A subset of parents find a safety-net prescription and pain control acceptable in the treatment of AOM, and antibiotic usage can be lowered with this strategy.
Purpose: Targeting epidermal growth factor receptor (EGFR) overexpressed by many epithelialderived cancer cells with anti-EGFR monoclonal antibodies (mAb) inhibits their growth. A limited number of clinical responses in patients treated with the anti-EGFR mAb, (cetuximab), may reflect variability in EGFR type or signaling in neoplastic cells. This study combines EGFR-targeting with the non-MHC^restricted cytotoxicity of anti-CD3 activated T cells (ATC) to enhance receptordirected cytotoxicity. Experimental Design: ATC from normal and patient donors were expanded ex vivo. Specific cytolytic activity of ATC armed with anti-CD3 Â anti-EGFR (EGFRBi) against EGFR-expressing cancer cells derived from lung, pancreas, colon, prostate, brain, skin, or EGFR-negative breast cancer cells was evaluated in 51 Cr release assays. In vivo studies comparing tumor growth delay induced by EGFRBi-armed ATCs or cetuximab were done in severe combined immunodeficient/Beige mice (SCID-Beige) bearing COLO 356/FG pancreatic and LS174T colorectal tumors. Results: At effector/target ratios from 3.125 to 50, both EGFRBi-armed normal and patient ATC were significantly more cytotoxic, by 23% to 79%, against EGFR-positive cells over ATC, cetuximab, anti-CD3 alone, or ATC armed with irrelevant BiAb directed at CD20. EGFRBi-armed ATC also secreted significantly higher levels of some T H1 /T H2 cytokines compared with ATC alone. In mice, i.v. infusions of EGFRBi-armed ATC (0.001 mg equivalent/ infusion) were equally effective as cetuximab (1 mg/infusion) alone for significantly delaying growth of established COLO 356/FG but not LS174T tumors compared with mice that received ATC alone or vehicle (P < 0.001).Conclusions: Combining EGFR antibody targeting withTcell^mediated cytotoxicity may overcome some limitations associated with EGFR-targeting when using cetuximab alone.
BACKGROUND: Neonates receiving extracorporeal membrane oxygenation (ECMO) support are transfused large volumes of red blood cells (RBCs) and platelets (PLTs). Transfusions are often administered in response to specific, but largely unstudied thresholds. The aim of this study is to examine the relationship between RBC and PLT transfusion rates and mortality in neonates receiving ECMO support. STUDY DESIGN AND METHODS:We retrospectively examined outcomes of neonates receiving ECMO support in the neonatal intensive care unit (NICU) for respiratory failure between 2010 and 2016 at a single quaternary-referral NICU. We examined the association between RBC and PLT transfusion rate (mL per kg per day) and in-hospital mortality, adjusting for confounding by using a validated composite baseline risk score (Neo-RESCUERS).RESULTS: Among the 110 neonates receiving ECMO support, in-hospital mortality was 28%. The median RBC transfusion rate (mL/kg/d) after cannulation was greater among non-survivors, compared to survivors: 12.4 (IQR 9.3-16.2) versus 7.3 (IQR 5.1-10.3), p < 0.001. Similarly, PLT transfusion rate was greater among non-survivors: 22.9 (9.3-16.2) versus 12.1 (8.4-20.1), p = 0.02. After adjusting for baseline mortality risk, both RBC transfusion (adjusted relative risk per 5 mL/kg/d increase: 1.33; 95% CI 1.05-1.69, p = 0.02) and PLT transfusion (adjusted relative risk per 5 mL/kg/d increase: 1.12; 95% CI 1.02-1.23, p = 0.02) were both associated with in-hospital mortality.CONCLUSIONS: RBC and PLT transfusion rates are associated with in-hospital mortality among neonates receiving ECMO. These data provide a basis for future studies evaluating more restrictive transfusion practices for neonates receiving ECMO support.From the
FB is a well-tolerated and safe procedure in critically ill pediatric patients on ECMO. FB may have a diagnostic as well as therapeutic benefit in such patients.
