Platelet Count and Volume and Pharmacological Closure with Paracetamol of Ductus Arteriosus in Preterm Infants

Background: Low platelet count might promote resistance to pharmacological closure with indomethacin and ibuprofen of a hemodynamically significant patent ductus arteriosus (hsPDA). However, no studies have investigated if this occurs with paracetamol. Methods: We retrospectively assessed the correlation between platelet count, mean platelet volume (MPV), and plateletcrit (PCT), as well as the effectiveness of paracetamol in closing hsPDA in infants born at 23+0–31+6 weeks of gestation who were treated with 15 mg/kg/6 h of i.v. paracetamol for 3 days. Results: We studied 79 infants: 37 (47%) Had closure after a course of paracetamol and 42 (53%) did not. Platelet count and PCT did not correlate with paracetamol success or failure in closing hsPDA, while MPV was lower at birth (10.7 ± 1.4 vs. 9.5 ± 1.1; p < 0.001) and prior to starting therapy (11.7 ± 1.9 vs. 11.0 ± 1.6; p = 0.079) in refractory infants. Regression analysis confirmed that the low MVP measured prior to starting the treatment increased the risk of hsPDA paracetamol closure failure (OR 1.664, 95% CI 1.153–2.401). Conclusions: The greater MPV correlated positively with the effectiveness of paracetamol in closing hsPDA, while platelet count and PCT did not influence closure rates. Additional studies are needed to confirm our results.

Transcatheter Closure of Patent Ductus Arteriosus via Different Approaches

Background: There have been marked advances in devices such as Amplatzer Duct Occluder II (ADO-II) or vascular plug through 5Fr delivery sheath for closure of patent ductus arteriosus (PDA) in the past five decades, making it possible for cardiologists to deliver occluders via different approaches. However, comparisons of these different approaches have not been reported. Therefore, the aim of this study was to summarize and compare the advantages of different approaches for PDA closure, and to guide clinical strategies.Methods: This retrospective study included all patients undergoing transcatheter closure of PDA from 2019 to 2020. Patients were matched by 1:1 propensity score matching (PSM). The retrograde femoral artery approach (FAA) and simple vein approach (SVA) groups were compared with the conventional arteriovenous approach (CAA).Results: The average age of the 476 patients was 21.05 ± 21.15 years. Their average weight was 38.23 ± 24.1 kg and average height was 130.14 ± 34.45 cm. The mean diameter of the PDA was 4.29 ± 2.25 mm. There were 127 men and 349 women, comprising 205 adults and 271 children. Among them, 197 patients underwent CAA, 223 underwent SVA, and 56 underwent retrograde FAA. The diameter in the FAA group was smaller than that in the other two groups, but was similar in adults and children. In the PSM comparison of CAA and SVA, 136 patients with CAA and 136 patients with SVA were recruited. Simple vein approach was associated with markedly reduced length of hospital stay, length of operation, and contrast medium usage as compared with CAA (all P &lt; 0.05). In the PSM comparison of FAA and CAA, 30 patients with CAA and 30 patients with FAA were recruited. The operation duration was longer in the CAA than in the FAA group. There were no significant differences in postoperative complications among groups.Conclusion: Patent ductus arteriosus closure by using the SVA and FAA is safe and effective, and has certain advantages in some respects as compared with CAA.

A Simple Non-Invasive Biomarker Can Reflect Both the Acute and Chronic Pulmonary Impact of Patent Ductus Arteriosus (PDA) Shunting

The SFR (Sp02/Fi02 ratio) offers a continuous, non-invasive reflection of pulmonary function regardless of whether the baby is ventilated or breathing spontaneously. We hypothesized that significant PDA shunting would impair pulmonary oxygen diffusion, in turn, reflected by decreased SFR; and that early PDA related decreases in SFR will predict subsequent chronic lung disease (CLD). Methods: We retrospectively examined records from preterm neonates <30 weeks gestational age. Ductal shunting was graded for severity by first week echocardiogram. SFR was calculated as SpO2/Fi02 and recorded on day 7 of life and at 36 weeks postmenstrual age (PMA). Results: We studied 104 infants: 65 with closed duct; 17 with hemodynamically insignificant PDA and 22 with hemodynamically significant (hsPDAs). CLD developed in 9 (14%) of those with closed ducts; 6 (35%) of those with hisPDA; and in 12 (55%) of those with hsPDA (p=0.005). Babies with hsPDA had significantly lower SFR values at both time points. SFRs in babies with hisPDA were decreased at 1 week postnatally, but were similar to those of babies with closed ducts at 36 weeks. SFR at 36 wks. was decreased only in infants with hsPDA [[467[461,467] vs. 467[413,471] vs. 369[262,436] respectively; p=0.000148]. Using ROC curve analysis, week 1 SFR was strongly associated with hsPDA (AUC=0.770; p<0.0001) and highly predictive (AUC=0.801; p<0.0001) of CLD at 36 weeks PMA. Conclusion: Early decreases in SFR reflect both the acute and chronic pulmonary impact of PDA shunting, possibly providing the missing link supporting an association between hemodynamically significant PDA and subsequent CLD.

Left Vocal Cord Paralysis, Lung Function and Exercise Capacity in Young Adults Born Extremely Preterm With a History of Neonatal Patent Ductus Arteriosus Surgery—A National Cohort Study

Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses.Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term.Methods: Adults born EP (&lt;28 weeks' gestation or birth weight &lt;1,000 g) in Norway during 1999–2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function.Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was −1.8 (−2.3, −1.2), −0.7 (−1.1, −0.3) and −0.3 (−0.5, −0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively.Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.

Aortic intimal resident macrophages are essential for maintenance of the non-thrombogenic intravascular state

Leukocytes and endothelial cells frequently cooperate to resolve inflammatory events. In most cases, these interactions are transient in nature and triggered by immunological insults. Here, we report that, in areas of disturbed blood flow, aortic endothelial cells permanently and intimately associate with a population of specialized macrophages. These macrophages are recruited at birth from the closing ductus arteriosus and share the luminal surface with the endothelium, becoming interwoven in the tunica intima. Anatomical changes that affect hemodynamics, such as in patent ductus arteriosus, alter macrophage seeding to coincide with regions of disturbed flow. Aortic resident macrophages expand in situ via direct cell renewal. Induced depletion of intimal macrophages leads to thrombin-mediated endothelial cell contraction, progressive fibrin accumulation and formation of microthrombi that, once dislodged, cause blockade of vessels in several organs. Together the findings reveal that intravascular resident macrophages are essential to regulate thrombin activity and clear fibrin deposits in regions of disturbed blood flow.