Trauma and Acute Care Surgery

Missing expectations: Windlass tourniquet use without formal training yields poor results Background Despite significant attempts to educate civilians in hemorrhage control, the majority remain untrained. We sought to determine if laypersons can successfully apply one of three commercially available tourniquets; including those endorsed by the United States Military and the American College of Surgeons. Methods Pre-clinical graduate health science students were randomly assigned a commercially-available windless tourniquet: SAM® XT, Combat Application Tourniquet® (CAT), or Special Operation Forces® Tactical Tourniquet (SOFT-T). Each was given up to one minute to read package instructions and asked to apply it to the HapMed® Leg Tourniquet Trainer. Estimated blood loss was measured until successful hemostatic pressure was achieved or simulated death occurred from exsanguination. Simulation survival, time to read instructions and stop bleeding, tourniquet pressure, and blood loss were analyzed. Results Of the 150 students recruited, 55, 46, and 49 were randomized to the SAM XT, CAT, SOFT-T, respectively. Mean overall simulation survival was less than 66% (61%, 72%, 65%; p=0.55). Of survivors, all three tourniquets performed similarly in median pressure applied (319 mmHg, 315 mmHg, and 329 mmHg; p=0.54) and median time to stop bleeding (91 sec, 70 sec, 77 sec; p=0.28). There was a statistical difference in median blood loss volume favoring SOFT-T (SAM XT 686 ml, CAT 624 ml, SOFT-T 433 ml; p=0.03). All 16 participants with previous experience were able to successfully place the tourniquet compared to 81 of 131 (62%) first-time users (p=0.008). Conclusion No one should die of extremity hemorrhage, and civilians are our first line of defense. We demonstrate that when an untrained layperson is handed a commonly accepted tourniquet, failure is unacceptably high. Current devices are not intuitive and require training beyond the enclosed instructions. Plans to further evaluate this cohort after formal "Stop the Bleed" training are underway. Level of Evidence Level II; Therapeutic study type First and Corresponding Authors: Andrew Dennis, DO, Department of Trauma and Burn Surgery, Cook County Health, Rush University, Midwestern University, adennis@cookcountytrauma.org Conflicts of Interest Statement: All authors have no conflicts of interest to disclose. Meetings at which paper presented: 49th Annual Meeting of the Western Trauma Association, March 3-8, 2019 in Snowmass, Colorado Funding Statement: No funding was received for this work from the National Institutes of Health (NIH); Wellcome Trust; or the Howard Hughes Medical Institute (HHMI). © 2019 Lippincott Williams & Wilkins, Inc.

Hypoxia/reoxygenation decreases endothelial glycocalyx via reactive oxygen species and calcium signaling in a cellular model for shock Background Ischemia/reperfusion injury (IRI) has been shown to cause endothelial glycocalyx (EG) damage. Whether the hypoxic/ischemic insult or the oxidative and inflammatory stress of reperfusion plays a greater part in glycocalyx damage is not known. Furthermore, the mechanisms by which IRI causes EG damage have not been fully elucidated. The aims of this study were to determine if hypoxia alone or hypoxia/reoxygenation (H/R) caused greater damage to the glycocalyx, and if this damage was mediated by reactive oxygen species (ROS) and Ca2+ signaling. Methods Human umbilical vein endothelial cells (HUVECs) were cultured to confluence and exposed to either normoxia (30 minutes), hypoxia (2% O2 for 30 minutes), or H/R (30 minutes hypoxia followed by 30 minutes normoxia). Some cells were pretreated with ROS-scavengers TEMPOL, MitoTEMPOL, Febuxostat, or Apocynin, or with the Ca2+ chelator BAPTA or Ca2+ channel blockers 2-APB, A967079, Pyr3, or ML204. Intracellular ROS was quantified for all groups. EG was measured using fluorescently-tagged wheat germ agglutinin and imaged with fluorescence microscopy. Results Glycocalyx thickness was decreased in both hypoxia and H/R groups, with the decrease being greater in the H/R group. TEMPOL, MitoTEMPOL, BAPTA, and 2-APB prevented loss of glycocalyx in H/R.ROS levels were likewise elevated compared to normoxia in both groups, but were increased in the H/R group compared to hypoxia alone. BAPTA did not prevent ROS production in either group. Conclusions In our cellular model for shock, we demonstrate that while hypoxia alone is sufficient to produce glycocalyx loss, hypoxia/reoxygenation causes a greater decrease in glycocalyx thickness. Under both conditions damage is dependent on ROS and Ca2+ signaling. Notably, we found that ROS are generated upstream of Ca2+, but that ROS-mediated damage to the glycocalyx is dependent on Ca2+. Study Type Basic science Level of Evidence Not applicable Author contribution statement: O.J.W. Conceived the study design, performed experiments, analyzed data, and wrote the manuscript. J.K.F. Conceived the study design, analyzed and interpreted data, and wrote the manuscript. L.A.R. aided in data acquisition. M.A.H. analyzed data. R.H.D. analyzed data. J.T.P. analyzed data. A.S. analyzed and interpreted data. C.G. conceived the study design and interpreted data. J.C.D. conceived the study design and interpreted data. Corresponding author: Olan Jackson-Weaver, Ph.D., Tulane School of Medicine, 1430 Tulane Ave, Dept. of Surgery, SL-22, New Orleans, LA 70112, Email: ojacksonweaver@tulane.edu, Phone: 504-988-2306, Fax: 504-988-3683 Conflicts of interest: No conflicts of interest are declared. This manuscript was presented at the 49th Annual Meeting of the Western Trauma Association, March 3-8, 2019, in Snowmass, CO, Scientific Session 3, March 5th. © 2019 Lippincott Williams & Wilkins, Inc.

Transition from Abdominal Aortic and Junctional Tourniquet (AAJT) to Zone 3 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is feasible with hemodynamic support after porcine class IV hemorrhage BACKGROUND Traumatic hemorrhage remains a major cause of death in rural civilian and combat environments. Potential interventions to control hemorrhage from the pelvis and lower junctional regions include the Abdominal Aortic and Junctional Tourniquet (AAJT) and Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA). The AAJT requires low technical skills and may thus be used by non-medical professionals, but is associated with time dependent ischemic complications. In combination with delayed patient evacuation, it may therefore be deleterious. Transition to zone 3 REBOA in higher levels of care may be a possibility to maintain hemostasis, mitigate adverse effects and enable surgery in patients resuscitated with the AAJT. It is possible that a transition between the interventions could lead to hemodynamic penalties. Therefore, we investigated the feasibility of replacing the AAJT with zone 3 REBOA in a porcine model of uncontrolled femoral hemorrhage. METHODS Domestic pigs (n=12) averaging 57 kg were exposed to a class IV uncontrolled hemorrhage from the common femoral artery. The animals were randomized to 60 min AAJT (n=6) or 30 min AAJT with transition to 30 min zone 3 REBOA. Hemodynamic-, and metabolic parameters and ultra-sonographic measurements of the common femoral artery were collected. RESULTS Transition from AAJT to zone 3 REBOA caused a significant decrease in mean arterial pressure (25 mm Hg). Hemostasis was maintained. The common femoral artery diameter decreased by 1,8 mm (38%) after hemorrhage and further 0,7 mm (23%) after aortic occlusion. CONCLUSION Transition from AAJT to zone 3 REBOA after a class IV bleeding is feasible with hemodynamic support. Vascular access to the femoral artery for REBOA insertion poses a technical challenge after hemorrhage and AAJT application. LEVEL OF EVIDENCE level IV, Laboratory animal study. Correspondence: Dr Andreas Brännström, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Sjukhusbacken 10, S1, SE-118 83 Stockholm, Sweden, Phone: +46 735 411 875, E-mail: andreas.brannstrom@ki.se Conflicts of interests: None © 2019 Lippincott Williams & Wilkins, Inc.

