Background: Pediatric acute lymphoblastic leukemia (ALL) treatment regimens are lengthy, and there is limited data on the systemic and individual economic burden associated with treatment of ALL. Objective: This study aims to examine healthcare resource utilization (HCRU) and costs accrued during the first year of therapy among pediatric ALL patients, and to compare costs among those who are Commercially and Medicaid insured. Methods: Administrative claims data from 2011-16 were analyzed utilizing IBM MarketScan. Newly-diagnosed ALL patients with at least 12 months of enrollment were studied. Demographics and HCRU and costs were stratified by insurance type. The mean (standard deviation (SD) HCRU and reimbursed costs were measured during the first year post-diagnosis. Multivariable generalized linear models were run for total healthcare costs. Results: 730 (528 Commercial) patients with median age of 6 years were studied. During the 12 months following diagnosis, the mean(SD) inpatient admissions and ER visits for Commercial and Medicaid patients was 6.2(3.7) vs. 6.0(4.6), p=0.6310 and 2.8(6.4) vs. 2.1(2.6),p=0.0380, respectively. Commercial patients experienced more outpatient visits (77.2(28.1) versus 57.4(33.3), p<0.0001) and less pharmacy claims (54.1(22.9) and 61.0(41.8),p<0.0001) versus Medicaid patients. Total healthcare costs were $535,135.89($547,506.23) versus $198,694.94($181,856.27),p<0.0001 for Commercial and Medicaid patients, respectively. When adjusted for age and gender, total healthcare costs in the year post-diagnosis for Commercial patients were 1.60 times the costs in patients with Medicaid. Conclusion: Pediatric ALL patients have high HCRU and incur significant economic burden. The total cost of care for Commercially insured patients is more than double that of Medicaid insured patients.

Background: Hepatoblastoma (HB) treatment has improved over time with established chemotherapy (Qtx) protocols, and liver resection or liver transplantation (LT). However, the right timing for LT and adequate patient selection are key to achieve acceptable disease-free survival rates in patients with unresectable HB. Few groups have reported such factors in the setting of living donor liver transplantation (LDLT). Procedure: This single-center retrospective analysis of 28 children with HB submitted to LDLT aimed at determining the pre-transplant factors associated with worse post-transplant event-free survival. Results: Patients were divided in groups according to the occurrence of the event (recurrence/death) after LDLT – 10 patients in the event-yes and 18 patients in the event-no. Probability of 5-y event-free survival was 63.9%. Alpha-fetoprotein (AFP) reduction post-Qtx > 70% had a good performance for the occurrence of the event, with a calculated AUC of 0.8. A scoring system was derived from the pre-transplant risk factors (AFP reduction < 70%, time from diagnosis to LDLT > 12 months, rescue LT) for the probability of the event: no risk factor present (15.4%), one risk factor present (33.3%), and > 2 risk factors present (66.7%), (p=0.02). Conclusion: LDLT for HB is the preferred treatment option for unresectable HB, with no distant metastasis and adequate response to Qtx. The pre-transplant factors composing the risk score should be critically evaluated in order to move forward with the LDLT. However, due to the limited number of patients in this study, a larger number of patients is required to corroborate these findings.

Objectives: This study aims to (i) investigate post-extubation dysphagia and dysphonia amongst adults intubated with SARS-COV-2 (COVID-19) and referred to speech and language therapy (SLT) in acute hospitals across the Republic of Ireland (ROI) between March and June 2020; (ii) identify variables predictive of post-extubation oral intake status and dysphonia and (iii) establish SLT rehabilitation needs and services provided to this cohort. Design: A multi-site prospective observational cohort study Participants: 100 adults with confirmed COVID-19 who were intubated across eleven acute hospital sites in ROI and who were referred to SLT services between March and June 2020 inclusive. Main Outcome Measures: Oral intake status, level of diet modification and perceptual voice quality. Results: Based on initial SLT assessment, 90% required altered oral intake and 59% required tube feeding with 36% unable for oral intake. Age (OR 1.064; 95% CI 1.018-1.112), proning (OR 3.671; 95% CI 1.128-11.943), and pre-existing respiratory disease (OR 5.863; 95% CI 1.521-11.599) were predictors of oral intake status post-extubation. Two-thirds (66%) presented with dysphonia post-extubation. Intubation injury (OR 10.471; 95% CI 1.060-103.466) and pre-existing respiratory disease (OR 24.196; 95% CI 1.609-363.78) were predictors of post-extubation voice quality. Thirty-seven percent required dysphagia rehabilitation post-extubation whereas 20% needed voice rehabilitation. Dysphagia and dysphonia persisted in 27% and 37% cases respectively at hospital discharge. Discussion: Post-extubation dysphagia and dysphonia were prevalent amongst adults with COVID-19 across the ROI. Predictors included iatrogenic factors and underlying respiratory disease. Prompt evaluation and intervention is needed to minimise complications and inform rehabilitation planning.

