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Background: The goal of chest compressions during neonatal resuscitation is to increase cerebral and coronary blood flow leading to the return of spontaneous circulation (ROSC). During chest compressions, bilateral femoral occlusion may increase afterload and promote carotid and coronary flow, an effect similar to epinephrine. Our objectives were to determine the impact of bilateral femoral occlusion during chest compressions on the incidence and timing of ROSC and hemodynamics., Methodology: In this randomized study, 19 term fetal lambs in cardiac arrest were resuscitated based on the Neonatal Resuscitation Program guidelines and randomized into two groups: femoral occlusion or controls. Bilateral femoral arteries were occluded by applying pressure using two fingers during chest compressions., Results: Seventy percent (7/10) of the lambs in the femoral occlusion group achieved ROSC in 5 ± 2 min and three lambs (30%) did not receive epinephrine. ROSC was achieved in 44% (4/9) of the controls in 13 ± 6 min and all lambs received epinephrine. The femoral occlusion group had higher diastolic blood pressures, carotid and coronary blood flow., Conclusion: Femoral occlusion resulted in faster and higher incidence of ROSC, most likely due to attaining increased diastolic pressures, coronary and carotid flow. This is a low-tech intervention that can be easily adapted in resource limited settings, with the potential to improve survival and neurodevelopmental outcomes.

Background: Current neonatal resuscitation guidelines recommend the use of epinephrine for bradycardia/arrest not responding to ventilation and chest compressions. Vasopressin is a systemic vasoconstrictor and is more effective than epinephrine in postnatal piglets with cardiac arrest. There are no studies comparing vasopressin with epinephrine in newly born animal models with cardiac arrest induced by umbilical cord occlusion. Objective: To compare the effect of epinephrine and vasopressin on the incidence and time to return of spontaneous circulation (ROSC), hemodynamics, plasma drug levels, and vasoreactivity in perinatal cardiac arrest. Design/Methods: Twenty-seven term fetal lambs in cardiac arrest induced by cord occlusion were instrumented and resuscitated following randomization to epinephrine or vasopressin through a low umbilical venous catheter. Results: Eight lambs achieved ROSC prior to medication. Epinephrine achieved ROSC in 7/10 lambs by 8 ± 2 min. Vasopressin achieved ROSC in 3/9 lambs by 13 ± 6 min. Plasma vasopressin levels in nonresponders were much lower than responders after the first dose. Vasopressin caused in vivo increased pulmonary blood flow and in vitro coronary vasoconstriction. Conclusions: Vasopressin resulted in lower incidence and longer time to ROSC compared to epinephrine in a perinatal model of cardiac arrest supporting the current recommendations for exclusive use of epinephrine in neonatal resuscitation.

Introduction: Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates., Methods: Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate ( N = 7) induced by 8.5% glucose and a low UF group ( N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment., Results: No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of -7 mL (-10.7% (95% confidence interval: -13.8% to -7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL)., Conclusion: Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.

Background: Currently, 21−30% supplemental oxygen is recommended during resuscitation of preterm neonates. Recent studies have shown that 58% of infants < 32 week gestation age are born with a heart rate (HR) < 100 bpm. Prolonged bradycardia with the inability to achieve a preductal saturation (SpO2) of 80% by 5 min is associated with mortality and morbidity in preterm infants. The optimal oxygen concentration that enables the achievement of a HR ≥ 100 bpm and SpO2 of ≥80% by 5 min in preterm lambs is not known. Methods: Preterm ovine model (125−127 d, gestation equivalent to human neonates < 28 weeks) was instrumented, and asphyxia was induced by umbilical cord occlusion until bradycardia. Ventilation was initiated with 30% (OX30), 60% (OX60), and 100% (OX100) for the first 2 min and titrated proportionately to the difference from the recommended preductal SpO2. Our primary outcome was the incidence of the composite of HR ≥ 100 bpm and SpO2 ≥ 80%, by 5 min. Secondary outcomes were to evaluate the time taken to achieve the primary outcome, gas exchange, pulmonary/systemic hemodynamics, and the oxidative injury. Results: Eighteen lambs (OX30-6, OX60-5. OX100-7) had an average HR < 91 bpm with a pH of <6.92 before resuscitation. Sixty seven percent achieved the primary outcome in OX100, 40% in OX60, and none in OX30. The time taken to achieve the primary outcome was significantly shorter with OX100 (6 ± 2 min) than with OX30 (10 ± 3 min) (* p = 0.04). The preductal SpO2 was highest with OX100, while the peak pulmonary blood flow was lowest with OX30, with no difference in O2 delivery to the brain or oxidative injury by 10 min. Conclusions: The use of 30%, 60%, and 100% supplemental O2 in a bradycardic preterm ovine model did not demonstrate a significant difference in the composite primary outcome. The current recommendation to use 30% oxygen did not achieve a preductal SpO2 of 80% by 5 min in any preterm lambs. Clinical studies to optimize supplemental O2 in depressed preterm neonates not requiring chest compressions are warranted.