Big Problems in Little Patients: Nationwide Blunt Cerebrovascular Injury Outcomes in the Pediatric Population Background Blunt cerebrovascular injuries (BCVI) are uncommon but potentially devastating. The epidemiology, outcomes, and screening criteria are well described in adults, but data in pediatric patients are extremely limited. The purpose of this study was to characterize pediatric BCVI in a large nationwide sample. We hypothesized that outcomes of BCVI in the pediatric blunt trauma population will vary by age. Methods We conducted a retrospective cohort study of the Kids' Inpatient Database for pediatric BCVI from 2000-2012. Epidemiology, associated injuries, outcomes (including stroke and mortality), and the utility of standard screening criteria were analyzed. Results 1182 cases of BCVI were identified, yielding an incidence of 0.21%. Patients were predominately male (69%), mean age 15±5years. Injuries were 59% carotid, 13% vertebral, and 28% unspecified, with 15% having bilateral or multivessel BCVI. Although younger patients (<11y) had significantly lower ISS and decreased severe associated injuries (all p<0.01), they had a similar mortality rate (10%) versus the older cohort. Additionally, the stroke rate was significantly higher among the younger patients versus their older peers (29% mortality for <11y vs. 15% for ≥11y, p<0.01). Only 4 of 7 commonly utilized risk factors were associated with BCVI overall, but none were significantly associated with BCVI in younger children (<11y). Conclusion This represents the first nationwide assessment of BCVI in the pediatric population. Pediatric BCVI carry considerable mortality and stroke risk. Despite being less severely injured, younger children (<11y) had similar a mortality rate and a significantly higher stroke rate compared to older pediatric patients. Furthermore, commonly utilized adult screening criteria had limited utility in the younger cohorts. These findings suggest pediatric BCVI may require screening and treatment protocols that are significantly different than currently utilized adult-based programs. Level of Evidence Level III, Prognostic/Epidemiological Study Name and Address for Correspondence: Matthew J. Martin, MD, FACS, Trauma and Emergency Surgery Service, Scripps Mercy Medical Center, 550 Washington Street, Suite 641, San Diego, CA 92103, (619) 299-2600, traumadoc22@gmail.com There are no conflicts of interest to declare for any author as regards to this manuscript. This paper was presented at the 49th Annual Meeting of the Western Trauma Association in Snowmass, CO on Friday, March 8, 2019. There are no further disclosures. © 2019 Lippincott Williams & Wilkins, Inc.

Blunt Rupture of Two Cardiac Chambers Following a Motor Vehicle Collision No abstract available

Short-Term vs. Long-Term Trauma Mortality: A Systematic Review STRUCTURED ABSTRACT Background Trauma is the leading cause of death in the United States for persons under 44 years and the 4th leading cause of death in the elderly. Advancements in clinical care and standardization of treatment protocols have reduced 30-day trauma mortality to less than 4%. However, these improvements do not seem to correlate with long-term outcomes. Some reports have shown a greater-than-20% mortality rate when looking at long-term outcomes. The aim of this study was to systematically review the incongruence between short- and long-term mortality for trauma patients. Methods For this systematic review, we searched the Cochrane Library, EMBASE, Ovid Medline, Google Scholar, and Web of Science database to obtain relevant English, German, French, and Portuguese articles from 1965 to 2018. Results Trauma patients have decreased long-term survival when compared to the general population and when compared to age-matched cohorts. Post-discharge trauma mortality is significantly higher (mean 4.6% at 3-6 months, 15.8% at 2-3 years, 26.3% at 5-25 years) compared to controls (mean 1.3%, 2.2% and 15.6%, respectively). Patient comorbidities likely contribute to long-term trauma deaths. Trauma patients discharged to a skilled nursing facility have worse mortality compared to those discharged either to home or a rehabilitation center. In contrast to data available which illustrate that short-term mortality has improved, quality of evidence was not sufficient to determine if any improvements in long-term trauma mortality outcomes have also occurred. Conclusions The decreased short-term mortality observed in trauma patients does not appear correlated with decreased long-term mortality. The extent to which increased long-term trauma mortality is related to the initial traumatic insult – versus rising population age and comorbidity burden as well as sub-optimal discharge location – requires further study. Level of Evidence Level IV Study Type Systematic Review These authors contributed equally to this work, Lynn M. Frydrych, Toby P. Keeney-Bonthrone Conflict of Interest and Sources of Funding: All authors declare no conflicts of interest. LMF would like to acknowledge T32 HL007517, which supported her during her research fellowship. TPKB would like to acknowledge TL1TR000435 and TL1TR002242, which supported him during his research year. MJD would like to acknowledge the 2015 Research and Education Foundation Scholarship from the American Association for the Surgery of Trauma, the 2016 Research Scholarship from the Shock Society, and the 2017 Faculty Early Career Investigator Research Fellowship from the American Surgical Association Foundation which funded this research. Correspondence should be directed to: Matthew J. Delano, M.D., Ph.D., Assistant Professor of Surgery, University of Michigan, Department of Surgery, Division of Acute Care Surgery, University Hospital, 1C340D, 1500 E. Medical Center Dr, SPC 5033, Ann Arbor, Michigan 48109-5033, (734) 936-3662, (734) 936-9657, Email:mjdelano@med.umich.edu © 2019 Lippincott Williams & Wilkins, Inc.

LESSER SAC FLUID AFTER BLUNT TRAUMA No abstract available

Execute on the Vision: Pyramids and Mirages in Shifting Sands No abstract available

Patients with Acute Cholecystitis Should be Admitted to a Surgical Service Background In bowel obstruction and biliary pancreatitis, patients receive more expedient surgical care when admitted to surgical compared with medical services. This has not been studied in acute cholecystitis. Methods Retrospective analysis of clinical and cost data from July 2013 to September 2015 for patients with cholecystitis who underwent laparoscopic cholecystectomy in a tertiary care inpatient hospital. 190 lower-risk (Charlson-Deyo) patients were included. We assessed admitting service, length of stay, time from admission to surgery, time from surgery to discharge, number of imaging studies, and total cost. Results Patients admitted to surgical (n=106) versus medical (n=84) service had shorter mean LOS (1.4 vs 2.6 days), shorter time from admission to surgery (0.4 vs 0.8 days), and shorter time from surgery to discharge (0.8 vs 1.1 days). Surgical service patients had fewer CT (38% vs 56%) and MRI (5% vs 16%) studies. Cholangiography (30 vs 25%) and ERCP (3 vs 8%) rates were similar. Surgical service patients had 39% lower median total costs ($7787 vs $12572). Conclusions Nonsurgical admissions of patients with cholecystitis are common, even among lower-risk patients. Routine admission to the surgical service should decrease LOS, resource utilization and costs. This is a retrospective comparative study without negative criterion and thus Level III evidence. The study type is "Therapeutic/Care Management." Presented at the 88th Annual Meeting of the Pacific Coast Surgical Association, February 17-20, 2017 in Indian Wells, California Ning Lu, Present address: Ryder Trauma Center, Jackson Memorial Hospital, 1800 NW 10th Ave, Miami, FL, 33136 USA Walter L. Biffl, Present address: Scripps Memorial Hospital La Jolla, 9888 Genesee Ave., La Jolla, CA, 92037, USA No conflicts of interest. Funding: There are no sources of funding. Correspondence: Walter L. Biffl, MD, 9888 Genesee Ave., MC LJ601, La Jolla, CA 92037, 858-626-6362, 858-626-6354, Biffl.walter@scrippshealth.org © 2019 Lippincott Williams & Wilkins, Inc.

