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An understanding of the interplay between both donor endothelial progenitors and the recipient endothelium (in the case of hematopoietic cell transplant) and recipient endothelial provenance upon the established donor endothelium (in the case of solid organ transplant) is unknown. It is postulated that this interplay and consequences of purported dual endothelial populations may be a component of the post-transplant disease process and contribute to complications of engraftment or rejection. To address this potential confounding and often overlooked arena of vascular biology, a directed brief overview primarily focused on literature presented over the last decade is presented herein., 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., (© 2023 Pace, Steiner, Vercellotti and Somani.)

Background: Acute limb ischemia due to microvascular malperfusion may be refractory to initial therapies. Medicinal leech therapy (hirudotherapy) has been attempted in plastic and reconstructive surgery to improve venous congestion in ischemic flaps; however, there are minimal reports related to ischemia secondary to arterial malperfusion. We evaluated a pediatric cohort from an academic intensive care unit with refractory limb ischemia in whom hirudotherapy was attempted to elucidate its use and outcomes., Method: Institutional patient database was queried to identify pediatric patients (<18 years) who received hirudotherapy in the pediatric critical care unit and met inclusion/exclusion criteria. Patient charts were evaluated for indices including demographics, primary disease, coagulative status, vascular access, vasoactive medication dosing, bleeding, leech use, limb and mortality outcomes. Data was evaluated to identify trends or suspected impact on outcomes., Results: Hirudotherapy was used in 7 patients for limb ischemia, 5 with congenital heart disease, and 2 others with viremic shock. Time to leech application following recognition of ischemia averaged 3 days, with duration of use averaging 3.9 days. Five patients discontinued therapy due to bleeding. Mortality rate was 57%, all secondary to multiorgan failure. In 3 surviving patients, 4 of 5 treated limbs resulted in at minimum partial amputation. Vasoactive-inotropic score tended higher prior to leech application, suggesting a vasoconstrictive pathway for arterial malperfusion. No identifiable trends appeared associated with salvaged limb or adverse effects. Blood loss predictably increased with leech application, as did total transfusion requirement., Conclusion: This case series establishes baseline data for use of hirudotherapy in critically ill children with acute limb ischemia caused by arterial malperfusion. Based on this retrospective cohort, we cannot recommend routine use of hirudotherapy for acute limb ischemia from arterial malperfusion in the pediatric intensive care unit. Application of leeches should be aligned with a protocol defining start and stop parameters, standardized leech utilization, and monitoring for adverse outcomes. Future study would benefit from consensus definitions of study outcomes, including perfusion recovery, tissue/limb salvage and bleeding manifestations. Additional prospective studies are needed prior to any standard or systematic recommendations for use., 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., (© 2023 Resch, Hedstrom, Steiner, Said and Somani.)

This brief review outlines a novel case study with targeted literature search. Patient X was a 21-month-old male who was receiving ongoing treatment for stage M MYCN-amplified high-risk neuroblastoma. Patient X's mother was considering refusal of further cancer-directed therapy because of the child's developmental regression noted during his prolonged hospitalization. Given the underlying malleability of the developing brain in early childhood, access to supportive services that facilitate ongoing neurodevelopment in hospitalized young children is of utmost importance; such services further reduce parental stress and likely enhances parental and medical team efficacy of care., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rapid response teams (RRTs) have been used by multiple hospital systems to enhance patient care and safety. However, processes to document rapid response events (RRE) are often varied among providers and teams, which can lead to suboptimal communication of recommendations to both the primary medical team and family., Methods: A preintervention chart review was conducted from January-March 2018 and revealed suboptimal baseline documentation following RREs. A literature review and survey of RRT team members led to the creation of a standardized document with an Epic SmartPhrase which included six key elements of RRE documentation: physical examination, intervention performed, response to intervention, plan of care, communication with care team, and communication with family. A postintervention chart review was completed from April-June 2019 to assess improvements in documentation with the use of this SmartPhrase., Results: There were 23 RRE activations in the postintervention period, of which 60.8% were due to respiratory distress. The documentation of the six key elements improved (p < .05) after SmartPhrase creation and serial educational interventions., Conclusions: Standardized RRE documentation of six key elements significantly improved with the implementation of an Epic SmartPhrase. Improved quality of documentation enhances communication between team members and can contribute to safer patient care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 National Association for Healthcare Quality.)

