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Objective: To study the applicability of on table extubation (OTE) protocol following congenital cardiac surgery in a low-resource setting and its impact on the length of intensive care unit (ICU) stay, hospital stay, hospitalization cost, parental anxiety, and nurse anxiety. Materials and Methods: In this prospective, nonrandomized, observational single-center study, we included all children above 1 year of age undergoing congenital cardiac surgery. We evaluated them for the feasibility of OTE using a prespecified protocol following separation from cardiopulmonary bypass. The data were prospectively collected on 60 children more than 1 year of age, belonging to the Risk Adjustment for Congenital Heart Surgery 1, 2, 3, and 4 groups and divided into two groups: those who underwent successful OTE and those who were ventilated for any duration postoperatively (30 children in each group). Duration of hospital stay, ICU stay, and total hospital cost were collected. Anxiety levels of the primary caregiver (nurse) in the ICU and the mother were assessed immediately after the arrival of the child in the ICU using the State Trait Anxiety Inventory (STAI). Results: Children who were extubated immediately following congenital cardiac surgery had significantly shorter ICU stay (median 20 [19, 22] h vs. 22 [20, 43] h [P < 0.05]). Patients extubated on table had a significant reduction in hospital cost {median Rs. 161,000 (138,330; 211,900), approximately USD 1970 (P < 0.05)} when compared to children who were ventilated postoperatively {median Rs. 201,422 (151,211; 211,900), approximately USD 2464}. The anxiety level in mothers was significantly less when their child was extubated in the operating room (STAI 36.5 ± 5.4 vs. 47.4 ± 7.4, P < 0.001). However, for the same subset of patients, anxiety level was significantly higher in the ICU nurse (STAI 46.0 ± 5.6 vs. 37.8 ± 4.1, P < 0.05). Conclusion: OTE following congenital cardiac surgery is associated with a shorter duration of ICU stay and hospital stay. It also reduces the total hospital cost and the anxiety level in mothers of children undergoing congenital heart surgery. However, the primary bedside caregiver during the child's ICU stay had increased anxiety managing patients with OTE. [ABSTRACT FROM AUTHOR]

Classic alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare congenital lung disorder presenting in the early neonatal period with refractory hypoxemic respiratory failure and pulmonary hypertension. No curative treatment is currently available. Although definitive diagnosis is obtained by histology, lung biopsy is often challenging in unstable, critically ill neonates. Molecular diagnosis has been achieved with chromosomal microarray and targeted gene sequencing; however, each of these modalities can be limited by turnaround time, coverage of the genome, and inability to detect all pathogenic variant types for ACDMPV. We present a case of ACDMPV diagnosed via rapid genome sequencing and posit that rapid genomic sequencing, including both rapid exome and genome sequencing, has an expanding role in severe neonatal respiratory failure as a comprehensive and noninvasive approach to timely diagnosis. [ABSTRACT FROM AUTHOR]

Tropomyosin (TM) is involved in [Ca.sup.2+]-mediated muscle contraction and relaxation in the heart. Striated muscle [alpha]-TM is the major isoform expressed in the heart. The expression of striated muscle [beta]-TM in the murine myocardium results in a decreased rate of relaxation and increased myofilament [Ca.sup.2+] sensitivity. Replacing the carboxyl terminus (amino acids 258-284) of [alpha]-TM with [beta]-TM (a troponin T-binding region) results in decreased rates of contraction and relaxation in the heart and decreased myofilament [Ca.sup.2+] sensitivity. We hypothesized that the putative internal troponin T-binding domain (amino acids 175-190) of [beta]-TM may be responsible for the increased myofilament [Ca.sup.2+] sensitivity observed when the entire [beta]-TM is expressed in the heart. To test this hypothesis, we generated transgenic mice that expressed chimeric TM containing [beta]-TM amino acids 175-190 in the backbone of [alpha]-TM (amino acids 1-174 and 191-284). These mice expressed 16-57% chimeric TM and did not develop cardiac hypertrophy or any other morphological changes. Physiological analysis showed that these hearts exhibited decreased rates of contraction and relaxation and a positive response to isoproterenol. Skinned fiber bundle analyses showed a significant increase in myofilament [Ca.sup.2+] sensitivity. Biophysical experiments demonstrated that the exchanged amino acids did not influence the flexibility of the TM. This is the first study to demonstrate that a specific domain within TM can increase the [Ca.sup.2+] sensitivity of the thin filament and affect sarcomeric performance. Furthermore, these results enhance the understanding of why TM mutations associated with familial hypertrophic cardiomyopathy demonstrate increased myofilament sensitivity to [Ca.sup.2+]. calcium sensitivity; contractile function; genetically altered mice

