Caring for the hypertensive newborn: a prospective evaluation of risk factors, clinical profile, management, and predictors of outcome of neonatal hypertension.

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.

The Utility of Serial Echocardiography Parameters in Management of Newborns with Congenital Diaphragmatic Hernia (CDH) and Predictors of Mortality.

Ventricular dysfunction may be found in 40% of newborns with CDH, and is not only a predictor of disease severity, but also mortality and need for ECMO. We conducted this study to assess the utility of serial echocardiography in management of newborns with CDH and their survival outcomes. This is a retrospective study, wherein the demographic, clinical and echocardiographic data from our local CDH registry and hospital clinical database were analyzed to study the correlation of timed echocardiographic findings with mortality and other outcomes. Fourty-two newborns with CDH were admitted during the study period (M/F:19/23), with median gestation of 38 weeks (IQR:36-39) and birth weight of 2.83 kg (IQR 2.45-3.17). Thirty-one were left-sided, seven right, one central, and three bilateral hernias. Twelve infants (28%) died in early infancy. Three infants were excluded from analysis due to either palliation at birth or significant cardiac anomaly. A total of 137 echos from 39 infants were analyzed. Seventy percent of newborns who died and had an echo within the first 72 h, were noted to have suffered from moderate to severe PH. Birth weight < 2.8 kg, RVSP > 45.5 in the first 72 h and postoperative VIS > 23.5 and RSS > 4.3 were good predictors of mortality. Markers of elevated pulmonary pressures and cardiac function were useful in guiding therapy. Serial timed functional echocardiography (f-Echo) monitoring allows targeted therapy of patients with CDH. Birth weight, initial severity of pulmonary hypertension and postoperative RSS and VIS may be useful in predicting mortality.

Multisystem inflammatory syndrome in neonates (MIS-N) associated with SARS-CoV2 infection: a case series.

Multisystem inflammatory syndrome in neonates (MIS-N) is hypothesised to be caused either following transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2. In this paper, we aim to discuss the clinical manifestations, laboratory features, and management of neonates diagnosed with MIS-N. We collated information from five participating hospitals in western India. A cohort of newborn infants presenting with multi-system involvement, along with the presence of SARS-CoV2 antibodies, was identified. Current proposed international diagnostic criteria for MIS-N were used to group the cases into three categories of Most likely, Possible, and Unlikely MIS-N. A total of 20 cases were reported with a diagnosis of MIS-N, all having high titres of SARS CoV2 IgG antibodies and negative for SARS CoV2 antigens. Most likely MIS (n = 5) cases presented with respiratory distress (4/5), hypotension and shock (4/5), and encephalopathy (2/5). Inflammatory markers like CRP (1/5), Procalcitonin (1/5), Ferritin (3/5), D-dimer (4/5), and LDH (2/5) were found to be elevated, and four of them had significantly high levels of proBNP. The majority of them (4/5) responded to immunomodulators, three neonates were discharged home, and two died. Possible MIS infants (n = 9) presented with fever (7/9), respiratory distress (4/9), refusal to feed (6/9), lethargy (5/9), and tachycardia (3/9). ProBNP as a marker of cardiac dysfunction was noted to be elevated in four (4/9) infants, correlating with abnormal echocardiography findings in two. In the Unlikely MIS (n = 6) category, three (3/6) infants presented with respiratory distress, one (1/6) with shock and cardiac dysfunction, and only one (1/6) with fever. All of them had elevated inflammatory markers. However, there were other potential diagnoses that could have been responsible for the clinical scenarios in these six cases.   Conclusion: MIS-N requires a high index of suspicion and should be considered in a neonate presenting with two or more systems involvement, in the presence of SARS-CoV2 antibodies, along with elevated inflammatory markers, once other common neonatal conditions have been ruled out. What is Known: • Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) associated multisystem inflammatory syndrome in children (MIS-C) is  widely reported in paediatric population, however only few reports of newborn affection. • MIS-C is known to cause by virus-induced post-infective antibody mediated immune dysregulation with severe multi-system affection. What is New: • MIS-N may present with varied clinical manifestations with multi-system involvement of variable severity with milder disease in term and severe disease with cardiac dysfunction in preterm newborns. • Multisystem inflammatory syndrome in newborns (MIS-N) is postulated to occur following immune dysregulation associated with transplacental transfer of SARS-CoV2 antibodies or antibodies developed in the neonate after infection with SARS-CoV-2.

Neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections during pregnancy: a national prospective study in Kuwait.

BACKGROUND: An increasing proportion of women are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during pregnancy. Intrauterine viral infections induce an increase in the levels of proinflammatory cytokines, which inhibit the proliferation of neuronal precursor cells and stimulate oligodendrocyte cell death, leading to abnormal neurodevelopment. Whether a maternal cytokine storm can affect neonatal brain development is unclear. The objective of the present study was to assess neurodevelopmental outcomes in neonates born to mothers with SARS-CoV-2 infections during pregnancy. METHODS: In this prospective cohort study, the neurodevelopmental status of infants (N = 298) born to women with SARS-CoV-2 infections during pregnancy was assessed at 10-12 months post-discharge using the Ages and Stages Questionnaire, 3rd edition (ASQ-3). The ASQ-3 scores were classified into developmental delays (cutoff scores ≤ 2 standard deviations (SDs) below the population mean) and no delays (scores > 2 SDs above the population mean). RESULTS: The majority (90%) of the infants born to mothers with SARS-CoV-2 infections during pregnancy had favorable outcomes and only 10% showed developmental delays. Two of the 298 infants tested positive for SARS-CoV-2, and both had normal ASQ-3 scores. The majority of the pregnant women had SARS-CoV-2 infections during their third trimester. The risk of developmental delays among infants was higher in those whose mothers had SARS-CoV-2 infections during the first (P = 0.039) and second trimesters (P = 0.001) than in those whose mothers had SARS-CoV-2 infections during the third trimester. CONCLUSION: The neurodevelopmental outcomes of infants born to mothers with SARS-CoV-2 infections seem favorable. However, more studies with larger sample sizes and longer follow-up periods are required.

Description of the marine predator Sericomyxa perlucida gen. et sp. nov., a cultivated representative of the deepest branching lineage of vampyrellid amoebae (Vampyrellida, Rhizaria).

The vampyrellids (Vampyrellida, Rhizaria) are naked amoebae of considerable genetic diversity. Three families have been well-defined (Vampyrellidae, Leptophryidae, and Placopodidae), but most vampyrellid lineages detected by environmental sequencing are poorly known or completely uncharacterized. In the brackish sediment of Lake Bras D'Or, Nova Scotia, Canada, we discovered an amoeba with a vampyrellid-like life history that was morphologically dissimilar from previously known vampyrellid taxa. We established a culture of this amoeba, studied its feeding behavior and prey range specificity, and characterized it with molecular phylogenetic methods and light and electron microscopy. The amoeba was a generalist predator (i.e. eukaryotroph), devouring a range of marine microalgae, with a strong affinity for some benthic diatoms and Chroomonas. Interestingly, the amoeba varied its feeding strategy depending on the prey species. Small diatoms were engulfed whole, while larger species were fed on through extraction with an invading pseudopodium. The SSU rRNA gene phylogenies robustly placed the amoeba in the most basal, poorly described lineage ("clade C") of the Vampyrellida. Based on the phylogenetic position and the distinct morphology of the studied amoeba, we here describe it as Sericomyxa perlucida gen. et sp. nov., and establish the new vampyrellid family Sericomyxidae for "clade C."

Reverse-phase chiral high-performance liquid chromatography for separation of a diastereomer in alalevonadifloxacin: A novel antibacterial agent.

