DNA replication dynamics during erythrocytic schizogony in the malaria parasites Plasmodium falciparum and Plasmodium knowlesi.

Malaria parasites are unusual, early-diverging protozoans with non-canonical cell cycles. They do not undergo binary fission, but divide primarily by schizogony. This involves the asynchronous production of multiple nuclei within the same cytoplasm, culminating in a single mass cytokinesis event. The rate and efficiency of parasite reproduction is fundamentally important to malarial disease, which tends to be severe in hosts with high parasite loads. Here, we have studied for the first time the dynamics of schizogony in two human malaria parasite species, Plasmodium falciparum and Plasmodium knowlesi. These differ in their cell-cycle length, the number of progeny produced and the genome composition, among other factors. Comparing them could therefore yield new information about the parameters and limitations of schizogony. We report that the dynamics of schizogony differ significantly between these two species, most strikingly in the gap phases between successive nuclear multiplications, which are longer in P. falciparum and shorter, but more heterogenous, in P. knowlesi. In both species, gaps become longer as schizogony progresses, whereas each period of active DNA replication grows shorter. In both species there is also extreme variability between individual cells, with some schizonts producing many more nuclei than others, and some individual nuclei arresting their DNA replication for many hours while adjacent nuclei continue to replicate. The efficiency of schizogony is probably influenced by a complex set of factors in both the parasite and its host cell.

Best Practices: Ultrasound Versus MRI in the Assessment of Pelvic Endometriosis.

Endometriosis is a common yet morbid disease. Imaging plays an important role in diagnosis and treatment planning. Both ultrasound (US) and MRI are used to detect disease. We performed a literature review to assess whether one is superior. A total of 33 studies from the 4482 identified in the initial search were found to assess the efficacy of US and/or MRI in detecting pelvic endometriosis. Most studies were performed at centers with extensive experience with endometriosis, using dedicated US and MRI protocols. A wide range of sensitivities and specificities was reported, but overall weighted means of diagnostic statistics between US and MRI were similar. The choice of dedicated US versus MRI in evaluation of endometriosis should therefore be based on the expertise in the region. The data also showed US had better accuracy for identifying depth of wall invasion in bowel wall disease, whereas MRI better visualized pelvic wall and extraperitoneal disease. Routine US and MRI protocols performed worse than dedicated US and MRI protocols, which may account for delays in diagnoses. Clinical and research efforts directed at improving the sensitivity of routine imaging for diagnosing deep endometriosis could improve patient access to appropriate care.

Contrast Media in Pregnant and Lactating Patients, From the AJR Special Series on Contrast Media.

IV contrast media improve the diagnostic power of radiology examinations. These media include gadolinium-based contrast media and iron-oxide nanoparticles for MRI, iodinated contrast material for CT, microbubbles for ultrasound, and radiopharmaceuticals for nuclear medicine. As for all medications, contrast media carry risks, which may be heightened in the conditions of pregnancy and lactation. Radiologists must understand the potential risks from contrast media exposure to the pregnant patient, fetus, and nursing infant, as well as understand these administrations' impact on examinations' clinical utility. This article reviews the available literature on these media, along with key regulatory bodies' and professional societies' current recommendations for their use, in the settings of pregnancy and lactation. This knowledge should help radiologists make well-reasoned risk-benefit analyses regarding contrast media administration and provide informed consent discussions with pregnant and nursing patients in whom contrast media administration is being considered. This information and analysis can also assist facilities in designing policies and standard operating procedures of possible clinical benefit to the pregnant patient, fetus, or nursing infant, balancing contrast media exposure considerations versus augmented diagnostic capabilities.

Utilization trends for MR arthrography of the hip and shoulder: a retrospective cross-sectional analysis of 20-year data from a tertiary care academic medical center.