Background: Malnutrition occurs in approximately 25% of pediatric intensive care patients and correlates with increased length of stay, prolonged ventilation, and mortality. Anthropometric measurements should be obtained at admission and throughout hospitalization to evaluate nutrition status. We aimed to increase documentation, reporting, and discussion of anthropometric measurements, including height/length, weight, and occipital frontal circumference (OFC) within 24 hours of admission and weekly., Methods: A multifaceted process improvement model was implemented over 1 month. Interventions included education, recruiting nurse champions, process mapping, new equipment, and formal discussion of nutrition status during rounds. A proportions hypothesis test compared frequency of anthropometric measures obtained during each study phase: preintervention, postintervention, and sustainment., Results: In terms of admission metrics over respective study phases, the PICU had fluctuation in weights (91%, 98%, and 97%) and height (49%, 73%, and 71%) and increased rates in OFC (36%, 61%, and 65%). The cardiovascular intensive care unit (CVICU) had stable weights (100%, 100%, and 100%) and increased rates in height (87%, 94%, and 95%) and OFC (28%, 64%, and 86%), respectively. In terms of weekly metrics over study phases, the PICU had fluctuation in weights (91%, 89%, and 93%) and increased rates in heights (38%, 69%, and 76%) and OFC (45%, 76%, and 100%). The CVICU had increased rates in weights (98%, 100%, and 100%) and fluctuations in heights (50%, 83%, and 75%), and OFC (48%, 84%, and 75%)., Conclusions: Interventions increased rates of measurements. During the sustainment phase, there was regression in rates, although these remained above baseline. Additional interventions may increase compliance and foster change in unit culture., (© 2021 American Society for Parenteral and Enteral Nutrition.)

This prospective observational study quantified screen media use within the night-time pre-sleep period in a pediatric intensive care unit and postulated possible implications. Seventy-five patients between the ages of newborn to 19 years old were observed 5 evenings per week for 3 weeks. Trained observers documented the patient's screen use, type of screen used, screen engagement, sleep state, light level, and parental presence. Patients in the ICU had on average 65 minutes of screen media use, per evening. The total screen media use averaged 59 minutes for the 0 to18-month age group; 83 minutes for the 18 to 24-month age group; 66 minutes for 2 to 6 year olds; 72 minutes for 6 to 13 year olds; and 74 minutes for those above 13. This research demonstrates that children are engaging in more screen time during the night hours than is recommended by the AAP., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Bronchiolitis patients are supported with non-invasive conventional modalities (HFNC, CPAP and BiPAP). Neurally Adjusted Ventilatory Assist (NAVA) is a newer mode which supports based on electrical activity of the diaphragm (Edi). It is unclear if non-invasive NAVA is used within optimal operational parameters. The study aim was to evaluate Edi compliance., Methods: A retrospective chart review of bronchiolitis patients admitted to the PICU from January 2015 to January 2018 was undertaken. NAVA compliance within optimal parameters (defined as Edi peak values between 5-15 μV and Edi min < 1μV) was assessed as the primary outcome. Secondary outcomes included PICU length of stay (LOS), duration to minimal respiratory support (defined as 4 L/min or less on HFNC) and intubation rate in the conventional (non-NAVA) and non-invasive NAVA., Results: Sixty-three patients with a mean age of 6.89 months with 30 on NAVA and 33 on non-NAVA support were analyzed. Compliance with optimal Edi peak and Edi min was 50.4% (±37.5%) and 33.8% (±26.2%) respectively. Regression models for PICU LOS with minimal respiratory support and for 1L/kg of HFNC showed adjusted R2= 0.96 and 0.92, respectively. The mean PICU stay for NAVA was 146.00 hrs. (±66.26) versus 69.58 hrs. (±57.69) for the non-NAVA group (p<0.001). Duration to minimal respiratory support was 125.40 hrs. (±54.90) for NAVA versus 58.03 hrs. (±58.97) for non-NAVA group (p<0.001). A higher intubation rate was found in the NAVA group (13.33% versus 3.03%, p=0.296)., Conclusions: We found suboptimal compliance with operational parameters with non-invasive NAVA support. There was longer PICU LOS, time to minimal respiratory support in the NAVA compared to the non-NAVA support.

