete resolution of ascites [17.1%vs.11.4%,p-0.014), diuretic tolerance (80%vs.60%,p-0.047) at higher doses(p-0.02) and lesser need for paracentesis. Patients in Gr.A also had greater reduction in variceal grade (75.7%vs.55.7%;p-0.01), plasma renin activity (54.4% from baseline) (p = 0.02). Mean HVPG reduction was greater in Gr.A than B [4.38 ± 2.81mmHg(23.5%) vs. 2.61 ± 2.87mmHg(14.5%),p-0.045]. Complications like post-paracentesis circulatory dysfunction and spontaneous bacterial peritonitis on follow-up were higher in Gr.B than A (22.8%vs.51.4%,p = 0.013 and 10%vs.15.7%, p = 0.03, respectively). Addition of midodrine facilitates effective use of propranolol in higher doses and greater HVPG reduction, thereby preventing first variceal bleed, reduced paracentesis requirements with fewer ascites- related complications in patients with cirrhosis with severe/refractory ascites.

Regimen for accelerated propranolol initial dosing (RAPID).

Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

Abstract LB135: Effects of acute psychological stress on DNA damage levels in peripheral blood mononuclear cells: An experimental study with healthy human volunteers

Abstract Increased levels of DNA damage in human peripheral blood mononuclear cells (PBMC), as indicated by classic alkaline comet and γ-H2AX assays, have been widely used in toxicology and epidemiology studies of potential environmental carcinogens. To date, however, little research has explored the possibility that exposure to acute psychological stresses in daily life may acutely increase levels of DNA damage and thus, much like repeated tobacco use, may cumulatively contribute to lifetime cancer risk. The purpose of the present experimental study was to provide a first critical test of the hypothesis that exposure of healthy humans to a brief psychological stress results in increased levels of DNA damage. We also tested preventative effects of a beta-adrenergic receptor blocker (propranolol), a mechanistic pathway for psychological stress effects on DNA supported by preclinical research. Healthy volunteers were recruited by multiple strategies including targeted outreach (telephone/email), with oversampling for age, sex, and minority status. Eligibility was confirmed by self-report, clinical testing (blood &amp; urine), and MD review. On the experimental day, participants were randomized to receive either a single dose of propranolol (80mg) or a placebo. After a 60 min rest period with video distraction, all participants (n=123; 48.8% ≥ 40yr; 52% women; 52% minority) underwent a well-established, 15-minute stress challenge, a speech task and mental arithmetic (Trier Social Stress Test, TSST), with psychological stress confirmed by visual analog scales. Blood samples were collected (via IV line) immediately before and after the TSST. As the primary study outcome, DNA damage in PBMC was assessed (blind) with Comet IV software (% tail intensity) following single cell gel electrophoresis under alkaline conditions with and without in vitro exposure to 25uM H2O2 (comet assay). For a subset of participants with sufficient frozen PBMC samples available (n=43), levels of pan-nuclear γ-H2AX were determined with a validated, sensitive, immunoblot method that detects H2AX phosphorylation at Ser139, and expresses γ-H2AX as the ratio of p-Ser139-H2AX to total H2AX. Exploratory nonparametric analyses revealed that undergoing the TSST significantly increased levels of DNA damage in PBMC (H2O2 comet assay [p&amp;lt;.001] and γ-H2AX biomarker [p=.03], Wilcoxon tests) in the group of participants that was randomized to pretreatment with placebo. In the group pretreated with propranolol before the TSST, a significant increase in γ-H2AX was not found. Conclusion. Supporting the study hypothesis that acute stress can increase levels of DNA damage, the results of the present study highlight the potential importance of additional research to address the possibility that repeated exposures to acute life stresses may cumulatively contribute to increased lifetime risk of cancer. Citation Format: Dana H. Bovbjerg, John Schmitz, Kurt D. Ackerman, Scott R. Beach, Albert D. Donnenberg, Jessica Manculich, Matthew F. Muldoon, Patricia L. Opresko, Patrick M. Tarwater, Hong Wang, Frank J. Jenkins. Effects of acute psychological stress on DNA damage levels in peripheral blood mononuclear cells: An experimental study with healthy human volunteers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB135.