Objective: Pediatric tracheostomy patients are at risk for lengthy hospitalizations and multiple readmissions with rare but potentially disastrous tracheostomy-related complications. Several centers have formed multidisciplinary teams for pediatric tracheostomy patients to coordinate care and enhance caregiver education to aid in safe care delivery. Current literature has shown encouraging change in pediatric tracheostomy care with these interventions, but there remains an opportunity to better gauge alterations of morbidity. We aimed to review our institution's experience before and after development of a pediatric tracheostomy care team., Methods: Pediatric tracheostomy patients (<19 years) who underwent tracheostomy between January 2010 and June 2020 were included. A pediatric tracheostomy care team including a nurse practitioner and registered nurse was established in July 2017. Rates of readmission, outpatient visits, decannulation rates, and mortality are examined before and after implementation of the care team. Bivariate and multivariable analyses were utilized., Results: 296 patients were included with 128 patients in the pre-intervention group, 82 in the post-intervention group, and 86 completing cross-over care. The groups were comparable in age at tracheostomy, tracheostomy indication, and underlying comorbidities. Mean outpatient visits per tracheostomy-year in the post-intervention group were higher than the pre-intervention group (2.3 vs. 2.2, p = .02). Fewer mean inpatient admissions per tracheostomy-year (0.02 vs. 0.11, p = .03) were observed after intervention. Time to decannulation did not differ significantly between the two groups (p = .57)., Conclusion: Implementation of a dedicated tracheostomy care team may help decrease inpatient admissions for tracheostomy-specific complications., Competing Interests: Declaration of competing interest David Zopf is cofounder of MakeMedical which is not related to this study., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Effective positive-pressure ventilation is a critical factor in newborn resuscitation. Neonatal endotracheal intubation (ETT) needs considerable training and experience, which poses a human factor challenge. Laryngeal mask airway (LMA) ventilation can be a secure and viable alternative during the initial stages of newborn resuscitation. However, there is limited evidence for its use during chest compression (CC)., Methods: Seventeen lambs were randomized into LMA or ETT ventilation post cord occlusion induced cardiac arrest. After 5 min of cardiac arrest, resuscitation was initiated as per NRP recommendations. Ventilation, oxygenation, systemic and pulmonary hemodynamic parameters were recorded till the return of spontaneous circulation (ROSC) or 20 min., Results: Baseline characteristics were similar between the groups. The incidence of ROSC was 75% (6/8) in the LMA group and 56% (5/9) in the ETT group (p = 0.74). The median (IQR) time to achieve ROSC was 6.85 min (6 min-9.1 min) in the LMA group and 7.50 min (5.33 min-18 min) in the ETT group (p = 0.65)., Conclusion: LMA ventilation during CC is feasible and non-inferior to ETT in this model., Impact: Laryngeal mask airway (LMA) ventilation with chest compression is feasible and non-inferior to endotracheal tube ventilation in this experimental near-term lamb model of asphyxial cardiac arrest. First translational study to evaluate the use of LMA as an airway device with chest compression. Evidence primer for clinical studies to evaluate and confirm the feasibility and efficacy of LMA ventilation with chest compression are necessary before randomized clinical trials in neonates. LMA use in neonatal cardiopulmonary resusciation (CPR) could have the potential to optimize advanced resuscitation, especially in resource-limited healthcare settings., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Neonatal Resuscitation Program does not recommend placental transfusion in depressed preterm neonates., Methods: Our objectives were to study the effect of delayed cord clamping (DCC) with ventilation for 5 min (DCCV, n-5), umbilical cord milking (UCM) without ventilation (n-6), UCM with ventilation (UCMV, n-6), early cord clamping followed by ventilation (ECCV, n-6) on red cell volume (RCV), and hemodynamic changes in asphyxiated preterm lambs. Twenty-three preterm lambs at 127-128 days gestation were randomized to DCCV, UCM, UCMV, and ECCV. We defined asphyxia as heart rate &lt;100/min., Results: The UCMV had the highest neonatal RCV as a percentage of fetoplacental volume compared to the other groups (UCMV 85.5 ± 10%, UCM 72 ± 10%, ECCV 65 ± 14%, DCCV 61 ± 10%, p &lt; 0.01). The DCCV led to better ventilation (66 ± 1 mmHg) and higher pulmonary blood flow (75 ± 24 ml/kg/min). The carotid flow was significantly higher in UCM without ventilation. The fluctuations in carotid flow with milking were 25 ± 6% higher from baseline during UCM, compared to 6 ± 3% in UCMV (p &lt; 0.01)., Conclusions: Cord milking with ventilation led to higher RCV than other interventions. Ventilation during cord milking reduced fluctuation in carotid flow compared to UCM alone. DCCV led to better ventilation and pulmonary blood flow but did not increase RCV., Impact: The best practice of placental transfusion in a depressed preterm neonate remains unknown. Ventilation with an intact cord improves gas exchange and hemodynamics in an asphyxiated preterm model. Cord milking without ventilation led to lower red cell volume but higher carotid blood flow fluctuations compared to milking with ventilation. Our data can be translated to bedside and could impact preterm resuscitation., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Over half a million newborn deaths are attributed to intrapartum related events annually, the majority of which occur in low resource settings. While progress has been made in reducing the burden of asphyxia, novel approaches may need to be considered to further decrease rates of newborn mortality. Administration of intravenous, intraosseous or endotracheal epinephrine is recommended by the Newborn Resuscitation Program (NRP) with sustained bradycardia at birth. However, delivery by these routes requires both advanced skills and specialized equipment. Intramuscular (IM) epinephrine may represent a simple, low cost and highly accessible alternative for consideration in the care of infants compromised at birth. At present, the bioavailability of IM epinephrine in asphyxia remains unclear., Methods: Four term fetal lambs were delivered by cesarean section and asphyxiated by umbilical cord occlusion with resuscitation after 5 min of asystole. IM epinephrine (0.1 mg/kg) was administered intradeltoid after 1 min of positive pressure ventilation with 30 s of chest compressions. Serial blood samples were obtained for determination of plasma epinephrine concentrations by ELISA., Results: Epinephrine concentrations failed to increase following administration via IM injection. Delayed absorption was observed after return of spontaneous circulation (ROSC) in half of the studies., Conclusions: Inadequate absorption of epinephrine occurs with IM administration during asphyxial cardiac arrest, implying this route would be ineffective in infants who are severely compromised at birth. Late absorption following ROSC raises concerns for risks of side effects. However, the bioavailability and efficacy of intramuscular epinephrine in less profound asphyxia may warrant further evaluation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer P-YC declared a past collaboration with one of the authors SL to the handling editor BN., (Copyright © 2022 Berkelhamer, Vali, Nair, Gugino, Helman, Koenigsknecht, Nielsen and Lakshminrusimha.)