We have investigated a unique cell type, blood outgrowth endothelial cells (BOEC), as a cell-based gene therapy approach to pulmonary hypertension. BOEC are bona fide endothelial cells, obtained from peripheral blood, that can be expanded to vast numbers, and are amenable to both cryopreservation and genetic modification. We established primary cultures of rat BOEC and genetically altered them to over-express human eNOS plus green fluorescent protein (rBOEC/eNOS) or to express GFP only (rBOEC/GFP). We gave monocrotaline to rats on day 0, and they developed severe pulmonary hypertension. As a Prevention model, we infused saline or rBOEC/GFP or rBOEC/eNOS on day 3, and then examined endpoints on day 24. The rBOEC/eNOS recipients developed elevated NOx (serum and lung) and less severe: elevation of right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary arteriolar muscularization and loss of alveolar density. As an Intervention model, we waited until day 21 to give the test infusions, and we examined endpoints on day 35. The rBOEC/eNOS recipients again developed elevated NOx and manifested the same improvements. Indeed, rBOEC/eNOS infusion not only prevented worsening of RVSP but also partially reversed established arteriolar muscularization. These data suggest that BOEC may be useful as a carrier cell for genetic strategies targeting pulmonary hypertension. Their properties render BOEC amenable to preclinical and scale-up studies, available for autologous therapies, and tolerant of modification and storage for potential future use in patients at risk for PAH, eg, as defined by genetics or medical condition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Elaboration of tumor necrosis factor (TNF) is a very early event in development of ischemia/reperfusion injury pathophysiology. Therefore, TNF may be a prominent mediator of endothelial cell and vascular wall dysfunction in sickle cell anemia, a hypothesis we addressed using NY1DD, S+S Antilles , and SS-BERK sickle transgenic mice. Transfusion experiments revealed participation of abnormally activated blood monocytes exerting an endothelial activating effect, dependent upon Egr-1 in both vessel wall and blood cells, and upon NFκB(p50) in a blood cell only. Involvement of TNF was identified by beneficial impact from TNF blockers, etanercept and infliximab, with less benefit from an IL-1 blocker, anakinra. In therapeutic studies, etanercept ameliorated multiple disturbances of the murine sickle condition: monocyte activation, blood biomarkers of inflammation, low platelet count and Hb, vascular stasis triggered by hypoxia/reoxygenation (but not if triggered by hemin infusion), tissue production of neuro-inflammatory mediators, endothelial activation (monitored by tissue factor and VCAM-1 expression), histopathologic liver injury, and three surrogate markers of pulmonary hypertension (perivascular inflammatory aggregates, arteriolar muscularization, and right ventricular mean systolic pressure). In aggregate, these studies identify a prominent-and possibly dominant-role for an abnormal monocyte-TNF-endothelial activation axis in the sickle context. Its presence, plus the many benefits of etanercept observed here, argue that pilot testing of TNF blockade should be considered for human sickle cell anemia, a challenging but achievable translational research goal., (© 2017 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.)

