Explore the vast range of titles available.

This multicenter, randomized trial showed significant benefit of propranolol for the treatment of infantile hemangiomas. Infantile hemangiomas are the most common soft-tissue tumors of childhood, occurring in 3 to 10% of infants. 1 – 4 Lesions are usually not developed at birth and are generally diagnosed during the first 4 to 6 weeks of life, with most growth during the first 5 months. 5 The characteristic evolution of nearly all infantile hemangiomas is proliferation, stabilization, and slow, spontaneous involution. Although most lesions follow an uncomplicated clinical course, approximately 12% result in complications requiring referral to a specialist. 6 , 7 Many infantile hemangiomas leave permanent sequelae, with potential psychological effects in the children and their parents. 8 , 9 Historically, systemic glucocorticoids . . .

Background Alcohol craving and relapse occur after the reactivation of alcohol reward memory. Previous studies suggest that drug-associated memory undergoes reconsolidation once retrieved by drug-associated stimuli. This study hypothesized that propranolol administration during memory reconsolidation induced by conditioned stimulus (CS) would significantly attenuate alcohol craving. Methods A total of 40 patients with alcohol dependence who met the diagnostic criteria for alcohol dependence in DSMV were enrolled. The patients were randomized located into the memory retrievalpropranolol group ( n  = 20) and the memory retrievalplacebo group ( n  = 20) using the random number table. The memory retrievalpropranolol group used propranolol combined with a memory retrieval reconsolidation procedure, while the memory retrievalplacebo group used a placebo combined with a memory retrieval reconsolidation procedure. The Visual Analog Scale (VAS) was used to evaluate the degree of alcohol craving induced by images at stages of baseline measures, relevance learning, and memory test. The systolic blood pressure, diastolic blood pressure, and heartrate were applied to evaluate cue responsiveness. Repeated measures analysis of variance was used to compare the craving degree and independent samples t-tests were used for comparing demographic characteristics, scale scores between alcohol-dependent patient groups, and pre-post differences in heart rate, systolic blood pressure, and diastolic blood pressure at each experimental phase. Results Relevance learning stage: Compared with before learning, the levels of systolic blood pressure, diastolic blood pressure, and heart rate of the two groups increased in varying degrees after learning conditional stimulationrelevance learning CS+(all P  < 0.05). Compared with pre-learning, both groups showed increased VAS scores during the Retrieval phase with statistically significant differences ( F  = 47.294、25.015, all P  < 0.001). The memory test stage, after re-exposure to learned CS+, both groups showed varying degrees of increase in heart rate, systolic blood pressure, and diastolic blood pressure, with all differences reaching statistical significance (all P  < 0.05). During the test phase, statistically significant between-group differences were found in heart rate difference, systolic blood pressure difference and diastolic blood pressure difference between the two groups (all P  < 0.05). the retrieval-propranolol group demonstrated decreased VAS scores with statistical significance ( F  = 56.017, P  < 0.001), while the retrieval-placebo group showed no statistically significant alterations in VAS scores ( F  = 0.183, P  > 0.05). Conclusions Our study demonstrated that propranolol administration after CS-induced retrieval could disrupt alcohol-associated memory reconsolidation and reduce alcohol craving. The finding provided a potential translational method to treat alcohol use disorder. Trial registration The protocol was registered at www.chictr.org.cn on October 13, 2023 (Chinese Clinical Trial Registry, identification number ChiCTR2300076633, Retrospectively registered).