Background Charge density mapping of atrial fibrillation (AF) reveals dynamic patterns of localised rotational activation (LRA), irregular activation (LIA) and focal firing (FF). Their spatial stability, conduction characteristics and the optimal duration of mapping required to reveal these phenomena and has not been explored. Methods Bi-atrial mapping of AF propagation was undertaken and variability of activation patterns quantified up to a duration of 30-seconds(s). The frequency of each pattern was quantified at each vertex of the chamber over 2 separate 30s recordings prior to ablation and R2 calculated to quantify spatial stability. Regions with the highest frequency were identified at increasing time durations and compared to the result over 30s using Cohen’s kappa. Properties of regions with the most stable patterns were assessed during sinus rhythm and extrastimulus pacing. Results In twenty-one patients, 62 paired LA and RA maps were obtained. LIA was highly spatially stable with R2 between maps of 0.83(0.71-0.88) compared to 0.39(0.24-0.57) and 0.64(0.54-0.73) for LRA and FF, respectively. LIA was also most temporally stable with a kappa of >0.8 reached by 12s. LRA showed greatest variability with kappa>0.8 only after 22s. Regions of LIA were of normal voltage amplitude (1.09mv) but showed increased conduction heterogeneity during extrastimulus pacing (p=0.0480). Conclusion Irregular activation patterns characterised by changing wavefront direction are temporally and spatially stable in contrast with rotational patterns that are transient with least spatial stability. Focal activation appears of intermediate stability. Regions of LIA show increased heterogeneity following extrastimulus pacing and may represent fixed anatomical substrate.

Aims: No study has evaluated the BET pharmacokinetics in twin pregnancies separated by chorionicity. The aim this study is to describe and compare the BET pharmacokinetic parameters in singleton, dichorionic (DC) and monochorionic (MC) twin pregnancies in the third trimester of pregnancy. Methods: Twenty-six pregnant women received an intramuscular dose of 6 mg of BET sodium phosphate plus 6 mg BET acetate. Serial blood samples were collected for 24 hours after the first intramuscular BET esters dose. BET plasma concentrations were quantified using a validated HPLC analytical method. BET pharmacokinetic parameters were obtained employing a non-compartment model, and were compared using ANOVA’s test with Tukey’s multiple comparisons test. Correlations between clinical features and pharmacokinetic parameters were analyzed using Pearson’s correlation. Preliminary data on the BET placental transfer were also presented. Results: The geometric mean (IC 95%) of AUC0-∞ 670.0 (504.3-805.2) vs 434.9 (311.2-539.6) ng.h/mL and the CL/F 18.38 (13.84-22.65) vs 29.40 (21.17-36.69) were significantly lower and higher, respectively, in DC twin pregnancies compared to singleton. Others pharmacokinetic parameters did not differ among the groups. Conclusions: Data from this study suggest that the presence of two fetoplacental units may increase the BET metabolism by CYP3A4 enzyme and increase its elimination. Pharmacokinetic-pharmacodynamic clinical studies are needed to investigate whether this BET pharmacokinetic changes have clinical repercussions for the newborns and require dose adjustment in DC twin pregnancies.

Lesson: Bernoulli´s principle.Grade: 7Suggested time: 50 min.OverviewStudents will learn why airplanes fly. They will learn the Bernoulli principle and how to apply it by performing various experiments.VocabularyStructural engineeringMechanical engineeringTransportationAeronauticsGravityAir resistanceFluidBernoulli´s principleObjectivesThey will learn the Bernoulli principle and how to apply it.Required projects MaterialsComputerPing pong ball 2 soda cansWaterPaper SheetCompressed air can or hairdryerMultimedia ResourcesThe LessonPart 1: Introduction (20 min)1. Ask Students Why do planes fly, what is aeronautics and where they apply the STEAM in aeronautics.2. They are asked to investigate who was Daniel Bernoulli.3. It is explained that it is the Bernoulli Principle. (Speed * pressure = energy).