Familial hypertrophic cardiomyopathy (FHC) is a disease caused by mutations in contractile proteins of the sarcomere. Our laboratory developed a mouse model of FHC with a mutation in the thin filament protein [alpha]-tropomyosin (TM) at amino acid 180 (Glul80Gly). The hearts of these mice exhibit dramatic systolic and diastolic dysfunction, and their myofilaments demonstrate increased calcium sensitivity. The mice also develop severe cardiac hypertrophy, with death ensuing by 6 mo. In an attempt to normalize calcium sensitivity in the cardiomyofilaments of the hypertrophic mice, we generated a chimeric [alpha]-/[beta]-TM protein that decreases calcium sensitivity in transgenic mouse cardiac myofilaments. By mating mice from these two models together, we tested the hypothesis that an attenuation of myofilament calcium sensitivity would modulate the severe physiological and pathological consequences of the FHC mutation. These double-transgenic mice 'rescue' the hypertrophic phenotype by exhibiting a normal morphology with no pathological abnormalities. Physiological analyses of these rescued mice show improved cardiac function and normal myofilament calcium sensitivity. These results demonstrate that alterations in calcium response by modification of contractile proteins can prevent the pathological and physiological effects of this disease. hypertrophy; contractile function; genetically altered mice; calcium sensitivity

Alteration in myofilament response to [Ca.sup.2+] is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to [Ca.sup.2+] are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament [Ca.sup.2+] sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD57033, which acts specifically to enhance myofilament response to [Ca.sup.2+]. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. [Ca.sup.2+]- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and [Ca.sup.2+]-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament [Ca.sup.2+] sensitivity are able to diminish the effect of I/R on cardiac function. troponin I; calcium sensitizers; phosphorylation; stunning; cross bridge-dependent activation

Pediatric healthcare professionals (HCPs) may experience events that lead to psychological distress or second victim experiences (SVEs). This project evaluates the impact of a newly implemented peer support program on SVEs and perceptions of supportive resources among pediatric HCPs. A second victim (SV) peer support program was implemented in the pediatric inpatient and intensive care units in September 2019. Multidisciplinary HCPs in these units were invited to participate in an anonymous survey that included the Second Victim Experience and Support Tool before and one-year after implementation. The survey assessed HCPs' SVEs, desired support, and perceptions of the peer support program. 52.0% (194/373) completed the pre-implementation survey, and 43.9% (177/403) completed the post-implementation survey. At both timepoints, participants reported SV-related psychosocial distress, physical distress, or low professional self-efficacy; the most desired support was 'a respected peer to discuss the details of what happened'. Following implementation of the peer support program, HCPs were significantly more likely to have heard of the term 'second victim' (51.8 vs. 74.0%; p < 0.001) and to have felt like there were adequate resources to support SVs (35.8% vs. 89.1%; p < 0.001). In the post-implementation survey, most respondents indicated a likelihood to use the program for themselves (65.7%) or colleagues (84.6%) after involvement in future traumatic clinical events. Implementation of a peer support program significantly influenced awareness and perceptions of support available for SV-related distress. Peer support programs should be implemented to help HCPs navigate SVEs and decrease SV-related turnover intentions. • Second victim peer support programs aim to offload emotional labor and normalize the second victim experience • There is a need to evaluate the impact of second victim peer support programs • The Second Victim Experience and Support Tool evaluated the impact of a peer support program on second victim experiences • Peer support programs may foster increased awareness of 'second victim' experiences and a decrease in turnover intentions [ABSTRACT FROM AUTHOR]

