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his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

To review the current state of the art of positive pressure ventilation (PPV) during resuscitation FINDINGS: The frequency of PPV during delivery room resuscitation varies across settings and gestational age subgroups. Goal targets and parameters for delivery room PPV remain undefined. The T-piece resuscitator provides the most consistent pressures during PPV and may improve clinical outcomes. The laryngeal mask may be an important alternative interface for PPV, but more data are needed to identify the optimal role of the supraglottic airway during PPV. No objective monitors of PPV have conclusively demonstrated improved outcomes to date.More information, including real-world data from population-based studies, is needed to provide data-driven guidelines for positive pressure ventilation during neonatal transition after birth.

In order to predict which newborns will require advanced resuscitation (ANR), we developed an ANR risk calculator (calculator.) using a bootstrap sample size of 52 973 from a case–control study of newborns ≥34 weeks gestation. Multivariable logistic regression coefficients were obtained for the 10 original risk factors and two interaction terms. The area under the receiving-operating characteristic curve predicting ANR was 0.9243. ANR prediction is improved by accounting for perinatal variables, beyond factors known prenatally. Prospective validation of this model is warranted in a clinical setting.

The aim of this study was to evaluate the level of training, awareness, experience, and confidence of neonatal practice providers in the use of laryngeal mask (LM), and to identify the barriers in its implementation in the neonatal population. Descriptive observational study utilizing an anonymous online questionnaire among healthcare providers at the Oklahoma Children's Hospital who routinely respond to newborn deliveries and have been trained in the Neonatal Resuscitation Program (NRP). Participants included physicians, trainees, nurse practitioners, nurses, and respiratory therapists. Ninety-five participants completed the survey (27.5% response rate). The sample consisted of 77 NRP providers (81%), 11 instructors (12%), and 7 instructor mentors (7%). Among 72 respondents who had undergone LM training, 51 (54%) had hands-on manikin practice, 4 (4%) watched the American Academy of Pediatrics (AAP) NRP educational video, and 17 (18%) did both. Nurses (39 out of 46) were more likely to have completed LM training than were physicians (31 out of 47). With only 11 (12%) participants having ever placed a LM in a newly born infant, the median confidence for LM placement during neonatal resuscitation was 37 on a 0 to 100 scale. Frequently reported barriers for LM use in neonates were limited experience (81%), insufficient training (59%), preference for endotracheal tube (57%), and lack of awareness (56%). While the majority of the neonatal practice providers were trained in LM placement, only a few had ever placed one in a live newborn, with a low degree of confidence overall. Future practice improvement should incorporate ongoing interdisciplinary LM education, availability of LM in the labor and delivery units, and promotion of awareness of LM as an alternative airway.· LM is underutilized as an alternative airway.. · Insufficient experience and training limit LM use.. · Providers confidence with LM placement is low..

The Neonatal Resuscitation Program, initially an expertise- and consensus-based approach, has evolved into an evidence-based algorithm. Ventilation remains the key component of successful resuscitation of neonates. Recent changes in recommendations include management of cord clamping, multiple methods to prevent hypothermia, rescinding of mandatory intubation and suction of the nonvigorous meconium-stained infant, electrocardiographic monitoring, and establishing an airway for ventilation before initiation of chest compressions. Emerging science, including issues such as cord milking, oxygen targeting, and laryngeal mask use, may lead to future program modifications. Technology such as video laryngoscopy and telemedicine will affect the way training and care is delivered.

Objective Simulation studies in adults and pediatrics demonstrate improvement in chest compression (CCs) quality as providers rotate every two minutes. There is paucity of studies in neonates on this matter. This study hypothesized that frequent rotation while performing CCs improves provider performance and decreases fatigue. Study design Prospective randomized, observational crossover study where 51 providers performed 3:1 compression-ventilation CPR as a pair on a term manikin. Participants performed CCs as part of 3 simulation models, rotating every 3, 5 and 10 minutes. Data on various CC metrics were collected. Participant vitals were recorded at multiple points during the simulation and participants reported their level of fatigue at completion of simulation. Results No statistically significant difference was seen in any of the compression metrics. However, differences in the providers’ fatigue scores were statistically significant. Conclusion CC performance metrics did not differ significantly, however, providers’ vital signs and self-reported fatigue scores significantly increased with longer CC durations.