In this case report, we describe a rare large right ventricular fibroma with sudden chest pain in a 9 year old child. The tumor was successfully surgical removed under cardiopulmonary bypass, but there was only a small remnant of the tumor to avoid rupture of the right ventricle and injury to the tricuspid valve. Pathological examination confirmed that the tumor was fibrous borderline tumor. The patient's heart function and the size of atrium and ventricles were normal, and there was no tricuspid regurgitation at 3-months follow-up. It was reported that the age less than 17 years old at time of diagnosis are associated with a poor prognosis, the long term outcome for this children patient needs further follow-up.

Research on species abundance patterns and the advanced elevational Rapoport rule (ERR) has been widespread in recent years; however, for the temperate mountainous regions in northeast Asia, such research is lacking. Here, we collected plant species from the Seorak Mountain in northeast Asia through field surveys. The species were divided into 11 groups according to the life-form types and phytogeography affinities of each species. The ERR was tested using Steven’s method and by examining the species abundance patterns of each group. The species abundance patterns revealed a positive multimodal pattern along the elevation gradient, but phytogeography affinities (increasing trend) and life-form (unimodal) exhibited different patterns. The elevation gradients (1350 m for the mean elevation-range relationships), which are affected by the boundary effect and different life-forms, did not consistently support the ERR. However, herbs as well as rare, endemic, and red list species showed consistent support for the ERR, which can be influenced by phytogeography affinities. Thus, the results from Seorak Mountain showed that the ERR was not consistent for different plant life-forms in the same area. The result of our field survey revealed that life-forms in the plant species did not support ERR, whereas phytogeography affinities could support and explain ERR.

Chronic myeloid leukemia (CML), a myeloproliferative disorder, is caused by overactivity of BCR-ABL1 (breakpoint cluster region-Abelson) has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in CML hematologic and cytogenetic responses compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and outcome of patients. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

Aim: To undertake a prospective study of the efficacy of two models (LACE and BOOST) in predicting unplanned hospital readmission. Methods: Data were collected from a single centre prospectively over a continuous 30-day period on all patients over 75 years old admitted to the acute medical unit. The primary outcome was the area under the curve for both models. Results: Area under the curve were calculated for both tools with BOOST score 0.667 (95% CI: 0.559-0.775, p=0.005) and C-statistic for LACE index 0.685 (95% CI: 0.579-0.792, p=0.002). Conclusion: In this prospective study, both the BOOST and LACE scores were found to be significant predictive models of hospital readmission. Recent hospitalisation was found to be the most significant contributing factor. Key Words: Elderly, prediction, readmission

Introduction: Most patients with COVID-19 have mild or moderate manifestations, however, there is a wide spectrum of clinical presentations and even more severe repercussions that require high diagnostic suspicion. Vital sign acquisition and monitoring are crucial for detecting and responding to patients with COVID-19. Objective: Thus, we conducted this study to demonstrate the impact of using a tool called Smart Check on the triage time of patients with suspected COVID-19 and to identify the main initial clinical manifestations in these cases. Methodology: We assessed triage times before and after the use of Smart Check in 11,466 patients. In this group, we identified 211 patients for the identification of COVID-19 clinical manifestations in a case-control analysis. Results: Smart Check was able to decrease the triage time by 33 seconds on average, with 75% of the exams being performed within 5 minutes, whereas with the usual protocol these steps were performed within 6 minutes. A range of clinical presentations made up the COVID-19 initial manifestations. Those with the highest frequency were dry cough (46.8%), fever (41.3%), dyspnea (35.8%), and headache (32.1%). Loss of appetite, fever, and ageusia were the manifestations that had a statistically significant association with the SARS-CoV-2 presence. Conclusions: Smart Check, a simple clinical evaluation tool, along with the targeted use of rapid PCR testing, can optimize triage time for patients with and without COVID-19. In triage centers, a number of initial signs and symptoms should be cause for SARS-CoV-2 infection suspicion, in particular the association of respiratory, neurological, and gastrointestinal manifestations. Keywords: new coronavirus, COVID-19, triage, clinical manifestations