Alalevonadifloxacin (ALA) is a novel antibacterial drug, recently launched in India to treat infections caused by Gram-positive bacteria. In present work, a chiral high-performance liquid chromatographic method was developed and validated for the quantification of a diastereomeric impurity (DI) in ALA. The separation was achieved on Pirkle type (R,R) Whelk-O1 chiral stationary phase, using ammonium formate buffer and acetonitrile in gradient fashion at a flow rate of 1.5 ml/min. The method was extensively validated for the quantification of DI in ALA. The detector response for DI was linear over the concentration range of 0.24-4.78 µg/ml. Limit of quantitation and limit of detection for DI were 0.24 and 0.07 µg/ml respectively. The mean recovery of the DI was 103.47 ± 5.14%. The impact of column temperature on the chiral separation was evaluated. The method was employed for controlling diastereomeric impurity in the batches of ALA used in preclinical studies.

Less Invasive Surfactant Administration (LISA) vs. Intubation Surfactant Extubation (InSurE) in Preterm Infants with Respiratory Distress Syndrome: A Pilot Randomized Controlled Trial.

OBJECTIVE: There has been an endeavor in recent years, to administer surfactant by minimally invasive techniques to neonates with surfactant deficiency. The objective of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery, using Less Invasive Surfactant Administration (LISA) technique and Intubation SURfactant Extubation (InSurE), in preterm infants with respiratory distress syndrome (RDS). METHODS: We conducted a pilot randomized control trial (RCT) at a tertiary care center over a period of 18 months. Preterm neonates with RDS (gestational age 28-36 weeks) were randomized to receive surfactant within 6 h of birth by InSurE or LISA. The primary outcome was need for intubation and mechanical ventilation within 72 h of birth. Infants were followed until discharge for adverse events and complications. RESULTS: A total of 40 infants were analyzed (20 in each group). There was no difference in the need for intubation and mechanical ventilation within 72 h of birth between the two groups [InSurE, 6 (30%) and LISA, 6 (30%), relative risk 1.0, 95% confidence interval 0.51-1.97]. About 15% of infants in both groups had adverse events during the procedure. There was no statistically significant difference in the rates of major complications or duration of respiratory support, hospital stay and mortality. CONCLUSION: We found LISA to be feasible and equally effective as InSurE for surfactant administration in the treatment of RDS in preterm infants. Future larger RCTs are required to compare the efficacy and long-term outcomes of LISA with the standard invasive methods of surfactant administration.

Two New Marine Species of Placopus (Vampyrellida, Rhizaria) That Perforate the Theca of Tetraselmis (Chlorodendrales, Viridiplantae).

Vampyrellids (Vampyrellida, Rhizaria) are a major group of predatory amoebae known primarily from freshwater and soil. Environmental sequence data indicate that there is also a considerable diversity of vampyrellids inhabiting marine ecosystems, but their phenotypic traits and ecology remain largely unexplored. We discovered algivorous vampyrellids of the filoflabellate morphotype in coastal habitats in Atlantic Canada, established cultures by single-cell isolation, and characterised three strains using light microscopy, SSU rRNA gene sequencing, feeding experiments and growth experiments at various salinities. These strains exhibit orange, discoid trophozoites with ventral filopodia, moving granules ("membranosomes"), and rolling locomotion, similar to freshwater species previously assigned to Hyalodiscus Hertwig & Lesser, but here moved to Placopus Schulze (due to homonymy with Hyalodiscus Ehrenberg). SSU rRNA gene phylogenies place our strains in two distinct positions within "lineage B3" (here referred to as Placopodidae). Based on these morphological, habitat and molecular data, we describe two new species, Placopus melkoniani sp. nov. and Placopus pusillus sp. nov., both of which feed on chlorophyte flagellates (Tetraselmis, Pyramimonas) and the cryptophyte Chroomonas. They perforate the theca of Tetraselmis to extract the protoplast, and thereby represent the first vampyrellids known to degrade the biochemically exotic cell wall of the Chlorodendrales (Chlorophyta, Viridiplantae).

Factors affecting N-terminal pro-B-type natriuretic peptide levels in preterm infants and use in determination of haemodynamic significance of patent ductus arteriosus.

