Outcome of Extracorporeal Cardiopulmonary Resuscitation in Pediatric Patients Without Congenital Cardiac Disease: Extracorporeal Life Support Organization Registry Study.

OBJECTIVES: To describe the use of extracorporeal cardiopulmonary resuscitation (ECPR) in pediatric patients without congenital heart disease (CHD) and identify associations with in-hospital mortality, with a specific focus on initial arrest rhythm. DESIGN: Retrospective cohort study using data from pediatric patients enrolled in Extracorporeal Life Support Organization (ELSO) registry between January 1, 2017, and December 31, 2019. SETTING: International, multicenter. PATIENTS: We included ECPR patients under 18 years old, and excluded those with CHD. Subgroup analysis of patients with initial arrest rhythm. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 567 patients: neonates (12%), infants (27%), children between 1 and 5 years old (25%), and children over 5 years old (36%). The patient cohort included 51% males, 43% of White race, and 89% not obese. Most suffered respiratory disease (26%), followed by acquired cardiac disease (25%) and sepsis (12%). In-hospital mortality was 59%. We found that obesity (adjusted odds ratio [aOR], 2.28; 95% CI, 1.21-4.31) and traumatic injury (aOR, 6.94; 95% CI, 1.55-30.88) were associated with greater odds of in-hospital mortality. We also identified lower odds of death associated with White race (aOR, 0.64; 95% CI, 0.45-0.91), ventricular tachycardia (VT) as an initial arrest rhythm (aOR, 0.36; 95% CI, 0.16-0.78), return of spontaneous circulation before cannulation (aOR, 0.56; 95% CI, 0.35-0.9), and acquired cardiac disease (aOR, 0.43; 95% CI, 0.29-0.64). Respiratory disease was associated with greater odds of severe neurologic complications (aOR, 1.64; 95% CI, 1.06-2.54). CONCLUSIONS: In children without CHD undergoing ECPR, we found greater odds of in-hospital mortality were associated with either obesity or trauma. The ELSO dataset also showed that other variables were associated with lesser odds of mortality, including VT as an initial arrest rhythm. Prospective studies are needed to elucidate the reasons for these survival differences.

Regionalization Patterns for Children with Serious Trauma in California (2005-2015): A Retrospective Cohort Study.

OBJECTIVE: Trauma centers provide coordinated specialty care and have been demonstrated to save lives. Many states do not have a comprehensive statewide trauma system. Variable geography, resources, and population distributions present significant challenges to establishing an effective uniform system for pediatric trauma care. We aimed to identify patterns of primary (field) triage and transfer of serious pediatric trauma throughout California. We hypothesized that pediatric primary triage to trauma center care would be positively associated with younger age, increased injury severity, and local emergency medical service (EMS) regions with increased resources. We hypothesized that pediatric trauma transfer would be associated with younger age, increased injury severity, and rural regions with decreased resources. Methods: We conducted a retrospective cohort study of the California Office of Statewide Health Planning and Development emergency department and inpatient discharge data (2005-2015). All patients with serious injury, defined as Injury Severity Score (ISS) >9 were included. Demographic, injury, hospital, and regional characteristics such as distances between patient residence and destination hospitals were tabulated. Univariate and multinomial logit analyses were conducted to analyze individual, hospital, and regional characteristics associated with the outcomes of location of primary triage and transfer. Estimates were converted into predicted probabilities for ease of data interpretation. Results: Primary triage to was to either a pediatric trauma center (37.8%), adult level I/II trauma center (35.0%), adult level III/IV trauma center (1.9%), pediatric non-trauma hospital (3.4%), or an adult non-trauma hospital (21.9%).Younger age, private non-HMO insurance, motor vehicle mechanism, and rural areas were the major factors influencing primary triage to any trauma hospital. Younger age, private non-HMO insurance, higher ISS, fall mechanism, <200 bed hospital, and rural areas were the major factors influencing transfer from a non-trauma hospital to any trauma center. Conclusions: We demonstrate statewide primary triage and transfer patterns for pediatric trauma in a large and varied state. Specifically we identified previously unrecognized individual, hospital, and EMS system associations with pediatric trauma regionalization. Knowledge of these de facto trauma care access patterns has policy and process implications that could improve care for all injured children in need.

Bisketene Equivalents as Diels-Alder Dienes.