Observations in people with cerebral cavernous malformations, and in preclinical models of this disorder, suggest that the β-blocker propranolol might reduce the risk of intracerebral haemorrhage. We aimed to evaluate the safety and efficacy of prolonged treatment with propranolol to reduce the incidence of symptomatic intracerebral haemorrhage or focal neurological deficit in people with familial cerebral cavernous malformations. We conducted a randomised, open-label, blinded-endpoint, phase 2 pilot trial (Treat_CCM) at six national reference centres for rare diseases in Italy. People aged 18 years or older with symptomatic familial cerebral cavernous malformation were eligible for enrolment. Participants were randomly assigned (2:1) to receive either oral propranolol (20–320 mg daily) plus standard care (intervention group), or standard care alone (control group), for 24 months. Participants, caregivers, and investigators were aware of treatment group assignment. Participants had clinical assessments and 3 T brain MRI at baseline and at 12 and 24 months. The primary outcome was new occurrence of symptomatic intracerebral haemorrhage or focal neurological deficit attributable to cerebral cavernous malformation over 24 months. Outcome assessors were masked to treatment group assignment. The primary analysis was done in the intention-to-treat population. Because of the pilot study design, we chose a one-sided 80% CI, which could either exclude a clinically meaningful effect or show a signal of efficacy. This trial is registered with EudraCT, 2017-003595-30, and ClinicalTrials.gov, NCT03589014, and is closed to recruitment. Between April 11, 2018, and Dec 5, 2019, 95 people were assessed for eligibility and 83 were enrolled, of whom 57 were assigned to the propranolol plus standard care group and 26 to the standard care alone group. The mean age of participants was 46 years (SD 15); 48 (58%) were female and 35 (42%) were male. The incidence of symptomatic intracerebral haemorrhage or focal neurological deficit was 1·7 (95% CI 1·4–2·0) cases per 100 person-years (two [4%] of 57 participants) in the propranolol plus standard care group and 3·9 (3·1–4·7) per 100 person-years (two [8%] of 26) in the standard care alone group (univariable hazard ratio [HR] 0·43, 80% CI 0·18–0·98). The univariable HR showed a signal of efficacy, according to predefined criteria. The incidence of hospitalisation did not differ between groups (8·2 cases [95% CI 7·5–8·9] per 100 person-years in the propranolol plus standard care group vs 8·2 [95% CI 7·1–9·3] per 100 person-years in the standard care alone group). One participant in the standard care alone group died of sepsis. Three participants in the propranolol plus standard care group discontinued propranolol due to side-effects (two reported hypotension and one reported weakness). Propranolol was safe and well tolerated in this population. Propranolol might be beneficial for reducing the incidence of clinical events in people with symptomatic familial cerebral cavernous malformations, although this trial was not designed to be adequately powered to investigate efficacy. A definitive phase 3 trial of propranolol in people with symptomatic familial cerebral cavernous malformations is justified. Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro, Swedish Science Council, Knut and Alice Wallenberg Foundation, CARIPLO Foundation, Italian Ministry of Health.

The objective of this study was to evaluate the efficacy and safety of propranolol hydrochloride tablets and oral solution in neonates with severe IHs. A retrospective cohort study included 184 consecutive neonates diagnosed with severe IHs and treated with propranolol from January 2016 to June 2023. Of these, 126 patients received propranolol tablets, and 58 received propranolol oral solution. The primary outcome assessed the treatment response post-discontinuation of propranolol, while the key secondary outcome measured changes in the hemangioma activity score (HAS). Out of 184 participants, 138 (75.5%) were female. The mean age at treatment initiation was 16 days (range: 10–22) for the tablet group and 14 days (range: 8–24) for the oral solution group. Following treatment, effective response rates were 74.6% in the tablet group and 87.9% in the oral solution group (P = 0.04). Improvement in the HAS was 63.95% for the tablet group and 65.57% for the oral solution group (P = 0.35). Adverse reactions included diarrhea in 29.0% of tablet group and 12.9% of oral solution group (P = 0.01), and sleep disturbances in 20.6% of tablet group and 8.6% of oral solution group (P = 0.04). In terms of sequelae, telangiectasia occurred in 34.9% of tablet group and 17.2% of oral solution group (P = 0.01). Propranolol oral solution showed superior efficacy and safety compared to tablets in treating neonates with severe IHs, suggesting it should be prioritized as the preferred treatment option for this vulnerable population.

Objective To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). Background Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. Methods This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16–64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. Results Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (− 5.4, 5.8), p  = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p  = 0.012), there were no between-group differences in the secondary outcomes. Conclusion Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.