Evaluation and Management of Abdominal Gunshot Wounds: A Western Trauma Association Critical Decisions Algorithm No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Environmental Sciences

Effect of water-driven changes in rice rhizosphere on Cd lability in three soils with different pH Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Jinjin Wang, Dongqin Li, Qin Lu, Yulong Zhang, Huijuan Xu, Xueli Wang, Yongtao Li Abstract Pot experiments were conducted to evaluate the effect of water management, namely continuous flooding (CF), intermittent flooding (IF) and non-flooding (NF), on Cd phytoavailaility in three paddy soils that differed in pH and in Cd concentrations. Diffusive gradients in thin films (DGT) technique was employed to monitor soil labile Cd and Fe concentrations simultaneously at three growth stages (tillering, heading and mature stage) of rice. The Cd phytoavailability were generally in the order of NF > IF > CF, and higher rice Cd (over permitted level, 0.2 mg/kg) were only found in neutral and acidic soils under NF conditions. DGT measured soil labile Cd rather than total Cd was the most reliable predictor for Cd accumulation in rice. CF enhanced the formation of root plaques, which related to oxidation of large quantities of available Fe on root surfaces due to the O2 secretion of rice root. The Cd concentration in root plaques shared the same trend with DGT-Cd. Generally, root plaques would inhibit Cd uptake by rice under CF conditions, while under IF and NF conditions, root plaques act as a temporarily store of Cd, and soil labile Cd is the key factor that controls the transfer of Cd from soil to rice. The results of principle component analysis revealed that water management had the greatest effect on soil Cd lability and rice Cd in acidic soil. Thus, it is important to consider the availability of Cd and soil pH when assessing current agricultural practices of contaminated soil in China. Graphical abstract

A human embryonic stem cell-based in vitro model revealed that ultrafine carbon particles may cause skin inflammation and psoriasis Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Zhanwen Cheng, Xiaoxing Liang, Shaojun Liang, Nuoya Yin, Francesco Faiola Abstract Air pollution has been linked to many health issues, including skin conditions, especially in children. Among all the atmospheric pollutants, ultrafine particles have been deemed very dangerous since they can readily penetrate the lungs and skin, and be absorbed into the bloodstream. Here, we employed a human embryonic stem cell (hESC)-based differentiation system towards keratinocytes, to test the effects of ultrafine carbon particles, which mimic ambient ultrafine particles, at environment related concentrations. We found that 10 ng/mL to 10 μg/mL ultrafine carbon particles down-regulated the expression of the pluripotency marker SOX2 in hESCs. Moreover, 1 μg/mL to 10 μg/mL carbon particle treatments disrupted the keratinocyte differentiation, and up-regulated inflammation- and psoriasis-related genes, such as IL-1β, IL-6, CXCL1, CXCL2, CXCL3, CCL20, CXCL8, and S100A7 and S100A9, respectively. Overall, our results provide a new insight into the potential developmental toxicity of atmospheric ultrafine particles. Graphical abstract

Impact of biosolids, ZnO, ZnO/biosolids on bacterial community and enantioselective transformation of racemic–quizalofop–ethyl in agricultural soil Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Qing Zhou, Xu Zhang Abstract The effects of biosolids, ZnO, and ZnO/biosolids on soil microorganism and the environmental fate of coexisting racemic–quizalofop–ethyl (rac-QE) were investigated. Microbial biomass carbon in native soil, soil/biosolids decreased by 62% and 52% in the presence of ZnO (2‰, weight ratio). The soil bacterial community structure differed significantly among native soil, soil/biosolids, soil/ZnO, and soil/biosolids/ZnO based on a principal co-ordinate analysis (PCoA) of OTUs and one-way ANOVA test of bacterial genera. Chemical transformation caused by ZnO only contributed 4% and 3% of the overall transformation of R-quizalofop-ethyl (R-QE) and S-quizalofop-ethyl (S-QE) in soil/ZnO. The inhibition effect of ZnO on the initial transformation rate of R-QE (rR-QE) and S-QE (rR-QE) in soil only observed when enantiomer concentration was larger than 10 mg/kg. Biosolids embedded with ZnO (biosolids/ZnO) caused a 17%–42% and 22%–38% decrease of rR-QE and rS-QE, although rR-QE and rS-QE increased by 0%–17% and 22%–58% by the addition of biosolids. The results also demonstrated that the effects of biosolids on agricultural soil microorganism and enantioselective transformation of chiral pesticide was altered by the embedded nanoparticles. Graphical abstract

In situ preparation of g-C3N4/Bi4O5I2 complex and its elevated photoactivity in Methyl Orange degradation under visible light Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Zhe Feng, Lin Zeng, Qingle Zhang, Shifeng Ge, Xinyue Zhao, Hongjun Lin, Yiming He A graphite carbon nitride (g-C3N4) modified Bi4O5I2 composite was successfully prepared in-situ via the thermal treatment of a g-C3N4/BiOI precursor at 400°C for 3 hr. The as-prepared g-C3N4/Bi4O5I2 showed high photocatalytic performance in Methyl Orange (MO) degradation under visible light. The best sample presented a degradation rate of 0.164 min−1, which is 3.2 and 82 times as high as that of Bi4O5I2 and g-C3N4, respectively. The g-C3N4/Bi4O5I2 was characterized by X-ray powder diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Raman, X-ray photoelectron spectroscopy (XPS), ultraviolet-visible diffuse reflectance spectra (DRS), electrochemical impedance spectroscopy (EIS) and transient photocurrent response in order to explain the enhanced photoactivity. Results indicated that the decoration with a small amount of g-C3N4 influenced the specific surface area only slightly. Nevertheless, the capability for absorbing visible light was improved measurably, which was beneficial to the MO degradation. On top of that, a strong interaction between g-C3N4 and Bi4O5I2 was detected. This interplay promoted the formation of a favorable heterojunction structure and thereby enhanced the charge separation. Thus, the g-C3N4/Bi4O5I2composite presented greater charge separation efficiency and much better photocatalytic performance than Bi4O5I2. Additionally, g-C3N4/Bi4O5I2 also presented high stability. •O2− and holes were verified to be the main reactive species. Graphical abstract

Town-scale microbial sewer community and H2S emissions response to common chemical and biological dosing treatments Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Elizabeth R. Mathews, Jennifer L. Wood, Dean Phillips, Nathan Billington, Dean Barnett, Ashley E. Franks Abstract Controlling hydrogen sulfide (H2S) odors and emissions using a single, effective treatment across a town-scale sewer network is a challenge faced by many water utilities. Implementation of a sewer diversion provided the opportunity to compare the effectiveness of magnesium hydroxide (Mg(OH)2) and two biological dosing compounds (Bioproducts A and B), with different modes of action (MOA), in a field-test across a large sewer network. Mg(OH)2 increases sewer pH allowing suppression of H2S release into the sewer environment while Bioproduct A acts to disrupt microbial communication through quorum sensing (QS), reducing biofilm integrity. Bioproduct B reduces H2S odors by scouring the sewer of fats, oils and grease (FOGs), which provide adhesion points for the microbial biofilm. Results revealed that only Mg(OH)2 altered the microbial community structure and reduced H2S emissions in a live sewer system, whilst Bioproducts A and B did not reduce H2S emissions or have an observable effect on the composition of the microbial community at the dosed site. Study results recommend in situ testing of dosing treatments before implementation across an operational system. Graphical abstract

Adsorption and recovery of phosphate from water by amine fiber, effects of co-existing ions and column filtration Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Jinshan Wei, Xiaoguang Meng, Xianghua Wen, Yonghui Song Abstract A weak-base adsorption fiber, acrylic amine fiber (AAF), was prepared for removal and recovery of phosphate from water. The adsorption properties of the AAF for phosphate and effects of co-existing ions were investigated using batch and column filtration experiments, scanning electron microscope, and Fourier transform infrared techniques. Experimental results showed that AAF had a high phosphate adsorption capacity of 119 mg/g at pH 7.0. The effects of calcium, sulfate, carbonate, nitrate, and fluoride showed that sulfate and calcium inhibited phosphate adsorption. However, AAF showed higher binding affinity toward phosphate than sulfate. Column filtration results showed that AAF could filter 1420 bed volumes of tap water containing 1.0 mg-P/L of phosphate. The saturated AAF could be regenerated using 0.5 mol/L hydrochloric acid solution and reused. After desorption, phosphate was recovered through precipitation of hydroxyapatite (Ca5(PO4)3OH). The easy of regeneration, good adsorption performance, and the fiber morphology of AAF make it an attractive alternative for phosphate recovery from multiple water sources. Graphical abstract