2,5-Bis(tert-butyldimethylsilyloxy)furans are established as vicinal bisketene equivalents for application as dienes in the Diels-Alder reaction. Cycloaddition with olefinic dienophiles, under exceptionally mild conditions, enables convergent access to highly substituted para-hydroquinones in unprotected form via a one-pot Diels-Alder/ring-opening/tautomerization sequence. The synthesis of para-benzoquinones from acetylenic dienophiles, including benzynes, is also demonstrated, and 2,5-bis(tert-butyldimethylsilyloxy)pyrroles are established as competent dienes for the synthesis of para-iminoquinones. Application in natural product synthesis enables gram-scale access to the neuroprotective agent (±)-indanostatin.

Variations in access to specialty care for children with severe burns.

BACKGROUND: Pediatric burns account for 120,000 emergency department visits and 10,000 hospitalizations annually. The American Burn Association has guidelines regarding referrals to burn centers; however there is variation in burn center distribution. We hypothesized that disparity in access would be related to burn center access. METHODS: Using weighted discharge data from the Nationwide Inpatient Sample 2001-2011, we identified pediatric patients with International Classification of Diseases-9th Revision codes for burns that also met American Burn Association criteria. Key characteristics were compared between pediatric patients treated at burn centers and those that were not. RESULTS: Of 54,529 patients meeting criteria, 82.0% (n = 44,632) were treated at burn centers. Patients treated at burn centers were younger (5.6 versus 6.7 years old; p < 0.0001) and more likely to have burn injuries on multiple body regions (88% versus 12%; p < 0.0001). In urban areas, 84% of care was provided at burn centers versus 0% in rural areas (p < 0.0001), a difference attributable to the lack of burn centers in rural areas. Both length of stay and number of procedures were significantly higher for patients treated at burn centers (7.3 versus 4.4 days, p < 0.0001 and 2.3 versus 1.1 procedures, p < 0.0001; respectively). There were no significant differences in mortality (0.7% versus 0.8%, p = 0.692). CONCLUSION: The majority of children who met criteria were treated at burn centers. There was no significant difference between geographical regions. Of those who were treated at burn centers, more severe injury patterns were noted, but there was no significant mortality difference. Further study of optimal referral of pediatric burn patients is needed.

A Broad-Spectrum Synthesis of Tetravinylethylenes.

The first general synthesis of compounds of the tetravinylethylene (TVE) family is reported. Ramirez-type dibromo-olefination of readily accessible penta-1,4-dien-3-ones generates 3,3-dibromo[3]dendralenes, which undergo twofold Negishi, Suzuki-Miyaura or Mizoroki-Heck reactions with a wide variety of olefinic coupling partners. This route delivers a broad range of unsymmetrically substituted tetravinylethylenes with up to three different alkenyl substituents attached to the central C=C bond. The extensive scope of the approach is demonstrated by the preparation of the first higher order oligo-alkenic through-conjugated/cross-conjugated hybrid compounds. An unsymmetrically substituted TVE is shown to undergo a domino electrocyclization-cycloaddition with high site-selectivity and diastereoselectivity, thereby demonstrating the substantial synthetic potential of substituted TVEs for controlled, rapid structural complexity generation.

Catalytic Enantioselective Transformations Involving C-H Bond Cleavage by Transition-Metal Complexes.

The development of new methods for the direct functionalization of unactivated C-H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C-H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge. Herein we comprehensively review all asymmetric transition-metal-catalyzed methodologies that are believed to proceed via an inner-sphere-type mechanism, with an emphasis on the nature of stereochemistry generation. Our analysis serves to document the considerable and rapid progress within in the field, while also highlighting limitations of current methods.

Visible-Light Photoredox Catalysis Enables the Biomimetic Synthesis of Nyingchinoids†A, B, and D, and Rasumatranin†D.

The total synthesis of nyingchinoids A and B has been achieved through successive rearrangements of a 1,2-dioxane intermediate that was assembled using a visible-light photoredox-catalysed aerobic [2+2+2] cycloaddition. Nyingchinoid D was synthesised with a competing [2+2] cycloaddition. Based on NMR data and biosynthetic speculation, we proposed a structure revision of the related natural product rasumatranin D, which was confirmed through total synthesis. Under photoredox conditions, we observed the conversion of a cyclobutane into a 1,2-dioxane through retro-[2+2] cycloaddition followed by aerobic [2+2+2] cycloaddition.

Comparing Percutaneous to Open Access for Extracorporeal Membrane Oxygenation in Pediatric Respiratory Failure.

