Is ibuprofen superior to indomethacin for patent ductus arteriosus in Japanese preterm infants?

BACKGROUND: Many clinical trials have indicated that ibuprofen (IBU) has similar effects to indomethacin (IND) on the closure of patent ductus arteriosus (PDA) with fewer adverse effects. Owing to the scarce evidence on IBU use in Japan because of its recent approval we performed this observational study to compare the efficacy and safety of IBU with the efficiency and safety of IND. METHODS: We included infants (gestational age < 30 weeks) with hemodynamically significant PDA under a prophylactic IND protocol for intraventricular hemorrhage who were treated with either IND (n = 30) or IBU (n = 30). We compared a PDA closing effect, changes in ultrasonography findings, and adverse effects between the groups. RESULTS: There was no significant difference in the rates of PDA closure in the first treatment course (IND vs IBU: 46.7% vs 50.0%, P = 0.796) and surgical closure (IND vs IBU: 20.0% vs 20.0%, P = 1.000) between the groups. Both groups showed significant oliguria (IND vs IBU: 30.0% vs 23.3%, P = 0.559) and increased serum creatinine levels after treatment. However, an increase in serum creatinine level by >0.3 mg/dL, a criterion for acute kidney injury, was less frequent in the IBU group (35.7%) compared with that in the IND group (84.2%, P = 0.004). There were no significant differences in echocardiographic changes and jaundice and hypoglycemia incidence rates between the groups. CONCLUSIONS: Except for an increase in serum creatinine levels by >0.3 mg/dL, which was less frequent with IBU, IBU had similar efficacy and safety as IND for preterm PDA. Ibuprofen and IND should be cautiously administered.

Safety and Feasibility of Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-/Ibuprofen-Resistant or -Contraindicated Preterm Infants: A Case Series.

Background Although indomethacin and ibuprofen are the standard treatments for hemodynamically significant patent ductus arteriosus (hsPDA), they are associated with renal impairment and gastrointestinal complications. Paracetamol for hsPDA closure does not provoke a peripheral vasoconstrictive effect and seems to have effects similar to those of indomethacin and ibuprofen. We have previously reported the safety of low-dose (7.5 mg/kg) intravenous paracetamol for preterm infants with hsPDA, who were indomethacin-resistant or -contraindicated but did not affect the need for surgical PDA ligation. However, reports considering the use of higher-dose (15 mg/kg) paracetamol for hsPDA have not been published in Japan. Cases In 16 premature infants in whom indomethacin or ibuprofen was contraindicated or ineffective, 15 mg/kg of paracetamol was intravenously administered every 6 hours for 3 days after obtaining parental consent. hsPDA closure or narrowing was observed in 14 infants (88%), with the need for surgical closure totally avoided in nine cases (56%). High plasma paracetamol levels were observed in three cases. No paracetamol-related side effects or adverse events were reported. Conclusion The intravenous administration of higher dose paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials to explore the optimized dose and timing of administration are needed.

Two Extremely Low Birth Weight Infants Who Survived Functional Pulmonary Atresia with Normal Intracardiac Anatomy.

For the first time, we report about two extremely low birth weight infants who were born at 25 and 22 weeks' gestation and who survived functional pulmonary atresia (fPA) with normal intracardiac anatomy. A slow, reflected, and bimodal blood flow pattern in the pulmonary artery (both cases) and the presence of pulmonary regurgitation (1 case) were useful for diagnosing fPA. Timely use of lipo-prostaglandin E1 to maintain adequate pulmonary flow and reduce pulmonary arterial resistance and sodium bicarbonate to improve acidosis were effective treatments to attain forward flow. As optimal management is essential for the intact survival of extremely early preterm infants and the accurate diagnosis of fPA is difficult without the awareness of the disease entity, our cases underline the importance of recognizing that fPA can occur even in extremely low birth weight infants with normal intracardiac anatomy.

First Pediatric Case of Infective Endocarditis Caused by Serratia Liquefaciens.

Infective endocarditis (IE) caused by Serratia liquefaciens has been reported in only 2 adults. We experienced the first pediatric (neonatal) case of IE caused by S. liquefaciens, with mitral valve vegetation 4 days after a palliative heart surgery. This report underscores the importance of treating for both gram-positive and gram-negative bacteria in IE cases until the blood cultures elucidate the details.