OBJECTIVE: The purpose of this study is to analyze changes in the utilization of MRA of the hip and shoulder at a large tertiary care academic medical center during a period of significant technological advancements over the last 20 years. MATERIALS AND METHODS: This retrospective cross-sectional analysis identified MRA of the hip and shoulder performed at our institution over a 20-year period (2/2003-2/2023) in relation to the total number of MR hip and shoulder examinations during the same period. Patient characteristics and referring provider demographic information were extracted. Descriptive statistics and trend analysis were performed. RESULTS: The total number of MRIs of the hip and shoulder increased overall, with small dips in 2020 and 2022. MRA of the hip increased significantly over the first 10 years of the study period (p = 0.0005), while MRA of the shoulder did not change significantly (p = 0.33). The proportion of both MRA of the hip and shoulder declined over the last 10 years (hip, p = 0.0056; shoulder, p = 0.0017). Over the same period, there was significant increase in the proportion of examinations performed at 3 Tesla versus 1.5 (p < 0.0001). CONCLUSION: Overall, there was a downward trend in MR shoulder and hip arthrogram utilization in the second half of this 20-year study period. However, utilization varied somewhat by referring specialties and credentials. These changes are likely reflective of both improvements in image quality and evolving practice recommendations. Awareness of such trends may be valuable in ensuring appropriate patient care, as well as for anticipating the needs of a musculoskeletal radiology practice.

Predictive value of joint fluid volume on advanced pre-procedure imaging related to success of arthrocentesis and presence of septic arthritis.

PURPOSE: Septic arthritis is a dangerous medical condition requiring prompt diagnosis, often via arthrocentesis. A "dry tap" occurs when no fluid is aspirated. We hypothesized that the absence of a joint effusion on pre-procedure advanced imaging would reliably predict a dry tap and exclude septic arthritis. METHODS: A cohort of 217 arthrocentesis cases of large joints (hips, shoulders, knees) from our institution, with pre-procedure advanced imaging (CT, MR, US) of the same joint performed within the previous 48 h, was analyzed. Exclusion criteria included non-native joints or inadequate imaging of the affected joint. These cases underwent blinded review by 4 radiologists who measured the deepest pocket of joint fluid on the pre-procedure imaging. Wilcoxon rank-sum test was performed comparing joint fluid pocket size to outcomes of successful aspiration and final diagnosis. RESULTS: A smaller average joint pocket fluid size was present on advanced imaging in both dry taps compared with successful arthrocenteses (p < .0001), and in uninfected joints compared with septic joints (p = .0001). However, the overlap of values was too great to allow for a perfectly predictive cutoff. 29% (5/17) of patients with no visible joint fluid on pre-aspiration imaging underwent successful arthrocentesis, one case representing septic arthritis. CONCLUSION: Volume of joint fluid on advanced pre-arthrocentesis imaging cannot reliably predict subsequent dry tap nor exclude septic arthritis.

Reliable, scalable functional genetics in bloodstream-form Trypanosoma congolense in vitro and in vivo.

Animal African trypanosomiasis (AAT) is a severe, wasting disease of domestic livestock and diverse wildlife species. The disease in cattle kills millions of animals each year and inflicts a major economic cost on agriculture in sub-Saharan Africa. Cattle AAT is caused predominantly by the protozoan parasites Trypanosoma congolense and T. vivax, but laboratory research on the pathogenic stages of these organisms is severely inhibited by difficulties in making even minor genetic modifications. As a result, many of the important basic questions about the biology of these parasites cannot be addressed. Here we demonstrate that an in vitro culture of the T. congolense genomic reference strain can be modified directly in the bloodstream form reliably and at high efficiency. We describe a parental single marker line that expresses T. congolense-optimized T7 RNA polymerase and Tet repressor and show that minichromosome loci can be used as sites for stable, regulatable transgene expression with low background in non-induced cells. Using these tools, we describe organism-specific constructs for inducible RNA-interference (RNAi) and demonstrate knockdown of multiple essential and non-essential genes. We also show that a minichromosomal site can be exploited to create a stable bloodstream-form line that robustly provides >40,000 independent stable clones per transfection-enabling the production of high-complexity libraries of genome-scale. Finally, we show that modified forms of T. congolense are still infectious, create stable high-bioluminescence lines that can be used in models of AAT, and follow the course of infections in mice by in vivo imaging. These experiments establish a base set of tools to change T. congolense from a technically challenging organism to a routine model for functional genetics and allow us to begin to address some of the fundamental questions about the biology of this important parasite.