Propranolol monotherapy in angiosarcoma – A window-of-opportunity study (PropAngio)

BackgroundAngiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment. MethodsPropranolol was dosed 80 mg to 240 mg/day for 3 to 6 weeks according to a dose titration schedule. The primary endpoint was clinical response (response according to RECIST 1.1 or stable disease with improvement of cutaneous lesions) in at least three patients. Exploratory objectives included histologic response (>30% decrease in Ki-67), FDG PET response, and β-receptor expression levels. ResultsFourteen patients were enrolled. The median duration of treatment was 26 days (range 21–42 days). The median highest propranolol dose was 160 mg/day (range 80 – 240 mg). Two patients showed clinical response (14%, 95% CI 3–100%). One of these patients showed a partial metabolic response on PET-CT. None of the tumors showed histologic response. The most common adverse event was grade 1/2 bradycardia (86%). There were no grade ≥ 3 adverse events. ADRB2 was overexpressed in 16 out of 18 tumors, in both responders and non-responders. None of the tumors showed ADRB1 overexpression. ConclusionsThis window-of-opportunity trial did not show clinical efficacy of propranolol monotherapy. However, two out of 14 patients did show clinical benefit. ADRB1/2 expression did not correlate with clinical response.

Periocular Capillary Hemangioma Treated With Low Dose Oral Propranolol - Presentation and Outcome of 2 patients

Introduction : Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. IH arises in the first few weeks of life, then displays a period of active growth followed by spontaneous involution.[1,2] Most IHs are uncomplicated, do not require intervention, and regress spontaneously.[3] Infantile hemangioma (IH) having an incidence of 4%–5%.[4-6]&#x0D; Case Illustration : First patient is 6 -month-old girl weighing 6.2 kg, with Periocular lesions on the superior palpebra since 2 weeks after birth. Second patient is 6-month-old girl weighing 6.3 kg, with Periocular lesions on the superior palpebra since 1 weeks after birth. The lesions rapidly increased in size within 1 months. The lesions made it difficult to open superior palpebra. Both patient was diagnosed with periocular infantile hemangioma. The diagnosis was established by clinical examination, and was given oral propranolol therapy. Initially, a dose of propranolol was 1 mg/kg body weight in divided doses for 2 weeks then increased to 2 mg/kg body weight. Patients have followed up at 4-week intervals until the final follow-up was reached according to the response of treatment. The lesions were significantly decreased and bith pastients could open their right eye normally after 3 months of propranolol therapy&#x0D; Discussion : Some cases of IH require early treatment. Early treatment is indicated for IH causing functional impairment. The use of propranolol in the management of IH is very effective in the reduction of the lesions and Has minimal side effects.&#x0D; Conclusion : Early diagnosis and intervention with propranolol for IH play an important role in determining the optimal outcomes

Periocular Capillary Hemangioma Treated With Low Dose Oral Propranolol - Presentation and Outcome of 2 patients

Introduction : Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. IH arises in the first few weeks of life, then displays a period of active growth followed by spontaneous involution.[1,2] Most IHs are uncomplicated, do not require intervention, and regress spontaneously.[3] Infantile hemangioma (IH) having an incidence of 4%–5%.[4-6]&#x0D; Case Illustration : First patient is 6 -month-old girl weighing 6.2 kg, with Periocular lesions on the superior palpebra since 2 weeks after birth. Second patient is 6-month-old girl weighing 6.3 kg, with Periocular lesions on the superior palpebra since 1 weeks after birth. The lesions rapidly increased in size within 1 months. The lesions made it difficult to open superior palpebra. Both patient was diagnosed with periocular infantile hemangioma. The diagnosis was established by clinical examination, and was given oral propranolol therapy. Initially, a dose of propranolol was 1 mg/kg body weight in divided doses for 2 weeks then increased to 2 mg/kg body weight. Patients have followed up at 4-week intervals until the final follow-up was reached according to the response of treatment. The lesions were significantly decreased and bith pastients could open their right eye normally after 3 months of propranolol therapy&#x0D; Discussion : Some cases of IH require early treatment. Early treatment is indicated for IH causing functional impairment. The use of propranolol in the management of IH is very effective in the reduction of the lesions and Has minimal side effects.&#x0D; Conclusion : Early diagnosis and intervention with propranolol for IH play an important role in determining the optimal outcomes

