Management of neonatal pulmonary hypertension-a survey of neonatal intensive care units in India.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition associated with significant morbidity and mortality. First-line diagnostic and treatment options such as echocardiography and inhaled nitric oxide (iNO) are not routinely available in resource limited settings and alternative treatment modalities need to be utilized. This study was conducted to assess current diagnostic and management strategies used for PPHN in Indian neonatal intensive care units (NICUs). METHODS: A questionnaire in multiple choice question format was sent to practising neonatologists in India via an online survey tool between July to August 2021. Information pertaining to demographic data, diagnostic criteria and management strategies of PPHN was requested. The responses were collated and information processed. RESULTS: There were 118 respondent NICUs (response rate 74%). The majority of neonatal units (65%) admitted an average of 1-3 patients of PPHN per month. Targeted neonatal echocardiography (TnECHO) was practised in 80% of the units. Most common management strategies being followed were pulmonary vasodilators (88.1%), inotropes (85.6%), conventional ventilation (68.6%) and high frequency ventilation (59.3%). The most preferred pulmonary vasodilator was sildenafil (79%) and inotropic agent was milrinone (32%). Only 25% of respondents reported use of iNO. None of the participating units used extracorporeal membrane oxygenation. CONCLUSION: We found wide variability in management practices of PPHN across Indian NICUs. Non-selective pulmonary vasodilators are more widely used than iNO. There is an urgent need for structured TnECHO training programs and evidence based national guidelines for standardized management of PPHN as per availability of resources in India. Additional research on low cost alternative therapies to iNO in Indian settings might be helpful.

Heated Humidified High-Flow Nasal Cannula vs. Nasal Continuous Positive Airway Pressure for Post-extubation Respiratory Support in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to compare the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) and nasal continuous positive airway pressure (nCPAP) for prevention of extubation failure in preterm infants. METHODS: Preterm infants (gestation ≥28 weeks) were randomized to HHHFNC or nCPAP after extubation. Primary outcome was extubation failure within 72 h of extubation. RESULTS: A total of 128 preterm infants were randomized to receive either HHHFNC (n = 63) or nCPAP (n = 65) after extubation. The primary outcome of extubation failure within 72 h after extubation was not different between the two groups (HHHFNC, 22.2% vs. nCPAP, 18.5%, risk difference of 3.7% and 95% CI -10.3 to 17.6, p = 0.604). The incidence of nasal trauma was significantly lower in the HHHFNC group than in the nCPAP group 6.3% vs. 21.5%, p = 0.020. CONCLUSIONS: In our study, HHHFNC was as effective as nCPAP for prevention of extubation failure in preterm infants. Also, HHHFNC was associated with significantly less nasal trauma compared with nCPAP.

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.

The evolution of complexity in social organization-A model using dominance-subordinate behavior in two social wasp species.

Dominance and subordinate behaviors are important ingredients in the social organizations of group living animals. Behavioral observations on the two eusocial species Ropalidia marginata and Ropalidia cyathiformis suggest varying complexities in their social systems. The queen of R. cyathiformis is an aggressive individual who usually holds the top position in the dominance hierarchy although she does not necessarily show the maximum number of acts of dominance, while the R. marginata queen rarely shows aggression and usually does not hold the top position in the dominance hierarchy of her colony. In R. marginata, more workers are involved in dominance-subordinate interactions as compared to R. cyathiformis. These differences are reflected in the distribution of dominance-subordinate interactions among the hierarchically ranked individuals in both the species. The percentage of dominance interactions decreases gradually with hierarchical ranks in R. marginata while in R. cyathiformis it first increases and then decreases. We use an agent-based model to investigate the underlying mechanism that could give rise to the observed patterns for both the species. The model assumes, besides some non-interacting individuals, the interaction probabilities of the agents depend on their pre-differentiated winning abilities. Our simulations show that if the queen takes up a strategy of being involved in a moderate number of dominance interactions, one could get the pattern similar to R. cyathiformis, while taking up the strategy of very low interactions by the queen could lead to the pattern of R. marginata. We infer that both the species follow a common interaction pattern, while the differences in their social organization are due to the slight changes in queen as well as worker strategies. These changes in strategies are expected to accompany the evolution of more complex societies from simpler ones.

Pulmonary hypertension in late onset neonatal sepsis using functional echocardiography: a prospective study.

PURPOSE: Pulmonary hypertension (PH) in the newborn period is associated with significant morbidity and mortality. Sepsis has been identified as an independent risk factor for PH in newborns. Data on the proportion and severity of PH in association with neonatal sepsis are scarce. This study was aimed to measure the pulmonary artery systolic pressure (PASP) in neonates with late onset sepsis (LOS) and to estimate the proportion of PH in neonatal sepsis using functional echocardiography (FnECHO). METHODS: This prospective observational study was conducted at a tertiary neonatal intensive care unit (NICU). All neonates admitted in the NICU with suspected LOS underwent FnECHO within 6 hours of onset of clinical signs and PASP was recorded. Pulmonary hypertension was defined as PASP of > 35 mmHg. PASP of neonates with positive culture results (proven LOS) was compared with that of gestational age-matched stable controls without sepsis. RESULTS: Thirty three neonates with proven LOS were analysed (study group). Sixteen neonates (49%) in the study group had PH. Mean PASP of the study group was significantly higher than that of the control group (35.3 ± 10.13 mmHg and 12.58 ± 3.92 mmHg, respectively; P < 0.0001). None of the neonates in the control group had PH. CONCLUSION: Pulmonary artery pressure was higher in neonates with late onset neonatal sepsis as compared to that of stable babies without sepsis. Pulmonary hypertension was seen in nearly half of term as well as preterm neonates with late onset sepsis.

