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Objectives: The paediatric intensive care unit changed heparin infusion dosing from a variable weight-based concentration to a fixed concentration strategy, when smart pump-based drug library was introduced. This change meant significantly lower rates of infusion were needed for the same dose of heparin in the neonatal population. We performed a safety and efficacy assessment of this change. Methods: We performed a retrospective single-centre evaluation based on data from respiratory VA-extracorporeal membrane oxygenation (ECMO) patients weighing ≤5 kg, pre and post the change to fixed strength heparin infusion. Efficacy was analysed by distribution of activated clotting times (ACT) and heparin dose requirements between the groups. Safety was analysed using thrombotic and haemorrhagic event rates. Continuous variables were reported as median, interquartile ranges, and non-parametric tests were used. Generalised estimating equations (GEE) were used to analyse associations of heparin dosing strategy with ACT and heparin dose requirements in the first 24 h of ECMO. Incidence rate ratios of circuit related thrombotic and haemorrhagic events between groups were analysed using Poisson regression with offset for run hours. Results: 33 infants (20 variable weight-based, 13 fixed concentration) were analysed. Distribution of ACT ranges and heparin dose requirements were similar between the two groups during the ECMO run and this was confirmed by GEE. Incidence rate ratios of thrombotic (fixed v weight-based) (1.9 [0.5–8], p =.37), and haemorrhagic events (0.9 [0.1–4.9], p =.95) did not show statistically significant differences. Conclusions: Fixed concentration dosing of heparin was at least equally effective and safe compared to a weight-based dosing. [ABSTRACT FROM AUTHOR]

Background: Inflammation plays an important role in neonatal hypoxia-induced organ damage. Newborns with perinatal asphyxia often develop persistent pulmonary hypertension of the neonate. This study aimed to early detection of pulmonary arterial hypertension in newborn to improve patient morbidity and mortality by estimated serum high mobility group box 1 protein (HMGB1) by enzyme-linked immunosorbent assay (ELISA). Methods: This case control study was conducted in Zagazig University Hospital, Pediatric (NICU) and clinical pathology departments, during a period of eight months from March 2020 to January 2021. Following were the three groups into which patients were split: Group 1: fifteen apparently healthy neonates included 11 male and 4 females, group 2: fifteen congenital heart diseases without pulmonary hypertension neonates included 10 male and 5 female and group 3: Fifteen congenital heart diseases with pulmonary hypertension neonates included 10 male and 5 female. Results: There is a statistically significant difference between the groups that were looked at for HMGB1 expression. When compared pairwise, congenital heart diseases (CHD) with pulmonary hypertension and the other groups show a significant difference (the greatest level was in CHD with pulmonary hypertension) hypertension then CHD without pulmonary hypertension then control group). Conclusion: HMGB1 levels in newborns with pulmonary hypertension increased. [ABSTRACT FROM AUTHOR]

Objective Safety and efficacy data on controlled hypothermia (CH) for neonates with moderate to severe hypoxic ischemic encephalopathy has been extrapolated to a subgroup of these patients who also require extracorporeal membrane oxygenation for refractory persistent pulmonary hypertension of the newborn (PPHN). However, safety data on the concomitant use of CH and extracorporeal membrane oxygenation (ECMO) are lacking. Methods This is a single-center retrospective study of neonates ≥35 weeks' gestation with refractory PPHN who required ECMO between January 2010 and December 2020. Study groups were divided into those receiving CH/ECMO versus ECMO only. Baseline characteristics, short-term outcomes, and brain magnetic resonance imaging (MRI) data were compared. Results A total of 36 neonates who received ECMO for refractory PPHN were included. Of these, 44.4% (n = 16) received CH/ECMO and 55.6% (n = 20) received ECMO only. Bleeding complications were more common in CH/ECMO group 50% (n = 8) versus ECMO only 15% (n = 3, p = 0.023). T1 brain MRI severity scores were higher in CH/ECMO group versus ECMO only group, however, there were no statistical difference in T2 and diffusion-weighted image scores. Functional status and survival to discharge were comparable between groups. Conclusion In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group with comparable functional status and survival at discharge. Key Points Safety data on the concomitant use of CH and ECMO are lacking in neonates. In our cohort, neonates who received CH/ECMO had higher bleeding complications than ECMO only group. Functional status and survival to discharge were no differences between the two groups. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Persistent pulmonary hypertension of the newborn (PPHN) is a life-threatening disease. Despite being considered the gold standard treatment scheme, inhaled nitric oxide (iNO) is not readily available in settings with limited resources. Therefore, in recent years, research on related drugs is being actively pursued. Herein, we aimed to use random-effects network meta-analysis to evaluate the efficacy and associated mortality of different PPHN therapies. DATA SOURCES: We electronically searched the PubMed, Embase, and Cochrane Library for data up to January 27, 2023. STUDY SELECTION: Randomized controlled trials involving neonates with PPHN assessing efficacy and mortality of various treatments. DATA EXTRACTION: Details of study population, treatments, and outcomes were extracted. DATA SYNTHESIS: Direct pairwise comparisons and a network meta-analysis was performed under random effects. The ranking probability was further assessed based on the surface under the cumulative ranking curve (SUCRA). We analyzed 23 randomized clinical trials involving 902 newborns with PPHN. Sixteen different treatment strategies were compared with each other and conventional therapy (CON). A median concentration of 10-20 parts per million (ppm) iNO (MNO) coupled with sildenafil orally administered at a dose of 1-3 mg/kg/dose every 6-8 hours (OSID) demonstrated the best efficacy (MNO + OSID vs. CON: odds ratio [OR] = 27.53, 95% CI, 2.36-321.75; SUCRA = 0.818, ranking first; moderate quality). OSID combined with milrinone administered IV also performed well in terms of efficacy (OSID + milrinone vs. CON: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.811, ranking second; low quality) and mortality reduction (CON vs. OSID + milrinone: OR = 25.13, 95% CI = 1.67-377.78; SUCRA = 0.786, ranking last; low quality). CONCLUSIONS: MNO + OSID is the most effective PPHN treatment. If iNO is not available, OSID + milrinone is preferred. [ABSTRACT FROM AUTHOR]

Background: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. Methods: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. Results: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. Conclusions: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs. [ABSTRACT FROM AUTHOR]

Nitric oxide was first identified as a novel and effective treatment for persistent pulmonary hypertension of the newborn (PPHN), and has since been found to be efficacious in treating acute respiratory distress syndrome (ARDS) and pulmonary hypertension. Physicians and researchers have also found it shows promise in resource-constrained settings, both within and outside of the hospital, such as in high altitude pulmonary edema (HAPE) and COVID-19. The treatment has been well tolerated in these settings, and is both efficacious and versatile when studied across a variety of clinical environments. Advancements in inhaled nitric oxide continue, and the gas is worthy of investigation as physicians contend with new respiratory and cardiovascular illnesses, as well as unforeseen logistical challenges. • Nitric oxide has been used as an effective treatment for a variety of respiratory disorders, including PPHN and ARDS. • It has also been used as a novel treatment for emerging illnesses, such as high altitude pulmonary edema (HAPE) and COVID-19. • Its versatility and safety profile make it an ideal therapy for new respiratory illnesses when logistical challenges exist. [ABSTRACT FROM AUTHOR]