During agonist stimulation of airway smooth muscle (ASM), agonists such as ACh induce a transient increase in cytosolic Ca2+ concentration ([Ca2+ ]cyt), which leads to a contractile response [excitation-contraction (E-C) coupling]. Previously, the sensitivity of the contractile response of ASM to elevated [Ca2+ ]cyt (Ca2+ sensitivity) was assessed as the ratio of maximum force to maximum [Ca2+ ]cyt. However, this static assessment of Ca2+ sensitivity overlooks the dynamic nature of E-C coupling in ASM. In this study, we simultaneously measured [Ca2+ ]cyt and isometric force responses to three concentrations of ACh (1, 2.6, and 10 μM). Both maximum [Ca2+ ]cyt and maximum force responses were ACh concentration dependent, but force increased disproportionately, thereby increasing static Ca2+ sensitivity. The dynamic properties of E-C coupling were assessed in several ways. The temporal delay between the onset of ACh-induced [Ca2+ ]cyt and onset force responses was not affected by ACh concentration. The rates of rise of the ACh-induced [Ca2+ ]cyt and force responses increased with increasing ACh concentration. The integral of the phase-loop plot of [Ca2+ ]cyt and force from onset to steady state also increased with increasing ACh concentration, whereas the rate of relaxation remained unchanged. Although these results suggest an ACh concentration-dependent increase in the rate of cross-bridge recruitment and in the rate of rise of [Ca2+ ]cyt, the extent of regulatory myosin light-chain (rMLC20) phosphorylation was not dependent on ACh concentration. We conclude that the dynamic properties of [Ca2+ ]cyt and force responses in ASM are dependent on ACh concentration but reflect more than changes in the extent of rMLC20 phosphorylation. [ABSTRACT FROM AUTHOR]

Background: Implementation of checklists has been shown to be effective in improving patient safety. This study aims to evaluate the effectiveness of implementation of a checklist for daily care processes into clinical practice of pediatric intensive care units (PICUs) with limited resources.Methods: Prospective before-after study in eight PICUs from China, Congo, Croatia, Fiji, and India after implementation of a daily checklist into the ICU rounds.Results: Seven hundred and thirty-five patients from eight centers were enrolled between 2015 and 2017. Baseline stage had 292 patients and post-implementation 443. The ICU length of stay post-implementation decreased significantly [9.4 (4-15.5) vs. 7.3 (3.4-13.4) days, p = 0.01], with a nominal improvement in the hospital length of stay [15.4 (8.4-25) vs. 12.6 (7.5-24.4) days, p = 0.055]. The hospital mortality and ICU mortality between baseline group and post-implementation group did not show a significant difference, 14.4% vs. 11.3%; p = 0.22 for each. There was a variable impact of checklist implementation on adherence to various processes of care recommendations. A decreased exposure in days was noticed for; mechanical ventilation from 42.6% to 33.8%, p < 0.01; central line from 31.3% to 25.3%, p < 0.01; and urinary catheter from 30.6% to 24.4%, p < 0.01. Although there was an increased utilization of antimicrobials (89.9-93.2%, p < 0.01).Conclusions: Checklists for the treatment of acute illness and injury in the PICU setting marginally impacted the outcome and processes of care. The intervention led to increasing adherence with guidelines in multiple ICU processes and led to decreased length of stay. [ABSTRACT FROM AUTHOR]