For infants born with respiratory distress syndrome (RDS), liquid bolus delivery of surfactant administered through an endotracheal tube is common practice. While this method is generally effective, complications such as transient hypoxia, hypercapnia, and altered cerebral blood flow may occur. Aerosolized surfactant therapy has been explored as an alternative. Unfortunately, past efforts have led to disappointing results as aerosols were generated outside the lungs with significant pharyngeal deposition and minimal intrapulmonary instillation. A novel aerosol generator (Microjet™) is evaluated herein for intrapulmonary aerosol generation within an endotracheal tube and tested with Curosurf and Infasurf surfactants. Compared with other aerosol delivery devices, this process utilizes low air flow (range 0.01-0.2 L/min) that is ideal for limiting potential barotrauma to the premature newborn lung. The mass mean diameter (MMD) of the particles for both tested surfactants was less than 4 μm, which is ideal for both uniform and distal lung delivery. As an indicator of phospholipid function, surfactant surface tension was measured before and after aerosol formation; with no significant difference. Moreover, this device has an outside diameter of <1mm, which permits insertion into an endotracheal tube (of even 2.0 mm). In the premature infant where intravenous access is either technically challenging or difficult, aerosol drug delivery may provide an alternative route in patient resuscitation, stabilization and care. Other potential applications of this type of device include the delivery of nutrients, antibiotics, and analgesics via the pulmonary route.

The journey from illness to health may be fraught with unfavorable outcomes, inadvertent errors, or even medical malpractice. Indeed, alleged medical negligence or malpractice is emblematic of the underlying dissonance in what should otherwise be an ideal therapeutic relationship between physicians and patients. The increasing incidence of alleged medical negligence in the West and in the Muslim world has led physicians to fear the threat of litigation. Consequently, this results in defensive medicine, avoiding higher- risk medical and surgical specialties or procedures, and potentially adversarial patient-physician interactions. Medical schools have adopted white coat ceremonies as a symbolic attempt to inculcate students in the healing tradition and; along with the pledging of the Hippocratic Oath, to imbue them with a sense of compassion and duty towards the ill. Such endeavors should serve to motivate trainees and physicians to respond to suffering with continued empathy and effort rather than with suspicion and fear of an unfavorable outcome or alleged negligence. Objective: The purpose of this papers to offer a novel, complimentary approach to the white coat ceremony and the pledging of the Hippocratic Oath, by discerning the Islamic principles of Iman (faith) and Ihsan (a call to virtue) to define an appropriate healing relationship between physicians and patients. In order to introduce students to this tradition of healing, this alternative approach may be introduced, taught, and modeled for physicians-in training in their actual clinical practice. Philosophical Perspective: Since inception of the white coat ceremony in 1993, the Hippocratic perspective has been applied to inculcate a sense of compassion and duty to the ill. Along with recognition of the Human Condition or Fitra; the concept of Iman and Ihsan within the Muslim world should be applied by physicians-in-training to define their duty and their approach to future patients, themselves and their Creator. Such and approach demands a higher level calling than that outlined by the expected standards of Islamic law or Shari'a. Conclusion: Instilling Iman and Ihsan principles as and embedded component of medical treatment potentially should curtail medical malpractice exposure, simplify due process, and improve patients, physician healing relationships.

Aim: To assess predictability of bone mineral density (BMD) of the lumbar spine (LS) determined by dual-energy x-ray absorptiometry (DXA) using by ultrasound speed of sound of the right and left radii (SOS-R and SOS-L) in patients with growth problems., Methods: Ultrasound and DXA were compared in patients with advanced, normal and delayed bone ages assessed by Greulich and Pyle (GP) and Tanner and Whitehouse (TW3) methods., Results: There was a strong correlation (r), of raw scores, between SOS-R and SOS-L, r = 0.81, p = 0.000 and their respective Z-scores, r = 0.78, p = 0.000. Z-score correlations were poor between SOS-R or SOS-L and LS-BMD. Sensitivity, specificity, positive and negative predictive values of SOS-R and Z-scores for predicting normal (>-1 to <1) and low (<-1) LS-BMD were poor. For high (>1) LS-BMD, Z-scores were 22%, 93%, 29% and 90%, respectively, for SOS-R and for SOS-L, 25%, 89%, 20% and 91%. For very low (<-2) LS-BMD, SOS-R and SOS-L were the same, respectively, 29%, 91%, 40% and 86%., Conclusion: Ultrasound of the radius is a poor predictor of radiologically assessed BMD at the LS, especially with delayed bone age., (©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