High concentrations of oxygen are often needed to optimize oxygenation in infants with persistent pulmonary hypertension (PPHN), but this can also increase the risk of hyperoxemia. We determined the occurrence of hyperoxemia in infants treated for PPHN. Medical records of infants ≥ 34 + 0 weeks gestational age (GA) who received inhaled nitric oxide (iNO) were retrospectively reviewed for oxygenation parameters during iNO therapy. Oxygen was manually titrated to target arterial oxygen tension (PaO2) 10–13 kPa and peripheral oxygen saturation (SpO2) 92–98%. The main study outcomes were the incidence and duration of hyperoxemia and hypoxemia and the fraction of inspired oxygen (FiO2). A total of 181 infants were included. The median FiO2 was 0.43 (IQR 0.34–0.56) and the maximum FiO2 was 1.0 in 156/181 (86%) infants, resulting in at least one PaO2 > 13 kPa in 149/181 (82%) infants, of which 46/149 (31%) infants had minimal one PaO2 > 30 kPa. SpO2 was > 98% in 179/181 (99%) infants for 17.7% (8.2–35.6%) of the iNO time. PaO2 < 10 kPa occurred in 160/181 (88%) infants, of which 81/160 (51%) infants had minimal one PaO2 < 6.7 kPa. SpO2 was < 92% in 169/181 (93%) infants for 1.6% (0.5–4.3%) of the iNO time. Conclusion: While treatment of PPHN is focused on preventing and reversing hypoxemia, hyperoxemia occurs inadvertently in most patients. What is Known: • High concentrations of oxygen are often needed to prevent hypoxemia-induced deterioration of PPHN, but this can also increase the risk of hyperoxemia. • Infants with persistent pulmonary hypertension may be particularly vulnerable to the toxic effects of oxygen, and hyperoxemia could further induce pulmonary vasoconstriction, potentially worsening the condition. What is New: • Hyperoxemia occurs in the majority of infants with PPHN during treatment with iNO. • Infants with PPHN spent a considerably longer period with saturations above the target range compared to saturations below the target range. [ABSTRACT FROM AUTHOR]

A study has found that two long non-coding RNAs (lncRNA16 and lncRNA19) are upregulated in response to low oxygen levels and play a role in promoting cell survival and angiogenesis. This discovery suggests that these lncRNAs could be potential targets for treating pulmonary hypertension and other lung diseases related to low oxygen levels. However, more research is needed to fully understand how these lncRNAs work and their potential clinical applications. Additionally, another study found that smoking may contribute to the development and progression of interstitial lung disease (ILD) and ILD-related pulmonary hypertension (PH) by increasing the expression of genes associated with inflammation and fibrosis. Further research is needed to better understand the underlying mechanisms and identify potential therapeutic targets. [Extracted from the article]

Key Clinical Message: Diagnosing FES is difficult and time‐consuming, and identify FES as an etiology of right ventricular volume overload for early diagnosis. Because FES is a reversible condition, even severe cases can be treated if the patient survives the acute phase. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory airways disease with reversible airflow obstruction, characterised in the majority by type 2 airway inflammation. Type 2 inflammation results in secretion of interleukin-4, -5 and -13 in the airways, recruitment of inflammatory cells (especially eosinophils and mast cells), and airway changes such as mucus hypersecretion and increased airway reactivity. Approximately 5 to 10% of people with asthma, despite optimal therapy and adherence to treatment with inhaled corticosteroids and long-acting beta2 agonists, are unable to obtain good symptom control and continue to experience exacerbations requiring oral corticosteroids; this is known as 'severe asthma'. In many cases, this is associated with persistent type 2 inflammation, indicated by the persistent elevation of blood eosinophils or fractional exhaled nitric oxide. In people with severe asthma and persistent type 2 inflammation, biologic (monoclonal antibody) therapy is indicated. Biologic therapies currently available in Australia for asthma are benralizumab, dupilumab, mepolizumab and omalizumab. They are administered subcutaneously and are generally well tolerated. Biologic asthma therapies are very effective in improving symptoms, and reducing the rate of exacerbations and use of oral corticosteroids, in people with severe asthma and persistent type 2 inflammation. Inhaled corticosteroid treatment should be continued in people using a biologic therapy. [ABSTRACT FROM AUTHOR]

Introduction: Bronchopulmonary dysplasia (BPD) poses a substantial global health burden. Individualized treatment strategies based on early prediction of the development of BPD can mitigate preterm birth complications; however, previously suggested predictive models lack early postnatal applicability. We aimed to develop predictive models for BPD and mortality based on immediate postnatal clinical data. Methods: Clinical information on very preterm and very low birth weight infants born between 2008 and 2018 was extracted from a nationwide Japanese database. The gradient boosting decision trees (GBDT) algorithm was adopted to predict BPD and mortality, using predictors within the first 6 h postpartum. We assessed the temporal validity and evaluated model adequacy using Shapley additive explanations (SHAP) values. Results: We developed three predictive models using data from 39,488, 39,096, and 40,291 infants to predict "death or BPD," "death or severe BPD," and "death before discharge," respectively. These well-calibrated models achieved areas under the receiver operating characteristic curve of 0.828 (95% CI: 0.828–0.828), 0.873 (0.873–0.873), and 0.887 (0.887–0.888), respectively, outperforming the multivariable logistic regression models. SHAP value analysis identified predictors of BPD, including gestational age, size at birth, male sex, and persistent pulmonary hypertension. In SHAP value-based case clustering, the "death or BPD" prediction model stratified infants by gestational age and persistent pulmonary hypertension, whereas the other models for "death or severe BPD" and "death before discharge" commonly formed clusters of low mortality, extreme prematurity, low Apgar scores, and persistent pulmonary hypertension of the newborn. Conclusions: GBDT models for predicting BPD and mortality, designed for use within 6 h postpartum, demonstrated superior prognostic performance. SHAP value-based clustering, a data-driven approach, formed clusters of clinical relevance. These findings suggest the efficacy of a GBDT algorithm for the early postnatal prediction of BPD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Persistent pulmonary hypertension of the neonate (PPHN) is a serious disorder. The long pentraxin 3 (PTX3) plays an important role in angiogenesis, cell proliferation, tissue repair and cell regulation. The present study aims to assess the diagnostic and clinical value of PTX3 in PPHN. METHODS: The present case-control 60 full-term neonates diagnosed with PPHN by echocardiography within 72 hours of birth. In addition, there were 30 age and sex-matched healthy neonates who served as controls. All participants were subjected to careful history taking and complete clinical examination, Laboratory investigations included complete blood count, C-reactive protein (CRP), blood culture and PTX3 level. Radiological investigations included plain X- ray and two-dimensional transthoracic echocardiography (TTE). RESULTS: Comparison between patients and controls revealed that patients had significantly higher CRP (6.12±2.18 versus 3.69±1.25 mg/dl, p < 0.001) and PTX3 levels (2.07±0.67 versus 0.96±0.21, p < 0.001) when compared with controls. Patients with associated PDA had significantly higher PTX3 levels when compared with patients without (2.58±0.5 versus 2.02±0.51 ng/ml, p = 0.002). Also, patients with associated PFO had significantly higher PTX3 levels when compared with patients without (2.12±1.05 versus 2.05±0.46, p = 0.002). ROC curve analysis identified good performance of CRP and PTX3 levels in diagnosis of PPHN with PTX3 showing better performance. CONCLUSIONS: There is a significant association between serum PTX3 levels and PPHN particularly those with associated PDA or PFO. [ABSTRACT FROM AUTHOR]

This article provides information on the treatment options for persistent pulmonary hypertension of the newborn (PPHN), a respiratory distress syndrome in newborns. The authors conducted a meta-analysis of 23 studies and found that a combination of inhaled nitric oxide and oral sildenafil is the most effective treatment for PPHN. However, more studies are needed to confirm these findings. The article also discusses the development of a core outcome set for neonatal research, which aims to establish standardized outcomes for future studies. This research is valuable for researchers and healthcare professionals in the field of neonatology. [Extracted from the article]

