Epidemiology of neonatal pneumothorax developed spontaneously and during respiratory supports in neonatal intensive care units.

BACKGROUND: Information on incidence and risk factors associated with different types of neonatal pneumothorax were lacking globally. OBJECTIVES: To determine incidences of pneumothorax developed spontaneously and during different modes of respiratory support, and risk factors associated with each type of pneumothorax. STUDY DESIGN: Retrospective observational study of neonates in the Malaysian National Neonatal Registry. SETTING: 44 Malaysian neonatal intensive care units (NICUs). PARTICIPANTS: All neonates born in 2015-2020 and admitted to NICUs. RESULTS: Pneumothorax developed in 3265 neonates: 37.5% occurred spontaneously, 62.5% during respiratory support. The incidence of all types of pneumothorax was 1.75 per 1000 livebirths, and of spontaneous pneumothorax was 0.58 per 1000 livebirths. Pneumothorax developed in 0.6% (450/70512) of neonates during continuous positive air way pressure therapy (nCPAPt), 1.8% (990/54994) of neonates during conventional mechanical ventilation (CMV), and 7.0% (599/8557) of neonates during high frequency ventilation (HFV). Term neonates had significantly higher pneumothorax rate than preterms (p<0.001). Multiple logistic regression analyses show that exposure to intermittent positive pressure ventilation and chest compression at birth were significant independent factors associated with increased risk of spontaneous pneumothorax and CMV, and persistent pulmonary hypertension was associated with increased risk of spontaneous pneumothorax and pneumothorax during CMV and HFV. CONCLUSIONS: The most common type of pneumothorax was spontaneous in-onset. Neonates on HFV had the highest and those on nCPAPt the lowest rate of pneumothorax. Improving training of resuscitation techniques at birth and strategies of use of invasive modes of respiratory support may reduce incidences of all types of pneumothorax.

Early-onset sepsis in Malaysian neonatal intensive care units.

OBJECTIVES: To determine the incidence, causative pathogens, morbidities, mortality, and risk factors associated with blood culture-positive early-onset sepsis (EOS, ≤72 hours of age) in symptomatic neonates admitted to the neonatal intensive care units (NICUs) of a middle-income country. STUDY DESIGN: Retrospective cohort study using data submitted prospectively to the Malaysian National Neonatal Registry (MNNR). SETTING: 44 Malaysian NICUs. PARTICIPANTS: All neonates born in 2015- 2020. RESULTS: EOS was reported in 991 neonates. The annual incidence of EOS increased from 0.46 to 0.49/1000 livebirths over the six years. The most common pathogen was Streptococcus agalactiae or Group B haemolytic streptococcus (GBS) (n=388, 39.2%), followed by Escherichia coli (E. coli) (n=80, 8.1%), Klebsiella spp (n=73, 7.4%), coagulase negative staphylococcus (CONS) (n=73, 7.4%), Pseudomonas spp (n=44, 4.4%) and methicillin-sensitive Staphylococcus aureus (n=34, 3.4%). The incidence of EOS due to GBS increased from 0.17 to 0.22/1000 livebirths. Morbidities and mortality were higher in those with EOS than without EOS. Multiple logistic regression analysis showed that Indian ethnic group, chorioamnionitis, gestation≥37weeks, female, spontaneous vaginal delivery, instrumental delivery, and surfactant therapy were significantly associated with increased risk of EOS due to GBS. Four factors were significantly associated with increased risk of non-GBS EOS (outborns, birthweight lt;1000 g, vaginal delivery, and surfactant therapy). Early continuous positive airway pressure was associated with significantly lower risk of EOS. CONCLUSION: The incidence of EOS showed an increasing trend in Malaysian NICUs. GBS was the most common causative pathogen. Several modifiable risk factors associated with EOS have been identified.

A coupled chlorinase-fluorinase system with a high efficiency of trans-halogenation and a shared substrate tolerance.

Enzymatic trans-halogenation enables radiolabeling under mild and aqueous conditions, but rapid reactions are desired. We developed a coupled chlorinase-fluorinase system for rapid trans-halogenation. Notably, the chlorinase shares a substrate tolerance with the fluorinase, enabling these two enzymes to cooperatively produce 5'-fluorodeoxy-2-ethynyladenosine (5'-FDEA) in up to 91.6% yield in 1 h.

Probing the molecular determinants of fluorinase specificity.

