Infantile hemangiomas are known to be the most common tumors of childhood. These vascular tumors have a distinctive clinical course characterized by a proliferation phase (early and late), followed by a plateau phase and lastly the involution phase. Despite the ability to involute, certain complications, ulcerations being the most common, indicate prompt treatment. Early intervention during the proliferative phase with oral propranolol has been emphasized to achieve an optimum outcome. In this case, a 7-month-old infant presented with a 4.4cm by 3.2cm infantile hemangioma (IH) with ulceration on the left intergluteal area during the late proliferative phase. Prior to propranolol treatment, routine laboratory workup, 21-lead electrocardiogram and ultrasound of the kidneys, ureter and bladder were done, revealing unremarkable results. The patient was referred to a Pediatric Cardiologist and assessment deemed no contraindications for beta-blocker treatment. That patient was placed on a 12-hour day admission for the initiation of oral propranolol at a starting dose of l.0mg/kg/dose and was later discharged, stable, at 1.5mg/kg/dose. Escalation of doses were done by 0.5 every 2 weeks under close supervision on subsequent follow-ups via telemedicine. Four months following the initiation of propranolol treatment regression of the size of the lesion with residual fibrosis were observed. Oral propranolol appears to be an effective and safe therapeutic approach for ulcerated infantile hemangiomas, even during the late proliferative phase. Results achieved significant contraction and resolution of the ulceration and rapid involution of the lesion.

OBJECTIVES: The use of anticholinergic drugs in the elderly may lead to negative events such as falls, delirium, urinary retention and cognitive decline, and the higher the number of anticholinergic drugs use, the more such negative events occur. This study aims to analyze the risk factors associated with the prescription of total anticholinergic drugs in elderly outpatients and evaluate the rationality of anticholinergic drugs, and to provide a reference for reducing the adverse effects of anticholinergic drugs. METHODS: A list of drugs with anticholinergic activity based on the Beers criteria was established. The basic information (such as age and gender), clinical diagnosis, and medications of elderly outpatient were extracted from hospital electronic medical records, and the Anticholinergic Cognitive Burden (ACB) Scale was used to calculate the anticholinergic burden for each patient. Logistic regression analysis was used to identify the potential risk factors for the occurrence of problems such as multiple medication and insomnia. RESULTS: A total of 1 840 prescriptions for elderly patients were reviewed. Of these patients, ACB score was more than or equal to 1 in 648 (35.22%) patients. Number of prescription medication (95% CI: 1.221 to 1.336) and insomnia (95% CI: 3.538 to 6.089) were independent factors affecting ACB scores (both P<0.01). Medications for patients of ACB scores were most commonly treated with the central nervous system drugs (such as alprazolam and eszopiclone) and for the cardiovascular system drugs (such as metoprolol and nifedipine). CONCLUSIONS There is a high rate of ACB drugs use in geriatric patients, and the clinical focus should be on multiple medication prescriptions, especially on the central nervous system drugs (such as alprazolam and eszopiclone) and cardiovascular system drugs (such as metoprolol and nifedipine). The prescription review should be emphasized to reduce adverse reactions to anticholinergic drugs in elderly patients.
Humans ; Aged ; Cholinergic Antagonists/adverse effects* ; Outpatients ; Metoprolol ; Alprazolam ; Eszopiclone ; Nifedipine ; Sleep Initiation and Maintenance Disorders ; Risk Factors

This paper aimed to investigate the effect of total flavonoids of buckwheat flower and leaf on myocardial cell apoptosis and Wnt/β-catenin/peroxisome proliferator-activated receptor γ(PPARγ) pathway in arrhythmic rats. SD rats were randomly divided into a control group, a model group, a low-dose(20 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a medium-dose(40 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a high-dose(80 mg·kg~(-1)) group of total flavonoids of buckwheat flower and leaf, a propranolol hydrochloride(2 mg·kg~(-1)) group, with 12 rats in each group. Except the control group, rats in other groups were prepared as models of arrhythmia by sublingual injection of 1 mL·kg~(-1) of 0.002% aconitine. After grouping and intervention with drugs, the arrhythmia, myocardial cells apoptosis, myocardial tissue glutathione peroxidase(GSH-Px), catalase(CAT), malondialdehyde(MDA), serum interleukin-6(IL-6), prostaglandin E2(PGE2) levels, myocardial tissue apoptosis, and Wnt/β-catenin/PPARγ pathway-related protein expression of rats in each group were measured. As compared with the control group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA levels in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels increased significantly in the model group, whereas the GSH-Px and CAT levels, and Bcl-2 and PPARγ protein expression levels in myocardial tissues reduced significantly. As compared with the model group, the arrhythmia score, the number of ventricular premature beats, ventricular fibrillation duration, myocardial cell apoptosis rate, MDA leve in myocardial tissues, serum IL-6 and PGE2 levels, Bax in myocardial tissues, and Wnt1 and β-catenin protein expression levels reduced in the drug intervention groups, whereas the GSH-Px and CAT levels and Bcl-2 and PPARγ protein expression levels in myocardial tissues increased. The groups of total flavonoids of buckwheat flower and leaf were in a dose-dependent manner. There was no significant difference in the levels of each index in rats between the propranolol hydrochloride group and the high-dose group of total flavonoids of buckwheat flower and leaf. The total flavonoids of buckwheat flower and leaf inhibit the activation of Wnt/β-catenin pathway, up-regulate the expression of PPARγ, reduce oxidative stress and inflammatory damage in myocardial tissues of arrhythmic rats, reduce myocardial cell apoptosis, and improve the symptoms of arrhythmia in rats.
Rats ; Animals ; PPAR gamma/metabolism* ; Fagopyrum/genetics* ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein ; beta Catenin/metabolism* ; Interleukin-6 ; Flavonoids/pharmacology* ; Propranolol/pharmacology* ; Ventricular Fibrillation ; Dinoprostone ; Wnt Signaling Pathway ; Plant Leaves/metabolism* ; Flowers/metabolism* ; Apoptosis ; Cardiac Complexes, Premature