Background: The electronic health record (EHR) is a contributor to serious patient harm occurring within a sociotechnical system. Chemotherapy ordering is a high‐risk task due to the complex nature of ordering workflows and potential detrimental effects if wrong chemotherapeutic doses are administered. Many chemotherapy ordering errors cannot be mitigated through systems‐based changes due to the limited extent to which individual institutions are able to customize proprietary EHR software. We hypothesized that simulation‐based training could improve providers' ability to identify and mitigate common chemotherapy ordering errors. Methods: Pediatric hematology/oncology providers voluntarily participated in simulations using an EHR testing ("Playground") environment. The number of safety risks identified and mitigated by each provider at baseline was recorded. Risks were reviewed one‐on‐one after initial simulations and at a group "lunch‐and‐learn" session. At three‐month follow‐up, repeat simulations assessed for improvements in error identification and mitigation, and providers were surveyed about prevention of real‐life safety events. Results: The 8 participating providers identified and mitigated an average of 5.5 out of 10 safety risks during the initial simulation, compared 7.4 safety risks at the follow up simulation (p=0.030). Two of the providers (25%) reported preventing at least one real‐world patient safety event in the clinical setting as a result of the initial training session. Conclusions: Simulation‐based training may reduce providers' susceptibility to chemotherapy ordering safety vulnerabilities within the EHR. This approach may be used when systems‐based EHR improvements are not feasible due to limited ability to customize local instances of proprietary EHR software. [ABSTRACT FROM AUTHOR]

BACKGROUND: ARDS remains a source of significant morbidity and mortality in the critically ill patient. The mainstay of therapy entails invasive mechanical ventilation utilizing a lung-protective strategy designed to limit lung injury associated with excessive stress and strain while the underlying etiology of respiratory failure is identified and treated. Less is understood about what to do once conventional ventilation parameters have been optimized but the patient’s respiratory status remains unchanged or worsens. In 2015, a protocolized, stepwise approach to mechanical ventilation with partially automated and clearly defined thresholds for management changes was implemented at our institution. We hypothesized that, by identifying appropriate patients earlier, time-to-escalation and rescue therapy implementation would be shortened. METHODS: Subjects with severe ARDS, treated with prone positioning based on our institution’s protocolized approach from December 2013 to August 2016 were included. Their baseline characteristics, severity of illness scores, and mechanical ventilation parameters were collected and analyzed. RESULTS: Baseline characteristics, tidal volumes, PaO2 /FIO2, duration of ventilation after proning, and mortality were similar in both groups. Median (interquartile range [IQR]) PEEP at the time of proning was higher after the protocol implementation (12.5 cm H2O [IQR 6.5–19.4] vs 18 cm H2O [IQR 10–22], P = .386), and mean (IQR) respiratory system driving pressure was lower (16 cm H2O [IQR 13–36.2] vs 12 cm H2O [IQR 9–19.6], P = .029). Median (IQR) time from refractory hypoxemia identification to proning was shorter after protocol implementation (42.2 h [IQR 6.83–347.2] vs 16.3 h [IQR 1–99.7], I = .02), and PaO2 /FIO2 at 1 h after proning was higher. ICU and hospital LOS were shorter after the protocol implementation. CONCLUSIONS: Following the implementation of an early, evidence-based, protocolized approach to optimizing mechanical ventilation, subjects with true refractory hypoxemia were identified earlier and time to proning was significantly shorter. Despite improvement in the evaluation and management of refractory hypoxemia as well as time to initiation of prone positioning, mortality was unchanged and there was variation in the duration of the position. [ABSTRACT FROM AUTHOR]

