Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

Impairment in Preextubation Alveolar Gas Exchange Is Associated With Postextubation Respiratory Support Needs in Infants After Cardiac Surgery.

OBJECTIVES: To determine if indices of alveolar gas exchange preextubation predict postextubation respiratory support needs as well as the need for escalation of therapies following infant cardiac surgery. DESIGN: Retrospective chart review. SETTING: Pediatric cardiac ICU in a quaternary-care teaching hospital. PATIENTS: Infants less than 1 year old who underwent biventricular repair from January 2015 to December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Preextubation alveolar-arterial gradient, oxygenation index, oxygen saturation index, Pao2/Fio2 ratio, and dead space ventilation (analyzed with both end-tidal carbon dioxide gradient and dead space fraction) were evaluated for each patient. All but dead space ventilation were associated with a higher level of noninvasive respiratory support immediately postextubation. Furthermore, impaired preextubation gas exchange was independently associated with escalation of respiratory support within the first 48-hour postextubation. CONCLUSIONS: Validated measures of alveolar gas exchange can be used as a tool to assess postextubation respiratory support needs including the risk of escalation of respiratory support in the first 48-hour postextubation. Prospective study with implementation of extubation guidelines, both for readiness and determination of early postextubation support, is needed to validate these findings.

Large-scale, high-throughput validation of short hairpin RNA sequences for RNA interference.

A method for high-throughput cloning and analysis of short hairpin RNAs (shRNAs) is described. Using this approach, 464 shRNAs against 116 different genes were screened for knockdown efficacy, enabling rapid identification of effective shRNAs against 74 genes. Statistical analysis of the effects of various criteria on the activity of the shRNAs confirmed that some of the rules thought to govern small interfering RNA (siRNA) activity also apply to shRNAs. These include moderate GC content, absence of internal hairpins, and asymmetric thermal stability. However, the authors did not find strong support for position specific rules. In addition, analysis of the data suggests that not all genes are equally susceptible to RNA interference (RNAi).

Vasoactive-ventilation-renal score reliably predicts hospital length of stay after surgery for congenital heart disease.

OBJECTIVES: We aimed to further validate the vasoactive-ventilation-renal score as a predictor of outcome in patients recovering from surgery for congenital heart disease. We also sought to determine the optimal time point within the early recovery period at which the vasoactive-ventilation-renal score should be measured. METHODS: We prospectively reviewed consecutive patients recovering from cardiac surgery within our intensive care unit between January 2015 and June 2015. The vasoactive-ventilation-renal score was calculated at 6, 12, 24, and 48 hours postoperatively as follows: vasoactive-ventilation-renal score = ventilation index + vasoactive-inotrope score + Δ creatinine [change in serum creatinine from baseline*10]. Primary outcome of interest was prolonged hospital length of stay, defined as length of stay in the upper 25%. Receiver operating characteristic curves were generated, and areas under the curve with 95% confidence intervals were calculated for all time points. Multivariable logistic regression modeling also was performed. RESULTS: We reviewed 164 patients with a median age of 9.25 months (interquartile range, 2.6-58 months). Median length of stay was 8 days (interquartile range, 5-17.5 days). The area under the curve value for the vasoactive-ventilation-renal score as a predictor of prolonged length of stay (>17.5 days) was greatest at 12 hours postoperatively (area under the curve = 0.93; 95% confidence interval, 0.89-0.97). On multivariable regression analysis, after adjustment for potential confounders, the 12-hour vasoactive-ventilation-renal score remained a strong predictor of prolonged hospital length of stay (odds ratio, 1.15; 95% confidence interval, 1.10-1.20). CONCLUSIONS: In a heterogeneous population of patients undergoing surgery for congenital heart disease, the novel vasoactive-ventilation-renal score calculated in the early postoperative recovery period can be a strong predictor of prolonged hospital length of stay.

Utilization of modified NFL combine testing to identify functional deficits in athletes following ACL reconstruction.

STUDY DESIGN: Case control. OBJECTIVES: To use modified NFL Combine testing methodology to test for functional deficits in athletes following anterior cruciate ligament (ACL) reconstruction following return to sport. BACKGROUND: There is a need to develop objective, performance-based, on-field assessment methods designed to identify potential lower extremity performance deficits and related impairments in this population. METHODS: Eighteen patients (mean ± SD age, 16.9 ± 2.1 years; height, 170.0 ± 8.7 cm; body mass, 71.9 ± 21.8 kg) who returned to their sport within a year following ACL reconstruction (95% CI: 7.8 to 11.9 months from surgery) participated (ACLR group). These individuals were asked to bring 1 or 2 teammates to serve as control participants, who were matched for sex, sport, and age (n = 20; mean ± SD age, 16.9 ± 1.1 years; height, 169.7 ± 8.4 cm; body mass, 70.1 ± 20.7 kg). Functional performance was tested using the broad jump, vertical jump, modified long shuttle, modified pro shuttle, modified agility T-test, timed hop, triple hop, single hop, and crossover hop tests. A 1-way multivariate analysis of variance (MANOVA) was used to evaluate group differences for dependent performance variables. RESULTS: The functional performance measurements of skills requiring bilateral involvement of both lower extremities showed no group differences between the ACLR and control groups (P>.05). An overall group difference (P = .006) was observed for the combined limb symmetry index (LSI) measures. However, the modified double-limb performance tasks (long shuttle, modified agility T-test, and pro shuttle) were not, independently, sufficiently sensitive to detect limb deficits in individuals with ACL reconstruction. Conversely, the LSI on the distance measures of the single-limb performance tasks all provided moderate to large effect sizes to differentiate between the ACLR and control groups, as the individuals who had ACL reconstruction demonstrated involved limb deficits on all measures (P<.05). Finally, the LSI for the timed hop test was not different between groups (P>.05). CONCLUSIONS: These findings indicate that, while unilateral deficits are present in individuals following ACL reconstruction, they may not be evident during bipedal performance or during modified versions of double-limb performance activities. Isolation of the involved limb with unilateral hopping tasks should be used to identify deficits in performance.