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH‐CKD) affects approximately 20%–40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH‐CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH‐CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end‐stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc‐PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc‐PH groups. Among a small subset (n = 14) who were subsequently treated with PAH‐targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH‐CKD. [ABSTRACT FROM AUTHOR]

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short‐term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO. We performed an iNO withdrawal test during right heart catheterization and after 3 days of iNO treatment. iNO significantly improved all variables examined in 22 patients with PAH and 11 with nCTEPH. Two patterns of response were observed after sudden iNO withdrawal. Twenty‐nine patients (88%) showed minimal hemodynamic, oxygenation and clinical changes. Four patients (12%) had a reduction in cardiac index ≥20% and PaO2 ≥ 5%, three patients did not show clinical deterioration, and one patient developed hemodynamic collapse that needed iNO administration. This retrospective study suggests that short‐term iNO improves hemodynamics and clinical conditions in some patients with PAH an nCTPEH. However, pulsed iNO withdrawal PH rebound could be a serious concern in these patients. Given the lack of evidence, we do not recommend the use of pulsed iNO in the treatment of patients with chronic PH. [ABSTRACT FROM AUTHOR]

With the advancement of neonatal care and routine blood pressure monitoring, neonatal hypertension (NHT) has been increasingly recognised over the past few decades. NHT is known to cause target organ damage and risk of renal dysfunction later in life. However, diagnosis and management of NHT remain challenging, and there is a lack of evidence on the persistence of hypertension beyond the neonatal period and factors predicting its severity. This study aimed to identify risk factors, clinical profiles, predictors of the severity of hypertension, and short-term outcomes of NHT. A cohort of neonates diagnosed with hypertension requiring pharmacotherapy from September 2019 to July 2021 was prospectively enrolled. Demographic data, risk factors, the severity of hypertension, target organ damage, and follow-up for the persistence of hypertension at 3, 6, and 12 months of age were recorded. Of 1682 neonates admitted during this period, 34 had hypertension requiring pharmacotherapy, with a hospital incidence rate of 2%. Of these, 19 (55.9%) were preterm, 14 (41.2%) very low birth weight, and 15 (44.1%) were small for gestational age. Malignant hypertension was seen in 29 (85%) cases, moderate hypertension in 5 (15%) cases, and target organ damage (heart, brain, liver) was seen in 10 (29.4%) cases. On univariate and multivariate regression, an increasing total number of postnatal risk factors was an independent predictor of the occurrence of hypertensive crisis (OR = 3.5, p = 0.04; 95% CI 1.06–11.42). A significant positive correlation (p = 0.004) was observed between total number of postnatal risk factors and the duration of hospital stay. Renal causes of hypertension were identified significantly earlier (day 14 vs. 23, p = 0.01, 95% CI 2.5–17) and had shorter hospital stay (24 vs 45 days, p = 0.002, 95% CI 834). At 3 months follow-up, 7 (20.6%) babies were still requiring antihypertensive therapy, and 1 (3%) required antihypertensives at 6 and 12 months of age. Conclusion: NHT is a clinically important but underrecognised entity. Hypertension was seen in preterm, low birth weight neonates and associated with certain maternal and postnatal risk factors, with majority responding to a single drug. Neonates with multiple comorbid illnesses need careful monitoring for hypertension as they are at a higher risk of developing hypertensive crisis. Most NHT cases were normotensive at the time of discharge and did not require pharmacotherapy beyond the neonatal period. What is Known: • Neonatal hypertension (NHT) is an under-recognised entity, and the spectrum of clinical presentation varies from asymptomatic to severe target organ damage. • Hypertension is commonly seen in preterm, low birth weight neonates and associated with certain maternal and postnatal risk factor. What is New: • NHT is mostly transient, but intrauterine growth retardation, use of antenatal steroids, renal dysfunction due to congenital anomalies, drugs, and chronic lung disease may lead to the persistence of hypertension beyond the neonatal period. • Neonates with multiple comorbid illnesses need careful monitoring for hypertension as they are at a higher risk of developing hypertensive crisis. Three-fourths of hypertensive neonates respond to a single antihypertensive drug, and only one-fourth of patients required an additional drug to control hypertension. Most neonates respond to short duration of treatment, and only a few patients require long-term therapy. [ABSTRACT FROM AUTHOR]

Ductal patency of preterm infants is potentially associated with long term morbidities related to either pulmonary overflow or systemic steal. When an interventional closure is needed, it can be achieved with either surgical ligation or a catheter-based approach. Transcatheter PDA closure is among the safest of interventional cardiac procedures and it is the first choice for ductal closure in adults, children, and infants weighing more than 6 kg. In preterm and very low birth weight infants, it is increasingly becoming a valid and safe alternative to ligation, especially for the high success rate and the minor invasiveness and side effects. Nevertheless, being it performed at increasingly lower weights and gestational ages, hemodynamic complications are possible events to be foreseen. Procedural steps, timing, results, possible complications and available monitoring systems, as well as future outlooks are here discussed. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension of the newborn, or PPHN, represents a challenging condition associated with high morbidity and mortality. Management is complicated by complex pathophysiology and limited neonatal specific evidence-based literature, leading to a lack of universal contemporary clinical guidelines for the care of these patients. To address this need and to provide consistent high-quality clinical care for this challenging population in our neonatal intensive care unit, we sought to develop a comprehensive clinical guideline for the acute stabilization and management of neonates with PPHN. Utilizing cross-disciplinary expertise and incorporating an extensive literature search to guide best practice, we present an approachable, pragmatic, and clinically relevant guide for the bedside management of acute PPHN. Key Points PPHN is associated with several unique diagnoses; the associated pathophysiology is different for each unique diagnosis. PPHN is a challenging, dynamic, and labile process for which optimal care requires frequent reassessment. Key management goals are adequate tissue oxygen delivery, avoiding harm. [ABSTRACT FROM AUTHOR]

Pulmonary artery stiffness (PAS) is a strong and independent predictor of mortality in adult patients with pulmonary hypertension (PH). But the change in PAS during perinatal period remains unknown. Here, we aimed to explore the feasibility and performance of PAS on predicting persistent pulmonary hypertension of the newborn (PPHN). 1325 fetuses underwent a dedicated echocardiography screening for fetal heart defects during second trimester, third-trimester and neonatal period with the measurement of acceleration time (PAAT) and maximal frequency shift (MFS) of pulmonary artery flow. PAS (MFS/PAAT ratio) was calculated. Six fetuses were diagnosed as PPHN. Compared with the normal fetuses, those with PH had greater values of PAS during each period of time (second trimester, 52.6(46.2–54.5) vs. 32.4(28.0–39.4) kHz/s, p = 0.0003; third trimester, 52.9(46.1–55.3) vs. 29.7(27.3–33.3) kHz/s, p = 0.0002; neonatal period, 127.4(85.2–150.8) vs. 26.6(22.7–35.0) kHz/s, p < 0.0001). There was a statistically significant correlation between PAS and mean pulmonary artery pressure (p < 0.05) but no correlation between PAS and gestational age (p > 0.05) whether in normal fetuses or not. The area under receiver operating characteristic curve (AUC) of 0.97 for PAS during third trimester was superior to that for PAS during second trimester (AUC, 0.94) in predicting PPHN. The optimal cutoff value of PAS during third trimester was 37.40 KHz/s, with a sensitivity of 100%, a specificity of 91%, and an accuracy of 92%. There was a significant difference in PAS between normal fetuses and those with PH. PAS has a power performance on predicting PPHN. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension is a debilitating condition that frequently develops in the setting of interstitial lung disease, likely related to chronic alveolar hypoxemia and pulmonary vascular remodeling. This disease process is likely to be identified more frequently by providers given recent advancements in definitions and diagnostic modalities, and provides practitioners with emerging opportunities to improve patient outcomes and quality of life. Despite years of data suggesting against the efficacy of pulmonary vasodilator therapy in patients with pulmonary hypertension due to interstitial lung disease, new data have emerged identifying promising advancements in therapeutics. The authors present to you a comprehensive review of pulmonary hypertension in interstitial lung disease, reviewing our current understanding of pathophysiology, updates in diagnostic approaches, and highlights of recent clinical trials which provide an effective approach for medical management. [ABSTRACT FROM AUTHOR]