Rewarming the intact heart after a period of hypothermia is associated with reduced myocardial contractility, decreased Ca2+ sensitivity, and increased cardiac troponin-I (cTnI) phosphorylation. We hypothesized that hypothermia/rewarming (H/R) induces left ventricular (LV) contractile dysfunction due to phosphorylation of cTnI at Ser23/24. To test this hypothesis, the response of wild-type mice (n = 7) to H/R was compared with transgenic (TG) mice expressing slow skeletal TnI (TG-ssTnI; n = 7) that lacks the Ser23/24 phosphorylation sites. Hypothermia was induced by surface cooling and maintained at 23-25°C for 3 h. Subsequently, the animals were rewarmed to 37°C. LV systolic and diastolic function was assessed using a 1.4 F pressure-volume Millar catheter introduced via the right carotid artery. At baseline conditions, there were no significant differences in LV systolic function between wild-type and TG-ssTnI mice, whereas measurements of diastolic function [isovolumic relaxation constant and end-diastolic pressure-volume relationship (EDPVR)] were significantly (P < 0.05) reduced in TGssTnI animals. Immediately after rewarming, significant differences between groups were found in cardiac output (CO; wild-type 6.6 ± 0.7 vs. TG-ssTnI 8.8 ± 0.7 mL/min), stroke work (SW; wildtype 796 ± 112 vs. TG-ssTnI 1208 ± 67 mmHg/L), and the preload recruited stroke work (PRSW; wild-type 38.3 ± 4.9 vs. TG-ssTnI 68.8 ± 8.2 mmHg). However, EDPVR and τ returned to control levels within 1 h in both groups. We conclude that H/R-induced LV systolic dysfunction results from phosphorylation of cTnI at Ser23/24. [ABSTRACT FROM AUTHOR]

Background: Disaster triage is an infrequent, high-stakes skill set used by emergency medical services (EMS) personnel. Screen-based simulation (SBS) provides easy access to asynchronous disaster triage education. However, it is unclear if the performance during a SBS correlates with immersive simulation performance. Methods: This was a nested cohort study within a randomized controlled trial (RCT). The RCT compared triage accuracy of paramedics and emergency medical technicians (EMTs) who completed an immersive simulation of a school shooting, interacted with an SBS for 13 weeks, and then completed the immersive simulation again. The participants were divided into two groups: those exposed vs. those not exposed to 60 Seconds to Survival© (60S), a disaster triage SBS. The aim of the study was to measure the correlation between SBS triage accuracy and immersive simulation triage accuracy. Improvements in triage accuracy were compared among participants in the nested study before and after interacting with 60S, and with improvements in triage accuracy in a previous study in which immersive simulations were used as an educational intervention. Results: Thirty-nine participants completed the SBS; 26 (67%) completed at least three game plays and were included in the evaluation of outcomes of interest. The mean number of plays was 8.5 (SD =7.4). Subjects correctly triaged 12.4% more patients in the immersive simulation at study completion (73.1% before, 85.8% after, P = 0.004). There was no correlation between the amount of improvement in overall SBS triage accuracy, instances of overtriage (P = 0.101), instances of undertriage (P = 0.523), and improvement in the second immersive simulation. A comparison of the pooled data from a previous immersive simulation study with the nested cohort data showed similar improvement in triage accuracy (P = 0.079). Conclusions: SBS education was associated with a significant increase in triage accuracy in an immersive simulation, although triage accuracy demonstrated in the SBS did not correlate with the performance in the immersive simulation. This improvement in accuracy was similar to the improvement seen when immersive simulation was used as the educational intervention in a previous study. [ABSTRACT FROM AUTHOR]

Introduction:Physicians in training, including those in Pediatric Critical Care Medicine, must develop clinical leadership skills in preparation to lead multidisciplinary teams during their careers. This study seeks to identify multidisciplinary perceptions of leadership skills important for Pediatric Critical Care Medicine fellows to attain prior to fellowship completion. Methods:We performed a multi-institutional survey of Pediatric Critical Care Medicine attendings, fellows, and nurses. Subjects were asked to rate importance of 59 leadership skills, behaviors, and attitudes for Pediatric Critical Care practitioners and to identify whether these skills should be achieved before completing fellowship. Skills with the highest ratings by respondents were deemed essential. Results:Five hundred and eighteen subjects completed the survey. Of 59 items, only one item (“displays honesty and integrity”) was considered essential by all respondents. When analyzed by discipline, nurses identified 21 behaviors essential, fellows 3, and attendings 1 (p < 0.05). Nurses differed (p < 0.05) from attendings in their opinion of importance in 64% (38/59) of skills. Conclusions:Despite significant variability among Pediatric Critical Care attendings, fellows, and nurses in identifying which clinical leadership competencies are important for graduating Pediatric Critical Care fellows, they place the highest importance on skills in self-management and self-awareness. Leadership skills identified as most important may guide the development of interventions to improve trainee education and interprofessional care. [ABSTRACT FROM PUBLISHER]