To evaluate vitamin D inadequacy among extremely low-birth-weight (ELBW, 1000 g) infants and the association between circulating vitamin D concentrations and perinatal-neonatal outcomes.Prospective cohort study of ELBW infants in the neonatal ICU. Blood was collected within the first 3 days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin D concentrations (25(OH)D) were quantified using liquid chromatography-tandem mass spectroscopy and classified as vitamin D deficient, insufficient, or adequate ( 20, 20-30, or 30 ng/mL, respectively). Associations between 25(OH)D and perinatal-neonatal outcomes were determined by multivariable regression, adjusted for covariates that differ in the bivariate analysis.Of the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15 (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were positively associated with fetal growth restriction and prolonged rupture of the membranes.Vitamin D inadequacy was frequent among ELBW infants. Circulating vitamin D concentrations were significantly associated with perinatal outcomes in this contemporary cohort.

Objective The objective of this study was to evaluate chest compression (CC) quality and operator fatigue during CC, with coordinated ventilation, on a neonatal simulator and to explore its association with provider aerobic activity and body mass index. Methods This was a prospective observational experimental study on pediatricians, neonatologists, and neonatal nurses who frequently deliver newborns and who have signed the informed consent. Subjects performed CC coordinated with ventilations at a ratio of 3:1 for 10 minutes on a neonatal mannequin. Proxy of fatigue was defined as four consecutive CC below target. Results Forty subjects participated; 62% were women. Twenty one (52%) evidenced weariness, as they performed. No gender-based differences were found in weariness. No subject abandoned the procedure due to fatigue. Subjects who participated in aerobic exercise had a significantly better performance than those who did not participate. Early fatigue was significantly associated with higher BMI. The reduction in effectiveness occurred at a mean time of 7.7 minutes (range 3.5–9 minutes). Conclusion CC performance quality decreased and fatigue was frequent before 10 minutes had elapsed on a neonatal simulator. Provider fatigue was associated with both lack of aerobic activity and BMI ≥ 25. Our findings support the need for guidelines requiring frequent rotation of CC providers during prolonged neonatal resuscitation.

In 2016, the neonatal resuscitation guidelines suggested electronic cardiac (ECG) monitoring to assess heart rate for an infant receiving positive pressure ventilation immediately after birth. Our aim was to study the impact of ECG monitoring on delivery room resuscitation interventions and neonatal outcomes.Observational cohort study compared maternal, perinatal and infant characteristics, before (retrospective cohort, calendar year 2015) and after (prospective cohort, calendar year 2017) implementation of ECG monitoring in the delivery room. Association of ECG monitoring with delivery room resuscitation practice interventions and neonatal outcomes was assessed using unadjusted and adjusted multivariable regression analyses.Of 632 newly born infants who received positive pressure ventilation in the delivery room, ECG monitoring was performed in 369 (the prospective cohort) compared with no ECG monitoring in 263 (the retrospective cohort). Compared to neonates in the retrospective cohort, neonates with ECG monitoring had a significantly lower endotracheal intubation rate (36% vs 48%, P .005) in the delivery room and higher 5-min Apgar scores (7 [5-8] vs 6 [5-8], P .05). There was no difference in mortality (31 [8%] vs 23 [9%]), but infants who received ECG monitoring had increased odds of receiving chest compressions with an adjusted odds ratio of 3.6 (95% confidence interval: 1.4-9.5).Introduction of ECG monitoring in the delivery room was associated with fewer endotracheal intubations, and an increase use of chest compressions with no difference in mortality.

Photoactivatable fluorophores are essential tools for studying the dynamic molecular interactions within important biological systems with high spatiotemporal resolution. However, currently developed photoactivatable fluorophores based on conventional dyes have several limitations including reduced photoactivation efficiency, cytotoxicity, large molecular size, and complicated organic synthesis. To overcome these challenges, we herein report a class of photoactivatable fluorescent N-hydroxyoxindoles formed through the intramolecular photocyclization of substituted o-nitrophenyl ethanol (ONPE). These oxindole fluorophores afford excellent photoactivation efficiency with ultra-high fluorescence enhancement (up to 800-fold) and are small in size. Furthermore, the oxindole derivatives show exceptional biocompatibility by generating water as the only photolytic side product. Moreover, structure–activity relationship analysis clearly revealed the strong correlation between the fluorescent properties and the substituent groups, which can serve as a guideline for the further development of ONPE-based fluorescent probes with desired photophysical and biological properties. As a proof-of-concept, we demonstrated the capability of a new substituted ONPE that has an uncaging wavelength of 365–405 nm and an excitation/emission at 515 and 620 nm, for the selective imaging of a cancer cell line (Hela cells) and a human neural stem cell line (hNSCs).