Body fluid analog chlorination: Application to the determination of disinfection byproduct formation kinetics in swimming pool water Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Lucie Tsamba, Nicolas Cimetière, Dominique Wolbert, Olivier Correc, Pierre Le Cloirec Abstract Disinfection by-products (DBPs) are formed in swimming pools by the reactions of bather inputs with the disinfectant. Although a wide range of molecules has been identified within DBPs, only few kinetic rates have been reported. This study investigates the kinetics of chlorine consumption, chloroform formation and dichloroacetonitrile formation caused by human releases. Since the flux and main components of human inputs have been determined and formalized through Body Fluid Analogs (BFAs), it is possible to model the DBPs formation kinetics by studying a limited number of precursor molecules. For each parameter the individual contributions of BFA components have been quantified and kinetic rates have been determined, based on reaction mechanisms proposed in the literature. With a molar consumption of 4 mol Cl2/mol, urea is confirmed as the major chlorine consumer in the BFA because of its high concentration in human releases. The higher reactivity of ammonia is however highlighted. Citric acid is responsible for most of the chloroform produced during BFA chlorination. Chloroform formation is relatively slow with a limiting rate constant determined at 5.50 × 10−3 L/mol/sec. L-histidine is the only precursor for dichloroacetonitrile in the BFA. This DBP is rapidly formed and its degradation by hydrolysis and by reaction with hypochlorite shortens its lifetime in the basin. Reaction rates of dichloroacetonitrile formation by L-histidine chlorination have been established based on the latest chlorination mechanisms proposed. Moreover, this study shows that the reactivity toward chlorine differs whether L-histidine is isolated or mixed with BFA components. Graphical abstract

Overview of key operation factors and strategies for improving fermentative volatile fatty acid production and product regulation from sewage sludge Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Wei Fang, Xuedong Zhang, Panyue Zhang, Jijun Wan, Hongxiao Guo, Dara S.M. Ghasimi, Xavier Carol Morera, Tao Zhang Abstract In recent years, volatile fatty acid (VFA) production through anaerobic fermentation of sewage sludge, instead of methane production, has been regarded as a high-value and promising roadmap for sludge stabilization and resource recovery. This review first presents the effects of some essential factors that influence VFA production and composition. In the second part, we present an extensive analysis of conventional pretreatment and co-fermentation strategies ultimately addressed to improving VFA production and composition. Also, the effectiveness of these approaches is summarized in terms of sludge degradation, hydrolysis rate, and VFA production and composition. According to published studies, it is concluded that some pretreatments such as alkaline and thermal pretreatment are the most effective ways to enhance VFA production from sewage sludge. The possible reasons for the improvement of VFA production by different methods are also discussed. Finally, this review also highlights several current technical challenges and opportunities in VFA production with spectrum control, and further related research is proposed. Graphical abstract

Bimetallic nickel molybdate supported Pt catalyst for efficient removal of formaldehyde at low temperature Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Gang Huang, Zhaoxiong Yan, Shuyuan Liu, Tingting Luo, Liang An, Zhihua Xu Abstract Efficient removal of formaldehyde from indoor environments is of significance for human health. In this work, a typical binary transition metal oxide that could provide various oxidation states, β-NiMoO4, was employed as a support to immobilize the active Pt component (Pt/NiMoO4) for catalytic formaldehyde elimination at low ambient temperature (15°C). The results showed that the hydrothermal preparation temperature and time had a noticeable impact on the morphology and catalytic activity of the samples. The catalyst prepared with hydrothermal temperature of 150°C for 4 hr (Pt-150-4) exhibited superior catalytic activity and stability mainly due to its distinctly porous structure, relative abundance of adsorbed surface hydroxyls/water, and high oxidation ability, which resulted from the interaction of Pt with Ni and Mo of the bimetallic NiMoO4 support. Our results might shed light on the rational design of multifunctional catalysts for removal of indoor air pollutants at low ambient temperature. Graphical abstract

Microtopographic modification conserves urban wetland water quality by increasing the dissolved oxygen in the wet season Publication date: January 2020 Source: Journal of Environmental Sciences, Volume 87 Author(s): Yali Liu, Jianqing Du, Panpan Hu, Mingzhu Ma, Dan Hu Abstract Microtopography affects hydrological processes and forms different microhabitats. Our previous study uncovered that riparian zone microtopography created various microhabitats with different soil environments and runoff-infiltration patterns. However, how riparian microtopography and microtopography within the water area (waterfall and tributary) affects downstream water quality remains unclear. Therefore, water samples were taken almost monthly in both the main stream and the tributary, before and after waterfalls, and near the bottom of three microtopographic types from June 2016 to March 2017. Compared with the dry season, the fact that water quality worsened in the wet season and that there were positive correlations for nitrate (NO3−) between water and the corresponding soil samples suggested that the riparian-soil environment affected the adjacent water quality mainly in the wet season. Nevertheless, riparian microtopography did not influence water quality downstream because of the low rainfall frequency and the weak leaching process due to plant interception. In the wet season, both the tributary and the waterfall increased the dissolved oxygen in the water body and, therefore, lowered the risk of eutrophication. The tributary has two pathways for improving the water quality, by increased disturbance and flow velocity, while the waterfall only has the former. However, such effects were not significant in the dry season. We conclude that the application of microtopographic modification is useful in maintaining urban wetland water quality in wet seasons.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Clinical Nuclear Medicine

Clinical Utility of Different Approaches for Detection of Late Pseudoprogression in Glioblastoma With O-(2-[18F]Fluoroethyl)-L-Tyrosine PET Purpose PET/CT using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) has proven valuable in differentiating tumor recurrence and progression from therapy-induced changes. This study aimed to investigate the diagnostic performance of several analytic approaches in the setting of suspected late pseudoprogression (PsP) in glioblastoma multiforme (GBM). Methods Retrospective analysis of tumor recurrence was performed in 36 patients with histopathologically confirmed GBM and suspicion of recurrence/disease progression more than 12 weeks from cessation of irradiation based on MRI and Response Assessment in Neuro-Oncology working group criteria. For differentiation of late PsP from true tumor recurrence, images were analyzed semiquantitatively employing tumor-to-brain ratios using 5 different approaches for tumor and normal brain reference region definition, respectively. Histopathology and/or clinical and imaging follow-up served as reference. Respective areas under the receiver operating characteristic curve were compared. Results 18F-FET PET was able to reliably differentiate PsP from true tumor progression with areas under the receiver operating characteristic curve ranging from 0.80 to 0.88 (all P < 0.01). Irrespective of the approach chosen, the classification differences between the applied methods were not significant (all P > 0.05), albeit approaches focusing on voxels with the highest uptake tended to perform superior. Conclusions Irrespective of the analytical approach, 18F-FET PET is a robust tool for detection of late PsP with only minor differences between different analytical approaches. However, methodological standardization and harmonization are needed to ensure comparability between different centers. Received for publication December 18, 2018; revision accepted April 11, 2019. P.T.M. and C.L. contributed equally to this work. Informed consent was obtained from all individual participants included in the study. All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Conflicts of interest and sources of funding: none declared. Authorship: Conception and design: O.K., M.I.M., T.L., A.F.K., P.T.M., C.L. Development of methodology: O.K., M.K., J.B., S.S., M.L., P.T.M., C.L. Acquisition of data: O.K., M.I.M., M.K., J.B., C.M.M., C.L. Analysis and interpretation of data: O.K., M.I.M., J.T.-G., J.B., C.M.M., C.L. Writing, review and/or revision of the manuscript: all authors. Administrative, technical, or material support: J.T.-G., S.S., R.-I.E., M.L., P.T.M. Supervision: R.-I.E., M.L., P.T.M., C.L. Correspondence to: Constantin Lapa, MD, Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080 Würzburg, Germany. E-mail: Lapa_c@ukw.de. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.nuclearmed.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

18F-DCFPyL PET/CT in a Single Large Metastasis With Prostate-Specific Antigen Level of 856 ng/mL Literature shows that prostate-specific membrane antigen (PSMA) PET/CT may detect biochemical recurrence of prostate cancer at low prostate-specific antigen (PSA) levels, including detection of oligometastatic disease and hence direct metastasis-directed therapy. Although it is generally accepted that higher PSA values indicate higher disease burden, few data are available on the relation between PSA levels and number of detected metastases on PSMA PET/CT. This report demonstrates a patient with high PSA levels (856 ng/mL) at time of biochemical recurrence that showed only 1 metastasis on PSMA PET/CT. Combined androgen deprivation therapy and radiation therapy resulted in a complete biochemical response. Received for publication March 5, 2019; revision accepted May 19, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Maurits Wondergem, MD, PhD, Wilhelminalaan 12 1815 JD Alkmaar, the Netherlands. E-mail: M.wondergem@nwz.nl. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