Objectives: Neonatal resuscitation guidelines recommend 0.5-1 mL saline flush following 0.01-0.03 mg/kg of epinephrine via low umbilical venous catheter for persistent bradycardia despite effective positive pressure ventilation (PPV) and chest compressions (CC). We evaluated the effects of 1 mL vs 3 mL/kg flush volumes and 0.01 vs 0.03 mg/kg doses on return of spontaneous circulation (ROSC) and epinephrine pharmacokinetics in lambs with cardiac arrest., Design: Forty term lambs in cardiac arrest were randomised to receive 0.01 or 0.03 mg/kg epinephrine followed by 1 mL or 3 mL/kg flush after effective PPV and CC. Epinephrine (with 1 mL flush) was repeated every 3 min until ROSC or until 20 min. Haemodynamics, blood gases and plasma epinephrine concentrations were monitored., Results: Ten lambs had ROSC before epinephrine administration and 2 died during instrumentation. Among 28 lambs that received epinephrine, 2/6 in 0.01 mg/kg-1 mL flush, 3/6 in 0.01 mg/kg-3 mL/kg flush, 5/7 in 0.03 mg/kg-1 mL flush and 9/9 in 0.03 mg/kg-3 mL/kg flush achieved ROSC (p=0.02). ROSC was five times faster with 0.03 mg/kg epinephrine compared with 0.01 mg/kg (adjusted HR (95% CI) 5.08 (1.7 to 15.25)) and three times faster with 3 mL/kg flush compared with 1 mL flush (3.5 (1.27 to 9.71)). Plasma epinephrine concentrations were higher with 0.01 mg/kg-3 mL/kg flush (adjusted geometric mean ratio 6.0 (1.4 to 25.7)), 0.03 mg/kg-1 mL flush (11.3 (2.1 to 60.3)) and 0.03 mg/kg-3 mL/kg flush (11.0 (2.2 to 55.3)) compared with 0.01 mg/kg-1 mL flush., Conclusions: 0.03 mg/kg epinephrine dose with 3 mL/kg flush volume is associated with the highest ROSC rate, increases peak plasma epinephrine concentrations and hastens time to ROSC. Clinical trials evaluating optimal epinephrine dose and flush volume are warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Changes in temperature, precipitation, sea level, and coastal storms will likely increase the vulnerability of infrastructure across the USA. Using models that analyze vulnerability, impacts, and adaptation, this paper estimates impacts to railroad, roads, and coastal properties under three infrastructure management response scenarios: No Adaptation; Reactive Adaptation, and Proactive Adaptation. Comparing damages under each of these potential responses provides strong support for facilitating effective adaptation in these three sectors. Under a high greenhouse gas emissions scenario and without adaptation, overall costs are projected to range in the $100s of billions annually by the end of this century. The first (reactive) tier of adaptation action, however, reduces costs by a factor of 10, and the second (proactive) tier reduces total costs across all three sectors to the low $10s of billions annually. For the rail and road sectors, estimated costs for Reactive and Proactive Adaptation scenarios capture a broader share of potential impacts, including selected indirect costs to rail and road users, and so are consistently about a factor of 2 higher than prior estimates. The results highlight the importance of considering climate risks in infrastructure planning and management.

The 7th edition of the Textbook of Neonatal Resuscitation recommends administration of epinephrine via an umbilical venous catheter (UVC) inserted 2-4 cm below the skin, followed by a 0.5-mL to 1-mL flush for severe bradycardia despite effective ventilation and chest compressions (CC). This volume of flush may not be adequate to push epinephrine to the right atrium in the absence of intrinsic cardiac activity during CC. The objective of our study was to evaluate the effect of 1-mL and 2.5-mL flush volumes after UVC epinephrine administration on the incidence and time to achieve return of spontaneous circulation (ROSC) in a near-term ovine model of perinatal asphyxia induced cardiac arrest. After 5 min of asystole, lambs were resuscitated per Neonatal Resuscitation Program (NRP) guidelines. During resuscitation, lambs received epinephrine through a UVC followed by 1-mL or 2.5-mL normal saline flush. Hemodynamics and plasma epinephrine concentrations were monitored. Three out of seven (43%) and 12/15 (80%) lambs achieved ROSC after the first dose of epinephrine with 1-mL and 2.5-mL flush respectively ( p = 0.08). Median time to ROSC and cumulative epinephrine dose required were not different. Plasma epinephrine concentrations at 1 min after epinephrine administration were not different. From our pilot study, higher flush volume after first dose of epinephrine may be of benefit during neonatal resuscitation. More translational and clinical trials are needed.