Treatment of infantile hemangioma: case report

Background: Although benign in origin, infantile hemangiomas can occasionally cause lifelong deformity, functional disability, and even life-threatening consequences. As a result, therapy is favored above an active observation plan. When treating infantile hemangiomas at high risk, the first line of therapy should be systemic propranolol. While oral propranolol is generally regarded as a safe and effective medication, it is important to consider potential adverse effects. Further research and evidence-based practices are needed to improve clinical results. Case report: Here, we describe a 3-month-old child who had an infantile hemangioma and how oral propranolol significantly improved the lesion. The patient's mother takes her to the hospital when she notices a reddish mass that extends from her nasal bridge to her right cheek. After three days, the patient's red mass had lessened. The kid was monitored in the clinic for three hours following the initial increase in propranolol dosage, which was raised to 2 mg/kg/day. Every week, the patient was monitored at the clinic. The child's weight had climbed to 7 kg after 4 weeks, and she had no side effects from an increased propranolol dosage. Conclusion: A critical factor is the early diagnosis of at-risk infantile haemangiomas, which calls for pediatricians, general practitioners, and health visitors to be more alert in order to spot potentially troublesome infantile haemangiomas in the first two to three weeks of life.

The role of beta-adrenoreceptors in postoperative ileus in rats

The aim of the research was to evaluate the influence of antagonists of specific beta-adrenergic receptor subtypes on bowel motility following abdominal surgery in rat model of postoperative ileus. Bowel motility was measured by the intestinal transit of Evans blue introduced via orogastric tube after surgical procedures of skin incision, laparotomy and laparotomy with gut manipulation. Male rats were given individual adrenergic receptor subtypes antagonists intraperitoneally, and the influence of administered agents on intestinal transit of Evans blue was then evaluated. No statistically significant differences in the length of intestine in tested rats were observed. Propranolol administered prior to surgical procedure has shown protective effect on Evans blue migration in rats undergoing laparotomy and gut manipulation. Intestinal dye transit for propranolol doses of 10, 30 and 45 mg/kg was 18.00 ± 1.88c m, 23.75 ± 1.71 cm and 22.5 ± 2.43 cm, respectively, and for last two doses, statistically significant increase of dye passage was noted, compared to Evans blue transit of 11.00 ± 2.43 cm in the control group. No acceleration of dye migration was seen following administration of beta1-, beta2- and beta3-selective adrenergic receptor antagonist metoprolol, ICI 118.551 and SR58894A, respectively. Our research confirmed that propranolol at high doses, as seen by other researchers, improved bowel motility in early phase of postoperative ileus. That slight acceleration of intestinal dye transit after surgery with gut manipulation is rather connected with membrane-stabilizing action, than the receptor blocking effect, as this effect was not observed after the application of selective antagonists of respective subtypes of beta-adrenergic receptor.

Efficacy of propranolol versus carvedilol in prophylaxis of variceal bleeding: Randomized clinical trial.