Background--Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease characterized by thickening of ventricular walls and decreased left ventricular chamber volume. The majority of HCM-associated mutations are found in genes encoding sarcomere proteins. Herein, we set out to functionally characterize a novel HCMassociated mutation (K206I-TNNI3) and elucidate the mechanism of dysfunction at the level of myofilament proteins. Methods and Results--The male index case was diagnosed with HCM after an out-of-hospital cardiac arrest, which was followed by comprehensive clinical evaluation, transthoracic echocardiography, and clinical genetic testing. To determine molecular mechanism(s) of the mutant human cardiac troponin I (K206I), we tested the Ca2+ dependence of thin filament-activated myosin-S1-ATPase activity in a reconstituted, regulated, actomyosin system comparing wild-type human troponin complex, 50% mix of K206I/wildtype, or 100% K206I. We also exchanged native troponin detergent extracted fibers with reconstituted troponin containing either wildtype or a 65% mix of K206I/wildtype and measured force generation. The Ca2+ sensitivity of the myofilaments containing the K206I variant was significantly increased, and when treated with 20 μmol/L (-)-epigallocatechin gallate (green tea) was restored back to wild-type levels in ATPase and force measurements. The K206I mutation impairs the ability of the troponin I to inhibit ATPase activity in the absence of calcium-bound human cardiac troponin C. The ability of calcium-bound human cardiac troponin C to neutralize the inhibition of K206I was greater than with wild-type TnI. Conclusions--Compromised interactions of K206I with actin and hcTnC may lead to impaired relaxation and HCM. [ABSTRACT FROM AUTHOR]

Objective. Achieving successful peripheral intravenous (PIV) vascular access in children can be difficult. In the prehospital setting, opportunities are rare. Obtaining access becomes vital in emergent and life-threating conditions, such as seizures, hypoglycemia, and cardiac arrest. This study examines prehospital pediatric PIV attempts, success rates, and the impact of patient age. Methods. This was a retrospective chart review of patients aged 18 years or younger receiving prehospital PIV attempts from January 1, 2003, through May 31, 2011. Included cases were identified by querying electronic patient care reports for PIV attempts within the specified age range. The documentation of PIV attempts and successes was reported by emergency medical service providers. This study was approved by an institutional review board. Results. Throughout the 101-month study period, there were 261,008 ambulance responses. PIV attempts were made in 4188 patients aged 18 years or younger. PIV placement was successful in 3699 patients (88.3%) and failed in 489 (11.7%). Age was significantly associated with success. Each 1-year increase in age was associated with an 11% increase in odds of PIV success (odds ratio, 1.11; 95% CI, 1.09-1.12; p < 0.001). Success was lowest in patients younger than 2 years old, with an overall success rate of 64.1% (141/220). Accounting for multiple attempts, success was achieved in 53.0% of attempts (141/266). Conclusions. Prehospital PIV attempts are uncommon (2% of emergent responses). Success rates are significantly associated with patient age in the pediatric population and lowest in those aged 2 years or less. Consideration of alternative forms of vascular access in this population may be beneficial. Key words: ambulance; emergency medical services; intraosseous; intravenous; pediatric [ABSTRACT FROM AUTHOR]