The allotetraploid species Brassica napus L. is a global crop of major economic importance, providing canola oil (seed) and vegetables for human consumption and fodder and meal for livestock feed. Characterizing the genetic diversity present in the extant germplasm pool of B. napus is fundamental to better conserve, manage and utilize the genetic resources of this species. We used sequence-based genotyping to identify and genotype 30,881 SNPs in a diversity panel of 782 B. napus accessions, representing samples of winter and spring growth habits originating from 33 countries across Europe, Asia, and America. We detected strong population structure broadly concordant with growth habit and geography, and identified three major genetic groups: spring (SP), winter Europe (WE), and winter Asia (WA). Subpopulation-specific polymorphism patterns suggest enriched genetic diversity within the WA group and a smaller effective breeding population for the SP group compared to WE. Interestingly, the two subgenomes of B. napus appear to have different geographic origins, with phylogenetic analysis placing WE and WA as basal clades for the other subpopulations in the C and A subgenomes, respectively. Finally, we identified 16 genomic regions where the patterns of diversity differed markedly from the genome-wide average, several of which are suggestive of genomic inversions. The results obtained in this study constitute a valuable resource for worldwide breeding efforts and the genetic dissection and prediction of complex B. napus traits.
Objectives: We examined a large single-institution experience in extracorporeal cardiopulmonary resuscitation (ECPR) in children having cardiac arrest refractory to conventional resuscitation measures with focus on factors affecting survival. Methods: Between 2002 and 2017, 184 children underwent ECPR at our institution. We entered demographic, anatomic, clinical, surgical, and ECPR support details into a multivariable logistic regression models to determine factors associated with mortality. Results: Median age was 54 days (interquartile range [IQR]: 11-272). In all, 157 (85%) patients had primary cardiac disease, including 136 (74%) with congenital heart disease (71 with single ventricle). Extracorporeal cardiopulmonary resuscitation occurred following cardiac surgery in 124 (67%) patients. Median cardiopulmonary resuscitation (CPR) duration was 27 minutes (IQR: 18-40) and median support duration was 3.0 days (IQR: 1.6-5.3). Overall, ECPR was weaned in 115 (63%), with 79 (43%) surviving to hospital discharge. Survival for patients with congenital heart disease, noncongenital cardiac, and noncardiac pathologies was 44%, 71%, and 15%, respectively. On multivariable regression analysis, risk factors associated with mortality were presupport pH <7.1 (odds ratio [OR] = 3.7, 95% confidence interval [CI]: 1.11-12.41, P = .033), mechanical complications (OR = 8.33, 95% CI: 1.91-36.25, P = .005), neurologic complications (OR = 6.27, 95% CI: 1.40-28.10, P = .017), and renal replacement therapy (OR = 3.31, 95% CI: 1.03-10.66, P = .045). Conclusions: Extracorporeal cardiopulmonary resuscitation plays a valuable role salvaging children with refractory cardiac arrest. Survival varies with underlying pathology and can be expected even with relatively longer CPR durations. Efforts to improve systemic output before and after institution of ECPR might mitigate some of the significant risk factors for mortality.
Pediatricians can decrease antibiotic use by treating acute otitis media (AOM) with a safety-net antibiotic prescription (SNAP). This study assessed whether the practitioners of the Practice-Based Research Network who participated in the study continued to use the SNAP and report a 60-day follow-up of the study patients. Charts were reviewed of study patients for 60 days following study enrollment. A survey on antibiotic use for AOM was mailed to the 17 study practitioners (SP) and 30 randomly selected community pediatricians (CP). Eight of the SP used the SNAP more than 20 times over the year following the study vs 1 of the CP. Sixty-two percent of patients never received antibiotics. The recurrence/relapse rate was greater in children younger than 2 years old compared to those older, 34% vs 10%. Practitioners who participate in a Practice-Based Research Network study are more likely to use a study intervention than others.
Phyllotreta cruciferae is an important insect pest of spring-planted Brassica crops, especially during the seedling stage. To determine the effect of early season P. cruciferae infestation on seed yield, 10 genotypes from each of two canola species (Brassica napus L. and Brassica rapa L.) and two mustard species (Brassica juncea L. and Sinapis alba L.) were grown in 2 yr under three different P. cruciferae treatments: (1) no insecticide control; (2) foliar applications of endosulfan; and (3) carbofuran with seed at planting plus foliar application of carbaryl. Averaged over 10 genotypes, B. rapa showed most visible P. cruciferae injury and showed greatest yield reduction without insecticide application. Mustard species (S. alba and B. juncea) showed least visible injury and higher yield without insecticide compared with canola species (B. napus and B. rapa). Indeed, average seed yield of S. alba without insecticide was higher than either B. napus or B. rapa with most effective P. cruciferae control. Significant variation occurred within each species. A number of lines from B. napus, B. juncea, anid S. alba showed less feeding injury and yield reduction as a result of P. cruciferae infestation compared with other lines from the same species examined, thus having potential genetic background for developing resistant cultivars.
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