Stimuli-responsive drug delivery vehicles have garnered immense interest in recent years due to unparalleled progress made in material science and nanomedicine. However, the development of stimuli-responsive devices with integrated real-time monitoring capabilities is still in its nascent stage because of the limitations of imaging modalities. In this paper, we describe the development of a polypeptide-wrapped mesoporous-silica-coated multicolor upconversion nanoparticle (UCNP@MSN) as an adenosine triphosphate (ATP)-responsive drug delivery system (DDS) for long-term tracking and real-time monitoring of drug release. Our UCNP@MSN with multiple emission peaks in UV-NIR wavelength range was functionalized with zinc-dipicolylamine analogue (TDPA-Zn(2+)) on its exterior surface and loaded with small-molecule drugs like chemotherapeutics in interior mesopores. The drugs remained entrapped within the UCNP-MSNs when the nanoparticles were wrapped with a compact branched polypeptide, poly(Asp-Lys)-b-Asp, because of multivalent interactions between Asp moieties present in the polypeptide and the TDPA-Zn(2+) complex present on the surface of UCNP-MSNs. This led to luminescence resonance energy transfer (LRET) from the UCNPs to the entrapped drugs, which typically have absorption in UV-visible range, ultimately resulting in quenching of UCNP emission in UV-visible range while retaining their strong NIR emission. Addition of ATP led to a competitive displacement of the surface bound polypeptide by ATP due to its higher affinity to TDPA-Zn(2+), which led to the release of the entrapped drugs and subsequent elimination of LRET. Monitoring of such ATP-triggered ratiometric changes in LRET allowed us to monitor the release of the entrapped drugs in real-time. Given these results, we envision that our proposed UCNP@MSN-polypeptide hybrid nanoparticle has great potential for stimuli-responsive drug delivery as well as for monitoring biochemical changes taking place in live cancer and stem cells.

Galactosialidosis (GS) is a rare autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal β-galactosidase and neuraminidase as a result of a genetic defect in the protective protein/cathepsin A gene. We report a case of unsuspected fetal galactosialidosis presenting as severe intrauterine growth restriction and oligohydramnios prenatally and as hyperinsulinemic hypoglycemia in the immediate postnatal period. Placental pathology examination showed striking vacuolations of the villous syncytiotrophoblast, extravillous trophoblast, and villous Hofbauer cells. Electron microscopy revealed numerous membrane-bound electron-lucent lysosomes, mainly within the syncytiotrophoblast. The characteristic histologic and ultrastructural placental findings prompted biochemical and molecular genetic testing for fetal storage disease. Enzyme activity of β-galactosidase was decreased in leukocytes and fibroblasts. Sialic acid content was elevated. Molecular genetic studies revealed 3 variants—c.108, 110delGCT(L37del), c.1045T>A (C349S), and c.1321C>T(R441C)—of the cathepsin A gene, the latter 2 of which have not been previously reported. These findings are consistent with galactosialidosis. We emphasize the importance of following the accepted practice guideline for the examination of the placenta in discovering unsuspected fetal metabolic disorders.

Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW

Stem cells, owing to their ability to differentiate into specialized cells that can serve a particular function, have enormous potential in the field of regenerative medicine, wherein these stem cell-based therapies can be used to treat a wide range of diseases including diabetes, heart disease, and liver disease.[1] However, the realization of stem cell-based therapies in the clinic is severely hampered by our current inability to achieve the efficient delivery of genetic materials into target cells, which is required to specifically direct differentiation. In particular, with regard to stem cell-based regenerative medicine, it is vital to achieve: i) the highly efficient transfection of targeted cells; ii) biocompatibility, with an emphasis on maintaining a high cell viability without altering migratory and differentiation potential; and iii) non-invasive monitoring for the long-term evaluation of therapy.[2]

