Analysis of High Flow Nasal Cannula Utilization During Pediatric Critical Care Transport.

OBJECTIVE: There are limited studies on the safety and efficacy of high flow nasal cannula (HFNC) use in pediatrics during interfacility critical care transport. This 15-month retrospective study aims to describe our transport team's utilization of HFNC within the pediatric population and evaluates the need for patient escalation in respiratory support within 24 hours of hospital admission including increased liter flow, transition to noninvasive ventilation, or intubation. METHODS: Retrospective charts were reviewed by study members from January 1, 2019, through March 31, 2020. Study dates were specifically chosen to reflect when HFNC was implemented in the transport department and before the beginning of the severe acute respiratory syndrome coronavirus disease 2019 (SARS-COVID-19) pandemic because of variability in respiratory support recommendations at the beginning of the pandemic. Patients were screened for inclusion criteria and were included if they were >30 days and <18 years of age, required HFNC at ≥4 L/min during transport, and were admitted to Children's Mercy Hospital. RESULTS: During the study period, we completed 6,279 pediatric transports, of which 382 had documented HFNC use and 358 met the inclusion criteria. Our HFNC patients had a median age of 0.7 years with an interquartile range (IQR) of 0.3 to 1 year, a median weight of 8.4 kg with an IQR of 6.2 to 11 kg, a median liter flow of 10 L/min and 1.2 L/kg/min, and required a median transport time of 80 minutes with an IQR of 69 to 115 min. Patients were tracked for 24 hours post-admission for any escalations in care; 33% required an escalation, 76% of those had an increase in flow, 24% required noninvasive ventilation, and 0% required intubation. CONCLUSION: Our study suggests HFNC is a safe and effective means for providing respiratory support to the pediatric population during interfacility critical care transport. Our data support utilization of 1 to 2 L/kg/min in the smaller pediatric population (<10 kg) during transport. There was minimal risk of escalation to noninvasive ventilation, and no patients required intubation within 24 hours post drop-off, likely because of the appropriate utilization of HFNC during transport. Additional studies, especially multicenter pediatric studies, are needed to analyze HFNC utilization with non-restricting circuits and vibrating mesh nebulizers.

Posterior rim loading of a low-conforming tibial insert in unrestricted kinematic alignment is caused by rotational alignment of an asymmetric baseplate designed for mechanical alignment.

PURPOSE: Because different targets are used for internal-external rotation, an asymmetric baseplate designed for mechanical alignment may lead to under-coverage and concomitant posterior rim loading in the lateral compartment following unrestricted kinematic alignment (KA) TKA. Recognizing that such loading can lead to premature wear and/or subsidence, our aim was to determine the cause(s) so that occurrence could be remedied. Our hypothesis was that baseplate design features such as asymmetric shape when aligned in KA would consistently contribute to posterior rim loading in the lateral compartment. METHODS: Based on analysis of fluoroscopic images of 50 patients performing dynamic, weight bearing deep knee bend and step up and of postoperative CT images, five possible causes were investigated. Causes included internal rotation of the baseplate when positioned in KA; posterior position of the lateral femoral condyle at extension; internal tibial rotation with flexion; internal rotational deviation of the baseplate from the KA rotation target; and posterior slope. RESULTS: The incidence of posterior rim loading was 18% (9 of 50 patients). When positioned in KA, the asymmetric baseplate left 15% versus 10% of the AP depth of the lateral compartment uncovered posteriorly for posterior rim loading and non-posterior rim loading groups, respectively (p = 0.009). The lateral femoral condyle at extension was more posterior by 4 mm for the posterior rim loading group (p = 0.003). CONCLUSIONS: Posterior rim loading in the lateral compartment was caused in part by the asymmetric design of the tibial baseplate designed for mechanical alignment which was internally rotated when positioned in KA thus under-covering a substantial percentage of the posterior lateral tibia. This highlights the need for new, asymmetric baseplates designed to maximize coverage when used in KA. LEVEL OF EVIDENCE: III.