OBJECTIVE: To explore the clinical and genetic characteristics of five children with Catecholaminergic polymorphic ventricular tachycardia (CPVT). METHODS: Five children with clinical manifestations consistent with CPVT admitted to the Department of Cardiology of Children's Hospital Affiliated to Zhengzhou University from November 2019 to November 2021 were selected as the study subjects. Their clinical data were collected. Potential variants were detected by whole exome sequencing, and Sanger sequencing was used to verify the candidate variants. All patients were treated with β-blocker propranolol and followed up. RESULTS: All patients had developed the disease during exercise and presented with syncope as the initial clinical manifestation. Electrocardiogram showed sinus bradycardia. The first onset age of the 5 patients were (10.4 ± 2.19) years, and the time of delayed diagnosis was (1.6 ± 2.19) years. All of the children were found to harbor de novo heterozygous missense variants of the RYR2 gene, including c.6916G>A (p.V2306I), c.527G>C (p.R176P), c.12271G>A (p.A4091T), c.506G>T (p.R169L) and c.6817G>A (p.G2273R). Among these, c.527G>C (p.R176P) and c.6817G>A (p.G2273R) were unreported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.527G>C (p.R176P) was classified as a pathogenic variant (PS2+PM1+PM2_Supporting+PM5+PP3+PP4), and the c.6817G>A (p.G2273R) was classified as a likely pathogenic variant (PS2+PM2_Supporting+PP3+PP4). The symptoms of all children were significantly improved with the propranolol treatment, and none has developed syncope during the follow up. CONCLUSION Discovery of the c.527G>C (p.R176P) and c.6817G>A (p.G2273R) variants has expanded the mutational spectrum of the RYR2 gene. Genetic testing of CPVT patients can clarify the cause of the disease and provide a reference for their genetic counseling.
Child ; Humans ; Mutation ; Propranolol ; Ryanodine Receptor Calcium Release Channel/genetics* ; Syncope ; Tachycardia, Ventricular/diagnosis* ; United States

OBJECTIVE: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options. METHODS: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed. RESULTS: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs. 28.08%, χ²= 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS. CONCLUSION POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.
Child ; Electrolytes ; Female ; Humans ; Male ; Metoprolol ; Midodrine ; Orthostatic Intolerance/therapy* ; Postural Orthostatic Tachycardia Syndrome/diagnosis* ; Retrospective Studies ; Salts ; Sitting Position ; Syncope, Vasovagal/diagnosis* ; Tilt-Table Test

BACKGROUND: Postural tachycardia syndrome (POTS) is a common childhood disease that seriously affects the patient's physical and mental health. This study aimed to investigate whether pre-treatment baseline left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) values were associated with symptom improvement after metoprolol therapy for children and adolescents with POTS. METHODS: This retrospective study evaluated 51 children and adolescents with POTS who received metoprolol therapy at the Peking University First Hospital between November 2010 and July 2019. All patients had completed a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated 3 months after starting metoprolol therapy. The pre-treatment baseline LVEF and LVFS values were evaluated for correlations with decreases in the symptom score after treatment (ΔSS). Multivariable analysis was performed using factors with a P value of <0.100 in the univariate analyses and the demographic characteristics. RESULTS: A comparison of responders and non-responders revealed no significant differences in demographic, hemodynamic characteristics, and urine specific gravity (all P > 0.050). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) than the non-responders. The baseline LVEF and LVFS were positively correlated with ΔSS (r = 0.378, P = 0.006; r = 0.363, P = 0.009), respectively. Logistic regression analysis revealed that LVEF was independently associated with the response to metoprolol therapy in children and adolescents with POTS (odds ratio: 1.201, 95% confidence interval: 1.039-1.387, P = 0.013). CONCLUSIONS Pre-treatment baseline LVEF was associated with symptom improvement after metoprolol treatment for children and adolescents with POTS.
Adolescent ; Child ; Humans ; Metoprolol/therapeutic use* ; Postural Orthostatic Tachycardia Syndrome/drug therapy* ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