High-Resolution PET Cisternography With 64Cu-DOTA for CSF Leak Detection Intracranial hypotension may lead to chronic, debilitating symptoms, and severe complications. The underlying CSF leak may be difficult to localize. To establish a new diagnostic option for the detection of CSF leaks, 64Cu-DOTA was developed as a tracer for PET imaging. PET/CT imaging was possible with high resolution and without complications. In one patient, the exact site of a dural tear was identified, enabling successful surgical treatment. PET cisternography with 64Cu-DOTA appears to be safe and able to locate a CSF leak. It has the potential to be a problem-solving modality in cases with inconclusive CT, MR, and/or scintigraphic findings. Received for publication February 8, 2019; revision accepted May 19, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Martin Freesmeyer, MD, Clinic of Nuclear Medicine, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. E-mail: martin.freesmeyer@med.uni-jena.de. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Stepwise Approach to Identify the Clinical Role of 18F-FDG PET/CT in Patients With Suspicious Bone Metastasis From an Unknown Primary Site In patients with suspicious bone metastasis, the clinical impact of PET/CT for differential diagnosis and primary lesion identification could differ according to 18F-FDG uptake patterns. We report the findings in patients with suspicious bone metastasis who underwent PET/CT for the evaluation of the primary lesion site and were classified in a stepwise manner, first based on the multiplicity of positive bone uptake and then the presence of extraskeletal uptake. Received for publication December 4, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: This study was supported by a grant from KOICA and the Chonnam National University Hwasun Hospital Institute for Biomedical Science (HCRI 17 922-21). None declared to all authors. Correspondence to: Seong Young Kwon, MD, PhD, Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeollanam-do, 58128, Republic of Korea. E-mail: kwonsy@jnu.ac.kr. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Celiac Disease on FDG PET/CT An FDG PET with diagnostic CT was performed on a 52-year-old man for investigation of lymphocytosis and the clinical suspicion of lymphoma. The PET/CT demonstrated diffuse small bowel uptake, prominent mesenteric lymph nodes without significant FDG uptake, and other features suggestive of celiac disease. Subsequently, the patient was found to have markedly elevated celiac disease antibodies (deamidated gliadin IgG and tissue transglutaminase IgA) and to be HLA DQ2 and DQ8 allele positive on genotyping for celiac disease. Gastroscopy and duodenal biopsy also confirmed the diagnosed. Received for publication December 18, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Anthony Cardin, MBBS, Barwon Medical Imaging, University Hospital Geelong, Ryrie St, Geelong, Victoria, 3220, Australia. E-mail: ancardin@barwonhealth.org.au. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Ileal Neuroendocrine Tumor With Bilateral Breast and Ovarian Metastases: Findings on 68Ga-DOTANOC PET/CT Scan Metastasis to the breast is a rare occurrence and constitutes less than 2% of all breast tumors. Similarly, ovarian metastases from neuroendocrine tumors are also uncommon, and if the adnexal masses are bilateral, then the chances of it being metastatic rather than being primary range from 88% to 94%. We present a case of 61-year-old woman who in the course of workup for abdominal pain and diarrhea was eventually diagnosed as ileal neuroendocrine tumor with breast, ovarian, and lymph nodal metastases on 68Ga-DOTANOC PET/CT scan. Received for publication December 30, 2018; revision accepted May 18, 2019. Conflicts of interest and sources of funding: none declared. Correspondence: Girish Kumar Parida, MD, Nuclear Medicine, Department of Nuclear Medicine, Delhi Institute of Functional Imaging, Hauz Khas, New Delhi 110016. E-mail: grissh135@gmail.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Adult Pancreatoblastoma With Liver Metastasis Diagnosed by 18F-FDG PET/CT and 2 Years' Postoperative Follow-up Pancreatoblastoma is an extremely rare malignant tumor of the pancreas. Most patients are infants and children; however, a few cases have been reported in adults. Herein, we present the case of a 49-year-old man with pancreatoblastoma and liver metastasis who underwent preoperative multimodal imaging, in which 18F-FDG PET/CT showed a markedly increased 18F-FDG uptake in the metastatic lesion and a slightly increased uptake in the primary lesion. Subsequently, the patient underwent complete resection of the primary and metastatic lesions. No recurrences or metastases were found in 2 years of follow-up. Received for publication March 27, 2019; revision accepted May 13, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Shu-Xia Wang, MD, PhD, Room 517, 5/F Weilun Building, Guangdong Provincial People's Hospital, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, China. E-mail: shuxia_wangGGH@outlook.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Adenocarcinoma of the Stomach Leading to Recurrent Regurgitation and Muscular Hypermetabolism on 18F-FDG PET/CT Skeletal muscle uptake of 18F-FDG can result from a variety of physiologic and pathologic conditions. It is important for the physician to interpret these uptake patterns in the correct context to avoid a misdiagnosis. We present a case of a 36-year-old man with progressive, repeated episodes of regurgitation who was diagnosed with adenocarcinoma of the stomach. 18F-FDG PET/CT showed increased tracer uptake in the primary tumor and in the intercostal and sternocleidomastoid muscles. The pattern of tracer uptake along with the clinical history and examination of the patient helped differentiate a physiologic variant from a pathologic cause. Received for publication April 15, 2019; revision accepted May 11, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Bhagwant Rai Mittal, MD, DNB, Department of Nuclear Medicine, Ground Floor, A-Block, Nehru Hospital, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. E-mail: brmittal@yahoo.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Evaluation of Lung Cancer and Neuroendocrine Neoplasm in a Single Scan by Targeting Both Somatostatin Receptor and Integrin αvβ3 Purpose This pilot study aimed to prove the complementary value of a novel 68Gallium-labeled heterodimeric peptide, 68Ga-NOTA-3P-TATE-RGD, in detection and evaluation of tumors with somatostatin receptor subtype 2 or integrin αvβ3 overexpression, including non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), neuroendocrine tumor (NET), and neuroendocrine carcinoma (NEC). Methods With institute review board approval and written informed consent, 32 patients with pathologically diagnosed lung cancer (18 NSCLC, 14 SCLC) and 12 patients with neuroendocrine neoplasm (8 NET, 4 NEC) patients were recruited to undergo 68Ga-NOTA-3P-TATE-RGD PET/CT. For comparison, the NSCLC patients also underwent 68Ga-NOTA-TATE PET/CT, the SCLC patients underwent 68Ga-NOTA-RGD PET/CT, and the neuroendocrine neoplasm patients underwent 18F-FDG PET/CT within 3 days. The maximum standardized uptake value (SUV) of the primary tumor (T) and mean SUV of the blood pool (B) were measured, and the T/B ratios were calculated for comparison. Results In the primary tumors of NSCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-TATE (4.54 ± 3.00 versus 4.10 ± 2.83, P = 0.0058). In SCLC, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were significantly higher than those of 68Ga-NOTA-RGD (6.06 ± 6.09 versus 2.65 ± 1.19, P = 0.0344). In NET, the T/B ratios of 68Ga-NOTA-3P-TATE-RGD were 36.13 ± 33.84, significantly higher than those of 18F-FDG (2.91 ± 1.71, P = 0.0234). In NEC, there were no significant difference between the T/B ratios of 68Ga-NOTA-3P-TATE-RGD (4.80 ± 0.85) and those of 18F-FDG (3.56 ± 0.74, P = 0.1833). Conclusions This proof-of-concept study preliminarily demonstrates the efficacy of the dual targeting 68Ga-NOTA-3P-TATE-RGD PET/CT in the evaluation of lung cancer and neuroendocrine neoplasm in a single scan. Received for publication November 12, 2018; revision accepted May 9, 2019. Conflicts of interest and sources of funding: This study was partly supported by the Key Special Project on Inter-Governmental Scientific and Technological Innovation Cooperation in National Key Research and Development Plan (2016YFE0115400), the Chinese Academy of Medical Science Major Collaborative Innovation Project (2016-I2M-1-011), National Nature Science Foundation (81741142, 81871392), and Beijing Municipal Natural Science Foundation (7161012). None declared to all authors. Correspondence to: Zhaohui Zhu, MD, Department of Nuclear Medicine, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and PUMC, Beijing 100730, People's Republic of China. E-mail: zhuzhh@pumch.cn. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Giant Melanotic Malignant Peripheral Nerve Sheath Tumor in the Pelvis: Contrast-Enhanced CT and 18F-FDG PET/CT Finding Melanotic malignant peripheral nerve sheath tumor is an extremely rare tumor, which originates from the neural crest, and more than half the cases are associated with Carney complex (myxomas, spotty pigmentation, and endocrine abnormalities). Herein, we have presented a case of a melanotic malignant peripheral nerve sheath tumor, which is not associated with Carney complex. The patient underwent preoperative nonenhanced CT, contrast-enhanced CT, and 18F-FDG PET/CT scans, which showed a large pelvic tumor with heterogeneous enhancement and increased 18F-FDG uptake. Subsequently, the patient underwent complete resection of the tumor. Received for publication April 4, 2019; revision accepted May 7, 2019. Conflicts of interest and sources of funding: none declared. Correspondence to: Shuxia Wang, MD, PhD, Room 517, 5/F, WeiLun Building of Guangdong Provincial People's Hospital, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong, People's Republic of China. E-mail: shuxia_wangGGH@outlook.com. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Pediatric Critical Care Medicine