Background Cerebral cavernous malformations (CCMs) are vascular malformations characterized by clusters of enlarged leaky capillaries in the central nervous system. They may result in intracranial haemorrhage, epileptic seizure(s), or focal neurological deficits, and potentially lead to severe disability. Globally, CCMs represent the second most common intracranial vascular malformation in humans, and their familial form (FCCMs) accounts for one-fifth of cases. Neurosurgical excision, and perhaps stereotactic radiosurgery, is the only available therapeutic option. Case reports suggest that propranolol might modify disease progression. Methods Treat_CCM is a prospective, randomized, open-label, blinded endpoint (PROBE), parallel-group trial involving six Italian clinical centres with central reading of brain magnetic resonance imaging (MRI) and adverse events. Patients with symptomatic FCCMs are randomized (2:1 ratio) either to propranolol (40–80 mg twice daily) in addition to standard care or to standard care alone (i.e. anti-epileptic drugs or headache treatments). The primary outcome is intracranial haemorrhage or focal neurological deficit attributable to CCMs. The secondary outcomes are MRI changes over time (i.e. de novo CCM lesions, CCM size and signal characteristics, iron deposition, and vascular leakage as assessed by quantitative susceptibility mapping and dynamic contrast enhanced permeability), disability, health-related quality of life, depression severity, and anxiety (SF-36, BDI-II, State-Trait Anxiety Inventory). Discussion Treat_CCM will evaluate the safety and efficacy of propranolol for CCMs following promising case reports in a randomized controlled trial. The direction of effect on the primary outcome and the consistency of effects on the secondary outcomes (even if none of them yield statistically significant differences) of this external pilot study may lead to a larger sample size in a definitive phase 2 trial. Trial registration ClinicalTrails.gov, NCT03589014 . Retrospectively registered on 17 July 2018.

The objective of this phase 1 study was to evaluate the pharmacokinetics (PK), pharmacodynamics, and cardiac effect following administration of ponesimod (a selective sphingosine‐1‐phosphate receptor modulator) and propranolol in healthy adults. In treatment period (TP) 1, participants received ponesimod (2 mg). In TP2, if resting heart rate (HR) was ≥ 55 bpm, the ponesimod up‐titration regimen was initiated. Participants were randomized to TP2A (placebo plus ponesimod up‐titration) or TP2B (80 mg propranolol plus ponesimod up‐titration). Concomitant administration resulted in an increased bradyarrhythmic effect on HR versus ponesimod alone. The mean maximum difference in mean hourly HR from time‐matched baseline for TP2B compared with TP2A during the first 12 h post‐dose was −12.4 bpm. This was observed after the first dose of ponesimod, persisted for the first 4 doses, then decreased to −7.4 bpm post‐up‐titration. The lowest mean of the HRnadir in TP2B was 48.9 bpm (95% CI: 46.4–51.3). There was no significant difference in the occurrence of 1st degree AV block between groups and no occurrences of 2nd or higher degree AV block. No clinically relevant changes were observed in the PK of ponesimod or propranolol. Overall, 88.5% of participants experienced ≥ 1 AE during the study. In TP2, the most reported TEAEs (≥ 5%) considered related to ponesimod were fatigue (12 [25.5%]) and dizziness (10 [21.3%]). No deaths were reported. Co‐administration of ponesimod with propranolol resulted in a greater HR‐lowering effect compared to ponesimod alone, without significant changes in PK parameters or serious cardiac adverse events in healthy adults.

Introduction Propranolol, a nonselective β-blocker, exerts an indirect effect on the vasculature by leaving α-adrenergic receptors unopposed, resulting in peripheral vasoconstriction. We have previously shown that propranolol diminishes peripheral blood following burn injury by increasing vascular resistance. The purpose of this study was to investigate whether wound healing and perioperative hemodynamics are affected by propranolol administration in severely burned adults. Methods Sixty-nine adult patients with burns covering ≥30% of the total body surface area (TBSA) were enrolled in this IRB-approved study. Patients received standard burn care with (n = 35) or without (control, n = 34) propranolol. Propranolol was administered within 48 hours of burns and given throughout hospital discharge to decrease heart rate by approximately 20% from admission levels. Wound healing was determined by comparing the time between grafting procedures. Blood loss was determined by comparing pre- and postoperative hematocrit while factoring in operative graft area. Data were collected between first admission and first discharge. Results Demographics, burn size, and mortality were comparable in the control and propranolol groups. Patients in the propranolol group received an average propranolol dose of 3.3 ± 3.0 mg/kg/day. Daily average heart rate over the first 30 days was significantly lower in the propranolol group ( P <0.05). The average number of days between skin grafting procedures was also lower in propranolol patients (10 ± 5 days) than in control patients (17 ± 12 days; P = 0.02), indicative of a faster donor site healing time in the propranolol group. Packed red blood cell infusion was similar between groups (control 5.3 ± 5.4 units vs. propranolol 4.4 ± 3.1 units, P = 0.89). Propranolol was associated with a 5 to 7% improvement in perioperative hematocrit during grafting procedures of 4,000 to 16,000 cm 2 compared to control ( P = 0.002). Conclusions Administration of propranolol during the acute hospitalization period diminishes blood loss during skin grafting procedures and markedly improves wound healing in severely burned adults. As burn patients require serial surgical interventions for motor and cosmetic repair, restricting blood loss during operative intervention is optimal.