This study aimed to investigate factors affecting N-terminal pro-B-type natriuretic peptide (NTproBNP) in preterm infants and the ability of NTproBNP to predict haemodynamically significant patent ductus arteriosus (HsPDA). Prospective cohort study of 51 infants < 30 weeks gestation. Blood NTproBNP and heart ultrasound were performed on day of life 3, 10, 28 and 36 weeks corrected age. NTproBNP levels analysed for prediction of HsPDA. The effect of gestational age, ventilation, hypoxia, bronchopulmonary dysplasia (BPD), creatinine and haemoglobin levels on NTproBNP levels were investigated. Infants with HsPDA had higher mean (SD) day 3 NTproBNP (1840 pmol/L (1058) versus 178 pmol/L (140) p < 0.001). Receiver operator curves of day 3 NTproBNP for prediction of day 3 and day 10 HsPDA had an area under the curve of 0.98 and 0.94, respectively. A chosen day 3 NTproBNP value of ≥ 287 pmol/L for the prediction of day 3 HsPDA correctly classified 92% (sensitivity 92%, specificity 92%). NTproBNP demonstrated only modest ability to predict severe BPD. Chronological but not gestational age affected NTproBNP. Ventilation, hypoxia and haemoglobin levels did not influence NTproBNP but creatinine level was positively correlated. CONCLUSION: Day 3 NTproBNP is a useful biomarker to predict HsPDA and may be a valuable tool in future trial design. What is Known: • NTproBNP is a cardiac hormone used to diagnose and monitor cardiac dysfunction in adults and has been shown to be higher in premature infants with haemodynamically significant ductus arteriosus (HsPDA). What is new: • NTproBNP is highly predictive of ultrasound-defined HsPDA and may be a useful tool for further triage • Early NTproBNP higher in infants who develop severe BPD and with renal impairment but not affected by gestational age, recent exposure to hypoxia or haemoglobin levels while late levels unexpectedly higher in those without BPD or HsPDA.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming.

OBJECTIVE: This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI). METHODS: Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4-5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified. RESULTS: Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106-159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48-42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours. CONCLUSION: Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Controversies in the identification and management of acute pulmonary hypertension in preterm neonates.

It is increasingly recognized that the abnormal physiologic consequences of pulmonary hypertension (PH) may contribute to poor cardiopulmonary health in premature babies. Conflicting literature has led to clinical uncertainty, pathological misinterpretation, and variability in treatment approaches among practitioners. There are several disorders with overlapping and interrelated presentations, and other disorders with a similar clinical phenotype but diverse pathophysiological contributors. In this review, we provide a diagnostic approach for acute hypoxemic respiratory failure in the preterm neonate, outline the pathophysiological conditions that may present as acute PH, and discuss the implications of high pulmonary vascular resistance (PVR) on the cardiovascular system. Although PVR and respiratory management are highly interrelated, there may be a population of preterm neonates in whom inhaled nitric oxide may improve illness severity and may relate to outcomes. A management approach based on physiology that considers common clinical conundrums is provided. A more comprehensive understanding of the physiology may help in informed decision-making in clinical situations where conclusive scientific evidence is lacking. Regardless, high-quality research is required, and appropriate definition of the target population is paramount. A thoughtful approach to cardiovascular therapy may also provide an avenue to improve neurodevelopmental outcomes while awaiting more clear answers.

Endothelin receptor antagonists for persistent pulmonary hypertension in term and late preterm infants.