The optimal timing of cord clamping in asphyxia is not known. Our aims were to determine the effect of ventilation (sustained inflation-SI vs. positive pressure ventilation-V) with early (ECC) or delayed cord clamping (DCC) in asphyxiated near-term lambs. We hypothesized that SI with DCC improves gas exchange and hemodynamics in near-term lambs with asphyxial bradycardia. A total of 28 lambs were asphyxiated to a mean blood pressure of 22 mmHg. Lambs were randomized based on the timing of cord clamping (ECC-immediate, DCC-60 s) and mode of initial ventilation into five groups: ECC + V, ECC + SI, DCC, DCC + V and DCC + SI. The magnitude of placental transfusion was assessed using biotinylated RBC. Though an asphyxial bradycardia model, 2-3 lambs in each group were arrested. There was no difference in primary outcomes, the time to reach baseline carotid blood flow (CBF), HR ≥ 100 bpm or MBP ≥ 40 mmHg. SI reduced pulmonary (PBF) and umbilical venous (UV) blood flow without affecting CBF or umbilical arterial blood flow. A significant reduction in PBF with SI persisted for a few minutes after birth. In our model of perinatal asphyxia, an initial SI breath increased airway pressure, and reduced PBF and UV return with an intact cord. Further clinical studies evaluating the timing of cord clamping and ventilation strategy in asphyxiated infants are warranted.

(1) Background: Optimal initial oxygen (O 2 ) concentration in preterm neonates is controversial. Our objectives were to compare the effect of delayed cord clamping with ventilation (DCCV) to early cord clamping followed by ventilation (ECCV) on O 2 exposure, gas exchange, and hemodynamics in an asphyxiated preterm ovine model. (2) Methods: Asphyxiated preterm lambs (127-128 d) with heart rate <90 bpm were randomly assigned to DCCV or ECCV. In DCCV, positive pressure ventilation (PPV) was initiated with 30-60% O 2 and titrated based on preductal saturations (SpO 2 ) with an intact cord for 5 min, followed by clamping. In ECCV, the cord was clamped, and PPV was initiated. (3) Results: Fifteen asphyxiated preterm lambs were randomized to DCCV (N = 7) or ECCV (N = 8). The inspired O 2 (40 ± 20% vs. 60 ± 20%, p < 0.05) and oxygen load (520 (IQR 414-530) vs. 775 (IQR 623-868), p-0.03) in the DCCV group were significantly lower than ECCV. Arterial oxygenation and carbon dioxide (PaCO 2 ) levels were significantly lower and peak pulmonary blood flow was higher with DCCV. (4) Conclusion: In asphyxiated preterm lambs, resuscitation with an intact cord decreased O 2 exposure load improved ventilation with an increase in peak pulmonary blood flow in the first 5 min.

Purpose: In-house computer-aided surgical design and computer-aided manufacturing (CAD/CAM) can be used in oral and maxillofacial surgery for virtual surgical planning and 3-dimensional printing of patient-specific models. The purpose of this study was to measure the cost and accuracy of an in-house CAD/CAM workflow for maxillofacial free flap reconstruction., Materials and Methods: A retrospective cohort study of patients undergoing mandibular resection and free flap reconstruction was performed between July 2017 and March 2018 in which in-house CAD/CAM was used. The predictor variable was the in-house CAD/CAM workflow. The outcome variables were in-house workflow cost, as measured by the material expenses, and accuracy, as measured by comparative distance, osteotomy angle, and surfaced overlay measurements and the root mean square (RMS) between the preoperative virtual reconstructive plan and the postoperative computed tomography scan. Additional variables evaluated were time required for in-house CAD/CAM workflow, and clinical and radiographic outcomes., Results: In-house CAD/CAM was used for 26 patients undergoing mandibular resection for benign or malignant disease and free flap reconstruction with fibula (n = 24) or scapula free flap (n = 2). Overall flap success rate was 95%. The mean in-house workflow cost per case was $3.87 USD. There were no significant differences between the mean comparative distance and osteotomy angle measurements between the planned and actual mandibular reconstructions with an RMS ranging from 5.11 to 9.00 mm for distance measurements and 17.41° for the osteotomy angle measurements. The mean surface overlay difference was 1.90 mm with an RMS of 3.72 mm., Conclusions: The in-house CAD/CAM workflow is a low cost and accurate option for maxillofacial free flap reconstruction. The in-house workflow should be considered as an alternative to current practices using proprietary systems in select cases., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Infants with hypoxic-ischemic injury often require cardiopulmonary resuscitation. Mitochondrial failure to generate adenosine triphosphate (ATP) during hypoxic-ischemic reperfusion injury contributes to cellular damage. Current postnatal strategies to improve outcome in hypoxic-ischemic injury need sophisticated equipment to perform servo-controlled cooling. Administration of intravenous pyruvate, an antioxidant with favorable effects on mitochondrial bioenergetics, is a simple intervention that can have a global impact. We hypothesize that the administration of pyruvate following the return of spontaneous circulation (ROSC) would improve cardiac function, systemic hemodynamics, and oxygen utilization in the brain in newborn lambs with cardiac arrest (CA)., Methods: Term lambs were instrumented, delivered by C-section and asphyxia induced by umbilical cord occlusion along with clamping of the endotracheal tube until asystole; Lambs resuscitated following 5 min of CA; upon ROSC, lambs were randomized to receive pyruvate or saline infusion over 90 min and ventilated for 150 min postinfusion. Pulmonary and systemic hemodynamics and arterial gases monitored. We measured plasma pyruvate, tissue lactate, and ATP levels (heart and brain) in both groups., Results: Time to ROSC was not different between the two groups. Systolic and diastolic blood pressures, stroke volume, arterial oxygen content, and cerebral oxygen delivery were similar between the two groups. The cerebral metabolic rate of oxygen was higher following pyruvate infusion; higher oxygen consumption in the brain was associated with lower plasma levels but higher brain ATP levels compared to the saline group., Conclusions: Pyruvate promotes energy generation accompanied by efficient oxygen utilization in the brain and may facilitate additional neuroprotection in the presence of hypoxic-ischemic injury., (© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Immunoglobulin replacement has been standard therapy for patients with primary immunodeficiency diseases (PIDD). Intravenous immunoglobin (IVIg) is delivered at the hospital, whereas subcutaneous immunoglobin (SCIg) is used for home-based treatment. The aim of the study was to determine the advantages and disadvantages of IVIg and SCIg in Polish children aged 1-5 years, with PIDD, and the satisfaction of their parents / caregivers regarding immunoglobulin replacement., Methods: The research involved parents of 23 children with PIDD, aged 1-5 years. All children were given IVIg therapy and after at least 6 months they were switched towards home SCIg therapy for at least 6 months. A questionnaire assessing advantages and disadvantages of preferred types of treatment and the quality of life of PIDD patients' families' lives was used., Results: The research showed that IVIg therapy was better accepted by parents than SCIg therapy (P = 0.034) for the following reasons: It made it possible for the children to receive treatment once per month (60%); it reduced the fear of injecting the children (60%), and it provided better control of the disease through regular visits to the hospital (53.33%). Parents noticed, however, that IVIg had a significant impact on absence at school or work (70%). Parents who preferred SCIg for their children were guided mainly by the smaller number of side effects (40%), and the fact that the treatment did not interfere with parents' work or the children's school (40%)., Conclusion: The results showed that IVIg therapy was better accepted by parents than SCIg therapy Parents of children with SCIg are less satisfied with their life, and feel anxiety about their children disease, which is related to administering the medicine by themselves., (© 2019 Japan Pediatric Society.)