Sensitivity of a Model Reptile, the Common Snapping Turtle (Chelydra serpentina), to In Ovo Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Other Dioxin-Like Chemicals.

Reptiles represent the least-studied group of vertebrates with regards to ecotoxicology and no empirical toxicity data existed for dioxin-like chemicals (DLCs). This lack of toxicity data represents a significant uncertainty in ecological risk assessments of this taxon. Therefore, the present study assessed early-life sensitivity to select DLCs and developed relative potencies in the common snapping turtle (Chelydra serpentina) as a model reptile. Specifically, survival to hatch and incidence of pathologies were assessed in common snapping turtle exposed in ovo to serial concentrations of the prototypical reference congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and three other DLCs of environmental relevance, namely, 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 2,3,7,8-tetrachlorodibenzofuran (TCDF), and 3,3',4,4',5-pentachlorobiphenyl (PCB 126). In ovo exposure to TCDD, PeCDF, TCDF, and PCB 126 caused a dose-dependent increase in early-life mortality, with median lethal doses (LD50s) of 14.9, 11.8, 29.6, and 185.9 pg/g-egg, respectively. Except for abnormal vasculature development, few pathologies were observed. Based on the measured LD50, common snapping turtle is more sensitive to TCDD in ovo than other species of oviparous vertebrates investigated to date. The potencies of PeCDF, TCDF, and PCB 126 relative to TCDD were 1.3, 0.5, and 0.08, respectively. These relative potencies are within an order of magnitude of World Health Organization (WHO) TCDD-equivalency factors (TEFs) for both mammals and birds supporting these TEFs as relevant for assessing ecological risk to reptiles. The great sensitivity to toxicities of the common snapping turtle, and potentially other species of reptiles, suggests a clear need for further investigation into the ecotoxicology of this taxon. Environ Toxicol Chem 2022;41:175-183. © 2021 SETAC.

A Novel Multispecies Toxicokinetic Modeling Approach in Support of Chemical Risk Assessment.

Standardized laboratory tests with a limited number of model species are a key component of chemical risk assessments. These surrogate species cannot represent the entire diversity of native species, but there are practical and ethical objections against testing chemicals in a large variety of species. In previous research, we have developed a multispecies toxicokinetic model to extrapolate chemical bioconcentration across species by combining single-species physiologically based toxicokinetic (PBTK) models. This "top-down" approach was limited, however, by the availability of fully parameterized single-species models. Here, we present a "bottom-up" multispecies PBTK model based on available data from 69 freshwater fishes found in Canada. Monte Carlo-like simulations were performed using statistical distributions of model parameters derived from these data to predict steady-state bioconcentration factors (BCFs) for a set of well-studied chemicals. The distributions of predicted BCFs for 1,4-dichlorobenzene and dichlorodiphenyltrichloroethane largely overlapped those of empirical data, although a tendency existed toward overestimation of measured values. When expressed as means, predicted BCFs for 26 of 34 chemicals (82%) deviated by less than 10-fold from measured data, indicating an accuracy similar to that of previously published single-species models. This new model potentially enables more environmentally relevant predictions of bioconcentration in support of chemical risk assessments.

Kinematically aligned TKA restores physiological patellofemoral biomechanics in the sagittal plane during a deep knee bend.