BACKGROUND: Endothelin, a powerful vasoconstrictor, is one of the mediators in the causation of persistent pulmonary hypertension of the newborn (PPHN). Theoretically, endothelin receptor antagonists (ETRA) have the potential to improve the outcomes of infants with PPHN. OBJECTIVES: To assess the efficacy and safety of ETRA in the treatment of PPHN in full-term, post-term and late preterm infants.To assess the efficacy and safety of selective ETRAs (which block only the ETA receptors) and non-selective ETRAs (which block both ETA and ETB receptors) separately. SEARCH METHODS: CENTRAL (Cochrane Central Register of Controlled Trials), MEDLINE, EMBASE and CINAHL databases were searched until December 2015. SELECTION CRITERIA: Randomised, cluster-randomised or quasi-randomised controlled trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently searched the literature, selected the studies, assessed the risk of bias and extracted the data. A fixed-effect model was used for meta-analysis. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the quality of evidence. MAIN RESULTS: Two randomised controlled trials of ETRA met the inclusion criteria. Both studies utilized oral Bosentan. The first study was done in a setting where inhaled nitric oxide (iNO) therapy was not available. Forty-seven infants (≥ 34 weeks' gestation) were randomised to receive either Bosentan or placebo. The second study was a multicentre study where iNO therapy was the standard of care for PPHN. Twenty-one infants were randomised to receive either 'iNO plus Bosentan' or 'iNO plus placebo'.In the first study, there was no significant difference in the incidence of death before hospital discharge between the Bosentan and placebo groups (1/23 vs 3/14; RR 0.20, 95% CI 0.02 to 1.77; RD -0.17, 95% CI -0.40 to 0.06). A higher proportion of infants in the Bosentan group showed improvement in oxygenation index (OI) at the end of therapy (21/24 vs 3/15; RR 4.38, 95% CI 1.57 to 12.17; RD 0.68, 95% CI 0.43 to 0.92; number needed to treat for a beneficial outcome (NNTB) 1.5). The duration of mechanical ventilation was lower in the Bosentan group (4.3 ± 0.9 vs 11.5 ± 0.6 days; MD -7.20, 95% CI -7.64 to -6.76). There was no significant difference in adverse neurological outcomes at six months (0/23 vs 4/14; RR 0.07, 95% CI 0.00 to 1.20; RD -0.29, 95% CI -0.52 to -0.05). The study suffered from a high risk of attrition bias since 8/23 infants in the placebo group were excluded from various analyses. Since the protocol for the study could not be accessed, the study suffered from unclear risk of reporting bias.In the second study, there was no significant difference in the incidence of treatment failure needing extracorporeal membrane oxygenation (ECMO) between the 'iNO plus Bosentan' vs 'iNO plus placebo' groups (1/13 vs 0/8; RR 1.93, 95% CI 0.09 to 42.35; RD 0.08, 95% CI -0.14 to 0.30). There was no significant difference in the median time to wean from iNO ('iNO plus Bosentan': 3.7 days (95% CI 1.17 to 6.95); 'iNO plus placebo': 2.9 days (95% CI 1.26 to 4.23); P = 0.34). There were no significant differences in the OI 0, 3, 5, 12, 24, 48 and 72 hours of treatment between the groups. There were no significant differences in the time to complete weaning from mechanical ventilation (median 10.8 days (CI 3.21 to 12.21) versus 8.6 days (CI 3.71 to 9.66); P = 0.24). The study had unequal distribution to the Bosentan group (N = 13) and the placebo group (N = 8). The methods used for generating random sequence numbers and allocation concealment were unclear, resulting in unclear risk of selection bias.Both studies reported that Bosentan was well tolerated and no major adverse effects were noted. Data from the two studies was not pooled given the heterogenous nature of the clinical settings and the modalities used for the treatment of PPHN.Overall, the quality of evidence was considered low, given the small sample size of the included studies, the numerical imbalance between the groups due to randomisation and attrition, and unclear risk of bias on some of the important domains. AUTHORS' CONCLUSIONS: There is inadequate evidence to support the use of ETRAs either as stand-alone therapy or as adjuvant to inhaled nitric oxide in PPHN. Adequately powered RCTs are needed.

Growth and developmental outcomes of infants with hirschsprung disease presenting in the neonatal period: a retrospective study.