OBJECTIVES: Evaluate trends in method of access (percutaneous cannulation vs open cannulation) for pediatric extracorporeal membrane oxygenation and determine the effects of cannulation method on morbidity and mortality. DESIGN: Retrospective cohort study. SETTING AND SUBJECTS: The Extracorporeal Life Support Organization's registry was queried for pediatric patients on extracorporeal membrane oxygenation for respiratory failure from 2007 to 2015. INVERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,501 patients identified, 77.2% underwent open cannulation, with the frequency of open cannulation decreasing over the study period from approximately 80% to 70% (p < 0.001). Percutaneous cannulation patients were more commonly male (24.2% vs 21.5%; p = 0.01), older (average 7.6 vs 4.5 yr; p < 0.001), and heavier (average 33.0 vs 20.2 kg; p < 0.001). Subset analysis of patients on venovenous extracorporeal membrane oxygenation revealed higher rates of mechanical complications due to blood clots (28.9% vs 22.6%; p = 0.003) or cannula problems (18.9% vs 12.7%; p < 0.001), cannula site bleeding (25.3% vs 20.2%; p = 0.01) and increased rates of cannula site repair in the open cannulation cohort. Limb related complications were not significantly different on subset analysis for venovenous extracorporeal membrane oxygenation patients stratified by access site. Logistic regression analysis revealed that method of access was not associated with a difference in mortality. CONCLUSIONS: The proportion of pediatric patients undergoing percutaneous extracorporeal membrane oxygenation cannulation is increasing. Mechanical and physiologic complications occur with both methods of cannulation, but percutaneous cannulation appears safe in this cohort. Further analysis is needed to evaluate long-term outcomes with this technique.

Axially Chiral Dibenzazepinones by a Palladium(0)-Catalyzed Atropo-enantioselective C-H Arylation.

Atropo-enantioselective C-H functionalization reactions are largely limited to the dynamic kinetic resolution of biaryl substrates through the introduction of steric bulk proximal to the axis of chirality. Reported herein is a highly atropo-enantioselective palladium(0)-catalyzed methodology that forges the axis of chirality during the C-H functionalization process, enabling the synthesis of axially chiral dibenzazepinones. Computational investigations support experimentally determined racemization barriers, while also indicating C-H functionalization proceeds by an enantio-determining CMD to yield configurationally stable eight-membered palladacycles.

Variations in Utilization of Inpatient Rehabilitation Services among Pediatric Trauma Patients.

OBJECTIVE: To assess clinical and nonclinical characteristics associated with the use of pediatric inpatient rehabilitation services among children with traumatic injuries. We hypothesized there would be no nonclinical variations in the use of pediatric inpatient rehabilitation services. STUDY DESIGN: Retrospective analysis of 1139 patients who were injured seriously (0-18 years of age) from our institutional trauma registry (2004-2014). Patients' nonclinical and clinical characteristics were analyzed. We used a full matching technique to compare characteristics between those admitted to rehabilitation (cases) to those discharged home (controls). We matched patients by age category, sex, maximum Abbreviated Injury Scale, and body region of maximum Abbreviated Injury Scale. We used survey-based multivariate logistic regression to identify characteristics associated with inpatient rehabilitation services, controlling for multiple injuries, distance from home to rehabilitation center, year of service, hospital length of stay, and clinically relevant interactions. RESULTS: Ninety-eight patients (8.6%) were admitted to inpatient rehabilitation and 968 (85.0%) were discharged home. Black and other minority patients had increased odds of receiving inpatient rehabilitation compared with white patients (OR, 7.6 [P< .001] and OR, 1.6 [P= .03], respectively). Patients with private compared with public insurance had increased odds of receiving inpatient rehabilitation (OR, 2.4; P< .001). CONCLUSIONS: Pediatric inpatient rehabilitation beds are a scarce resource that should be available to those with the greatest clinical need. The mechanism creating differences in the use of inpatient rehabilitation based on nonclinical characteristics such as race/ethnicity or insurance status must be understood to prevent disparities in access to inpatient rehabilitation services.

One-Step Multigram-Scale Biomimetic Synthesis of Psiguadial†B.

A gram-scale synthesis of psiguadial B, a purported inhibitor of human hepatoma cell growth, has been achieved in one step by a biomimetic three-component coupling of caryophyllene, benzaldehyde, and diformylphloroglucinol. This cascade reaction is catalyzed by N,N'-dimethylethylenediamine, and proceeds at ambient temperature to generate four stereocenters, two rings, one C-O bond, and three C-C bonds. Combined computational and experimental investigations suggest the biosynthesis of the natural product is non-enzyme mediated, and is the result of a Michael addition between caryophyllene and a reactive ortho-quinone methide, followed by two sequential intramolecular cationic cyclization events.