PURPOSE: Although patellofemoral complications after kinematically aligned (KA) TKA are infrequent, the patellar flexion angle and proximal-distal patellar contact location through flexion, and incidence of patellar loss of contact at full extension are unknown. The present study determined whether the patellar flexion angle and proximal-distal patellar contact location of a KA TKA performed with anatomic, fixed-bearing, posterior cruciate-retaining (PCR) components differed from those of the native contralateral knee during a deep knee bend, and determined the incidence of patellar loss of contact at full extension for KA TKA only. METHODS: During a deep knee bend from full extension to maximum flexion, both knees were imaged in a lateral view using single-plane fluoroscopy for 25 patients with a calipered KA TKA and a healthy native knee in the contralateral limb. The patellar flexion angle and proximal-distal patellar contact location were measured on images from full extension to maximum flexion in 30° increments. Paired t tests at each flexion angle determined the significance of the difference between the KA TKA knees and the native contralateral knees. In the KA TKA knees, the incidence of patellar loss of contact at full extension was determined. Patient-reported outcome scores also were recorded including the Oxford Knee Score. RESULTS: Mean patellar flexion angles were not different between the KA TKA knees and the native contralateral knees throughout the motion arc. The largest statistically significant difference in the mean proximal-distal patellar contact locations was 4 mm. The incidence of patellar loss of contact in the KA TKA knees at full extension was 8% (2 of 25 patients). The median Oxford Knee Score was 46 out of 48. CONCLUSIONS: Calipered KA TKA performed with anatomic, fixed-bearing, PCR components restored patellar flexion angles to native and largely restored the proximal-distal patellar contact locations, which at most differed from the native contralateral knee by approximately 10% of the mean proximal-distal patellar length. In the KA TKA knees, the incidence of patellar loss of contact was infrequent. These objective biomechanical results are consistent with the relatively high subjective patient-reported outcome scores herein and support the low incidence of patellofemoral complications following KA TKA previously reported. LEVEL OF EVIDENCE: Therapeutic, level III.

Small differences in tibial contact locations following kinematically aligned TKA from the native contralateral knee.

PURPOSE: Kinematically aligned (KA) TKA strives to restore native limb and knee alignments without ligament release with the premise that knee function likewise will be closely restored to native to the extent enabled by the components used. This study determined differences in anterior-posterior (AP) tibial contact locations of a KA TKA performed with asymmetric, fixed bearing, posterior cruciate-retaining (PCR) components from those of the native contralateral knee and also determined the incidence of posterior rim contact of the tibial insert during a deep knee bend and a step-up. METHODS: Both knees were imaged using single-plane fluoroscopy for 25 patients with a calipered KA TKA and a native knee in the contralateral limb. AP tibial contact locations in each compartment were determined following 3D model-to-2D image registration. Differences in mean AP tibial contact locations in each compartment between the KA TKA knees and the native contralateral knees were analysed. Contact locations either on or beyond the most posterior point of the tibial insert determined the occurrence of posterior rim contact. RESULTS: Mean AP tibial contact locations for both native and KA TKA knees remained relatively centred in the medial compartment but moved posterior in the lateral compartment during flexion. In both the medial and lateral compartments, differences in mean AP tibial contact locations between the KA TKA knees and the native contralateral knees were more posterior and greatest at 0° flexion for both activities (4 mm, p = 0.0009 and 7 mm, p < 0.0001 for deep knee bend and 6 mm, p < 0.0001 and 8 mm, p < 0.0001 for step-up in the medial and lateral compartments, respectively). The incidence of posterior rim contact of the tibial insert was 16% (4 of 25 patients) but the lowest Oxford Knee Score was 43 for these patients. The median Oxford Knee Score for all patients was 46 (out of 48). CONCLUSIONS: Calipered KA TKA with asymmetric, fixed bearing, PCR components resulted in mean AP tibial contact locations which were relatively centred in the compartments and differed at most from those of the native contralateral knee by approximately 15% of the AP dimension of a mid-sized tibial baseplate. Although posterior rim contact occurred in some patients, all such patients had high patient-reported outcome scores. LEVEL OF EVIDENCE: Therapeutic, Level III.

Does the condylar lift-off method or the separation method better detect loss of contact between tibial and femoral implants based on analysis of single-plane radiographs following total knee arthroplasty?