OBJECTIVES: To describe the presentation and progress over the first year of life of neonates with Hirschsprung disease, to describe their physical and developmental outcomes at 12 months of age, and to compare the outcomes of infants with short- vs long-segment Hirschsprung disease. STUDY DESIGN: A retrospective study of neonates born with Hirschsprung disease in Western Australia between January 1, 2001, and December 31, 2010, to review their presentation, progress, growth, and development at 12 months of age. RESULTS: Fifty-four infants were identified (40 with short and 11 with long segment and 3 with total colonic aganglionosis); 9 infants had a recognized syndrome and 1 infant died, unrelated to Hirschsprung disease. A primary pull-through procedure was performed in 97% and 21% of neonates with short- and non-short-segment Hirschsprung disease, respectively; 17 (31%) infants developed anal stenosis requiring dilatations. Enterocolitis occurred in 14 (26%) infants. Griffiths Mental Development Scale scores (1 year) were available in 31 of 45 nonsyndromic survivors: mean general quotient (94.2, SD 8.89) was significantly less than the population mean (P = .007), but the number of infants with developmental delay was within the expected range. Physical growth, except length, appeared adequate in nonsyndromic infants. There were no significant differences in the outcomes of infants with short- vs non-short-segment Hirschsprung disease. CONCLUSIONS: At 1 year of age, many infants with Hirschsprung disease have ongoing gastrointestinal problems. Their overall growth appears satisfactory, and most infants are developing normally; however, their mean general quotient appears shifted to the left. Longer-term studies will better define developmental outcomes.

Contractile vacuoles: a rapidly expanding (and occasionally diminishing?) understanding.

Osmoregulation is the homeostatic mechanism essential for the survival of organisms in hypoosmotic and hyperosmotic conditions. In freshwater or soil dwelling protists this is frequently achieved through the action of an osmoregulatory organelle, the contractile vacuole. This endomembrane organelle responds to the osmotic challenges and compensates by collecting and expelling the excess water to maintain the cellular osmolarity. As compared with other endomembrane organelles, this organelle is underappreciated and under-studied. Here we review the reported presence or absence of contractile vacuoles across eukaryotic diversity, as well as the observed variability in the structure, function, and molecular machinery of this organelle. Our findings highlight the challenges and opportunities for constructing cellular and evolutionary models for this intriguing organelle.

Comparative efficacy of volume expansion, inotropes and vasopressors in preterm neonates with probable transitional circulatory instability in the first week of life: a systematic review and network meta-analysis.

BACKGROUND: There exists limited agreement on the recommendations for the treatment of transitional circulatory instability (TCI) in preterm neonates OBJECTIVE: To compare the efficacy of various interventions used to treat TCI METHODS: Medline and Embase were searched from inception to 21st July 2023. Two authors extracted the data independently. A Bayesian random effects network meta-analysis was used. Recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. INTERVENTIONS: Dopamine, dobutamine, epinephrine, hydrocortisone, vasopressin, milrinone, volume and placebo. MAIN OUTCOME MEASURES: Mortality, major brain injury (MBI) (intraventricular haemorrhage > grade 2 or cystic periventricular leukomalacia), necrotising enterocolitis (NEC) ≥stage 2 and treatment response (as defined by the author). RESULTS: 15 Randomized Controlled Trials (RCTs) were included from the 1365 titles and abstracts screened. Clinical benefit or harm could not be ruled out for the critical outcome of mortality. For the outcome of MBI, epinephrine possibly decreased the risk when compared to dobutamine and milrinone (very low certainty). Epinephrine was possibly associated with a lesser risk of NEC when compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Dopamine was possibly associated with a lesser risk of NEC when compared with dobutamine (very low certainty). Vasopressin possibly decreased the risk of NEC compared with dopamine, dobutamine, hydrocortisone and milrinone (very low certainty). Clinical benefit or harm could not be ruled out for the outcome response to treatment. CONCLUSIONS: Epinephrine may be used as the first-line drug in preterm neonates with TCI, the evidence certainty being very low. We suggest future trials evaluating the management of TCI with an emphasis on objective criteria to define it.

Association of inhibitors of gastric acid secretion and higher incidence of necrotizing enterocolitis in preterm very low-birth-weight infants.