Hepatocellular carcinoma (HCC) remains lethal despite multitargeted tyrosine kinase inhibitors and immunotherapy, motivating the repurposing of safe, widely available agents. To delineate the anti-HCC potential of propranolol through an in-silico network pharmacology and molecular structure-based study, 70 intersecting potential anti-HCC targets were retrieved from the SwissTargetPrediction and GeneCards databases. Protein–protein interaction (PPI) analysis identified a network of 64 interconnected nodes exhibiting a high average node degree of 9.84, highlighting target centrality. Subsequent hub analysis isolated nine pivotal proteins (SRC, EGFR, CCND1, JAK2, ERBB2, PARP1, CDK4, CDK2, CHEK1) with degree centrality values exceeding 23.2, more than twice the network average. Gene Ontology and KEGG enrichment analyses underscored robust involvement in oncogenic pathways, including PI3K–Akt, MAPK, and immune checkpoints. Molecular docking revealed strong binding affinities of propranolol toward key kinases, notably JAK2 (–8.14 kcalmol -1 ), ERBB2 (–7.80 kcalmol -1 ), EGFR (–7.76 kcalmol -1 ), and CDK2 (–7.44 kcalmol -1 ). Molecular dynamics simulations confirmed the complex stability, with RMSD values stably maintained below 4.5 Å over 100 ns simulations. The sustained hydrogen-bond occupancy ranged from 30% to 68% per trajectory, corroborating stable ligand engagement. Collectively, these factorial results provide compelling evidence that propranolol may interact with core oncogenic kinase cluster and potential modulation of the critical signaling cascades implicated in HCC pathogenesis. Collectively, these computational findings support the hypothesis that propranolol possesses the molecular characteristics of a viable therapeutic candidate for HCC, thereby substantiating the need for rigorous experimental and translational investigation to validate its clinical potential.

Memory reconsolidation interventions offer an exciting alternative to exposure treatment because they may target fear memories directly, thereby preventing relapse. A previous reconsolidation intervention for spider fear abruptly reduced avoidance behaviour, whereas changes in self-reported fear followed later. In this pre-registered placebo-controlled study, we first aimed to conceptually replicate these effects in spider phobia. Second, we investigated whether re-encountering the phobic cue after the reconsolidation intervention is necessary for changes in self-reported fear to occur. Third, we tested whether the window to trigger such changes is time limited. Individuals with spider phobia ( N  = 69) were randomized into three groups and underwent a memory reactivation procedure with a tarantula, followed immediately by propranolol (reconsolidation intervention) or placebo. One reconsolidation intervention group and the placebo group re-encountered spiders two days after treatment in behavioural approach tasks, whereas another reconsolidation intervention group re-encountered spiders after four weeks. Changes in spider avoidance behaviour and self-reported fear were followed for one year. In the short term, the reconsolidation intervention was not more effective than placebo: both conditions benefited from the intervention. In the long term, the reconsolidation intervention was more effective than placebo, but only when the phobic stimulus was re-encountered within days after treatment. Specifically, we found less tarantula avoidance behaviour and self-reported fear over the course of one year when spiders were re-encountered two days after the reconsolidation intervention, but not when the behavioural test was conducted four weeks after the intervention. These findings challenge the idea that a reconsolidation-inspired intervention alone is sufficient to treat clinical fears: Experiencing the behavioural change during the re-encounter within days after the reconsolidation window has closed seems crucial to observe a lasting fear reduction.