We describe the development of a versatile fluorescence resonance energy transfer (FRET)-based real-time monitoring system, consisting of (a) coumarin-labeled-cysteine tethered mesoporous silica nanoparticles (MSNs) as the drug carrier, (b) a fluorescein isothiocyanate-β-cyclodextrin (FITC-β-CD) as redox-responsive molecular valve blocking the pores, and (c) a FRET donor-acceptor pair of coumarin and FITC integrated within the pore-unlocking event, thereby allowing for monitoring the release of drugs from the pores in real-time. Under non-reducing conditions, when the disulfide bond is intact, the close proximity between coumarin and FITC on the surface of MSNs results in FRET from coumarin to FITC. However, in the presence of the redox stimuli like glutathione (GSH), the disulfide bond is cleaved which leads to the removal of molecular valve (FITC-β-CD), thus triggering drug release and eliminating FRET. By engineering such a FRET-active donor-acceptor structure within the redox-responsive molecular valve, we can monitor the release of the drugs entrapped within the pores of the MSN nanocarrier, following the change in the FRET signal. We have demonstrated that, any exogenous or endogenous change in the GSH concentration will result in a change in the extent of drug release as well as a concurrent change in the FRET signal, allowing us to extend the applications of our FRET-based MSNs for monitoring the release of any type of drug molecule in real-time.

OBJECTIVE: To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at

Multiple dysregulated pathways in tumors necessitate targeting multiple oncogenic elements by combining orthogonal therapeutic moieties like short-interfering RNAs (siRNA) and drug molecules in order to achieve a synergistic therapeutic effect. In this manuscript, we describe the synthesis of cyclodextrin-modified dendritic polyamines (DexAMs) and their application as a multicomponent delivery vehicle for translocating siRNA and anticancer drugs. The presence of β-cyclodextrins in our DexAMs facilitated complexation and intracellular uptake of hydrophobic anticancer drugs-Suberoylanilide hydroxamic acid (SAHA) and Erlotinib, whereas the cationic polyamine backbone allowed for electrostatic interaction with the negatively charged siRNA. The DexAMs complexes were found to have minimal cytotoxicity over a wide range of concentrations and were found to efficiently deliver siRNA, thereby silencing the expression of targeted genes. As a proof-of concept, we demonstrated that upon appropriate modification with targeting ligands, we were able to simultaneously deliver multiple payloads -siRNA against oncogenic receptor, EGFRvIII and anti-cancer drugs (SAHA or erlotinib) efficiently and selectively to glioblastoma cells. Co-delivery of siRNA-EGFRvIII and SAHA/Erlotinib in glioblastoma cells was found to significantly inhibit cell proliferation and induce apoptosis, as compared to the individual treatments.

An effective therapeutic approach against cancer typically requires the combination of several modalities, such as chem-otherapy, radiation, and hyperthermia. In this regard, the development of multifunctional nanomaterial-based systems with combined therapeutic and molecular imaging capabili-ties has shown great potential but has not been fully explored. In particular, magnetic nanomaterials have been at the fore-front of cancer research as noninvasive imaging probes as well as multifunctional therapeutics.

A woman, who had not received adequate prenatal care, arrived in labour at 38 weeks’ gestation and rapidly delivered a 3 kg baby boy via repeat caesarean section. At the time of arrival, the head was engaged in the pelvis, and a vaginal hand was used during the delivery. Fetal heart rate patterns were unknown prior to delivery, due to scant fetal monitoring. She reported a history of depression and tobacco use during pregnancy. Soon after birth, at about 3 minutes, the advanced neonatal resuscitation team was called. The infant was floppy and without heart beats detectable by pulse oximetry, despite initial standard neonatal resuscitation efforts. He was receiving …

