No abstract

We report on a neonate with a huge congenital hemangioma of the scalp presenting as high-output heart failure and Kasabach-Merritt syndrome. The condition was successfully treated by means of surgical excision. A prematurely born (gestational age=36 weeks; birth weight=2,316 g), three-day-old female infant was referred to our institution for a huge scalp tumor (Fig. 1), already detected by fetal ultrasonography at six months of gestation. Head computed tomography scan revealed a hypervascular tumor of the scalp with strong heterogeneous enhancement. Magnetic resonance imaging demonstrated multiple feeding arteries, mainly consisting of an anastomosis of bilateral superficial temporal arteries and branches of the internal carotid artery. There was no evidence of intracranial hemorrhage. The patient had early heart failure signs including progressive respiratory distress and tachycardia. A small patent ductus arteriosus was present (1.2 mm in size). Thrombocytopenia (134Â10 9 /L) on the 1st day of life progressed to the lowest level (107Â10 9 /L) on day 3. On day 4, normocytic anemia (hemoglobin=11.5 g/dL) was present, prothrombin time was prolonged (16.3 seconds) as was partial thromboplastin time (79 seconds). Direct Coombs_ test was negative and both fibrin split products (80-160 mg/ml; normal<10 mg/ml) and D-Dimer (1.94 mg/ml; normal<0.5 mg/ml) were increased.The early heart failure signs improved soon after oxygen hood. Dopamine (5 mg/kg/min) and parenteral furosemide were administered beginning on the 3rd day of life. On the 5th day of life surgical excision following ligation of the feeding arteries was successful apart from the need for a whole-blood transfusion for surgery-related blood loss of approximately 300 mL. Indirect hyperbilirubinemia on the day subsequent to surgery complicated patient recovery, followed by the need for a double-volume blood-exchange transfusion in order to deal with a total bilirubin level escalating to 23.8 mg/dL. The patient_s thrombocytopenia resolved from the 14th day of life. Dopamine and furosemide were discontinued three days following surgery and the baby was discharged in good condition two weeks later. The histological findings from the excised lesion revealed a number of vascular channels located beneath the scalp and surrounded by fibrotic and myxoid stroma. Low cellularity and scant mitotic figures were noted without any malformed vessels.Hemangioma is present in more than 10% of normal newborns with a strong female predominance [4]. Approximately 60% of the hemangiomas of infancy appear on the head and neck [3], ninety-five percent will regress spontaneously without sequelae [1]. By contrast, 3-5% of hemangiomas involve vital organs or produce life-threatening complications requiring the need for aggressive therapy [5]. The management of hemangioma is generally divided into conservative treatment and intervention therapy. A response rate to treatment of 45%, but a cure rate of only 18% has been reported following prednisone therapy (3-10 mg/kg/day) for six to eight...

IMPORTANCE In 2019, the US Food and Drug Administration (FDA) received a citizen petition indicating that ranitidine contained the probable human carcinogen N-nitrosodimethylamine (NDMA). In addition, the petitioner proposed that ranitidine could convert to NDMA in humans; however, this was primarily based on a small clinical study that detected an increase in urinary excretion of NDMA after oral ranitidine consumption.OBJECTIVE To evaluate the 24-hour urinary excretion of NDMA after oral administration of ranitidine compared with placebo. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-controlled, crossover clinical trial at a clinical pharmacology unit (West Bend, Wisconsin) conducted in 18 healthy participants. The study began in June 2020, and the end of participant follow-up was July 1, 2020.INTERVENTIONS Participants were randomized to 1 of 4 treatment sequences and over 4 periods received ranitidine (300 mg) and placebo (randomized order) with a noncured-meats diet and then a cured-meats diet. The cured-meats diet was designed to have higher nitrites, nitrates (nitrate-reducing bacteria can convert nitrates to nitrites), and NDMA. MAIN OUTCOME AND MEASURE Twenty-four-hour urinary excretion of NDMA.RESULTS Among 18 randomized participants (median age, 33.0 [interquartile range {IQR}, 28.3 to 42.8] years; 9 women [50%]; 7 White [39%], 11 African American [61%]; and 3 Hispanic or Latino ethnicity [17%]), 17 (94%) completed the trial. The median 24-hour NDMA urinary excretion values for ranitidine and placebo were 0.6 ng (IQR, 0 to 29.7) and 10.5 ng (IQR, 0 to 17.8), respectively, with a noncured-meats diet and 11.9 ng (IQR, 5.6 to 48.6) and 23.4 ng (IQR, 8.6 to 36.7), respectively, with a cured-meats diet. There was no statistically significant difference between ranitidine and placebo in 24-hour urinary excretion of NDMA with a noncured-meats diet (median of the paired differences, 0 [IQR, −6.9 to 0] ng; P = .54) or a cured-meats diet (median of the paired differences, −1.1 [IQR, −9.1 to 11.5] ng; P = .71). No drug-related serious adverse events were reported. CONCLUSIONS AND RELEVANCEIn this trial that included 18 healthy participants, oral ranitidine (300 mg), compared with placebo, did not significantly increase 24-hour urinary excretion of NDMA when participants consumed noncured-meats or cured-meats diets. The findings do not support that ranitidine is converted to NDMA in a general, healthy population.