The goal of this study was to determine if we could establish a mesenchymal stromal line from zebrafish that would support hematopoietic cells. Such a coculture system would be a great benefit to study of the hematopoietic cell-stromal cell interaction in both in vitro and in vivo environments. Zebrafish stromal cells (ZStrC) were isolated from the "mesenchymal" tissue of the caudal tail and expanded in a specialized growth media. ZStrC were evaluated for phenotype, gene expression, and ability to maintain zebrafish marrow cells in coculture experiments. ZStrC showed mesenchymal and endothelial gene expression. Although ZStrC lacked the ability to differentiate into classic mesenchymal stromal cell lineages (i.e., osteocytes, adipocytes, chondrocytes), they did have the capacity for endotube formation on Matrigel and low-density lipoprotein uptake. ZStrC supported marrow cells for >2 weeks in vitro. Importantly, marrow cells were shown to retain homing ability in adoptive transfer experiments. ZStrC were also shown to improve hematopoietic recovery after sublethal irradiation after adoptive transfer. As the zebrafish model grows in popularity and importance in the study of hematopoiesis, new tools to aid in our understanding of the hematopoietic cell-stromal cell interaction are required. ZStrC represent an additional tool in the study of hematopoiesis and will be useful in understanding the factors that mediate the stromal cell-hematopoietic cell interactions that are important in hematopoietic cell maintenance., (Copyright © 2012 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

Studies have demonstrated that increased oxidative stress contributes to the pathogenesis and the development of pulmonary artery hypertension (PAH). Extracellular superoxide dismutase (SOD3) is essential for removing extracellular superoxide anions, and it is highly expressed in lung tissue. However, it is not clear whether endogenous SOD3 can influence the development of PAH. Here we examined the effect of SOD3 knockout on hypoxia-induced PAH in mice and a loss-of-function SOD3 gene mutation (SOD3(E124D)) on monocrotaline (40 mg/kg)-induced PAH in rats. SOD3 knockout significantly exacerbated 2 weeks of hypoxia-induced right ventricular (RV) pressure and RV hypertrophy, whereas RV pressure in SOD3 knockout mice under normoxic conditions is similar to wild-type controls. In untreated control rats at age of 8 weeks, there was no significant difference between wild-type and SOD3(E124D) rats in RV pressure and the ratio of RV weight:left ventricular weight (0.25±0.02 in wild-type rats versus 0.25±0.01 in SOD3(E124D) rats). However, monocrotaline caused significantly greater increases of RV pressure in SOD3(E124D) rats (48.6±1.8 mm Hg in wild-type versus 57.5±3.1 mm Hg in SOD3(E124D) rats), of the ratio of RV weight:left ventricular weight (0.41±0.01 versus 0.50±0.09; P<0.05), and of the percentage of fully muscularized small arterioles in SOD3(E124D) rats (55.2±2.3% versus 69.9±2.6%; P<0.05). Together, these findings indicate that the endogenous SOD3 has no role in the development of PAH under control conditions but plays an important role in protecting the lung from the development of PAH under stress conditions.

The microcirculation is not merely a passive conduit for red cell transport, nutrient and gas exchange, but is instead a dynamic participant contributing to the multiple processes involved in the maintenance of metabolic homeostasis and optimal end-organ function. The microcirculation's angioarchitechture and surface properties influence conduit function and flow dynamics over a wide spectrum of conditions, accommodating many different mechanical, pathological or organ-specific responses. The endothelium itself plays a critical role as the interface between tissues and blood components, participating in the regulation of coagulation, inflammation, vascular tone, and permeability. The complex nitric oxide pathways affect vasomotor tone and influence vascular conduit caliber and distribution density, alter thrombotic propensity, and modify adhesion molecule expression. Nitric oxide pathways also interact with red blood cells and free hemoglobin moieties in normal and pathological conditions. Red blood cells themselves may affect flow dynamics. Altered rheology and compromised NO bioavailability from medical storage or disease states impede microcirculatory flow and adversely modulate vasodilation. The integration of the microcirculation as a system with respect to flow modulation is delicately balanced, and can be readily disrupted in disease states such as sepsis. This review will provide a description of these varied and intricate functions of the microvasculature., ((c) 2010 Elsevier Ltd. All rights reserved.)