BACKGROUND: Loss of contact between the femoral and tibial implants following total knee arthroplasty (TKA) has been related to accelerated polyethylene wear and other complications. Two methods have been used to detect loss of contact in single-plane fluoroscopy, the condylar lift-off method and the separation method. The objectives were to assess the ability of each method to detect loss of contact. METHODS: TKA was performed on ten cadaveric knee specimens. Tibial force was measured in each compartment as specimens were flexed from 0° to 90° while internal-external and varus-valgus moments were applied. Single-plane radiographs taken simultaneously with tibial force were analyzed for loss of contact using the two methods. Receiver operating characteristic (ROC) and optimum threshold distances were determined. RESULTS: For the lift-off method and the separation method, the areas under the ROC curves were 0.89 vs 0.60 for the lateral compartment only and 0.81 vs 0.70 for the medial compartment only, respectively. For the lift-off method, the optimum threshold distances were 0.7 mm in the lateral compartment only and 0.1 mm in the medial compartment only but the false positive rate for the medial compartment only almost doubled. For both compartments jointly, the areas under the ROC curves decreased to 0.70 and 0.59 for the lift-off and separation methods, respectively. CONCLUSION: When detecting loss of contact using single-plane fluoroscopy, the lift-off method is useful for the lateral compartment only but not for the medial compartment only and not for both compartments jointly. The separation method is not useful.

Force and Contact Location Measurement Errors of the VERASENSE.

BACKGROUND: The OrthoSensor VERASENSE knee system is a commercially available instrumented tibial insert that provides real-time intraoperative measurements of tibial contact force and contact location to guide surgeons toward improving outcomes in total knee arthroplasty (TKA). However, the device has been used contrary to the manufacturer's recommendations in several studies and lacks published accuracy data. Therefore, the primary objectives of this study were to evaluate the device's error in tibial contact force when used according to and contrary to the manufacturer's recommendations, and also to evaluate the device's error in anterior-posterior (A-P) and medial-lateral (M-L) contact locations. METHODS: The error in tibial contact force in single compartment distributed loading was evaluated by applying known forces in ranges within and exceeding that recommended by the manufacturer, with rezeroing as recommended by the manufacturer, and without rezeroing. The error in tibial contact location in single compartment concentrated loading was evaluated by applying known forces at known locations on the articular surface. RESULTS: Exceeding the maximum allowable load and not rezeroing did not adversely affect the bias (i.e. average error) (p > 0.05). The maximum absolute bias without rezeroing was 2.9 lbf. Rezeroing more than doubled the bias. The maximum root mean squared error in tibial contact location was 1.5 mm in the A-P direction. CONCLUSION: The device measures tibial contact force with comparable error well above the maximum allowable load and without rezeroing, contrary to the manufacturer's instructions.

A multimarker real-time RT-PCR for MAGE-A gene expression allows sensitive detection and quantification of the minimal systemic tumor load in patients with localized cancer.

INTRODUCTION: Distant metastases of solid tumors are usually associated with fatal outcome. Disseminated cancer cells are considered early indicators of metastasis. Their sensitive detection and quantification would be a valuable tool for staging of disease and as guidance for therapeutic decisions. EXPERIMENTAL DESIGN: We established a highly sensitive and quantitative multimarker real-time RT-PCR assay for amplification of cancer-related genes MAGE-A1, -A2, -A3/6, -A4, -A10 and -A12 using SYBR green I to detect one single tumor cell in 2 mL of blood or bone marrow. The feasibility of the assay was tested in a large cohort of 177 patients with locally confined prostate carcinoma. RESULTS: Analysis revealed frequent MAGE expression in venous blood and bilateral bone marrow samples (25.5% of all cases) and yielded the first quantitative profile of MAGE expression with a broad range of transcript concentrations for individual markers in the minimal systemic tumor load of patients with localized cancer. CONCLUSIONS: Rare transcripts of different MAGE-A genes can be quantified in clinical samples of cancer patients by a sensitive multimarker real-time RT-PCR. Because of frequent expression of MAGE genes in various types of cancer the multimarker MAGE real-time RT-PCR may be generally useful for detection, quantification and characterization of the individual disseminated tumor load in cancer patients.