Evaluation of Pediatric Cardiac ICU Advanced Practice Provider Education and Practice Variation Objectives: The education, training, and scope of practice of cardiac ICU advanced practice providers is highly variable. A survey was administered to cardiac ICU advanced practice providers to examine specific variations in orientation format, competency assessment during and at the end of orientation, and scope of clinical practice to determine gaps in resources and need for standardization. Design: This study was a cross-sectional descriptive study utilizing survey responses. Setting: Pediatric cardiac ICUs in the United States. Subjects: The survey was delivered to a convenience sample of advanced practice providers currently practicing in pediatric cardiac ICUs. Interventions: A list of pediatric cardiothoracic surgery programs was generated from the Society of Thoracic Surgery database. A self-administered, electronic survey was delivered via email to advanced practice providers at those institutions. Descriptive data were compared using a chi-square test or Fisher exact test depending on the normalcy of data. Continuous data were compared using a Student t test or Mann-Whitney U test. Measurements and Main Results: Eighty-three of 157 advanced practice providers responded (53% response rate, representing 36 institutions [35% of institutions]). Sixty-five percent of respondents started as new graduates. Ninety-three to one-hundred percent obtain a history and physical, order/interpret laboratory, develop management plans, order/titrate medications, and respiratory support. Ability to perform invasive procedures was highly variable but more likely for those in a dedicated cardiac ICU. Seventy-seven percent were oriented by another advanced practice provider, with a duration of orientation less than 4 months (66%). Fifty percent of advanced practice providers had no guidelines in place to guide learning/competency during orientation. Sixty-seven percent were not evaluated in any way on their knowledge or skills during or at the end of orientation. Orientation was rated as poor/fair by the majority of respondents for electrophysiology (58%) and echocardiography (69%). Seventy-one percent rated orientation as moderately effective or less. Respondents stated they would benefit from more structured didactic education with clear objectives, standardized management guidelines, and more simulation/procedural practice. Eighty-five percent were very/extremely supportive of a standardized cardiac ICU advanced practice provider curriculum. Conclusions: Orientation for cardiac ICU advanced practice providers is highly variable, content depends on the institution/preceptor, and competency is not objectively defined or measured. A cardiac ICU advanced practice provider curriculum is needed to standardize education and promote the highest level of advanced practice provider practice. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. Address requests for reprints to: Lindsey Justice, DNP, APRN, CPNP-AC, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229. E-mail: Lindsey.Justice@cchmc.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Extracorporeal Membrane Oxygenation for Severe Adenoviral Pneumonia in Neonatal, Pediatric, and Adult Patients Objectives: We examined data on patients with severe adenoviral pneumonia from the international registry of the Extracorporeal Life Support Organization to identify risk factors for mortality in patients receiving extracorporeal membrane oxygenation. Design: Retrospective analysis. Setting: International Registry of Extracorporeal Life Support Organization. Patients: We collected de-identified data on all patients with adenoviral pneumonia who needed extracorporeal membrane oxygenation from 1992 to 2016 using International Classification of Diseases, 9th Edition, criteria. Interventions: Our primary outcome measure was in-hospital mortality. We also collected data on demographics, preextracorporeal membrane oxygenation ventilator settings, biochemical variables, extracorporeal membrane oxygenation mode, duration, and complications. Initial bivariate analysis assessed potential associations between mortality and various preextracorporeal membrane oxygenation variables as well as extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis that identified predictors of mortality. Measurements and Results: There were 542 patients with adenoviral pneumonia who were supported with extracorporeal membrane oxygenation. Overall mortality was 58% (307/529 patients) (neonates 86.4% [108/125 patients], children 49% [158/327 patients], and adults 49% [41/83 patients]). Multivariate regression identified hypercapnia (PCO2 > 45.7; odds ratio > 3.2; p < 0.001), immunosuppression (odds ratio, 4.44; 95% CI, 1.69–11.61; p = 0.002] and lack of pharmacologic paralysis (odds ratio, 0.30; 95% CI, 0.16–0.57; p < 0.001] as significant preextracorporeal membrane oxygenation factors for mortality. Neonatal patients had significantly higher mortality than pediatric or adult patients (odds ratio, 10.9; 95% CI, 3.2–37.3; p < 0.001). The presence of renal (odds ratio, 4.4; 95% CI, 2.5–7.7; p < 0.001), neurologic (odds ratio, 2.5; 95% CI, 1.2–5.1; p = 0.014), hemorrhagic (odds ratio, 2.2; 95% CI, 1.2–4.0; p = 0.014), or cardiovascular complications (odds ratio, 2.4; 95% CI, 1.3–4.6; p = 0.006) was associated with higher mortality on extracorporeal membrane oxygenation. Conclusions: Patients with adenoviral pneumonia supported on extracorporeal membrane oxygenation had mortality of 58% over a 25-year-old period. We identified risk factors both before and during extracorporeal membrane oxygenation which were associated with higher mortality. Mortality in neonatal patients was particularly high. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. This work was performed at Cardiothoracic ICU, National University Heart Centre, Singapore. For information regarding this article, E-mail: ram_ramanathan@nuhs.edu.sg ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial Objectives: It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass. Design: Two-center, double-blinded, prospective, randomized clinical trial. Setting: The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki). Patients: Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass. Interventions: Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours. Measurements and Main Results: The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups. Conclusions: Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot. † Deceased January 9, 2018. Drs. Thorlacius and Castellheim received support for article research from European Society of Anesthesiology, Scandinavian Society of Anesthesiology and Intensive Care Medicine, The Gothenburg Society of Medicine, Queen Silvia's Jubilee Fund, Swedish Society for Anesthesiology and Intensive Care, The Samariten foundation for pediatric research, and funds under the ALF agreement (the Swedish governmental funds for research and education). Drs. Thorlacius, Suominen, Wåhlander, Vistnes, and Castellheim disclosed off-label product use of levosimendan as an inodilator, which is off-label for pediatric patients in Finland and Sweden. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: elin.thorlacius@gu.se ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Matched Retrospective Cohort Study of Thiamine to Treat Persistent Hyperlactatemia in Pediatric Septic Shock Objectives: Thiamine deficiency may propagate lactate production by limiting pyruvate dehydrogenase activity, and studies suggest benefit for thiamine administration in septic adults. We studied the effect of thiamine on physiologic and clinical outcomes for children with septic shock and hyperlactatemia. Design: Retrospective matched cohort study. Setting: Single academic PICU. Patients: Six thiamine-treated cases and nine matched controls. Interventions: None. Measurements and Main Results: The primary outcome was change in blood lactate from prethiamine (T0, cases) or maximum (T0, controls) lactate through 24 hours later (T24). Secondary outcomes were change in lactate over 48 hours (T48) and 72 hours (T72), time to lactate normalization, changes in vasoactive-inotrope score, organ dysfunction severity (daily Pediatric Logistic Organ Dysfunction 2 score), and creatinine, PICU length of stay, and hospital mortality. Lactate was greater than 5 mmol/L for a median of 39 hours (range, 16.1–64.3 hr) prior to thiamine administration for cases compared with 3.4 hours (range, 0–22.9 hr) prior to maximum lactate for controls (p = 0.002). There was no difference in median (interquartile range) change in lactate from T0 to T24 between thiamine-treated cases and controls (–9.0, –17.0 to -5.0 vs –7.2, –9.0 to –5.3 mmol/L, p = 0.78), with both groups exhibiting a rapid decrease in lactate. There were also no differences in secondary outcomes between groups. Conclusions: Treatment of pediatric septic shock with thiamine was followed by rapid improvement in physiologic and clinical