Background: Persistent pulmonary hypertension of the newborn manifesting with refractory and severe cyanosis is the consequence of high pulmonary vascular resistance causing extrapulmonary right-to-left shunt. Acidosis and hypoxemia produce pulmonary vasoconstriction. Persistent pulmonary hypertension of the newborn occurs due to numerous disorders and has been rarely reported as a manifestation of methylmalonic acidemia. We report a newborn with methylmalonic acidemia who presented with persistent pulmonary hypertension of the newborn. Case presentation: A 1-day-old Iranian girl presented with respiratory distress and refractory metabolic acidosis. She was born at 39 + 5 weeks gestational age with Apgar scores of 8 and 9 in the 1st and 5th minutes, respectively, and was in good condition up to 10 hours of life. After that, she presented with cyanosis, tachypnea, retraction, and hypotonia. Despite receiving oxygen, she had low oxygen saturation. Echocardiography revealed severe pulmonary hypertension and right-to-left shunt through patent ductus arteriosus and foramen ovale. Her acidosis worsened despite receiving full support and medical therapy. So, she was started on peritoneal dialysis. Unfortunately, she did not respond to treatment, and after she had died, biochemical tests confirmed methylmalonic acidemia. Conclusion: Persistent pulmonary hypertension of the newborn is a very rare manifestation of methylmalonic acidemia. Severe inborn errors of metabolism may cause irreversible damage with adverse lifelong morbidity, and early diagnosis may help to prevent such complications. Furthermore, diagnosis of these disorders aids in prenatal diagnosis through the use of cultured amniocytes or chorionic villi to detect gene mutations, as well as biochemical analyses of amniotic fluid for subsequent pregnancies. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to clarify the characteristics and their mortality‐related factors in very low birthweight infants with Down syndrome (DS) in Japan. Methods: This retrospective case–control study enrolled newborns with DS weighing <1500 g admitted to neonatal intensive care unit (NICU) of the perinatal centre registered with the Neonatal Research Network of Japan (NRNJ) database from 2008 to 2019. The clinical characteristics and their mortality‐related factors were compared among the Dead group (newborns with DS who died in the NICU), the Survival group (newborns with DS who were alive from the NICU) and the Control group (newborns without congenital or chromosomal condition). Results: A total of 53 656 newborns weighing <1500 g were registered in the NRNJ database for 12 years. Of these, 310 (0.6%) were diagnosed with DS: 62 newborns in the Dead group, 248 in the Survival group and 49 786 in the Control group without chromosomal condition. Logistic analysis revealed that there was a significant difference in the mortality‐related factors in congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn; the adjusted odds ratios were 8.6, 121 and 9.5, respectively. Newborns with DS weighing <1000 g showed the earliest death in the NICU on the Kaplan–Meier survival curve (P < 0.01). Conclusion: The mortality rate for newborns with DS weighing <1500 g was 20% (5% in the Control group). The mortality‐related factors were complications of congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn. [ABSTRACT FROM AUTHOR]

Background: The most prevalent kind of RNA methylation modification existing in eukaryotes is N6-methyladenosine (m6A), which is a reversible type of posttranscriptional modification. Summary: Many studies have reported that m6A participates in cell differentiation, self-renewal, invasion, and apoptosis by modifying protein synthesis. Furthermore, m6A modification is also involved in disease progression and pulmonary vascular remodeling in pulmonary hypertension. However, very few researchers have investigated the effect of m6A modifications on pulmonary hypertension. Key Messages: Here, we have reviewed the latest research advances in the field of m6A RNA methylation in pulmonary hypertension and explored its regulatory role in pulmonary hypertension development and progression. [ABSTRACT FROM AUTHOR]

Persistent pulmonary hypertension of the newborn (PPHN) is one of the diseases of the neonate with severe potential morbidity and mortality. Inhaled iloprost, a stable prostacyclin analog, has been suggested as an alternative treatment for inhaled nitric oxide (iNO). However, more data on neonates' dosing, setting, and effectiveness still needs to be solved. This study suggests using inhaled iloprost as rescue therapy for PPHN based on our experience. This was a retrospective study. The data from medical records of six newborns diagnosed with PPHN and had received inhaled iloprost from December 2019 to April 2022 were collected. Demographic and clinical features, dosing regimen, changes in oxygenation index, echocardiographic findings, and mortality were evaluated. The inhalation dose was 2-4 mcg/dose, and 3-48 inhalations per day were applied over 2-7 days. Inhaled iloprost was effective in all patients. No side effects were attributable to inhaled iloprost, and no mortality was recorded. Our experience suggests that inhaled iloprost can be used as a first-line therapy in newborn infants with PPHN when iNO is unavailable. However, there are large fluctuations in the oxygenation index due to the setting. [ABSTRACT FROM AUTHOR]

Background: Inhaled nitric oxide (iNO) has been widely used in patients with COVID-19-related acute respiratory distress syndrome (C-ARDS), though its physiological effects and outcome are debated in this setting. The objective of this cohort study was to describe the modalities of iNO use, clinical response, and outcomes in a large cohort of C-ARDS patients. Methods: Multicentre, retrospective cohort study conducted in France. Results: From end February to December 2020, 300 patients (22.3% female) were included, 84.5% were overweight and 69.0% had at least one comorbidity. At ICU admission, their median (IQR) age, SAPS II, and SOFA score were 66 (57–72) years, 37 (29–48), and 5 (3–8), respectively. Patients were all ventilated according to a protective ventilation strategy, and 68% were prone positioned before iNO initiation. At iNO initiation, 2%, 37%, and 61% of patients had mild, moderate, and severe ARDS, respectively. The median duration of iNO treatment was 2.8 (1.1–5.5) days with a median dosage of 10 (7–13) ppm at initiation. Responders (PaO2/FiO2 ratio improving by 20% or more) represented 45.7% of patients at 6 h from iNO initiation. The severity of ARDS was the only predictive factor associated with iNO response. Among all evaluable patients, the crude mortality was not significantly different between responders at 6 h and their counterparts. Of the 62 patients with refractory ARDS (who fulfilled extracorporeal membrane oxygenation criteria before iNO initiation), 32 (51.6%) no longer fulfilled these criteria after 6 h of iNO. The latter showed significantly lower mortality than the other half (who remained ECMO eligible), including after confounder adjustment (adjusted OR: 0.23, 95% CI 0.06, 0.89, p = 0.03). Conclusions: Our study reports the benefits of iNO in improving arterial oxygenation in C-ARDS patients. This improvement seems more relevant in the most severe cases. In patients with ECMO criteria, an iNO-driven improvement in gas exchange was associated with better survival. These results must be confirmed in well-designed prospective studies. [ABSTRACT FROM AUTHOR]