Regulation of reproduction in the primitively eusocial wasp Ropalidia marginata: on the trail of the queen pheromone.

Queens and workers are not morphologically differentiated in the primitively eusocial wasp, Ropalidia marginata. Upon removal of the queen, one of the workers becomes extremely aggressive, but immediately drops her aggression if the queen is returned. If the queen is not returned, this hyper-aggressive individual, the potential queen (PQ), will develop her ovaries, lose her hyper-aggression, and become the next colony queen. Because of the non-aggressive nature of the queen, and because the PQ loses her aggression by the time she starts laying eggs, we hypothesized that regulation of worker reproduction in R. marginata is mediated by pheromones rather than by physical aggression. Based on the immediate loss of aggression by the PQ upon return of the queen, we developed a bioassay to test whether the queen's Dufour's gland is, at least, one of the sources of the queen pheromone. Macerates of the queen's Dufour's gland, but not that of the worker's Dufour's gland, mimic the queen in making the PQ decrease her aggression. We also correctly distinguished queens and workers of R. marginata nests by a discriminant function analysis based on the chemical composition of their respective Dufour's glands.

A possible novel function of dominance behaviour in queen-less colonies of the primitively eusocial wasp Ropalidia marginata.

Unlike the queens of other primitively eusocial species, Ropalidia marginata queens are strikingly docile and non-aggressive individuals, never at the top of the behavioural dominance hierarchy of their colonies. Nevertheless, these queens are completely successful at suppressing worker reproduction, suggesting that they do not use aggression but employ some other mechanism (e.g. pheromones) to do so. Upon removal of the queen from a colony, a single worker, the 'potential queen', immediately begins to display highly elevated levels of aggression towards her nest mates. This individual becomes the next docile queen if the original queen is not returned. We attempt to understand the function of the temporary and amplified dominance behaviour displayed by the potential queen. We find that the dominance behaviour shown by the potential queen is unrelated to the number of her nest mates, their dominance ranks or ovarian condition. This suggests that aggression may not be used to actively suppress other workers and counter threat. Instead we find evidence that dominance behaviour is required for the potential queen's rapid ovarian development, facilitating her speedy establishment as the sole reproductive individual in the colony.

Surfactant Therapy for Early Onset Pneumonia in Late Preterm and Term Neonates Needing Mechanical Ventilation.

INTRODUCTION: Pathophysiology of pneumonia involves leakage of plasma proteins into the airways and accumulation of cytokines within the lung. Several in vitro and in vivo studies have demonstrated that this proteinaceous material and lung inflammation inhibit surfactant function. AIM: To evaluate whether exogenous surfactant therapy improves oxygenation and gas exchange in late preterm and term neonates with early onset pneumonia and respiratory failure. MATERIALS AND METHODS: This prospective interventional cohort study was conducted at a tertiary care neonatal unit. Twenty four late preterm and term neonates with early onset pneumonia requiring mechanical ventilation for respiratory failure were included and received surfactant therapy. Oxygenation index, arterial/alveolar PO2 (a/A ratio), mean airway pressure and fraction of inspired oxygen were calculated from arterial blood gases obtained before and after surfactant therapy. Wilcoxon signed rank sum test was used for assessment of change in oxygenation variables 12 hours after surfactant therapy. Data regarding clinical outcomes and complications were collected and analysed. RESULTS: Just over half (54.2%) of the study neonates were of term gestation. After surfactant therapy, the median Oxygenation Index (OI) decreased from 11.15 to 3.7 at one hour and the change was sustained and significant at 12 hours (p<0.05). The median a/A PO2 ratio improved from 0.09 to 0.3 within one hour of surfactant replacement and the improvement was significant at 12 hours (p<0.01). Twenty two neonates (92%) survived to discharge. Median duration of hospital stay was 15 days. CONCLUSION: Significant and rapid improvement in oxygenation in late preterm and term neonates with early onset pneumonia was seen after surfactant therapy, which is sustained for a longer period. There could be a substantial role for the use of surfactant in early onset pneumonia, although larger controlled trials are needed before definite recommendations can be made.

How do workers of the primitively eusocial wasp Ropalidia marginata detect the presence of their queens?

Queens in primitively eusocial insect societies are morphologically indistinguishable from their workers, and occupy the highest position in the dominance hierarchy. Such queens are believed to use aggression to maintain worker activity and reproductive monopoly in the colony. However, in the primitively eusocial wasp Ropalidia marginata, the queen is a strikingly docile individual, who interacts rarely with her workers. If the queen is experimentally removed, one of the workers becomes extremely aggressive within minutes, and eventually becomes the new queen of the colony. We designate her as the potential queen. Experimental evidence suggests that the queen probably uses a non-volatile pheromone to signal her presence to her workers. Here we attempt to identify the mechanism by which the queen transmits information about her presence to the workers. We designate the time taken for the potential queen to realize the absence of the queen as the realization time and model the realization time as a function of the decay time of the queen's signal and the average signal age. We find that the realization time obtained from the model, considering only direct interactions (193.5 min) is too large compared to the experimentally observed value of 30 min. Hence we consider the possibility of signal transfer through relay. Using the Dijkstra's algorithm, we first establish the effectiveness of relay in such a system and then use experimental data to fit the model. We find that the realization time obtained from the model, considering relay (237.1 min) is also too large compared to the experimentally observed value of 30 min. We thus conclude that physical interactions, both direct and indirect (relay), are not sufficient to transfer the queen's signal in R. marginata. Finally, we discuss the possibility that the queen applies her pheromone on the nest material from where the workers can perceive it without having to physically interact with the queen.