Asymmetric Catalysis Powered by Chiral Cyclopentadienyl Ligands.

Application of chiral derivatives of the versatile and ubiquitous cyclopentadienyl ligand has long remained an underdeveloped area in asymmetric catalysis. In this Perspective we highlight recent exciting results that demonstrate their enormous potential. In particular, we provide a comparative analysis of the available ligand families, an overview of their complexation chemistry, and an examination of their application in catalytic enantioselective reactions. We also discuss current limitations and speculate on the developments that are necessary to advance the field further.

Plasma acylcarnitines during insulin stimulation in humans are reflective of age-related metabolic dysfunction.

The purpose of this study was to determine if plasma acylcarnitine (AC) profiling is altered under hyperinsulinemic conditions as part of the aging process. Fifteen young, lean (19-29 years) and fifteen middle-to older-aged (57-82 years) individuals underwent a 2-hr euglycemic-hyperinsulinemic clamp. Plasma samples were obtained at baseline, 20 min, 50 min, and 120 min for analysis of AC species and amino acids. Skeletal muscle biopsies were performed after 60 min of insulin-stimulation for analysis of acetyl-CoA carboxylase (ACC) phosphorylation. Insulin infusion decreased the majority of plasma short-, medium-, and long-chain (SC, MC, and LC, respectively) AC. However, during the initial 50 min, a number of MC and LC AC species (C10, C10:1, C12:1, C14, C16, C16:1, C18) remained elevated in aged individuals compared to their younger counterparts indicating a lag in responsiveness. Additionally, the insulin-induced decline in skeletal muscle ACC phosphorylation was blunted in the aged compared to young individuals (-24% vs. -56%, P < 0.05). These data suggest that a desensitization to insulin during aging, possibly at the level of skeletal muscle ACC phosphorylation, results in a diminished ability to transition to glucose oxidation indicative of metabolic inflexibility.

[5]Radialene.

The [n]radialenes are a unique family of fundamental [n]-membered carbocyclic structures with radiating alkenes, which have attracted significant synthetic and theoretical attention. Whereas [3]-, [4]-, and [6]radialenes have been prepared and studied, all efforts to synthesize the five-membered ring compound have thus far met with failure. Here we describe the first synthesis of the fundamental hydrocarbon [5]radialene, C10H10. Our approach was a departure from previous radialene syntheses in that it utilized a low-temperature decomplexation of a stable organometallic compound, rather than high-temperature elimination or rearrangement. Our strategy was guided by analysis of previous radialene syntheses, which indicated rapid decomposition in oxygen, and ab initio calculations, which revealed an extraordinary susceptibility of [5]radialene to undergo Diels-Alder dimerization/polymerization. The origin of this susceptibility was traced to a small distortion energy associated with the formation of the transition structure geometry from the relaxed reactant monomers and to a narrow HOMO-LUMO gap.

Total synthesis of the pseudopterosin aglycones.

The pseudopterosin natural products have been the focus of a substantial number of synthetic studies since the first members were isolated almost 30 years ago. Herein we review all total and formal syntheses of this family of glycosylated diterpenes, with an emphasis on the synthetic strategies employed.

The impact of perianal disease in young patients with inflammatory bowel disease.

BACKGROUND: Perianal disease is a potentially significant source of morbidity for patients with inflammatory bowel disease (IBD). We sought to identify the impact of perianal disease on IBD outcomes in children, adolescents, and young adults. METHODS: We studied 12,465 inpatient admissions for patients ≤20 years old with IBD in 2009 using the Kids' Inpatient Database (KID). Patients were stratified by their principal diagnosis of ulcerative colitis (UC) or Crohn's disease (CD). Perianal disease (perianal abscess, anal fissure, or anal fistula), complex fistulas (rectourethral, rectovaginal, or enterovesical), and growth failure were defined by ICD-9 codes. Logistic regression was performed adjusting for CD or UC, gender, age, need for surgical intervention, fistulas, or growth failure. RESULTS: Of the 511 (4.1%) patients with perianal disease, 480 had CD (94%, p < 0.001). Girls were less likely to suffer perianal disease (OR = 0.63, CI 0.52-0.76, p < 0.001). Those with perianal disease were more likely to suffer complex fistulas (OR = 3.5, CI 1.98-6.20, p < 0.001) but less likely to suffer enteroenteral fistulas (OR = 0.30, CI 0.15-0.63, p = 0.001) than those without perianal disease. Perianal disease did not increase the incidence of growth failure (p = 0.997) but doubled the likelihood of an operation of any type during admission (p < 0.001). Additionally, patients with perianal disease spent on average 1.29 more days in the hospital (7.45 vs. 6.16 days, p < 0.001) and accrued $5838 extra in hospital charges (p = 0.005). CONCLUSIONS: Perianal disease in younger patients is associated with a longer length of stay, higher hospital charges, and increased rates of both perineal and abdominal operative procedures. These data support the notion that, similar to adults, the presence of perianal disease in pediatric Crohn's patients is associated with a more severe course.