Objective: To compare the efficacy of carvedilol and propranolol for prophylaxis of variceal bleeding in cirrhotic patients. Study Design: Randomized Controlled Trial. Setting: Department of Gastroenterology and Hepatology, PIMS, Islamabad. Period: 1st January 2022 to 31st of December 2022. Material &amp; Methods: A total of 260 patients reporting at the department suffering from liver cirrhosis with medium or large esophageal varices and had never reported for variceal bleeding previously. The patients were randomized in to 2 equal groups of 130 each through computer generated randomization. Patients in Group-A were started on dose of carvedilol 6.25mg once daily initially for 1 week, subsequently titrated to twice daily 6.25mg and titrated up if needed to maximum of 25mg twice daily. Patients in Group-B received a dosage of propranolol 20 mg BID which then escalated weekly in 20 mg steps if needed and doses were adjusted as per targeted heart rate and systolic BP. Patients were followed up over 1 year for any event of variceal bleeding. Results: Mean overall age in this study was 42.13±10 years. The ratio of male patients was higher than female patients (60% VS 40%). Carvedilol prevented variceal bleeding in 86.15% of the patients while propranolol was effective in preventing variceal bleeding in 75.38% of the patients. Hence carvedilol was significantly more effective than propranolol in preventing variceal bleeding (p=0.02). Conclusion: Carvedilol is significantly more effective in prophylaxis of variceal bleeding than propranolol in patients with medium or large esophageal varices.

Effect of propranolol on temporomandibular joint pain in repeatedly stressed rats.

Stress substantially increases the risk of developing painful temporomandibular disorders (TMDs) by influencing the release of endogenous catecholamines. Propranolol, an antagonist of β-adrenergic receptors, has shown potential in alleviating TMD-associated pain, particularly when the level of catecholamines is elevated. The aim of this study was to explore whether intra-articular propranolol administration is effective in diminishing temporomandibular joint (TMJ) pain during repeated stress situations. Additionally, we investigated the effect of repeated stress on the expression of genes encoding β-adrenoceptors in the trigeminal ganglion. In the present study, rats were exposed to a stress protocol induced by sound, then to the administration of formalin in the TMJ (to elicit a nociceptive response), followed immediately afterward by different doses of propranolol, after which the analgesic response to propranolol was evaluated. We also assessed the levels of beta-1 and beta-2 adrenergic receptor mRNAs (Adrb1 and Adrb2, respectively) using reverse transcription-quantitative PCR (RT-qPCR). Our findings revealed that propranolol administration reduces formalin-induced TMJ nociception more effectively in stressed rats than in non-stressed rats. Furthermore, repeated stress decreases the expression of the Adrb2 gene within the trigeminal ganglion. The findings of this study are noteworthy as they suggest that individuals with a chronic stress history might find potential benefits from β-blockers in TMD treatment.

FRI570 Repatha Induced Thyroid Storm

Abstract Disclosure: L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. L. El Musa Penna: None. W. Medina-Torres: None. M.A. Ortiz-Rivera: None. A. Rosado-Burgos: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. Introduction: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are an effective medical therapy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol ability of statins. In 2020, a case of transient hyperthyroidism secondary to evolocumab was reported. We present a case of impending thyroid storm after a patient received evolocumab. Patient description: 60 y/o female patient with medical history remarkable for hyperlipidemia, anti-TPO positive non-toxic multinodular goiter, hypertension, fibromyalgia, and coronary artery disease who presented with heat intolerance, palpitations, tremors, and insomnia after second dose of evolocumab. At physical exam found with tachycardia, hypertension, anxious mood, tremors, leg pitting edema +1 bilateral, and deep tendon reflexes +3 in lower extremities, although no palpable or painful goiter. Laboratories compatible with hyperthyroidism [TSH &amp;lt; 0.008 uIU/mL (0.3 – 3.0 uIU/mL), Free T4 4.29 ng/dL (0.89 – 1.76 ng/dL), Total T4 20.03 ug/dL (4.5-12 ug/dL)] and clinically with severe thyrotoxicosis. Patient was sent to ED for further evaluation and management. Case outcomes: Upon admission patient presented with a tonic-clonic seizure with short post ictal state. Burch-Wartofsky scale Point Scale 35, consistent with impending thyroid storm. Thyrotoxicosis management given requiring high doses of PTU, hydrocortisone and propranolol, including the need to add cholestyramine to the regime. By day 9 of therapy, patient was transitioned to methimazole 30mg daily with discontinuation of hydrocortisone and cholestyramine. Upon discharge, 2 weeks later, thyroid function tests had normalized to a FT4 of 1.39 ng/dL and a Total T4 of 9.6 ug/dL. Case discussion: A case of transient hyperthyroidism with PCSK9 inhibitor was previously reported requiring only symptomatic treatment. In this case a patient presented with severe thyrotoxicosis after she received her second dose of evolocumab. PCSK9 inhibitor therapy immunological influence on thyroid remains unknown. This case shows the importance of thyroid function test follow up in patients on PCSK9 inhibitor therapy and the possibility of immunological influence on the thyroid. Presentation: Friday, June 16, 2023