Congenital diaphragmatic hernia (CDH) is a neonatal anomaly that includes pulmonary hypoplasia and hypertension. We hypothesized that microvascular endothelial cell (EC) heterogeneity is different in CDH lungs and related to lung underdevelopment and remodeling. To test this, we evaluated rat fetuses at E21.5 in a nitrofen model of CDH to compare lung transcriptomes among healthy controls (2HC), nitrofen-exposed controls (NC) and nitrofen-exposed subjects with CDH. Single-cell RNA sequencing with unbiased clustering revealed 3 distinct microvascular EC clusters: a general population (mvEC), a proliferative population and a population high in hemoglobin. Only the CDH mvEC cluster had a distinct inflammatory transcriptomic signature as compared to the 2HC and NC endothelial cells, e.g. greater activation and adhesion of inflammatory cells and production of reactive oxygen species. Furthermore, CDH mvECs had downregulated Ca4, Apln and Ednrb gene expression. Those genes are markers for ECs important to lung development, gas exchange and alveolar repair (mvCa4+). mvCa4+ ECs were reduced in CDH (2HC [22.6%], NC [13.1%] and CDH [5.3%], p < 0.0001). Overall, these findings identify transcriptionally distinct microvascular endothelial cell clusters in CDH, including the distinctly inflammatory mvEC cluster and the depleted group of mvCa4+ ECs, which together may contribute to pathogenesis. [ABSTRACT FROM AUTHOR]

Cardiorenal syndromes type 1 and 2 are complex disorders in which cardiac dysfunction leads to kidney dysfunction. However, the mechanisms remain incompletely explained, during pulmonary hypertension in particular. The objective of this study is to develop an original preclinical model of cardiorenal syndrome secondary to a pulmonary hypertension in piglets. Twelve 2-month-old Large White piglets were randomized in two groups: (1) induction of pulmonary hypertension by ligation of the left pulmonary artery and iterative embolizations of the right lower pulmonary artery, or (2) Sham interventions. We evaluated the cardiac function using right heart catheterization, echocardiography and measurement of biochemistry markers). Kidney was characterized using laboratory blood and urine tests, histological evaluation, immunostainings for renal damage and repair, and a longitudinal weekly assessment of the glomerular filtration rate using creatinine-based estimation and intravenous injection of an exogenous tracer on one piglet. At the end of the protocol (6 weeks), the mean pulmonary artery pressure (32 ± 10 vs. 13 ± 2 mmHg; p = 0.001), pulmonary vascular resistance (9.3 ± 4.7 vs. 2.5 ± 0.4 WU; p = 0.004) and central venous pressure were significantly higher in the pulmonary hypertension group while the cardiac index was not different. Piglets with pulmonary hypertension had higher troponin I. We found significant tubular damage and an increase in albuminuria in the pulmonary hypertension group and negative correlation between pulmonary hypertension and renal function. We report here the first porcine model of cardiorenal syndrome secondary to pulmonary hypertension. [ABSTRACT FROM AUTHOR]

B Conclusion: b COVID-19 vaccines prevent SARS-CoV-2 infection, severe COVID-19 and all-cause mortality in pregnant women. Perinatal COVID-19 status was checked only in confirmed COVID-19 mothers with a positive 18.9% of infants with confirmed COVID-19 status in the case group. There were 5 stillbirths and 2 NNDs during pre-COVID period, while there were 6 stillbirths and 0 NND during post-COVID period. PP.0109 Risk factors for SARS-CoV-2 positivity in neonates born to mothers with COVID-19 Sangamithra Ravi 1; Oluwadamilola Akande 1; Halimah Khalil 1; Maurie Kuha Kumaran 1; Jame... 1 College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK; 2 Institu... B Objective: b To evaluate outcomes of SARS-CoV-2 positive neonates born to SARS-CoV-2 positive mothers, determine maternal and perinatal risk factors associated with neonatal SARS-CoV-2 positivity and report positivity rates in different regions. [Extracted from the article]

OBJECTIVE: To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. ANIMALS 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. PROCEDURES: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arterial pressure < 70 mmHg) was treated using dobutamine after 30 minutes of PiNO delivery. Following the discontinuation of PiNO, dobutamine administration was discontinued in 3 ponies and was continued in 3 ponies. The lung was imaged at 30, 60, and 105 minutes. Anesthetic 2: hypotension persisted throughout anesthesia. The lung was imaged at 30, 60, and 90 minutes. At all time points, arterial and mixed venous blood samples were analyzed and cardiac output (Qt) was measured. Pulmonary perfusion was calculated from CT image analysis. RESULTS: During PiNO delivery, perfusion to well-ventilated lungs increased if ponies were normotensive, leading to increased arterial oxygenation, reduced alveolar dead space, and reduced alveolar to arterial oxygen tension gradient. When PiNO was stopped and dobutamine administration continued, alveolar dead space and venous admixture increased, in contrast to when dobutamine and PiNO were both discontinued. CLINICAL RELEVANCE: If PiNO is administered to mechanically ventilated, anesthetized ponies with concurrent hypotension and low 'Q t, this must be supported to achieve favorable redistribution of pulmonary perfusion to improve pulmonary gas exchange. [ABSTRACT FROM AUTHOR]

Micro-arousals and the repeated desaturation of oxyhemoglobin, which are typical in obstructive sleep apnea syndrome (OSAS), have adverse effects on the health of patients, leading to a wide range of complications such as cardiovascular (arterial hypertension, pulmonary hypertension, chronic heart failure, arrhythmias, myocardial infarction), cerebrovascular (strokes), metabolic (insulin resistance, obesity, diabetes mellitus, metabolic syndrome), gastrointestinal (non-alcoholic liver disease), urinary (chronic renal failure), and neuropsychiatric complications as well as a wide range of malignancies. These, in turn, have multilateral effects on familial, occupational, and social life, as well as increasing the risks of road traffic accidents and accidents at the workplace. Awareness, timely screening, and the prevention of complications play important roles in diagnosing and treating comorbid conditions. This review focuses on comorbidities in OSAS and the effect of Continuous Positive Airway Pressure (CPAP) therapy on their prognoses. [ABSTRACT FROM AUTHOR]

Background: Mild asthma is often characterized by normal spirometric values and a negative bronchodilation test (BDT), which makes accurate diagnosis challenging. The aim of our study was to evaluate the diagnostic accuracy of fractional exhaled nitric oxide (FeNO) in mild asthma. Methods: In adults with symptoms suggestive of asthma and normal spirometry values, BDT, FeNO, BPT and skin prick testing were performed. Patients with positive BPT started inhaled corticosteroid (ICS) therapy. Those with positive response to ICS were considered asthmatics. Results: There were 142 asthmatics and 140 non-asthmatics. No significant difference was found in BDT between the groups, p = 0.233. Median FeNO levels were significantly higher in the asthma group (49.5 ppb) than in the non-asthma group (23 ppb), p < 0.001. BPT was positive in 145 (51.42%) and negative in 137 (48.58%) patients. Positive response to ICS treatment was recorded in 142/145 (97.9%) patients. In diagnosing asthma, FeNO ≥ 25 ppb had a sensitivity of 75.4% and specificity of 47.9%. Conclusions: FeNO has insufficient sensitivity and specificity in mild asthma and the application of BPT is often necessary to establish an accurate diagnosis. [ABSTRACT FROM AUTHOR]

Background: The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy. Objective: We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence. Results: Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19–81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap. Conclusions: This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drugs should be used as a second-line treatment during pregnancy (after first-line psychotherapy, according to the guidelines). The risk of major congenital malformations could be prevented by observing guidelines that discourage the use of paroxetine and fluoxetine. Second, to decrease heterogeneity and bias, future MAs should adjust for maternal psychiatric disorders and antidepressant drug dosage, and perform analyses by timing of exposure. [ABSTRACT FROM AUTHOR]