OBJECTIVE: To study the clinical effect of oral propranolol in the treatment of respiratory hemangioma in infants and young children. METHODS: A retrospective analysis was performed from the chart review data of children with respiratory hemangioma treated by oral propranolol and diagnosed by bronchoscopy and laryngeal plain enhanced CT/MRI from November 2012 to December 2019. RESULTS: A total of 20 children were enrolled. All children had improvement in the symptoms of laryngeal stridor and dyspnea after oral administration of propranolol for 1-2 days. The median treatment time was 10 months (range 6-12 months). The median follow-up time was 10 months (range 3-15 months). Of the 20 children, 19 (95%) achieved regression of tumor, and 1 (5%) experienced an increase in tumor size during reexamination at 6 months after drug withdrawal and had no recurrence after the treatment with an increased dose of propranolol for 6 months. Only 1 child (5%) had adverse reactions, and 1 child (5%) was still under treatment. CONCLUSIONS Oral propranolol can quickly relieve the symptoms such as dyspnea and achieve tumor regression, with few adverse events, and it is therefore an effective method for the treatment of respiratory hemangioma in infants and young children.
Administration, Oral ; Adrenergic beta-Antagonists ; Child ; Child, Preschool ; Hemangioma ; Humans ; Infant ; Neoplasm Recurrence, Local ; Propranolol ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To study the effect of CYP2D610 (c.100 C>T) on plasma trough concentrations of metoprolol and its metabolite α-hydroxy metoprolol, blood pressure and heart rate in patients with coronary artery disease. METHODS: The patients with coronary artery disease taking metoprolol tablets (=128) and those taking metoprolol sustained-release tablets (=126) were genotyped for CYP2D610 using Taqman real-time quantitative PCR. The trough concentrations of metoprolol and α-hydroxy metoprolol were determined with UPLC-MS/MS, and the dose-normalized concentrations (C/D) were compared among the patients with different CYP2D610 genotypes in both groups. Resting blood pressure and heart rate were recorded in all the patients when the concentration of metoprolol reached the steady state and were compared among the patients with different genotypes. RESULTS: In patients taking metoprolol sustained-release tablets, the plasma trough concentration of α-hydroxy metoprolol was significantly associated with the systolic blood pressure (=0.0204). The CYP2D610 poor metabolizers showed a significant association with the C/D of metoprolol and α-hydroxy metoprolol ( < 0.01) in patients receiving metoprolol in both formulations, and in both groups, the C/D of metoprolol was significantly higher in the patients with a TT genotype than in those with a CC or CT genotype ( < 0.01); compared with those with the CT genotype, the patients with the TT genotype had a significantly lower C/D of α-hydroxy metoprolol ( < 0.01). In patients taking metoprolol sustained-release tablets, those with the CT (=0.0281) and TT (=0.0196) genotypes had lower diastolic blood pressure than patients with the CC genotypes, but the systolic blood pressure or heart rate did not differ significantly among them. CONCLUSIONS CYP2D610T allele mutation can reduce the metabolism of metoprolol, increase the C/D of metoprolol and decrease the C/D of α-metoprolol and diastolic blood pressure in patients with coronary artery disease, but CYP2D610 variation does not significantly affect systolic blood pressure or heart rate in the patients when the concentration of metoprolol reaches a steady state.
Adrenergic beta-Antagonists ; Chromatography, Liquid ; Coronary Artery Disease ; Cytochrome P-450 CYP2D6 ; Genotype ; Humans ; Metoprolol ; Tandem Mass Spectrometry

Gorham-Stout disease (GSD) was first described by Gorham and colleagues in 1954, but its precise mechanism and cause remain to be elucidated. In this condition, voluminous and potentially fatal chylous effusions into the thorax can occur. Herein, we describe a case of GSD in which the patient presented with massive pleural effusions and mottled osteolytic bone lesions. We performed multiple operations, including thoracic duct ligation using video-assisted thoracoscopic surgery and thoracotomic decortication, but these procedures did not succeed in preventing recurrent pleural effusion and chest wall lymphedema. After administering sirolimus (0.8 mg/m2, twice a day) and propranolol (40 mg, twice a day), the process of GSD in this patient has been controlled for more than 2 years.
Chylothorax ; Humans ; Ligation ; Lymphedema ; Osteolysis, Essential ; Pleural Effusion ; Propranolol ; Sirolimus ; Thoracic Duct ; Thoracic Surgery, Video-Assisted ; Thoracic Wall ; Thorax

OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.
Antidepressive Agents ; Antipsychotic Agents ; Aripiprazole ; Benzodiazepines ; Cholinergic Antagonists ; Clinical Decision-Making ; Clozapine ; Consensus ; Depression ; Dihydroergotamine ; Drug Therapy ; Humans ; Injections, Intramuscular ; Metformin ; Naltrexone ; Propranolol ; Psychiatry ; Schizophrenia ; Serotonin Uptake Inhibitors ; Substance-Related Disorders ; Suicide ; Varenicline