Molecular determinants of FlA1 fluorinase specificity were probed using 5'-chloro-5'-deoxyadenosine (5'-ClDA) analogs as substrates and FlA1 active site mutants. Modifications at F213 or A279 residues are beneficial towards these modified substrates, including 5'-chloro-5'-deoxy-2-ethynyladenosine, ClDEA (>10-fold activity improvement), and conferred novel activity towards substrates not readily accepted by wild-type FlA1.

Effects of a meal on hemodynamic function at rest and during exercise in patients with hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy experience postprandial exacerbation of their symptoms. The vasodilation associated with eating may be deleterious in hypertrophic cardiomyopathy, especially during exercise. To examine the hemodynamic effects of a meal in hypertrophic cardiomyopathy, 11 patients were studied with invasive hemodynamic monitoring during exercise testing in the fasting state and 45 min after a 740 kcal (3,100 J) meal. The meal induced a decrease in systemic vascular resistance index at rest (mean +/- SD, -17 +/- 14%), increases in mean right atrial (31 +/- 21%), mean pulmonary artery (14 +/- 14%) and mean pulmonary capillary wedge (17 +/- 14%) pressures and an increase in cardiac index (18 +/- 10%) due to an increased heart rate without any significant change in stroke volume. During postprandial exercise, heart rate, rate-pressure product, cardiac index and cardiac filling pressures were higher than during fasting exercise and one patient had a decrease in exercise blood pressure compared with the fasting test. Five patients with postprandial exacerbation of symptoms in everyday life had a lesser increase in systemic arterial pressure and stroke volume during both exercise tests and a smaller increase in cardiac index after the meal than did the six patients without postprandial symptom exacerbation, suggesting more severe cardiac disease. It is concluded that patients with hypertrophic cardiomyopathy have an abnormal hemodynamic response to food, in which stroke volume fails to increase and pulmonary capillary wedge and pulmonary artery pressures increase. These adverse changes persist during postprandial exercise and may predispose to exertional collapse in certain patients.

Effect of preload change on resting and exercise cardiac performance in hypertrophic cardiomyopathy.

The purpose of this study was to investigate the hemodynamic responses, at rest and on exercise, of patients with hypertrophic cardiomyopathy to changes in circulating volume. After Swan-Ganz and radial arterial cannulation, 13 patients with hypertrophic cardiomyopathy performed maximal exercise tests after diuretic (frusemide 20 mg intravenously) and after fluid loading (0.9% saline at 10 ml/kg body weight intravenously) on different days. At rest, right atrial and pulmonary capillary wedge pressures increased with volume loading and decreased with a diuretic. There were no significant changes in the resting, supine cardiac or stroke indexes but in the upright position, the cardiac index and stroke index were higher after volume loading (2.5 +/- 0.7 vs 2.2 +/- 0.5 liters/min/m2, p less than 0.05; 33 +/- 11 vs 27 +/- 9 ml/m2, p less than 0.005, respectively). Although the right atrial, pulmonary arterial and pulmonary capillary wedge pressures were higher during exercise after volume loading, there were no significant differences in exercise heart rate, systemic blood pressure, cardiac index, stroke index, systemic vascular resistance index or overall exercise capacity compared to exercise after diuresis. The data show that the cardiac index and stroke index, at supine rest and during upright exercise, were not influenced by the preload changes induced in these patients with hypertrophic cardiomyopathy. The results suggest that these patients are operating on the plateau of left ventricular Frank-Starling function (filling pressure/output) curve.

Placebo controlled trial of xamoterol versus digoxin in chronic atrial fibrillation.

Thirteen patients in chronic atrial fibrillation with a normal resting heart rate but with exercise tachycardia and episodes of bradycardia were randomised to treatment periods of two weeks on xamoterol (200 mg twice daily), low dose digoxin, or placebo, in a blind crossover study. The results (mean SEM) of symptom scores, a treadmill exercise test, and 24 hour ambulatory electrocardiographic monitoring were obtained. Xamoterol improved symptom scores and controlled exercise heart rate better than digoxin. Xamoterol was better than digoxin or placebo in reducing the heart rate response to exercise and tended to improve exercise duration. Xamoterol, by reducing the daytime maximum hourly heart rate and increasing the night time minimum hourly heart rate, significantly reduced the difference between the two compared with placebo. In contrast, digoxin tended to reduce both the maximum and minimum hourly heart rates through day and night. Both the frequency and duration of ventricular pauses were reduced by xamoterol but tended to increase with digoxin. Xamoterol reduced both the circadian variation in ventricular response to atrial fibrillation and exercise tachycardia by modulating the heart rate according to the prevailing level of sympathetic activity. These changes were translated into symptomatic benefit for the patients studied.