COMPARISON OF BASAL INSULIN REGIMENS ON GLYCEMIC VARIABILITY IN NONCRITICALLY ILL PATIENTS WITH TYPE 2 DIABETES.

OBJECTIVE: To evaluate the impact of different subcutaneous basal insulin regimens on glycemic variability (GV) and hospital complications in non-intensive care unit (ICU) patients with type 2 diabetes (T2D). METHODS: This study is a post hoc analysis of 279 general medicine and surgery patients treated with either a "Basal Bolus" insulin regimen using glargine once daily and glulisine before meals or a "Basal Plus" regimen using glargine once daily plus correction doses of glulisine before meals for glucose >140 mg/dL. GV was calculated as mean delta (Δ) daily glucose, mean SD, and mean amplitude of glycemic excursions (MAGE). RESULTS: Treatment with Basal Bolus and Basal Plus regimens resulted in similar mean daily glucose, hypoglycemia, length of stay (LOS), and hospital complications (all P>.05). There were no differences in GV between treatment groups by Δ change (72.5 ± 36 vs. 69.3 ± 34 mg/dL), SD (38.5 ± 18 vs. 37.1 ± 16 mg/dL) and MAGE (67.5 ± 34 vs. 66.1 ± 39 mg/dL) (all P>.05). Surgery patients treated with Basal Bolus had higher GV compared to those treated with Basal Plus (Δ daily glucose and SD: P = .02, MAGE: P = .009), but no difference in GV was found between treatment groups for the general medicine patients (P>.05). Patients with hypoglycemia events had higher GV compared to subjects without hypoglycemia (P<.05), but no association was found between GV and hospital complications (P>.05). CONCLUSION: Treating hospitalized, non-ICU, diabetic patients with Basal Plus insulin regimen resulted in similar glucose control and GV compared to the standard Basal Bolus insulin regimen. Higher GV was not associated with hospital complications.

Glucose variability is an independent predictor of mortality in hospitalized patients treated with total parenteral nutrition.

OBJECTIVE: Hyperglycemia is associated with increased mortality in critically ill patients treated with total parenteral nutrition (TPN). The role of glucose variability (GV) in predicting outcomes in these patients is not known. METHODS: This retrospective study included medical and surgical patients receiving TPN in a community teaching hospital. GV was calculated by standard deviation (SD) of blood glucose (BG) values and by mean BG daily (Δ) change (daily max - daily minimum). RESULTS: A total of 276 medical and surgical patients (mean age: 51 ± 18 years), 19% with a history of diabetes mellitus (DM), and 74% with intensive care unit (ICU) admission were treated with TPN. During TPN, the mean daily BG was 142.9 ± 33 mg/dL; frequencies of hypoglycemia < 70 and < 40 mg/dL were 41% and 3%, respectively; and hospital mortality was 27.2%. The mean GV by SD was 38 ± 21 mg/dL and by mean (D) change 58 ± 34 mg/dL. GV was significantly higher in deceased patients (SD: 48 ± 25 vs. 34 ± 18 mg/dL and Δ change: 75 ± 39 vs. 51 ± 29 mg/dL, both P < .01) than surviving patients. Multivariate analysis adjusted for age, DM status, gender, APACHE (Acute Physiology and Chronic Health Evaluation) score, mean daily glucose, and hypoglycemia revealed that GV was an independent predictor of hospital mortality (P < .05). The association between GV and mortality was limited to patients without a history of DM and was not present in patients with DM. CONCLUSION: High GV is associated with increased hospital mortality independent of the presence and severity of hyperglycemia or hypoglycemia during TPN therapy. Prospective randomized trials are needed to determine if reduction in GV with intensive glycemic control improves clinical outcomes in patients treated with TPN.