Importance Hypothermia at 33.5°C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models. Objective To determine if longer duration cooling (120 hours), deeper cooling (32.0°C), or both are superior to cooling at 33.5°C for 72 hours in neonates who are full-term with moderate or severe hypoxic ischemic encephalopathy. Design, Setting, and Participants A randomized, 2 × 2 factorial design clinical trial performed in 18 US centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network between October 2010 and November 2013. Interventions Neonates were assigned to 4 hypothermia groups; 33.5°C for 72 hours, 32.0°C for 72 hours, 33.5°C for 120 hours, and 32.0°C for 120 hours. Main Outcomes and Measures The primary outcome of death or disability at 18 to 22 months is ongoing. The independent data and safety monitoring committee paused the trial to evaluate safety (cardiac arrhythmia, persistent acidosis, major vessel thrombosis and bleeding, and death in the neonatal intensive care unit [NICU]) after the first 50 neonates were enrolled, then after every subsequent 25 neonates. The trial was closed for emerging safety profile and futility analysis after the eighth review with 364 neonates enrolled (of 726 planned). This report focuses on safety and NICU deaths by marginal comparisons of 72 hours’ vs 120 hours’ duration and 33.5°C depth vs 32.0°C depth (predefined secondary outcomes). Results The NICU death rates were 7 of 95 neonates (7%) for the 33.5°C for 72 hours group, 13 of 90 neonates (14%) for the 32.0°C for 72 hours group, 15 of 96 neonates (16%) for the 33.5°C for 120 hours group, and 14 of 83 neonates (17%) for the 32.0°C for 120 hours group. The adjusted risk ratio (RR) for NICU deaths for the 120 hours group vs 72 hours group was 1.37 (95% CI, 0.92-2.04) and for the 32.0°C group vs 33.5°C group was 1.24 (95% CI, 0.69-2.25). Safety outcomes were similar between the 120 hours group vs 72 hours group and the 32.0°C group vs 33.5°C group, except major bleeding occurred among 1% in the 120 hours group vs 3% in the 72 hours group (RR, 0.25 [95% CI, 0.07-0.91]). Futility analysis determined that the probability of detecting a statistically significant benefit for longer cooling, deeper cooling, or both for NICU death was less than 2%. Conclusions and Relevance Among neonates who were full-term with moderate or severe hypoxic ischemic encephalopathy, longer cooling, deeper cooling, or both compared with hypothermia at 33.5°C for 72 hours did not reduce NICU death. These results have implications for patient care and design of future trials. Trial Registration clinicaltrials.gov Identifier:NCT01192776

A novel therapy is demonstrated utilizing magnetic nanoparticles for the dual purpose of delivering microRNA and inducing magnetic hyperthermia. In particular, the combination of lethal-7a microRNA (let-7a), which targets a number of the survival pathways that typically limit the effectiveness of hyperthermia, with magnetic hyperthermia greatly enhances apoptosis in brain cancer cells.

To examine circulating levels of inter-alpha inhibitor protein (IaIp) in infants with necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and matched controls to assess the diagnostic accuracy of IaIp to differentiate NEC from SIP and to compare receiver operating characteristics of IaIp for NEC with C-reactive protein (CRP).A prospective, nested case-control study of infants with feeding intolerance was carried out. Blood and clinical data were collected from 27 infants diagnosed with NEC or SIP and from 26 matched controls admitted to our unit. Infants with modified Bell criteria stage 2 or greater were included as NEC. Clinical, radiologic, and/or surgical findings were used to identify infants with SIP. Controls were matched for gestational age, postnatal age, sex, and birth weight.Mean ± SD IaIp blood levels were 147 ± 38 mg/L, 276 ± 67 mg/L, and 330 ± 100 mg/L in infants with NEC, SIP, and matched controls, respectively (P .004 and P .01). Receiver operating characteristics analysis to establish the predictive value of NEC demonstrated areas under curve of 0.98 and 0.63 for IaIp and CRP, respectively.IaIp levels were significantly decreased in infants with NEC compared with SIP and matched controls. The diagnostic accuracy of IaIp for NEC was superior to that of CRP.

The existence of different solid-state forms such as polymorphs, solvates, hydrates, and amorphous form in pharmaceutical drug substances and excipients, along with their downstream consequences in drug products and biological systems, is well documented. Out of these solid states, amorphous systems have attracted considerable attention of formulation scientists for their specific advantages, and their presence, either by accident or design is known to incorporate distinct properties in the drug product. Identification of different solid-state forms is crucial to anticipate changes in the performance of the material upon storage and/or handling. Quantitative analysis of physical state is imperative from the viewpoint of both the manufacturing and the regulatory control aimed at assuring safety and efficacy of drug products. Numerous analytical techniques have been reported for the quantification of amorphous/crystalline phase, and implicit in all quantitative options are issues of accuracy, precision, and suitability. These quantitative techniques mainly vary in the properties evaluated, thus yielding divergent values of crystallinity for a given sample. The present review provides a compilation of the theoretical and practical aspects of existing techniques, thereby facilitating the selection of an appropriate technique to accomplish various objectives of quantification of amorphous systems.