Medication-related osteonecrosis of jaws (MRONJ) is one of the most complicated inflammatory conditions in oral and maxillofacial region. It is very difficult to correctly evaluate the degree and extent of necrosis and infection. This refractory osteonecrosis often needs extended surgery, leading to impaired quality-of-life. We have performed hyperbaric oxygen therapy (HBO) combined with conservative surgery for advanced cases. We have appraised the value of FDG-PET and 3-phase bone scintigraphy in the diagnosis and management of this condition. MRONJ showed significantly higher SUV max on FDG-PET than the others. Although the 3 phase pool bone images did not change significantly, perfusion and static bone image as well as PET showed remarkable response to HBO for MRONJ. SUV max after HBO was significantly lower than those of before HBO. These preliminary results indicate that FDG-PET is useful for monitoring the effect of HBO for MRONJ.

The current guidelines recommend the use of 100% O₂ during resuscitation of a neonate requiring chest compressions (CC). Studies comparing 21% and 100% O₂ during CC were conducted in postnatal models and have not shown a difference in incidence or timing of return of spontaneous circulation (ROSC). The objective of this study is to evaluate systemic oxygenation and oxygen delivery to the brain during CC in an ovine model of perinatal asphyxial arrest induced by umbilical cord occlusion. Pulseless cardiac arrest was induced by umbilical cord occlusion in 22 lambs. After 5 min of asystole, lambs were resuscitated with 21% O₂ as per Neonatal Resuscitation Program (NRP) guidelines. At the onset of CC, inspired O₂ was either increased to 100% O₂ ( n = 25) or continued at 21% ( n = 9). Lambs were ventilated for 30 min post ROSC and FiO₂ was gradually titrated to achieve preductal SpO₂ of 85-95%. All lambs achieved ROSC. During CC, PaO₂ was 21.6 ± 1.6 mm Hg with 21% and 23.9 ± 6.8 mm Hg with 100% O₂ ( p = 0.16). Carotid flow was significantly lower during CC (1.2 ± 1.6 mL/kg/min in 21% and 3.2 ± 3.4 mL/kg/min in 100% oxygen) compared to baseline fetal levels (27 ± 9 mL/kg/min). Oxygen delivery to the brain was 0.05 ± 0.06 mL/kg/min in the 21% group and 0.11 ± 0.09 mL/kg/min in the 100% group and was significantly lower than fetal levels (2.1 ± 0.3 mL/kg/min). Immediately after ROSC, lambs ventilated with 100% O₂ had higher PaO₂ and pulmonary flow. It was concluded that carotid blood flow, systemic PaO₂, and oxygen delivery to the brain are very low during chest compressions for cardiac arrest irrespective of 21% or 100% inspired oxygen use during resuscitation.