Objective: Not all infants with persistent pulmonary hypertension of the newborn (PPHN) respond to inhaled nitric oxide (iNO) therapy, as it is known to improve oxygenation in only 50% to 60% of cases. In this study, we investigated whether ABO blood groups were a relevant factor affecting the improvement of oxygenation by nitric oxide (NO) therapy in infants with PPHN. Methods: This study was a retrospective, multicenter, and cohort-controlled trial that involved 37 medical units. Infants with PPHN who met the inclusion criteria and were treated with NO (a vasodilator) alone from July 1, 2015, to June 30, 2020, were selected and assigned into three groups: blood type A, blood type B, and blood type O (there were only 7 cases of blood type AB, with a small number of cases, and therefore, blood type AB was excluded for further analysis). The response to iNO therapy was defined as an increase in the ratio of the partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) > 20% from the basal value after treatment. Oxygenation was assessed mainly based on the two values, oxygenation index (OI) and PaO2/FiO2. The correlation of ABO blood groups with responses to iNO therapy and their influence on the efficacy of iNO therapy was analyzed based on the collected data. Results: The highest proportion of infants with PPHN who eventually responded to iNO therapy was infants with blood type O. Infants with blood type O more readily responded to iNO therapy than infants with blood type B. Oxygenation after iNO treatment group was optimal in the blood type O group and was the worst in the blood type A group among the three groups. Infants with blood type O showed better efficacy than those with blood types A and B. Conclusion: ABO blood groups are correlated with responses to iNO therapy in infants with PPHN, and different blood groups also affect the efficacy of NO therapy in infants with PPHN. Specifically, infants with blood type O have a better response and experience the best efficacy to iNO therapy. [ABSTRACT FROM AUTHOR]

The article focuses on comparing the prevalence of acute kidney injury (AKI) in pediatric patients receiving vancomycin before and after transitioning from trough to area under the curve (AUC) monitoring. The study also analyzes data from 20,316 vancomycin courses and suggests that the type of monitoring strategy used may not provide a significant safety benefit in terms of preventing AKI.

Aim: To perform a systematic literature review to determine the effect of inhaled nitric oxide (iNO) on oxygenation, mortality and morbidity in preterm neonates with preterm prelabour rupture of membranes (PPROM) and early hypoxaemic respiratory failure (HRF). Methods: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Zetoc and ProQuest were searched. Studies including neonates <34 weeks' gestation with PPROM, oligohydramnios or pulmonary hypoplasia and HRF in the first 28 days of life treated with iNO were included. Studies were critically appraised and assessed for potential risk of bias using standardised checklists. Results: Six hundred and two records remained after duplicates were removed. Seven studies were included in the critical appraisal process. Quality of available evidence was very low to low. Six studies described an improvement in oxygenation after commencement of iNO. One hundred and three of 284 (36%) neonates exposed to iNO died. Seventy‐seven of 92 (84%) neonates that had an echocardiogram performed before commencement of iNO had pulmonary hypertension (PH) present. Conclusion: iNO may improve oxygenation when standard care fails. Improvement in oxygenation is likely associated with increase in survival. Survival may lead to an increase in morbidity. Efficacy of iNO in this cohort is likely secondary to relatively high prevalence of PH. [ABSTRACT FROM AUTHOR]

The article offers information on reducing risk factors for pulmonary hypertension (PH) which is an important step in preventing the development of the disease. It highlights several ways to reduce risk factors that can lead to pulmonary hypertension such as quitting smoking which can significantly reduce the risk of developing the disease, regular exercise can help to improve heart and lung health, which can reduce the risk of PH.

Introduction: We aimed to identify maternal and fetal complications and investigate postnatal and long-term outcomes of fetal hydrothorax (FHT) treated with pleuro-amniotic shunting (shunt). Methods: Single-center retrospective observational cohort of shunt cases performed from 2000 to 2021. Risk factors for maternal complications, fetal demise, neonatal death (NND), and postnatal outcomes were identified. Results: Out of 88 cases, 70 (79.5%) were complicated by hydrops, with an average gestational age (GA) at diagnosis of 27 weeks (range 16–34). In 16 cases, definitive etiology of FHT was identified; five cases of Noonan syndrome and three cases of monogenic disorders diagnosed by whole-exome sequencing (EPHB4, VEGFR3, RASA1). Shunt was performed at an average GA of 28 weeks (20–34), with a dislodgement in 10 cases (11.4%). Maternal: Complications occurred in three cases; survival rate was 76.1% (67/88). Follow-up data were available for 57/67 (85.1%) children. Incidence of severe neurodevelopmental impairment and pneumopathy (broncho dysplasia, persistent pulmonary hypertension of newborn, and asthma) was 5.3% and 8.8%, respectively. Post-treatment persistence of hydrops, FHT associated with genetic syndromes, and GA at birth were risk factors for fetal demise, NND, and postnatal complications. Conclusion: In truly isolated FHT, whenever indicated, pleuro-amniotic shunting is a safe procedure associated with good survival rate and long-term outcome. [ABSTRACT FROM AUTHOR]

This study aimed to examine the relationship between maternal health during pregnancy and low birth weight (LBW), as well as the impact of COVID-19 on the socio-economic status of pregnant women and its effect on LBW. The study was conducted in Amman, Jordan, and included 2260 mothers who visited Abu-Nusair comprehensive health center between January and December 2020. A matched case-control design was used with 72 cases and 148 controls selected for data collection through medical records and face-to-face interviews. Results showed that factors such as a monthly income of 400 JD or less, living with an extended family, exposure to passive smoking, maternal weight gain of 6-10 kg, maternal anemia, maternal hypertension, delivery by cesarean section, and previous history of LBW newborns were positively associated with an increased risk of LBW. Conversely, factors such as a monthly income above 700 JD, living with a core family, daily intake of iron, calcium, and vitamin D, prenatal visits, healthy food intake, and planning for pregnancy were associated with a lower risk of LBW. COVID-19 infection and its effects on work, family finances, antenatal care visits, and food supply were also positively linked with LBW. In conclusion, socioeconomic status, maternal health, COVID-19, and its impacts were significant risk factors for LBW. [ABSTRACT FROM AUTHOR]

However, Yamamoto I et al i . report one patient with cardiomegaly but an otherwise structurally normal heart.[4] The patient had no other associated abnormalities with no anaemia or thrombocytopenia. Similarly, fetal microangiopathic anaemia following haemolysis within tumour vessels exacerbates strain on the heart and can, both independently and in combination with cardiac dysfunction, result in hydrops. The placenta should always be examined for a cause of cardiomegaly and/or cardiomyopathy in the neonate, particularly where antenatal ultrasound findings do not adequately explain the fetal appearances. The cardiomegaly and RV dilatation were therefore unlikely related to a high cardiac output state associated with anaemia or increased blood flow through the tumour. [Extracted from the article]

Pulmonary vascular remodeling is the critical structural alteration and pathological feature in pulmonary hypertension (PH) and involves changes in the intima, media and adventitia. Pulmonary vascular remodeling consists of the proliferation and phenotypic transformation of pulmonary artery endothelial cells (PAECs) and pulmonary artery smooth muscle cells (PASMCs) of the middle membranous pulmonary artery, as well as complex interactions involving external layer pulmonary artery fibroblasts (PAFs) and extracellular matrix (ECM). Inflammatory mechanisms, apoptosis and other factors in the vascular wall are influenced by different mechanisms that likely act in concert to drive disease progression. This article reviews these pathological changes and highlights some pathogenetic mechanisms involved in the remodeling process. [ABSTRACT FROM AUTHOR]