FRI512 Thyrotoxic Periodic Paralysis With Extreme Hypokalemia Precipitated By Acute Alcohol Intoxication In A Patient With Graves’ Disease

Abstract Disclosure: J. Batra: None. A.R. Ankireddypalli: None. J. Kaur: None. Introduction: Thyrotoxic periodic paralysis (TPP) is a muscle and electrolyte disorder, mostly seen in the setting of hyperthyroidism. It is characterized by reversible painless muscle weakness and hypokalemia. Prevalence is highest in East Asian populations, approximately 2%, and 0.1-0.2% in other populations. Males are much more likely to be affected. Common provoking factors include exercise, fasting, and changes in diet. Clinical case: A 29-year-old male of East Asian ethnicity presented to the hospital with the complaint of multiple bouts of inability to lift his extremities for 1 day. He also complained of generalized weakness. He did not have any changes in his mental status and was fully oriented at the time of the presentation. No breathing difficulty was reported. He had been drinking the night before with his friends and drank 1 L of vodka. His past medical history was significant for hyperthyroidism secondary to Graves’ disease, which was diagnosed a year ago. He had been prescribed methimazole but had not been adherent to the medication. The basic metabolic panel revealed undetectable serum potassium of &amp;lt;1.5 (3.4 to 5.3 mmol/L). The rest of the electrolytes and renal function were unremarkable. TSH was suppressed at &amp;lt;0.01 (0.3 to 4.20 uIU/L) and free T4 levels were significantly elevated at 7.77 (0.9 to 1.70 ng/dL). The thyrotropin receptor antibody was 33 (0.00 to 1.75 IU/L). EKG showed sinus tachycardia with nonspecific T-wave abnormalities. Thyroid ultrasound showed diffusely heterogenous parenchyma with diffusely increased blood flow throughout the thyroid on doppler. Echocardiogram showed a normal ejection fraction of 55-60% with mild concentric left ventricular wall thickening consistent with left ventricular hypertrophy. He was initially treated with intravenous potassium replacement and high doses of propylthiouracil, hydrocortisone, and propranolol, leading to the resolution of his symptoms. He was discharged on methimazole and propranolol therapies. Learning points: • Patients with Graves’ disease are routinely counseled against tobacco use to avoid worsening of orbitopathy. Hyperthyroid patients should also be counseled regarding avoidance or moderation of alcohol intake to avoid this rare but potentially life-threatening complication of thyrotoxic periodic paralysis. • The incidence of TPP is significantly higher in the East Asian populations, especially among males (8.7-13%). Counseling regarding provoking factors, the importance of adherence to medications, and the maintenance of euthyroidism to avoid TPP is essential. Presentation: Friday, June 16, 2023

Left cardiac sympathetic denervation in children with Jervell Lange-Nielsen syndrome and drug refractory torsades - A case series.