The relative contributions of the hydrophilic surfactant proteins (SP)-A and -D to early inflammatory responses associated with lung dysfunction after experimental allogeneic hematopoietic stem cell transplantation (HSCT) were investigated. We hypothesized that the absence of SP-A and SP-D would exaggerate allogeneic T cell-dependent inflammation and exacerbate lung injury. Wild-type, SP-D-deficient (SP-D(-/-)), and SP-A and -D double knockout (SP-A/D(-/-)) C57BL/6 mice were lethally conditioned with cyclophosphamide and total body irradiation and given allogeneic bone marrow plus donor spleen T cells, simulating clinical HSCT regimens. On day 7, after HSCT, permeability edema progressively increased in SP-D(-/-) and SP-A/D(-/-) mice. Allogeneic T cell-dependent inflammatory responses were also increased in SP-D(-/-) and SP-A/D(-/-) mice, but the altered mediators of inflammation were not identical. Compared with wild-type, bronchoalveolar lavage fluid (BALF) levels of nitrite plus nitrate, GM-CSF, and MCP-1, but not TNF-alpha and IFN-gamma, were higher in SP-D-deficient mice before and after HSCT. In SP-A/D(-/-) mice, day 7 post-HSCT BALF levels of TNF-alpha and IFN-gamma, in addition to nitrite plus nitrate and MCP-1, were higher compared with mice lacking SP-D alone. After HSCT, both SP-A and SP-D exhibited anti-inflammatory lung-protective functions that were not completely redundant in vivo.

Objective: To assess the validity of bone age assessment by ultrasonography (US)., Study Design: Wrist US was performed on children (n = 100) undergoing radiographic bone age and compared with bone age estimation by a radiologist in the clinic and by endocrinologists under blinded conditions with Greulich and Pyle (GP) and Tanner and Whitehouse (TW3) methods., Results: The strongest correlation (r(2)) was seen in the radiographic bone age assessment between the 2 endocrinologists using the GP method (96.7%). The poorest correlation was seen when comparing radiographic methods to US of either wrist (74.6% to 82.6%). When bone age correlations were divided into normal, delayed or advanced, the highest correlation between the radiographic and US methods was found in the normal bone age group (80.9% to 86.1%) with weaker correlations for the delayed bone age group (77.1% to 86.9%) and the advanced bone age group (62.2% to 81.1%). US tended to overread delayed bone age and underread advanced bone age. US had poor positive and negative predictive value for identification of a normal or delayed bone age. The negative predictive value of US was 91% for an advanced bone age., Conclusions: On the basis of our data, US assessment should not yet be considered a valid replacement for radiographic bone age determination.

Endothelial cells are an attractive vehicle for gene therapy because they may be used in an autologous fashion and may allow for direct exposure of the gene product into the intravascular space. To explore this future potential, a reproducible system was developed for the culture of murine blood outgrowth endothelial cells. These cells demonstrated acetylated low-density lipoprotein (LDL) incorporation, matrigel tube formation, and specific endothelial staining characteristics, namely P1H12, VeCAD, vascular cell adhesion molecule (VCAM), vWF, platelet endothelial cell adhesion molecule (PECAM-1), and vascular endothelial growth factor receptor-2 (VEGFR2). They were also negative for smooth muscle actin and monocytic markers CD11b, CD14, and CD16. Moreover, these cells were amendable to gene transfer with red fluorescent and green fluorescent expression vectors as well as human Factor VIII (hFVIII) while maintaining endothelial characteristics. Both source- and gene-introduced cells also manifested excellent proliferative potential. Furthermore, murine blood outgrowth endothelial cells (BOECs) demonstrated persistent in vivo seeding in the liver, lung, spleen, and bone morrow of recipient mice.