BACKGROUND: Inhibitors of gastric acid (IGA) are used for upper gastrointestinal bleeding or gastroesophageal reflux in preterm infants. The resultant increase in gastric pH may enhance the growth of pathogens and increase the risk of necrotizing enterocolitis (NEC). Our systematic review examined the association between IGA and NEC in preterm infants. METHODS: Standard methodology of systematic reviews was followed. PubMed, Embase, Cochrane, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched in August 2012. RESULTS: One case-control and one prospective cohort study (n = 11,346), both evaluating H2-blockers as IGA, were included. Meta-analysis showed a significant association between NEC and IGA (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.4, 2.27, p < 0.00001). The prospective cohort study found higher incidence of infection (sepsis, pneumonia, urinary tract infection) with IGA (37.4% versus 9.8%, OR: 5.5, 95% CI: 2.9 to 10.4, p < 0.001). CONCLUSIONS: Exposure to H2 receptor antagonists may be associated with increased risk of NEC and infections in preterm infants.

Comparative Genomics for Evolutionary Cell Biology Using AMOEBAE: Understanding the Golgi and Beyond.

Taking an evolutionary approach to cell biology can yield important new information about how the cell works and how it evolved to do so. This is true of the Golgi apparatus, as it is of all systems within the cell. Comparative genomics is one of the crucial first steps to this line of research, but comes with technical challenges that must be overcome for rigor and robustness. We here introduce AMOEBAE, a workflow for mid-range scale comparative genomic analyses. It allows for customization of parameters, queries, and taxonomic sampling of genomic and transcriptomics data. This protocol article covers the rationale for an evolutionary approach to cell biological study (i.e., when would AMOEBAE be useful), how to use AMOEBAE, and discussion of limitations. It also provides an example dataset, which demonstrates that the Golgi protein AP4 Epsilon is present as the sole retained subunit of the AP4 complex in basidiomycete fungi. AMOEBAE can facilitate comparative genomic studies by balancing reproducibility and speed with user-input and interpretation. It is hoped that AMOEBAE or similar tools will encourage cell biologists to incorporate an evolutionary context into their research.

The role of bedside functional echocardiography in the assessment and management of pulmonary hypertension.

Pulmonary hypertension is an emergency in neonatal intensive care units with high morbidity and mortality. Its timely assessment and management is crucial for intact survival. Over the last couple of decades, there have been significant advances in management and techniques, which have resulted in improved survival. The use of neonatologist-performed echocardiography (NPE) is now increasingly utilized on neonatal intensive care units to understand the pathophysiology of the disease and to direct the treatment to the underlying cause. Its use is now established not only in cases of congenital diaphragmatic hernia and in the newborn with refractory hypoxemia, but also in other conditions such as bronchopulmonary dysplasia and the premature infant with difficulty in oxygenation. The use of NPE, however, requires the availability of trained personnel, equipment, and a close working relationship with pediatric cardiology.

Multisystemic Inflammatory Syndrome in Neonates: A Systematic Review.

INTRODUCTION: Multisystem inflammatory syndrome in neonates (MIS-N) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has increasingly been reported worldwide amid the spread of the SARS-CoV-2 pandemic. METHODS: We searched PubMed, EMBASE, and CINAHL and preprint servers (BioRxiv.org and MedRxiv.org) using a specified strategy integrating Medical Subject Headings terms and keywords until October 20, 2021. Our aim was to systematically review demographic profiles, clinical features, laboratory parameters, complications, treatments, and outcomes of neonates with MIS-N. Studies were selected when fulfilling the inclusion criteria. Articles were included if they fulfilled the World Health Organization (WHO), Centers for Disease Control (CDC) definitions of MIS-C, or our proposed definition. RESULTS: Sixteen reports of MIS-N including 47 neonates meeting MIS-N criteria were identified. Presentation included cardiovascular compromise (77%), respiratory involvement (55%), and fever in (36%). Eighty-three percent of patients received steroids, and 76% received immunoglobulin. Respiratory support was provided to 60% of patients and inotropes to 45% of patients. Five (11%) neonates died. CONCLUSION: The common presentation of MIS-N included cardiorespiratory compromise with the possibility of high mortality. Neonates with MIS-N related to SARS-CoV-2 may be at higher risk of adverse outcomes.