Long QT syndrome is an inherited malignant channelopathy which leads to life-threatening arrhythmia, with multiple genotypes. Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive subtype of this disease, characterized by congenital sensorineural deafness and a high incidence of sudden cardiac death (SCD). We prospectively followed up six children who underwent left cardiac sympathetic denervation (LCSD) for JLNS in view of high-risk features despite being on maximally tolerated doses of oral propranolol. Mean age at diagnosis was 2.75±0.39 years, with a significant delay between onset of symptoms and diagnosis (mean 7.2±3.5 months). All had sensorineural hearing loss, conforming to the JLNS phenotype. Mean QTc interval was 603±93ms, with T wave alternans (TWA) seen in all cases. All were started on propranolol and subsequently subjected to LCSD, and 3 underwent AAI permanent pacemaker implantation. Over a mean follow-up of 20 months, there was a significant reduction in QTc (603±93ms to 501±33ms, p=.04), which was persistent on follow-up (525±41ms) and only two out of six had persistent T wave alternans on ECG (p<.01). None of these children had presyncope, syncope, seizures, torsades de pointes, cardiac arrest or death on follow up following LCSD. Jervell Lange-Nielsen syndrome is a subtype of LQTS with high-risk features. LCSD, an effective therapeutic option for those having symptoms despite being on propranolol, results in significant reduction of QTc interval and amelioration of symptoms.

Propranolol treatment during repetitive mild traumatic brain injuries induces transcriptomic changes in the bone marrow of mice.

There are 1.5 million new mild traumatic brain injuries (mTBI) annually in the US, with many of the injured experiencing long-term consequences lasting months after the injury. Although the post injury mechanisms are not well understood, current knowledge indicates peripheral immune system activation as a causal link between mTBI and long-term side effects. Through a variety of mechanisms, peripheral innate immune cells are recruited to the CNS after TBI to repair and heal the injured tissue; however, the recruitment and activation of these cells leads to further inflammation. Emerging evidence suggests sympathetic nervous system (SNS) activity plays a substantial role in the recruitment of immune cells post injury. We sought to identify the peripheral innate immune response after repeated TBIs in addition to repurposing the nonselective beta blocker propranolol as a novel mTBI therapy to limit SNS activity and mTBI pathophysiology in the mouse. Mice underwent repetitive mTBI or sham injury followed by i.p. saline or propranolol. Isolated mRNA derived from femur bone marrow of mice was assayed for changes in gene expression at one day, one week, and four weeks using Nanostring nCounter® stem cell characterization panel. Differential gene expression analysis for bone marrow uncovered significant changes in many genes following drug alone, mTBI alone and drug combined with mTBI. Our data displays changes in mRNA at various timepoints, most pronounced in the mTBI propranolol group, suggesting a single dose propranolol injection as a viable future mTBI therapy in the acute setting.

Factors associated with early relapse of infantile haemangioma in children treated for at least six months with oral propranolol: A case-control study using the 2014–2021 French Ouest DataHub

BackgroundThe factors associated with early relapse of infantile haemangioma (IH) after a first course of treatment with oral propranolol for at least six months (initiated after the marketing authorization had been granted) have not previously been investigated. ObjectivesTo identify factors associated with the risk of early relapse in children with IH treated with oral propranolol according to the current prescribing guidelines. MethodsWe performed a multicentre, retrospective, case-control study, using the Ouest Data Hub database. All children treated for at least 6 months with oral propranolol for IH between 31 June 2014 and 31 December 2021, and with a follow-up visit at least three months after treatment discontinuation were included. A case was defined as relapse of IH within three months of treatment discontinuation; each case was matched for age at treatment initiation and for centre, with four (relapse-free) controls. The association between relapse and treatment or IH characteristics was expressed as an odds ratio (OR) from univariate and multivariate conditional logistic regressions. ResultsA total of 225 children were included. Of these, 36 (16%) relapsed early. In a multivariate analysis, a deep IH component was a risk factor for early relapse [OR = 8.93; 95%CI: 1.0–78.9, p = 0.05]. A propranolol dosage level of less than 3 mg/kg/day protected against early relapse [OR = 0.11; 95%CI: 0.02–0.7, p = 0.02]. Tapering before propranolol discontinuation was not associated with a lower risk of early relapse. ConclusionThe risk factors for late and early relapse are probably different. Investigation of the risk factors for early vs. late IH relapse is now warranted.