Background: Options to treat pulmonary hypertension (PH) in neonates with bronchopulmonary dysplasia (BPD) are few and largely ineffective. Improving the bioavailability of nitric oxide (NO) might be an efficacious treatment for BPD-PH. When administered orally, the NO-l-arginine precursor, l-citrulline, increases NO production in children and adults, however, pharmacokinetic (PK) studies of oral l-citrulline have not been performed in infants and children. Objectives: This study characterized the PK of enterally administered l-citrulline in neonates at risk of developing BPD-PH to devise a model-informed dosing strategy. Methods and results: Ten premature neonates (≤ 28 weeks gestation) were administered a single dose of 150 mg/kg (powder form solubilized in sterile water) oral l-citrulline at 32 ± 1 weeks postmenstrual age. Due to the need to limit blood draws, time windows were used to maximize the sampling over the dosing interval by assigning neonates to one of two groups (ii) samples collected pre-dose and at 1- and 2.5-h post-dose, and (ii) pre-dose and 0.25- and 3-h post-dose. The l-arginine concentrations (µmol/L) and the l-citrulline (µmol/L) plasma concentration-time data were evaluated using non-compartmental analysis (Phoenix WinNonlin version 8.1). Optimal dosage strategies were derived using a simulation-based methodology. Simulated doses of 51.5 mg or 37.5 mg/kg given four times a day produced steady-state concentrations close to a target of 50 µmol/L. The volume of distribution (V/F) and clearance (CL/F) were 302.89 ml and 774.96 ml/h, respectively, with the drug exhibiting a half-life of 16 minutes. The AUC from the time of dosing to the time of last concentration was 1473.3 h*μmol/L, with Cmax and Tmax of 799 μmol/L and 1.55 h, respectively. Conclusion: This is the first PK study in neonates presenting data that can be used to inform dosing strategies in future randomized controlled trials evaluating enteral l-citrulline as a potential treatment to reduce PH associated with BPD in premature neonates. Registration: Clinical trials.gov Identifier: NCT03542812. [ABSTRACT FROM AUTHOR]

Objectives: (1) To investigate whether neonates with perinatal asphyxia and therapeutic hypothermia more often developed PPHN compared to a control group with perinatal asphyxia not treated with hypothermia; (2) To identify risk factors for severe PPHN during hypothermia and evaluate short-term outcome. Methods: This single-center retrospective cohort study included (near-)term neonates with perinatal asphyxia admitted between 2004 and 2016. Neonates with perinatal asphyxia and hypothermia were compared to a historical control group without hypothermia. Primary outcome was PPHN, defined as severe hypoxemia requiring mechanical ventilation and inhaled nitric oxide, confirmed by echocardiography. Short-term adverse outcome was defined as mortality within one month and/or severe brain injury on MRI. Results: Incidence of PPHN was 23% (26/114) in the hypothermia group and 11% (8/70) in controls. In multivariate analysis, PPHN was 2.5 times more common among neonates with hypothermia. Neonates developing PPHN during hypothermia often had higher fraction of inspired oxygen at baseline. PPHN was not associated with a higher risk of severe brain injury. However, early mortality was higher and three infants died due to severe refractory PPHN during hypothermia. Conclusions: In this study PPHN occurred more often since the introduction of therapeutic hypothermia. This was usually reversible and did not lead to overall increased adverse outcome. However, in individual cases with PPHN deterioration occurred rapidly. In such cases the benefits of hypothermia should be weighed against the risk of a complicated, fatal course. [ABSTRACT FROM AUTHOR]

Introduction The prevalence of persistent pulmonary hypertension of newborn (PPHN) has been estimated 1.9/1000 live births. Although the efficacy of inhaled nitric oxide and extracorporeal membrane oxygenation in PPHN is well established but it is difficult to administer and monitor in resource limited countries. Owing to this, other treatment options need to be evaluated. Method This is a prospective observational study conducted in the Pediatric Cardiology Department, NICVD, Karachi, from February 2020 to October 2020 after the approval from the Institutional Ethical Review Committee. All the neonates referred to our Unit were screened by echocardiography (echo) and those who fulfilled the inclusion criteria were included. Echo were done before starting sildenafil and after 72 h to assess the pressure gradient across tricuspid valve and right to left or bidirectional shunt across patent ductus arteriosus, patent foramen ovale, or both. Sildenafil was started with a dose of 1 mg/kg/dose thrice a day and increased to 2 mg/kg/dose after 48 h if partial pressure of oxygen (PO1] did not increase. In neonates who did not respond to increased dose of Sildenafil were added on oral Bosentan 1 mg/kg/dose twice a day. Results Total 82 newborns were enrolled. Fifty-two patients improved after 48 h so were continued on same treatment. Sildenafil dose was increased in 30 (37.9%) patients whose PO2 did not increase to at least 10% from baseline after 48 h of starting treatment. Three patients expired within 48–72 h. Out of 27 remaining patients, only four responded whereas 23 patients did not show any improvement. In these patients, Bosentan was supplemented along with sildenafil. Conclusion The results of our study show effectiveness of oral Sildenafil in treating PPHN. The overall improvement observed in the patients was overwhelming. Combination of Sildenafil with Bosentan is beneficial in patients who did not respond on Sildenafil alone. [ABSTRACT FROM AUTHOR]

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism with poor clinical outcomes. Therapeutic approaches to prevention of fibrotic remodeling of the pulmonary vascular bed in CTEPH are limited. In this work, we tested the hypothesis that Janus kinase 1/2 (JAK1/2) inhibition with ruxolitinib might prevent and attenuate CTEPH in a rat model. CTEPH was induced by repeated embolization of the pulmonary artery with partially biodegradable 180 ± 30 μm alginate microspheres. Two weeks after the last injection of microspheres, ruxolitinib was administered orally at doses of 0.86, 2.58, and 4.28 mg/kg per day for 4 weeks. Prednisolone (1.475 mg/kg, i.m.) was used as a reference drug. Ruxolitinib in all doses as well as prednisolone reduced pulmonary vascular wall hypertrophy. Ruxolitinib at a dose of 2.58 mg/kg and prednisolone reduced vascular wall fibrosis. Prednisolone treatment resulted in decreased right ventricular systolic pressure. Pulmonary vascular resistance was lower in the prednisolone and ruxolitinib (4.28 mg/kg) groups in comparison with the placebo group. The plasma level of brain natriuretic peptide was lower in groups receiving ruxolitinib at doses of 2.58 and 4.28 mg/kg versus placebo. This study demonstrated that JAK1/2 inhibitor ruxolitinib dose-dependently reduced pulmonary vascular remodeling, thereby preventing CTEPH formation in rats. [ABSTRACT FROM AUTHOR]

Babies in Neonatal Intensive Care Units (NICU) have an additional risk for hearing loss due to various risk factors like, prematurity, low birth weight, mechanical ventilation, hyperbillirubinemia, ototoxic drugs, low APGAR score etc. as compared to the babies from well baby nursery (WBN) who, poses risk factors mostly family history, syndromic deafness. So the present study was aimed know the risk factors responsible for hearing loss in NICU and WBN babies and to assess the incidence of deafness. A total of 800 babies from NICU (n = 402) and WBN (n = 398) underwent hearing screening from a tertiary care center. Hearing screening was done using two staged screening protocol as per JCIH guidelines with Distortion product Evoked Otoacoustic Emissions (DPOAE) and Automated Auditory Brainstem Responses (A-ABR). According to DPOAE test, 311 from NICU and 383 from WBN passed the test and during second screening, 80 out of 91 from NICU and 11 out of 13 from WBN passed the DPOAE test. Further BERA was done at the 3rd month of corrected age where 6 out of 11 showed positive responses from NICU and 3 babies from WBN had profound hearing loss. Data analysis revealed that family history of deafness, anemia and hypertension in ANC, TORCH in mother, low Apgar score and hyperbillirubinemia in newborns were a major risk factor for hearing impairment. We conclude that the diagnoses of auditory disorders at early stage due to various risk factors are important since appropriate therapeutic intervention and rehabilitation would help in better development of children. [ABSTRACT FROM AUTHOR]