outcomes after prolonged hyperlactatemia. Although we are not able to infer that thiamine provided benefit over usual care, the rapid decline in lactate after thiamine despite a prolonged period of hyperlactatemia raises the possibility that thiamine helped to reverse lactate production. Supported, in part, by grant from the National Institute of General Medical Sciences K23GM110496 (to Dr. Weiss) and the Department of Anesthesiology and Critical Care at the Children's Hospital of Philadelphia. Drs. Weiss's and Blowey's institutions received funding from National Institute of General Medical Sciences K23GM110496. Drs. Weiss, Blowey, and Ganetzky received support for article research from the National Institutes of Health (NIH). Dr. Ganetzky received funding from the NIH. Dr. Sutton's institution received funding from NIH National Heart, Lung, and Blood Institute R01; he received funding from Zoll Medical (speaking honoraria); and he disclosed he is a writing group member of the Pediatric Advanced Life Support Guidelines and Chair of the American Heart Association's Get With the Guidelines-Resuscitation Pediatric Research Task Force. The remaining authors have disclosed that they do not have any potential conflicts of interest. This study was performed at the Children's Hospital of Philadelphia. Address requests for reprints to: Scott L. Weiss, MD, MSCE, FCCM, Department of Anesthesiology and Critical Care, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3401 Civic Center Blvd, Wood Building 6th Floor, Suite 6026A, Philadelphia, PA 19104. E-mail: WeissS@email.chop.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Strengths and Difficulties Questionnaire Assessment of Long-Term Psychological Outcome in Children After Intensive Care Admission Objectives: We investigated the long-term psychologic symptoms of patients who survived pediatric intensive care admission. Design: Longitudinal follow-up study. Setting: Nationwide cohort study based on a national ICU register and a questionnaire survey. Patients: All pediatric patients (0–16 yr old) who were admitted to an ICU in Finland in 2009–2010. Interventions: None. Measurements and Main Results: Six years after ICU admission, all surviving patients were sent the Strengths and Difficulties Questionnaire, and questionnaires regarding chronic diseases and need for medication and therapy. At the end of the follow-up period, there were 3,674 surviving children who had been admitted to an ICU in 2009–2010. Of these children, 1,105 completed the Strengths and Difficulties Questionnaire 6 years after admission. Strengths and Difficulties Questionnaire scores were abnormal for 84 children (7.6%), borderline for 80 (7.2%), and normal for 941 (85.2%). Participants with abnormal scores were younger at admission to the ICU (3.06 vs 4.70 yr; p = 0.02), and more commonly had a chronic disease (79.5% vs 47.4%; p < 0.001), a need for continuous medication (49.4% vs 31.7%; p < 0.001), a need for therapy (58.5% vs 15.9%; p < 0.001), and a need for annual healthcare visits (91.4% vs 85.2%; p = 0.05). Abnormal Strengths and Difficulties Questionnaire scores were associated with higher rates of neurologic (32.1% vs 10.2%), gastrointestinal (7.1% vs 3.9%), psychiatric (3.6% vs 0.5%), and chromosomal disorders (9.5% vs 1.3%), as well as with long-term pain (1.2% vs 0.6%). Conclusions: Participants with abnormal Strengths and Difficulties Questionnaire scores (poor psychologic outcome) at 6 years after childhood ICU admission more commonly suffered neurologic, chromosomal, or psychiatric diagnoses or long-term pain, and generally required higher levels of healthcare services, therapies, and medication. Dr. Kyösti received support for article research from Alma and K. A. Snellman Foundation Finnish grant for Pediatric Research. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: elina.kyosti@ppshp.fi ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Innovation in Central Venous Access Device Security: A Pilot Randomized Controlled Trial in Pediatric Critical Care Objectives: Central venous access devices enable many treatments during critical illness; however, 25% of pediatric central venous access devices fail before completion of treatment due to infection, thrombosis, dislodgement, and occlusion. This is frequently attributed to inadequate securement and dressing of the device; however, high-quality research evaluating pediatric central venous access device securement innovation to prevent central venous access device failure is scarce. This study aimed to establish the feasibility of a definitive randomized control trial examining the effectiveness of current and new technologies to secure central venous access devices in pediatrics. Design: Single-center, parallel group, superiority, pilot randomized control trial. Setting: Anesthetic and intensive care departments of a tertiary pediatric hospital Subjects: One-hundred eighty pediatric patients with nontunneled central venous access device Interventions: Participants were randomized to receive central venous access device securement via standard care (bordered polyurethane dressing, with prolene sutures, chlorhexidine gluconate disc), tissue adhesive (Histoacryl, B Braun, Melsungen, Germany) in addition to standard care; or integrated dressing securement (SorbaView SHIELD [Centurion Medical Products, Franklin, MA], with prolene sutures and chlorhexidine gluconate disc). Outcomes: Primary: Feasibility (including effect size estimates, acceptability); central venous access device failure; central venous access device complications; secondary: individual central venous access device complications, skin damage, dressing performance, and product cost. Measurements and Main Results: Feasibility criteria were achieved as recruitment occurred with acceptable eligibility, recruitment, missing data, and attrition rates, as well as good protocol adherence. Family members and staff-reported comparable levels of acceptability between study arms; however, tissue adhesive was reported as the most difficult to apply. Overall, 6% of central venous access devices failed, including 6% (3/54; incident rate, 13.2 per 1,000 catheter days) standard care, 2% (1/56; incident rate, 3.65 per 1,000 catheter days) integrated, and 8% (5/59; 25.0 per 1,000 catheter days) tissue adhesive. Conclusions: It is feasible to conduct an efficacy randomized control trial of the studied interventions. Further research is required to definitively identify clinical, cost-effective methods to prevent central venous access device failure by examining new dressing and securement technologies and techniques. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Dr. Ullman's institution has received an unrestricted research grant from Centurion Medical Products (dressing manufacturers) to support research, 3M (dressing manufacturers) to support research, Becton Dickinson (dressing manufacturers) to support research. Drs. Ullman and Rickards' institutions received investigator-initiated grants, or consultancy payments on behalf of Ms. Rickard from vascular access product manufacturers (3M, Adhezion, Angiodynamics, Bard, Baxter, Becton Dickinson, BBraun, Centurion Medical Products, Entrotech, Medtronic, and Smiths Medical). Dr. Long's institution received funding from Griffith University (payment for recruitment and data entry). The remaining authors have disclosed that they do not have any potential conflicts of interest. Clinical trial registration: ACTRN12615000977572. For information regarding this article, E-mail: a.ullman@griffith.edu.au ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Bleeding and Thrombosis With Pediatric Extracorporeal Life Support: A Roadmap for Management, Research, and the Future From the Pediatric Cardiac Intensive Care Society (Part 1) Objectives: To make practical and evidence-based recommendations on improving understanding of bleeding and thrombosis with pediatric extracorporeal life support and to make recommendations for research directions. Data Sources: Evaluation of literature and consensus conferences of pediatric critical care and extracorporeal life support experts. Study Selection: A team of 10 experts with pediatric cardiac and extracorporeal membrane oxygenation experience and expertise met through the Pediatric Cardiac Intensive Care Society to review current knowledge and make recommendations for future research to establish "best practice" for anticoagulation management related to extracorporeal life support. Data Extraction/Synthesis: The first of a two-part white article focuses on clinical understanding and limitations of medications in use for anticoagulation, including novel medications. For each medication, limitations of current knowledge are addressed and research recommendations are suggested to allow for more definitive clinical guidelines in the future. Conclusions: No consensus on best practice for anticoagulation exists. Structured scientific evaluation to answer questions regarding anticoagulant medication and bleeding and thrombotic events should occur in multicenter studies using standardized approaches and well-defined endpoints. Outcomes related to need for component change, blood product administration, healthcare outcome, and economic assessment should be incorporated into studies. All centers should report data on patients receiving extracorporeal life support to a registry. The Extracorporeal Life Support Organization registry, designed primarily for quality improvement purposes, remains the primary and most successful data repository to date. Drs. Penk and Reddy contributed equally as first coauthors. The work for this project occurred during monthly phone meetings and at each of the institutions listed above for the authors. Dr. Reddy's institution received funding from the National Institutes of Health and the American Heart Association. Dr. Thiagarajan's institution received funding from Bristol Myers Squibb and Pfizer. Dr. Dalton received funding from Innovative ECMO Concepts (consultant), and she disclosed off-label product use of extracorporeal membrane oxygenation. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: jamiepenk@gmail.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Severity and Mortality Predictors of Pediatric Acute Respiratory Distress Syndrome According to the Pediatric Acute Lung Injury Consensus Conference Definition Objectives: The objective of this study was to assess the prevalence, severity, and outcomes of pediatric acute respiratory distress syndrome in a resource-limited country. In addition, we sought to explore the predisposing factors that predicted the initial severity, a change from mild to moderate-severe severity, and mortality. Design: Retrospective study. Setting: PICU in Songklanagarind Hospital, Songkhla, Thailand. Patients: Children 1 month to 15 years old with acute respiratory failure admitted to the PICU from January 2013 to December 2016. Interventions: None. Measurements and Main Results: From a total of 1,738 patients admitted to PICU, 129 patients (prevalence 7.4%) were diagnosed as pediatric acute respiratory distress syndrome using the Pediatric Acute Lung Injury Consensus Conference definition. The patients were categorized by severity. Fifty-seven patients (44.2%) were mild, 35 (27.1%) were moderate, and 37 (28.1%) were severe. After multivariable analysis was performed, factors significantly associated with moderate to severe disease at the initial diagnosis were Pediatric Risk of Mortality III score (odds ratio, 1.08; 95% CI, 1.03–1.15; p = 0.004), underlying oncologic/hematologic disorder (odds ratio, 0.32; 95% CI, 0.12–0.77; p = 0.012), and serum albumin level (odds ratio, 0.46; 95% CI, 0.27–0.80; p = 0.006), whereas underlying oncologic/hematologic disorder (odds ratio, 5.33; 95% CI, 1.33–21.4) and hemoglobin (odds ratio, 0.63; 95% CI, 0.44–0.89) predicted the progression of this syndrome within 7 days. The 30-day all-cause mortality rate was 51.2% (66/129). The predictors of mortality were the Pediatric Risk of Mortality III score (odds ratio, 1.12; 95% CI, 1.02–1.24; p = 0.017), underlying oncologic/hematologic disorder (odds ratio, 7.81; 95% CI, 2.18–27.94; p = 0.002), receiving systemic steroids (odds ratio, 4.04; 95% CI, 1.25–13.03; p = 0.019), having air leak syndrome (odds ratio, 5.45; 95% CI, 1.57–18.96; p = 0.008), and presenting with multiple organ dysfunction (odds ratio, 7.41; 95% CI, 2.00–27.36; p = 0.003). Conclusions: The prevalence and mortality rate of pediatric acute respiratory distress syndrome in a developing country are high. The oncologic/hematologic comorbidity had a significant impact on the severity of progression and mortality. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://journals.lww.com/pccmjournal). Supported, in part, by grant from the Faculty of Medicine, Prince of Songkla University Research Funding. The author(s) have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: pharsai_16@yahoo.com ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Antipyretic Efficacy of Acetaminophen and Ibuprofen in Critically Ill Pediatric Patients Objectives: To determine the antipyretic efficacy of acetaminophen (IV, enteral, rectal) and ibuprofen (enteral) in critically ill febrile pediatric patients. Design: Retrospective cohort study. Setting: Quaternary care pediatric hospital ICUs. Patients: Pediatric patients less than 19 years old who were febrile (≥ 38.0°C), received a dose of IV acetaminophen, enteral acetaminophen, rectal acetaminophen, or enteral ibuprofen and had at least one temperature measurement in the following 6 hours. Interventions: None. Measurements and Main Results: A total of 3,341 patients (55.8% male, median age 2.5 yr [interquartile range, 0.63–9.2 yr]) met study criteria. Baseline temperature was median 38.6°C (interquartile range, 38.3–38.9°C) measured via axillary (76.9%) route. Patients became afebrile (87.5%) at median 1.4 hours (interquartile range, 0.77–2.3 hr) after the first dose of medication, a –2.9 ± 1.6% change in temperature. Antipyretic medications included as follows: enteral acetaminophen (n = 1,664), IV acetaminophen (n = 682), rectal acetaminophen (n = 637), and enteral ibuprofen (n = 358). Enteral ibuprofen had a significantly greater odds of defervescence on multivariable logistic regression analysis (p = 0.04) with a decrease of –1.97 ± 0.89°C while IV acetaminophen was significant for a decreased time to defervescence at median 1.5 hours (interquartile range 0.8–2.3 hr) after a dose (p = 0.03). Patient age, presence of obesity, and baseline temperature were significant for decreased antipyretic efficacy (p < 0.05). Conclusions: Enteral ibuprofen was the most efficacious antipyretic and IV acetaminophen had the shortest time to defervescence. Dr. Moffett disclosed off-label product use of IV acetaminophen for antipyresis in children. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: bsmoffet@texaschildrens.org ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Mortality and Factors Associated With Hemorrhage During Pediatric Extracorporeal Membrane Oxygenation Objectives: To quantify and identify factors associated with bleeding events during pediatric extracorporeal membrane oxygenation. Design: Retrospective cohort study with primary outcome of bleeding days on extracorporeal membrane oxygenation. Setting: Single tertiary care children's hospital. Subjects: One-hundred twenty-two children supported with extracorporeal membrane oxygenation for greater than 12 hours during January 2015 through December 2016. Interventions: Bleeding days were identified if mediastinal or cannula site exploration, activated factor VII administration, gastrointestinal, pulmonary, or intracranial hemorrhages occurred. Logistic regression was used to assess factors associated with bleeding days. Measurements and Main Results: Study population was identified from institutional extracorporeal membrane oxygenation database. Clinical, laboratory, and survival data were obtained from medical records. Only data from patients' first extracorporeal membrane oxygenation run were used. One-hundred twenty-two patients with median age of 17 weeks (interquartile range, 1–148 wk) were analyzed. Congenital heart disease (n = 56, 46%) was the most common diagnosis. Bleeding days comprised 179 (16%) of the 1,121 observed extracorporeal membrane oxygenation-patient-days. By extracorporeal membrane oxygenation day 4, 50% of users had experienced a bleeding day. Central rather than peripheral cannulation (odds ratio, 2.58; 95% CI, 1.47–4.52; p < 0.001), older age (odds ratio, 1.31 per increased week; 95% CI, 1.14–1.52; p < 0.001), higher lactate (odds ratio, 1.08 per 1 mmol/L increase; 95% CI, 1.05–1.12; p < 0.001), and lower platelets (odds ratio, 0.87 per 25,000 cell/μL increase; 95% CI, 0.77–0.99; p = 0.005) were associated with bleeding days. Patients who experienced more frequent bleeding (> 75th percentile) had fewer ventilator-free and hospital-free days in the 60 days after cannulation (0 vs 31; p = 0.002 and 0 vs 0; p = 0.008) and higher in-hospital mortality (68 vs 34%; p < 0.001). Conclusions: Central cannulation, older age, low platelets, and high lactate are associated with bleeding days during pediatric extracorporeal membrane oxygenation. Patients who bleed more frequently during extracorporeal membrane oxygenation have higher in-hospital mortality, longer technological dependence, and reduced hospital-free days. This study was performed at Boston Children's Hospital, Boston, MA. Supported, in part, by grant from the Callahan Family Chair Fund. Dr. Thiagarajan's institution received funding from Bristol Myers Squibb and Pfizer. Dr. Alexander's institution received funding from Novartis and Tenax Therapeutics (supply therapeutic agent, levosimendan, only as part of an Expanded Access clinical trial). Dr. Alexander's institution received consultation fees from Novartis. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: conor.ohalloran@childrens.harvard.edu ©2019The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com