Background: Distressed infants in the delivery room and those that have completed postnatal transition are both resuscitated according to established neonatal resuscitation guidelines, often with endotracheal (ET) epinephrine at the same dose. We hypothesized that ET epinephrine would have higher bioavailability in a post-transitional compared to transitioning newborn model due to absence of fetal lung liquid and intra-cardiac shunts., Methods: 15 term fetal (transitioning newborn) and 6 postnatal lambs were asphyxiated by umbilical cord and ET tube occlusion respectively. Lambs were resuscitated after 5 min of asystole. ET epinephrine (0.1 mg/kg) was administered after 1 min of positive pressure ventilation (PPV) and chest compressions, and repeated 3 min later, followed by intravenous (IV) epinephrine (0.03 mg/kg) every 3 min until return of spontaneous circulation (ROSC). Serial plasma epinephrine concentrations were measured., Results: Peak plasma epinephrine concentrations were lower in transitioning newborns as compared to postnatal lambs: after a single ET dose (145.36 ± 135.5 ng/ml vs 553.54 ± 215 ng/ml, p < 0.01) and after two ET doses (443 ± 192.49 ng/ml vs 1406 ± 420.8 ng/ml, p < 0.01). The rates of ROSC with a single ET dose were similar in both groups (40% vs 50% in newborn and postnatal respectively, p > 0.99). There was a higher incidence of post-ROSC tachycardia and increased carotid blood flow in the postnatal group., Conclusions: In the postnatal period, ET epinephrine at currently recommended doses resulted in higher peak epinephrine concentrations, post-ROSC tachycardia and cerebral reperfusion without significant differences in incidence of ROSC. Further studies evaluating the optimal dose of ET epinephrine during the postnatal period are warranted., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The Neonatal Resuscitation Program recommends initial resuscitation of preterm infants with low oxygen (O 2 ) followed by titration to target preductal saturations (SpO 2 ). We studied the effect of resuscitation with titrated O 2 on gas exchange, pulmonary, and systemic hemodynamics., Methodology: Twenty-nine preterm lambs (127 d gestation) were randomized to resuscitation with 21% O 2 (n = 7), 100% O 2 (n = 6), or initiation at 21% and titrated to target SpO 2 (n = 16). Seven healthy term control lambs were ventilated with 21% O 2 ., Results: Preductal SpO 2 achieved by titrating O 2 was within the desired range similar to term lambs in 21% O 2 . Resuscitation of preterm lambs with 21% and 100% O 2 resulted in SpO 2 below and above the target, respectively. Ventilation of preterm lambs with 100% O 2 and term lambs with 21% O 2 effectively decreased pulmonary vascular resistance (PVR). In contrast, preterm lambs with 21% O 2 and titrated O 2 demonstrated significantly higher PVR than term lambs on 21% O 2 ., Conclusion(s): Initial resuscitation with 21% O 2 followed by titration of O 2 led to suboptimal pulmonary vascular transition at birth in preterm lambs. Ventilation with 100% O 2 in preterm lambs caused hyperoxia but reduced PVR similar to term lambs on 21% O 2 . Studies evaluating the initiation of resuscitation at a higher O 2 concentration followed by titration based on SpO 2 in preterm neonates are needed.

Birth asphyxia accounts for nearly one million deaths worldwide each year, and is one of the primary causes of early neonatal morbidity and mortality. Many aspects of the current neonatal resuscitation guidelines remain controversial given the difficulties in conducting randomized clinical trials owing to the infrequent and often unpredictable need for extensive resuscitation. Most studies on neonatal resuscitation stem from manikin models that fail to truly reflect physiologic changes or piglet models that have cleared their lung fluid and that have completed the transition from fetal to neonatal circulation. The present protocol provides a detailed step-by-step description on how to create a perinatal asphyxiated fetal lamb model. The proposed model has a transitioning circulation and fluid-filled lungs, which mimics human newborns following delivery, and is, therefore, an excellent animal model to study newborn physiology. An important limitation to lamb experiments is the higher associated cost.

Objective: Continuous chest compressions are more effective during resuscitation in adults. Sustained inflation rapidly establishes functional residual capacity in fluid-filled lungs at birth. We sought to compare the hemodynamics and success in achieving return of spontaneous circulation in an asphyxial cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs between subjects receiving continuous chest compressions during sustained inflation and those receiving conventional 3:1 compression-to-ventilation resuscitation., Design: Prospective, randomized, animal model study., Setting: An experimental laboratory., Subjects: Fourteen newborn term gestation lambs., Interventions: Lambs were randomized into two groups: 3:1 compression-to-ventilation (control) and continuous chest compressions during sustained inflation. The umbilical cord was occluded to induce asphyxia and asystole. The control group was resuscitated per NRP guidelines. In the sustained inflation + continuous chest compressions group, sustained inflation at 35 cm H2O was provided for 30 seconds with 1-second interruptions before another sustained inflation was provided. One hundred twenty chest compressions/min started after the initial sustained inflation. The first dose of IV epinephrine was given at 6 minutes if return of spontaneous circulation was not achieved and then every 3 minutes until return of spontaneous circulation or for a total of four doses., Measurement and Results: All lambs achieved return of spontaneous circulation in a comparable median time (interquartile range) of 390 seconds (225-405 s) and 345 seconds (204-465 s) in the sustained inflation + continuous chest compressions and control groups, respectively. Four of seven (sustained inflation + continuous chest compressions) and three of six (control) lambs required epinephrine to achieve return of spontaneous circulation. Diastolic blood pressures were lower in the sustained inflation + continuous chest compressions (4 ± 2 mm Hg) compared to the control group (7 ± 2 mm Hg), p < 0.05. PaCO2, PaO2, and lactate were similar between the groups during the study period., Conclusion: In this perinatal cardiac arrest lamb model with transitioning fetal circulation and fluid-filled lungs, sustained inflation + continuous chest compressions is as effective as 3:1 compression-to-ventilation resuscitation in achieving return of spontaneous circulation. Half the lambs achieved return of spontaneous circulation without epinephrine. continuous chest compressions during sustained inflation reduced diastolic pressures but did not alter gas exchange or carotid blood flow compared to 3:1 compression-to-ventilation resuscitation.