Background A dose of 5mg/kg lidocaine is considered appropriate for paediatric airway topicalisation. Existing literature suggests younger children are susceptible to toxic lidocaine plasma levels and achieve this at a faster rate. Aims The primary outcome of this study was to ascertain peak plasma lidocaine levels after topicalisation for airway endoscopy. Secondary endpoints included: time to peak lidocaine plasma levels, signs of lidocaine toxicity (restricted to ECG changes or seizures when under anaesthesia) and clinical adverse events of laryngospasm, coughing or desaturation during the procedure. Methods Data was collected prospectively over 18 months at Royal Manchester Children’s Hospital. Children aged 0-8 years undergoing elective diagnostic or therapeutic airway endoscopy were included within the study. Standardised 2% lidocaine was used for airway topicalisation. Dose varied depending upon practitioner usual practice. Venous blood sampling occurred at 5, 10, 15 and 20 minutes post administration and plasma lidocaine levels (ng/ml) analysed. Results A significant relationship exists between higher peak plasma levels and ages <18 months (p=0.00973). Strong linear correlation exists between weight and age for our cohort (r=0.88). Higher peak plasma lidocaine levels occur with total dose volumes between 2 and 3mls of 2% lidocaine local anaesthetic (p=0.03) compared with <2ml total dose volumes. Data suggests a potential relationship of lower weights achieving higher peak plasma levels (p=0.0516). Reduced IQR variation of peak plasma lidocaine levels exists when lidocaine dosing is <5mg/kg. Conclusions Age and total dose volume of topicalised lidocaine have a significant relationship with plasma lidocaine levels. A dose of 5mg/kg topicalised lidocaine for paediatric airway endoscopy is safe and provides good operating conditions. Lower patient weights trend toward higher peak lidocaine plasma concentrations and require further investigation.

Freshwater biodiversity is declining dramatically, and the current biodiversity crisis requires defining bold goals and mobilizing substantial resources to meet the challenges. While the reasons are varied, both research and conservation of freshwater biodiversity lag far behind efforts in the terrestrial and marine realms. We identify fifteen pressing global needs to support informed global freshwater biodiversity stewardship. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated action towards its sustainable management and conservation.

The production of vaccines in plant cells, termed as plant-made pharmaceuticals or molecular farming, is a promising technology. Compared to mammalian cell lines, like HEK293 and CHO as established platform, plants can be grown cost effectively on a large-scale without necessitating any sophisticated technologies. An innovative application of this alternative system is the production of vaccines in edible tissues that can be consumed orally to deliver protein antigen without any further processing. In this project we reported stable expression of TM-1 protein of MG as vaccine candidate antigen against Chronic Respiratory Disease (CRD) in wheat seeds tissues. The molecular and Immunoblotting analysis confirmed the integration of recombinant protein of 41.8 kDa with expression level of 1.03mg/g DW in endosperm tissues. When orally delivered, the plant made vaccine were highly effective in terms of developing antibodies in chicken without any detectable weight loss. Two doses of orally delivered plant-made TM-1 vaccine candidate elicited an immune response and protective effect against MG virus challenge at the level comparable to commercially available inactivated vaccine against CRD. Our study demonstrated that plant-made vaccines are not only safe but also similarly effective to commercially available vaccines.

Because of their excellent therapeutic potential, mesenchymal stem cells (MSCs) have been used as cell therapeutics for various diseases. However, the survival rate and duration of MSCs after transplantation are extremely low and short, respectively. To solve these problems, in this study, we prepared multicellular spheroids of MSCs and investigated their survival and function after intravenous injection in mice. The murine adipose-derived MSC line m17.ASC was cultured in agarose-based microwell plates to obtain size-controlled m17.ASC spheroids of an average diameter and cell number of approximately 170 μm and 1100 cells/spheroid, respectively. The intravenously injected m17.ASC spheroids mainly accumulated in the lung and showed a higher survival rate than suspended m17.ASC cells during the experimental period of 7 days. m17.ASC spheroids efficiently reduced the lipopolysaccharide-induced increase in plasma concentrations of interleukin-6 and tumor necrosis factor-α. These results indicate that spheroid formation improved the pulmonary delivery and survival of MSCs, as well as their therapeutic potential against inflammatory pulmonary diseases.

Theory and some evidence suggest that biodiversity promotes stability. However, evidence of how trophic interactions and environmental changes modulate this relationship in multitrophic communities is lacking. Given the current scenario of biodiversity loss and climate changes, where top predators are disproportionately more affected, filling these knowledge gaps is crucial. We simulated climate warming and top predator loss in natural microcosms to investigate their direct and indirect effects on temporal stability of microbial communites. We also investigated the role of underlying stabilizing mechanisms on community stability. Community stability was insensitive to warming, but indirectly decreased due to top predator loss via increased mesopredator abundance and consequent reduction of species asynchrony and stability. The magnitude of destabilizing effects differed among trophic levels, being disproportionally higher at lower trophic levels (e.g. producers). Our study unravels major patterns and causal mechanisms by which trophic downgrading destabilizes large food webs, regardless of climate warming scenarios.