Background. Intraosseous (IO) access is attempted when intravenous access cannot be established during an emergency. The U.S. Food and Drug Administration-cleared semiautomatic IO access device (EZ-IO; Vidacare Corp., Shavano Park, TX) has been shown to be safe and effective. Objective. To examine the characteristics of pediatric patients receiving IO infusions, primary clinical impressions of emergency medical services providers, success rates, and subsequent treatment after use of a manual IO device or the semiautomatic IO device. Methods. A midwestern, 12-site, statewide ambulance service began using the semiautomatic device instead of a manual IO device in 2007. Retrospective review included analysis of device placement rates and subsequent treatment of children (younger than 18 years) who underwent an IO access procedure with either the manual device (January 2003 through February 2007) or the semiautomatic device (March 2007 through May 2009). Results. First-attempt success was achieved in 80.6%% of patients (25 of 31) in the manual device group and in 83.9%% of patients (52 of 62) in the semiautomatic device group (p == 0.98). In the manual device group, there were 37 attempts for 25 successful device placements (67.6%% success), and in the semiautomatic group, there were 72 attempts for 58 successful placements (80.6%% success) (p == 0.52). Intravenous attempts were made before IO attempts in 35.5%% of patients (11 of 31) in the manual group and in 1.7%% of patients (1 of 60) in the semiautomatic group (p < 0.001). Treatment (medication use, excluding lidocaine for local anesthetic purposes and intravenous crystalloid) was administered IO in 84.0%% of the patients (21 of 25) in the manual device group and in 73.2%% of the patients (41 of 56) in the semiautomatic device group. Conclusions. For the pediatric cohort, use of a semiautomatic IO access device in place of a manual device offered no statistically significant difference in first-attempt success (3.3%%) or in success per attempt (13.0%%). However, the rate at which IO access was used by emergency medical services providers more than tripled with use of the semiautomatic device. [ABSTRACT FROM AUTHOR]

Abstract: Changes in metabolic and myofilament phenotypes coincide in developing hearts. Posttranslational modification of sarcomere proteins influences contractility, affecting the energetic cost of contraction. However, metabolic adaptations to sarcomeric phenotypes are not well understood, particularly during pathophysiological stress. This study explored metabolic adaptations to expression of the fetal, slow skeletal muscle troponin I (ssTnI). Hearts expressing ssTnI exhibited no significant ATP loss during 5min of global ischemia, while non-transgenic littermates (NTG) showed continual ATP loss. At 7min ischemia TG-ssTnI hearts retained 80±12% of ATP versus 49±6% in NTG (P<0.05). Hearts expressing ssTnI also had increased AMPK phosphorylation. The mechanism of ATP preservation was augmented glycolysis. Glycolytic end products (lactate and alanine) were 38% higher in TG-ssTnI than NTG at 2min and 27% higher at 5min. This additional glycolysis was supported exclusively by exogenous glucose, and not glycogen. Thus, expression of a fetal myofilament protein in adult mouse hearts induced elevated anaerobic ATP production during ischemia via metabolic adaptations consistent with the resistance to hypoxia of fetal hearts. The general findings hold important relevance to both our current understanding of the association between metabolic and contractile phenotypes and the potential for invoking cardioprotective mechanisms against ischemic stress. This article is part of a Special Issue entitled "Possible Editorial". [Copyright &y& Elsevier]

Abstract: Familial hypertrophic cardiomyopathy (FHC) is a leading cause of sudden cardiac death among young athletes but the functional effects of the myofilament mutations during FHC-associated ischemia and acidosis, due in part to increased extravascular compressive forces and microvascular dysfunction, are not well characterized. We tested the hypothesis that the FHC-linked tropomyosin (Tm) mutation Tm-E180G alters the contractile response to acidosis via increased myofilament Ca2+ sensitivity. Intact papillary muscles from transgenic (TG) mice expressing Tm-E180G and exposed to acidic conditions (pH 6.9) exhibited a significantly smaller decrease in normalized isometric tension compared to non-transgenic (NTG) preparations. Times to peak tension and to 90% of twitch force relaxation in TG papillary muscles were significantly prolonged. Intact single ventricular TG myocytes demonstrated significantly less inhibition of unloaded shortening during moderate acidosis (pH 7.1) than NTG myocytes. The peak Ca2+ transients were not different for TG or NTG at any pH tested. The time constant of re-lengthening was slower in TG myocytes, but not the rate of Ca2+ decline. TG detergent-extracted fibers demonstrated increased Ca2+ sensitivity of force and maximal tension compared to NTG at both normal and acidic pH (pH 6.5). Tm phosphorylation was not different between TG and NTG muscles at either pH. Our data indicate that acidic pH diminished developed force in hearts of TG mice less than in NTG due to their inherently increased myofilament Ca2+ sensitivity, thus potentially contributing to altered energy demands and increased propensity for contractile dysfunction. [Copyright &y& Elsevier]