Background: In neonates requiring chest compression (CC) during resuscitation, neonatal resuscitation program (NRP) recommends against relying on a single feedback device such as end-tidal carbon dioxide (ETCO 2 ) or saturations (SpO 2 ) to determine return of spontaneous circulation (ROSC) until more evidence becomes available., Methods: We evaluated the role of monitoring ETCO 2 during resuscitation in a lamb model of cardiac arrest induced by umbilical cord occlusion (n = 21). Lambs were resuscitated as per NRP guidelines. Systolic blood pressure (SBP), carotid and pulmonary blood flows along with ETCO 2 and blood gases were continuously monitored. Resuscitation was continued for 20 min or until ROSC (whichever was earlier). Adequate CC was arbitrarily defined as generation of 30 mmHg SBP during resuscitation. ETCO 2 thresholds to predict adequacy of CC and detect ROSC were determined., Results: Significant relationship between ETCO 2 and adequate CC was noted during resuscitation (AUC-0.735, P < 0.01). At ROSC (n = 12), ETCO 2 rapidly increased to 57 ± 20 mmHg with a threshold of ≥32 mmHg being 100% sensitive and 97% specific to predict ROSC., Conclusion: In a large mammalian model of perinatal asphyxia, continuous ETCO 2 monitoring predicted adequacy of CC and detected ROSC. These findings suggest ETCO 2 in conjunction with other devices may be beneficial during CC and predict ROSC.

Purpose: Current knowledge about pulmonary/systemic hemodynamics and gas exchange during neonatal resuscitation in a model of transitioning fetal circulation with fetal shunts and fluid-filled alveoli is limited. Using a fetal lamb asphyxia model, we sought to determine whether hemodynamic or gas-exchange parameters predicted successful return of spontaneous circulation (ROSC)., Methods: The umbilical cord was occluded in 22 lambs to induce asphyxial cardiac arrest. Following five minutes of asystole, resuscitation as per AHA-Neonatal Resuscitation Program guidelines was initiated. Hemodynamic parameters and serial arterial blood gases were assessed during resuscitation., Results: ROSC occurred in 18 lambs (82%) at a median (IQR) time of 120 (105-180) seconds. There were no differences in hemodynamic parameters at baseline and at any given time point during resuscitation between the lambs that achieved ROSC and those that did not. Blood gases at arrest prior to resuscitation were comparable between groups. However, lambs that achieved ROSC had lower PaO2, higher PaCO2, and lower lactate during resuscitation. Increase in diastolic blood pressures induced by epinephrine in lambs that achieved ROSC (11 ±4 mmHg) did not differ from those that were not resuscitated (10 ±6 mmHg). Low diastolic blood pressures were adequate to achieve ROSC., Conclusions: Hemodynamic parameters in a neonatal lamb asphyxia model with transitioning circulation did not predict success of ROSC. Lactic acidosis, higher PaO2 and lower PaCO2 observed in the lambs that did not achieve ROSC may represent a state of inadequate tissue perfusion and/or mitochondrial dysfunction.

Background: Epinephrine administered by low umbilical venous catheter (UVC) or endotracheal tube (ETT) is indicated in neonates who fail to respond to positive pressure ventilation and chest compressions at birth. Pharmacokinetics of ETT epinephrine via fluid-filled lungs or UVC epinephrine in the presence of fetal shunts is unknown. We hypothesized that epinephrine administered by ETT or low UVC results in plasma epinephrine concentrations and rates of return of spontaneous circulation (ROSC) similar to right atrial (RA) epinephrine., Methods and Results: Forty-four lambs were randomized into the following groups: RA epinephrine (0.03 mg/kg), low UVC epinephrine (0.03 mg/kg), postcompression ETT epinephrine (0.1 mg/kg), and precompression ETT epinephrine (0.1 mg/kg). Asystole was induced by umbilical cord occlusion. Resuscitation was initiated following 5 minutes of asystole. Thirty-eight of 44 lambs achieved ROSC (10/11, 9/11, and 12/22 in the RA, UVC, and ETT groups, respectively; subsequent RA epinephrine resulted in a total ROSC of 19/22 in the ETT groups). Median time (interquartile range) to achieve ROSC was significantly longer in the ETT group (including those that received RA epinephrine) compared to the intravenous group (4.5 [2.9-7.4] versus 2 [1.9-3] minutes; P =0.02). RA and low UVC epinephrine administration achieved comparable peak plasma epinephrine concentrations (470±250 versus 450±190 ng/mL) by 1 minute compared to ETT values of 130±60 ng/mL at 5 minutes; P =0.03. Following ROSC with ETT epinephrine alone, there was a delayed peak epinephrine concentration (652±240 ng/mL)., Conclusions: The absorption of ETT epinephrine is low and delayed at birth. RA and low UVC epinephrine rapidly achieve high plasma concentrations resulting in ROSC., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Oral and Maxillofacial Surgeons have increasing opportunities to train in head and neck oncologic and reconstructive surgery. The development of a fellowship training programs within our speciality has had a transformative effect on the speciality. This survey by the commitee on Maxillofacial Oncology and Reconstructive is aimed to evaluate the impact of fellowship training on the careers of the fellows and speciality from 2005-2015., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: There are no effective treatment options for patients with advanced adenoid cystic carcinoma (ACC). Here, we evaluated the effect of a new small molecule inhibitor of the MDM2-p53 interaction (MI-773) in preclinical models of ACC., Experimental Design: To evaluate the anti-tumor effect of MI-773, we administered it to mice harboring three different patient-derived xenograft (PDX) models of ACC expressing functional p53. The effect of MI-773 on MDM2, p53, phospho-p53, and p21 was examined by Western blots in 5 low passage primary human ACC cell lines and in MI-773-treated PDX tumors., Results: Single-agent MI-773 caused tumor regression in the 3 PDX models of ACC studied here. For example, we observed a tumor growth inhibition index of 127% in UM-PDX-HACC-5 tumors that was associated with an increase in the fraction of apoptotic cells (P = 0.015). The number of p53-positive cells was increased in MI-773-treated PDX tumors (P < 0.001), with a correspondent shift in p53 localization from the nucleus to the cytoplasm. Western blots demonstrated that MI-773 potently induced expression of p53 and its downstream targets p21, MDM2, and induced phosphorylation of p53 (serine 392) in low passage primary human ACC cells. Notably, MI-773 induced a dose-dependent increase in the fraction of apoptotic ACC cells and in the fraction of cells in the G1 phase of cell cycle (P < 0.05)., Conclusions: Collectively, these data demonstrate that therapeutic inhibition of the MDM2-p53 interaction with MI-773 activates downstream effectors of apoptosis and causes robust tumor regression in preclinical models of ACC. Clin Cancer Res; 22(14); 3550-9. ©2016 AACR., (©2016 American Association for Cancer Research.)

