Topical Formulations of Propranolol for Infantile Hemangiomas: Characteristics of Formulations and Three Cases of Infants Administered Topical Propranolol Cream.

Propranolol is used as the first-line treatment for infantile hemangiomas (IHs). As oral formulations can cause systemic adverse drug reactions (ADRs), we prepared topical propranolol formulations and evaluated their pharmaceutical profiles. We also present three cases of pediatric patients with IHs who were treated with the propranolol formulations. Propranolol cream (hydrophilic cream, 1, 3, and 5%) and gels (carboxyvinyl polymer, hydroxypropyl methylcellulose, gellan gum, 1%) were prepared. The in vitro skin permeability of these formulations was assessed using Franz-type diffusion cells. The pharmaceutical profiles, including propranolol content, pH, and ductility, of the propranolol creams were evaluated. For the stability test, similar pharmaceutical evaluations were performed after the creams were stored at 25 °C and 56% relative humidity for 3 months. We examined three patients treated with propranolol cream to investigate the clinical course of IH and adverse events after the propranolol cream was applied for 5-12 months. In the in vitro skin permeability assay, topical propranolol formulations made of hydrophilic cream and gellan gum permeated the most. The amount of propranolol that permeated increased with propranolol concentration. After storage for 3 months, no substantial changes were observed in any pharmaceutical profile. The IHs were discolored in all patients. Tumor size also decreased in some patients. Furthermore, no adverse events caused by propranolol cream were observed during application. In conclusion, propranolol cream can be prepared as a hospital formulation with adequate quality. Topical propranolol therapy is effective in reducing the incidence of systemic ADRs.

Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer.

BACKGROUND: Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature. Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases. METHODS: The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021. RESULTS: Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy. CONCLUSIONS: Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

Inherited catecholaminergic polymorphic ventricular tachycardia due to RYR2 mutation.

We report the case of an 11-year-old boy who was diagnosed with catecholaminergic polymorphic ventricular tachycardia (CPVT). The patient had a medical history of three episodes of syncope. The last episode was cardiac arrest while swimming. After resuscitation using automated external defibrillator, he was placed under cerebral hypothermia, examined for long QT syndrome, and underwent insertion of implantable cardioverter defibrillator. He was subsequently discharged from hospital without any adverse sequelae. The patient was diagnosed with CPVT after detection of ryanodine receptor 2 mutation. His father also carried the same mutation, although he did not have any symptoms nor did he have a history of syncope. We propose that CPVT should be included in the differential diagnosis in children with recurrent episodes of syncope.

Skull involvement in a pediatric case of chronic recurrent multifocal osteomyelitis.

An 11-year-old boy was diagnosed with chronic recurrent multifocal osteomyelitis (CRMO) and presented with right sacro-femoral and occipital lesions. Initially, a tumor was suspected. However, the bone biopsy showed osteomyelitis with a negative bacterial culture. Bone scintigraphy revealed inflammatory changes on multiple bone lesions. The slight elevation in inflammatory markers such as C-reactive protein was of little clinical value. He was diagnosed with CRMO by sacral biopsy, and the clinical course progressed, with the presence of a new occipital lesion observed after the 1-year follow-up. The administration of non-steroidal anti-inflammatory drugs successfully improved his clinical symptoms. The presence of a skull lesion in the occipital bone of a pediatric patient with CRMO has not been previously reported.

Transient renal dysfunction with reversible splenial lesion.

We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.

Hereditary spherocytosis diagnosed with the eosin-5'-maleimide binding test.

We describe three cases of hereditary spherocytosis (HS) diagnosed using the eosin-5'-maleimide (EMA) binding test and discuss the relevance of the EMA binding test. In Japan, this test is not widely used because the prevalence of HS is low. This test is a valuable screening test for the diagnosis of HS.

Critical findings of severe influenza A (H1N1) pneumonia in children.

BACKGROUND: Pandemic influenza A (H1N1) causes severe pneumonia in children. The mechanism of development of respiratory failure in pneumonia patients remains unknown. This report describes clinical features of childhood influenza A pneumonia. METHODS: The clinical and laboratory findings of 31 H1N1 pneumonia patients hospitalized in Iwata City Hospital from 1 October 2009 to 31 January 2010 were reviewed. Intubation and mechanical ventilation were required due to respiratory failure in eight patients, who were classified as the intubation group. Other patients without mechanical ventilation were classified as the non-intubation group. Clinical features and laboratory findings were compared between the two groups. RESULTS: The median age was 6.3 years (range, 3-10 years). The male to female ratio was 22:9. Clinical manifestations of tachycardia, tachypnea and cyanosis were significant findings in the intubation group at admission. Lymphocytopenia was observed in both groups. Leukocytosis with neutrophilia was the risk factor for intubation. CONCLUSIONS: Tachycardia, tachypnea, cyanosis and leukocytosis with neutrophilia, could be useful predictors at admission to identify high-risk influenza A (H1N1) pneumonia in children.

Severe, widespread vasculopathy in late-onset group B streptococcal meningitis.

Although improvements in antimicrobial therapy during the last few decades have decreased mortality in childhood bacterial meningitis, some patients are left with neurologic sequelae. Cerebrovascular complications are often associated with unfavorable clinical outcome of the disease. We report a 36-day-old infant with severe, widespread cerebrovascular complications due to group B streptococcal meningitis. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) contributed to a non-invasive demonstration of meningeal inflammatory changes and vascular lesions with the meningitis in this patient.