This work deals with the finite element approximation of a prestressed shell model using a new formulation where the unknowns (the displacement and the rotation of fibers normal to the midsurface) are described in Cartesian and local covariant basis respectively. Due to the constraint involved in the definition of the functional space, a penalized version is then considered. We obtain a non robust a priori error estimate of this penalized formulation, but a robust one is obtained for its mixed formulation. Moreover, we present a reliable and efficient a posteriori error estimator of the penalized formulation. Numerical tests are included that confirmthe efficiency of our residual a posteriori estimator.

BJOG exchange

We describe an adult patient with a large right atrial mass which was found to have the same echotexture as adjacent liver tissue on two-dimensional transesophageal echocardiography (2DTEE). By using live/real-time three-dimensional transesophageal echocardiography (3DTEE), we were able to examine the mass by meticulous cropping and confirm the echotexture was similar to liver tissue throughout its extent. Three-dimensional cropping also redemonstrated in a definitive manner that the mass was in continuity with liver. Thus, in our patient 3DTEE served to increase the confidence level of making a definitive diagnosis of a supernumerary lobe of liver. To the best of our knowledge, the incremental value of 3DTEE over 2DTEE in diagnosing a supernumerary liver lobe has not been reported previously. The mass was surgically resected and the findings confirmed as liver tissue by pathological examination.

Subcutaneous emphysema of the extremities can be associated with necrotizing fasciitis, a surgical emergency. It can sometimes also be caused by local spreading of air from a retroperitoneal bowel perforation. Other than this specific symptom, the diagnosis of retroperitoneal perforation is usually impeded by lack of signs of peritoneal irritation.

Aims to evaluate the incidence of cardiac arrhythmias during a lockdown period due to COVID-19 pandemics in a population followed by remote monitoring through implanted cardiac defibrillators. Methods and results In this retrospective, multicentre cohort study, we included 574 remotely monitored automatic (AICD) and cardiac resynchronization devices (CRT-D) recipients implanted before January 1st 2019 at seven Hospitals of Campania Region, comparing the incidence of arrhythmias occurred during the lockdown period due to COVID-19 epidemics (from March 9th to May 1st 2020) with the arrhythmias rate of the corresponding period in 2019. An effective retrospective data collection was performed through remote monitoring, as this tool allows the direct transfer of the the information stored by the implantable devices to medical personnel. During the lockdown period, we observed ventricular tachyarrhythmias (ventricular tachycardia or fibrillation) in 25 (4.8%) patients as compared to 12 (2.3%) during the corresponding 2019 period (p < 0.04); new-onset atrial fibrillation was detected in 38 (8.2%) subjects during lockdown period and in 24 (5.2%) during the reference period (p < 0.004). Conclusion During pandemics lockdown period we observed an higher incidence of arrhythmic events in ICD/CRT-D patients followed up through device remote monitoring by seven hospitals of Campania region.

The following is a case report of an infant born with cri du chat syndrome that has evidence of left ventricular non compaction . Cri du chat syndrome is a rare association of growth retardation, intellectual severe disability, hypertelorism and typical catlike cry, typically combined to congenital heart defect, the occurrence of myocardial non compaction among the associated cardiac anomalies has not been reported so far.

Abstract The purpose of this paper is to report a case diagnosed by bedside echocardiography in which bone cement infiltrated into the paravertebral vein system after percutaneous vertebroplasty (PVP) and caused intracardiac cement embolism (ICE). A 79-year-old female patient had suddenly become unconscious 14 hours after PVP. Emergency bedside echocardiogram showed that the patient had a strong echo in the right heart with a small amount of pericardial effusion, suspected of causing cardiogenic shock. Computed tomography (CT) showed high density in the distal branches of both pulmonary arteries and a high density in the right heart.Combined with the history of surgery, the clinician considers the foreign body as bone cement and the diagnosis was ICE. The bone cement in the heart was removed under emergency cardiopulmonary bypass. The patient recovered and was discharged smoothly.

A document by Ju-wook Baek. Click on the document to view its contents.