Transcatheter aortic valve replacement (TAVR) is gaining favor as a treatment for aortic stenosis in patients at high risk for the open surgical approach. The following is a report of a 95-year-old woman with severe aortic stenosis who presented for TAVR with an Edwards SAPIEN valve. Her medical history included pacemaker-dependent complete heart block and a recent episode of congestive heart failure secondary to a non-ST segment elevation myocardial infarction. The TAVR was performed successfully through an open left femoral artery approach, and the patient was found to have a new perimembranous ventricular septal defect identified postoperatively.

A small sub-population of cells characterized by increased tumorigenic potential, ability to self-renew and to differentiate into cells that make up the tumor bulk, has been characterized in some (but not all) tumor types. These unique cells, namedcancer stem cells, are considered drivers of tumor progression in these tumors. The purpose of this work is to understand if cancer stem cells play a functional role in the tumorigenesis of salivary gland mucoepidermoid carcinomas. Here, we investigated the expression of putative cancer stem cell markers (ALDH, CD10, CD24, CD44) in primary human mucoepidermoid carcinomas by immunofluorescence, in vitro salisphere assays, and in vivo tumorigenicity assays in immunodeficient mice. Human mucoepidermoid carcinoma cells (UM-HMC-1, UM-HMC-3A, UM-HMC-3B) sorted for high levels of ALDH activity and CD44 expression (ALDHhighCD44high) consistently formed primary and secondary salispheres in vitro, and showed enhanced tumorigenic potential in vivo (defined as time to tumor palpability, tumor growth after palpability), when compared to ALDHlowCD44low cells. Cells sorted for CD10/CD24, and CD10/CD44 showed varying trends of salisphere formation, but consistently low in vivo tumorigenic potential. And finally, cells sorted for CD44/CD24 showed inconsistent results in salisphere formation and tumorigenic potential assays when different cell lines were evaluated. Collectively, these data demonstrate that salivary gland mucoepidermoid carcinomas contain a small population of cancer stem cells with enhanced tumorigenic potential and that are characterized by high ALDH activity and CD44 expression. These results suggest that patients with mucoepidermoid carcinoma might benefit from therapies that ablate these highly tumorigenic cells.

Objectives: To evaluate the anti-tumor effect of BM-1197, a new potent and highly specific small molecule inhibitor of Bcl-2/Bcl-xL, in preclinical models of human adenoid cystic carcinoma (ACC)., Methods: Low passage primary human adenoid cystic carcinoma cells (UM-HACC-2A,-2B,-5,-6) and patient-derived xenograft (PDX) models (UM-PDX-HACC) were developed from surgical specimens obtained from 4 patients. The effect of BM-1197 on cell viability and cell cycle were evaluated in vitro using this panel of low passage ACC cells. The effect of BM-1197 on tumor growth, recurrence and tumor cell apoptosis in vivo was evaluated with the PDX model of ACC (UM-PDX-HACC-5)., Results: Exposure of low passage primary human ACC cells to BM-1197 mediated an IC50 of 0.92-2.82 μM. This correlated with an increase in the fraction of apoptotic cells (p<0.0001) and an increase in caspase-3 activity (p<0.0001), but no noticeable differences in cell cycle (p>0.05). In vivo, BM-1197 inhibited tumor growth (p=0.0256) and induced tumor cell apoptosis (p=0.0165) without causing significant systemic toxicities, as determined by mouse weight over time. Surprisingly, weekly BM-1197 decreased the incidence of tumor recurrence (p=0.0297), as determined by Kaplan-Meier analysis., Conclusion: These data demonstrated that single agent BM-1197 induces apoptosis and inhibits tumor growth in preclinical models of adenoid cystic carcinoma. Notably, single agent BM-1197 inhibited tumor recurrence, which is considered a major clinical challenge in the clinical management of adenoid cystic carcinoma. Collectively, these results suggest that patients with adenoid cystic carcinoma might benefit from therapy with a BH3-mimetic small molecule., (Copyright © 2015 Elsevier Ltd. All rights reserved.)