M-mode Diagnosis of Tachyarrhythmia Can be Erroneous Owing to "Pseudo 1:1 Atrioventricular Movement" of the Atrial Wall Adjacent to the Atrioventricular Valve Possibly due to Atrioventricular Constraint: A Case of Neonatal Atrial Flutter With 2:1 Atrioventricular Conduction.

M-mode echocardiography has been playing an important role in the diagnosis of fetal tachyarrhythmia. We recently encountered a neonatal case of atrial flutter with 2:1 atrioventricular conduction. However, M-mode erroneously indicated 1:1 atrioventricular movement. While the movement of the atrial wall far from the atrioventricular valve was much faster than that of the ventricular wall, the atrial wall adjacent to the atrioventricular valve fully synchronized to that of the ventricular wall. Thus, to avoid this novel pitfall, it would be important to add an additional assessment focusing on the movement of the atrial wall far from the ventricle.

Low-Dose Intravenous Paracetamol for Patent Ductus Arteriosus in Indomethacin-Resistant or Contraindicated Preterm Infants: Three Cases Reports.

Background Although indomethacin (IND) is the standard treatment for hemodynamically significant patent ductus arteriosus (hsPDA) in Japan, it may be associated with renal impairment and gastrointestinal complications. The use of paracetamol for hsPDA closure has recently increased. Unlike IND, paracetamol does not have a peripheral vasoconstrictive effect and can be given to infants with contraindications to IND. Based on limited data available from randomized trials, paracetamol and IND seem to have similar effects. However, there have been no reports of the use of paracetamol for hsPDA in Japan. Cases Our drug administration protocol was approved by the institutional ethics committee after purchasing a clinical trial insurance. In three premature infants in whom IND was contraindicated or ineffective, a 7.5 mg/kg of paracetamol was intravenously administered every 6 hour for 3 days after obtaining parental consents. A temporary hsPDA closure was observed in two of the three infants. However, all three infants eventually needed surgical closure. No side effects, such as hepatic and renal dysfunctions, and adverse events were reported. Conclusion The intravenous administration of paracetamol was safe and feasible in premature infants with hsPDA. Future clinical trials with optimized dose and timing of administration are needed.

N-Alkynyl imides (ynimides): synthesis and use as a variant of highly labile ethynamine.

This study describes the first reliable synthesis of N-alkynyl imides (ynimides). This was accomplished with a copper-catalyzed coupling reaction between alkynyl(triaryl)bismuthonium salts and five-membered imides. We also found that it was possible to utilize N-ethynyl phthalimide as a variant of the highly labile ethynamine. 4-Amino-1,2,3-triazole was successfully obtained via the CuAAC reaction of N-ethynyl phthalimide with azide followed by hydrazinolysis of the phthaloyl protecting group.

Evolution of subpatent parasitaemia in Trypanosoma cruzi chronically infected mice with the help of a cyclophosphamide amplification transfer assay

Avaliamos o potencial do ensaio classico de subinoculacao, modificado pelo tratamento com ciclofosfamida dos animais receptores, na deteccao de parasitemias ocultas em camundongos com infeccao cronica pelo Trypanosoma cruzi. O ensaio, alem de simples, mostrou ter uma alta sensibilidade; assim, utilizando-se parasitas da fase aguda, o tratamento com ciclofosfamida revelou parasitemias em 53,8 por cento dos animais infectados com um tripanosoma da cepa y, e em 20 por cento dos animais infectados com um tripanosoma da cepa CL. O tratamento com ciclofosfamida aumentou a sensibilidade do ensaio de subinoculacao nas infeccoes pela cepa CL, e resultou em igual sensibilidade quando utilizada a cepa Y. Nos camundongos de fase cronica, obtidos a partir de diversos esquemas de imunoprofilaxia (BCG, soro de camundongo imune) ou quimioterapia, o ensaio revelou parasitemias ocultas em 99 por cento dos animais. Auxiliados pelo metodo da subinoculacao-ciclofosfamida estudamos no espaco de um ano a evolucao das parasitemias ocultas em um grupo de camundongos infectados que soberviveram a fase aguda pelo tratamento com Benzonidazol. O ensaio revelou parasitemias ocultas em 100 por cento dos animais. Entretanto, padroes continuos e descontinuos de positividade puderam ser detectados.