Abstract: Congenital intrahepatic arterioportal fistula is a rare entity that most often presents with symptoms of portal hypertension and malabsorption. We discuss a patient who presented with distributive shock, congestive heart failure, pulmonary hypertension, ascites, and a history of severe constipation. [ABSTRACT FROM AUTHOR]

Alteration in myofilament response to Ca2+ is a major mechanism for depressed cardiac function after ischemia-reperfusion (I/R) dysfunction. We tested the hypothesis that hearts with increased myofilament response to Ca2+ are less susceptible to I/R. In one approach, we studied transgenic (TG) mice with a constitutive increase in myofilament Ca2+ sensitivity in which the adult form of cardiac troponin I (cTnI) is stoichiometrically replaced with the embryonic/neonatal isoform, slow skeletal TnI (ssTnI). We also studied mouse hearts with EMD57033, which acts specifically to enhance myofilament response to Ca2+. We subjected isolated, perfused hearts to an I/R protocol consisting of 25 min of no-flow ischemia followed by 30 min of reperfusion. After I/R, developed pressure and rates of pressure change were significantly depressed and end-diastolic pressure was significantly elevated in nontransgenic (NTG) control hearts. These changes were significantly blunted in TG hearts and in NTG hearts perfused with EMD-57033 during reperfusion, with function returning to nearly baseline levels. Ca2+- and cross bridge-dependent activation, protein breakdown, and phosphorylation in detergent-extracted fiber bundles were also investigated. After I/R NTG fiber bundles exhibited a significant depression of cross bridge-dependent activation and Ca2+-activated tension and length dependence of activation that were not evident in TG preparations. Only NTG hearts demonstrated a significant increase in cTnI phosphorylation. Our results support the hypothesis that specific increases in myofilament Ca2+ sensitivity are able to diminish the effect of I/R on cardiac function. [ABSTRACT FROM AUTHOR]

Ca[sup 2+]-sensitizers are inotropic agents that modify the response of myofilaments to Ca[sup 2+], and are potentially valuable drugs in the treatment of heart failure. These agents have diverse chemical structures, and in some cases also have effects as inhibitors of phosphodiesterase activity. Advantages of their actions include vasodilation combined with inotropic effects. Reduction in the amounts of Ca[sup 2+] required to activate the myofilaments also lowers the oxygen consumption required for Ca[sup 2+] transport, lowers the threat of arrhythmias, and may blunt Ca[sup 2+]-dependent transcriptional and translational mechanisms leading to hypertrophy and failure. Although diastolic abnormalities and impaired relaxation were thought to be potential undesirable effects of Ca[sup 2+] -sensitizers, studies of hearts beating in situ indicate that this may not be a major problem. We focus here on Ca[sup 2+]-sensitizers that act on cardiac troponin C, the Ca[sup 2+] receptor that triggers activation of the actin-myosin interaction. Structural studies have identified a unique mode of Ca[sup 2+] signaling in cardiac troponin C that should aid in targeting drugs to the heart. Moreover, identification of docking sites of Ca[sup 2+]-sensitizers on troponin C suggest new directions for rational drug design. [ABSTRACT FROM AUTHOR]