Standard Therapies for ARDS Regardless of the severity of ARDS, the standard approach to the management of ARDS includes low tidal volume ventilation [[10]]. Acute respiratory distress syndrome, ARDS, COVID-19, COVID acute respiratory distress syndrome, CARDS 33296498 60 COVID-19 and Inhaled NOAvailable online: https://clinicaltrials.gov/ct2/results?cond=COVID-19&term=Nitric+oxide&cntry=&state=&city=&dist=(accessed on 10 September 2022) 61 Longobardo A., Montanari C., Shulman R., Benhalim S., Singer M., Arulkumaran N. Inhaled nitric oxide minimally improves oxygenation in COVID-19 related acute respiratory distress syndrome. Keywords: acute respiratory distress syndrome; ARDS; COVID-19; COVID acute respiratory distress syndrome; CARDS EN acute respiratory distress syndrome ARDS COVID-19 COVID acute respiratory distress syndrome CARDS 1766 19 11/17/22 20221101 NES 221101 1. [Extracted from the article]

Objective  The study aimed to evaluate the effects of inhaled iloprost on oxygenation indices in neonates with persistent pulmonary hypertension of the newborn (PPHN). Study Design  We conducted a retrospective chart review of 30 patients with PPHN from January 2014 to November 2018, who did not respond to inhaled nitric oxide (iNO) alone and received inhaled iloprost. Twenty-two patients met the inclusion criteria and eight patients were excluded from the study (complex cardiac disease and extreme prematurity). Patients were categorized as responders or nonresponders (patients who required extracorporeal membrane oxygenation or died). Oxygenation index, mean airway pressure (MAP), and arterial partial pressure of oxygen (PaO 2) were recorded. Results  Among a total of 22 patients who were included in the study, 10 were classified as nonresponders as they required either extracorporeal membrane oxygenation or died. Gestational age and gender did not differ between responders and nonresponders. The median PaO 2 was lower (37 vs. 42 mm Hg; p  < 0.05) and median MAP was higher (20 vs. 17 cm H 2 O; p  < 0.02) in nonresponders compared with responders just prior to initiating iloprost. Iloprost responders had a significant increase in median PaO 2 and decrease in median oxygenation index in the 24 hours after initiating treatment (p  < 0.05), with no significant change in required mean airway pressure over that same period. There was no change in vasopressor use or clinically significant worsening of platelets count, liver, and kidney functions after initiating iloprost. Conclusion  Inhaled iloprost is well tolerated and seems to have beneficial effects in improving oxygenation indices in neonates with PPHN who do not respond to iNO. There is a need of well-designed prospective trials to further ascertain the benefits of using inhaled iloprost as an adjunct treatment in neonates with PPHN who do not respond to iNO alone. Key Points Inhaled iloprost seems to have beneficial effects in improving oxygenation indices in PPHN. Inhaled iloprost is generally well tolerated in newborns with PPHN. There is a need for prospective randomized controlled trials to further ascertain the benefits of using inhaled iloprost. [ABSTRACT FROM AUTHOR]

Background. Sustained hypoxia can trigger a progressive rise in pulmonary artery pressure and cause serious pulmonary diseases. Macrophages play important roles along the progression of pulmonary hypertension. However, the state of macrophage polarization during the early stage of pulmonary hypertension is unclear. Methods. Unlike traditional sequencing method, single-cell sequencing can accurately distinguish among cell types and better understand cell-to-cell relationships. In this study, we investigated the polarization of macrophages in pulmonary hypertension via single-cell RNA-sequencing in a mice hypoxia model, which was then validated in patients with pulmonary hypertension. Results. We identified that the intermittent exposure to hypoxic conditions could lead to the production of more M2-type macrophages than M1-type macrophages in a mouse model. Further validation analysis was performed by analyzing lung tissue of patients with pulmonary hypertension, revealing that the number of disease-associated M2 macrophages was substantially increased. Conclusions. In this study, the active anti-inflammatory response of macrophage involved in pulmonary hypertension has been identified, suggesting that intervention against the polarization of macrophages to the M2 type may be a potential way to reduce chronic pulmonary inflammation, pulmonary vascular remodeling, and artery pressure. Thus, investigation of macrophage polarization associated with hypoxia could help us better understand disease mechanism and craft effective prevention strategies and approaches. [ABSTRACT FROM AUTHOR]

Background. Sustained hypoxia can trigger a progressive rise in pulmonary artery pressure and cause serious pulmonary diseases. Macrophages play important roles along the progression of pulmonary hypertension. However, the state of macrophage polarization during the early stage of pulmonary hypertension is unclear. Methods. Unlike traditional sequencing method, single-cell sequencing can accurately distinguish among cell types and better understand cell-to-cell relationships. In this study, we investigated the polarization of macrophages in pulmonary hypertension via single-cell RNA-sequencing in a mice hypoxia model, which was then validated in patients with pulmonary hypertension. Results. We identified that the intermittent exposure to hypoxic conditions could lead to the production of more M2-type macrophages than M1-type macrophages in a mouse model. Further validation analysis was performed by analyzing lung tissue of patients with pulmonary hypertension, revealing that the number of disease-associated M2 macrophages was substantially increased. Conclusions. In this study, the active anti-inflammatory response of macrophage involved in pulmonary hypertension has been identified, suggesting that intervention against the polarization of macrophages to the M2 type may be a potential way to reduce chronic pulmonary inflammation, pulmonary vascular remodeling, and artery pressure. Thus, investigation of macrophage polarization associated with hypoxia could help us better understand disease mechanism and craft effective prevention strategies and approaches. [ABSTRACT FROM AUTHOR]

Introduction: The neonatal near-miss cases are subject to factors that are major causes of early neonatal deaths. For every death, more newborns suffer a life-threatening complication. Nearly 98% of neonatal death unduly existed in developing countries. Though there were few prior studies in other regions, they failed in identifying the factors of NNM. Besides, there has been no prior study in the study area. Therefore, this study aimed to assess factors associated with neonatal near-miss. Methods: A case-control study was employed on a total of 252 cases and 756 controls using a systematic random sampling technique. Data were collected using pre-tested and interview administered questionnaires adapted from similar studies and medical records from December 2020 –March 2021. Pragmatic and management criteria definition of neonatal near miss were utilized. Epi-Data version 3.1 and SPSS version 23 were used for data entry and analysis respectively. Bivariable and multivariable analyses were done to identify factors associated with a neonatal near-miss by using COR and AOR with a 95% confidence interval. Finally, the statistical significance was declared at a p-value < 0.05. Results: There were a response rate of 100% for both cases, and controls. Factors that affects neonatal near miss were non-governmental/private employee (AOR, 1.72[95%CI: 1.037, 2.859]), referral in (AOR, 1.51[95%CI: 1.079, 2.108]), multiple birth (AOR, 2.50[95%CI: 1.387, 4.501]), instrumental assisted delivery (AOR, 4.11[95%CI: 1.681, 10.034]), hypertensive during pregnancy (AOR, 3.32[95%CI: 1.987, 5.530]), and male neonates (AOR, 1.71[95%CI: 1.230, 2.373]), paternal education of secondary school (AOR, 0.43[95%CI: 0.210, 0.868]) and college/above (AOR, 0.25[95%CI: 0.109, 0.578]), monthly income (1500–3500 birr) (AOR, 0.29[95%CI: 0.105, 0.809]) and >3500 birr (AOR, 0.34[95%CI: 0.124, 0.906]). Conclusion: Maternal occupation, paternal education, income, referral, multiple births, mode of delivery, hypertension during pregnancy, and sex of the neonate have identified factors with neonatal near-miss. Better to create job opportunities, improving education, and income generation. Counseling on multiple birth and hypertension, and minimizing instrumental delivery should be done at the health facility level. [ABSTRACT FROM AUTHOR]