Risk of Acute Kidney Injury Following IV Iodinated Contrast Media Exposure: 2023 Update, From the AJR Special Series on Contrast Media.

Iodinated contrast material (ICM) has revolutionized the field of diagnostic radiology through improvements in diagnostic performance and expansion in clinical indications for radiographic and CT examinations. Historically, nephrotoxicity was a feared complication of ICM use, thought to be associated with a significant risk of morbidity and mortality. Such fears often precluded use of ICM in imaging evaluations, commonly at the expense of diagnostic performance and timely diagnosis. Over the past 20 years, the nephrotoxic risk of ICM has become a topic of debate, as more recent evidence from higher-quality studies now suggest that many cases of what was considered contrast-induced acute kidney injury (CI-AKI) were likely cases of mistaken causal attribution; most of these cases represented either acute kidney injury (AKI) caused by any of myriad other known factors that can adversely affect renal function and were coincidentally present at the time of contrast media exposure (contrast-associated AKI (CA-AKI)) or a manifestation of the normal variation in renal function that increases with worsening renal function. This review discusses the current state of knowledge on CI-AKI and CA-AKI including the incidence, risk factors, outcomes, and prophylactic strategies in the identification and management of these clinical conditions.

Pilot study to determine whether reduced-dose photon-counting detector chest computed tomography can reliably display Brody II score imaging findings for children with cystic fibrosis at radiation doses that approximate radiographs.

BACKGROUND: The Brody II score uses chest CT to guide therapeutic changes in children with cystic fibrosis; however, patients and providers are often reticent to undergo chest CT given concerns about radiation. OBJECTIVE: We sought to determine the ability of a reduced-dose photon-counting detector (PCD) chest CT protocol to reproducibly display pulmonary disease severity using the Brody II score for children with cystic fibrosis (CF) scanned at radiation doses similar to those of a chest radiograph. MATERIALS AND METHODS: Pediatric patients with CF underwent non-contrast reduced-dose chest PCD-CT. Volumetric inspiratory and expiratory scans were obtained without sedation or anesthesia. Three pediatric radiologists with Certificates of Added Qualification scored each scan on an ordinal scale and assigned a Brody II score to grade bronchiectasis, peribronchial thickening, parenchymal opacity, air trapping and mucus plugging. We report image-quality metrics using descriptive statistics. To calculate inter-rater agreement for Brody II scoring, we used the Krippendorff alpha and intraclass correlation coefficient (ICC). RESULTS: Fifteen children with CF underwent reduced-dose PCD chest CT in both inspiration and expiration (mean age 8.9 years, range, 2.5-17.5 years; 4 girls). Mean volumetric CT dose index (CTDIvol) was 0.07 ± 0.03 mGy per scan. Mean effective dose was 0.12 ± 0.04 mSv for the total examination. All three readers graded spatial resolution and noise as interpretable on lung windows. The average Brody II score was 12.5 (range 4-19), with moderate inter-reader reliability (ICC of 0.61 [95% CI=0.27, 0.84]). Inter-rater reliability was moderate to substantial for bronchiectasis (0.52), peribronchial thickening (0.55), presence of opacity (0.62) and air trapping (0.70) and poor for mucus plugging (0.09). CONCLUSION: Reduced-dose PCD-CT permits diagnostic image quality and reproducible identification of Brody II scoring imaging findings at radiation doses similar to those for chest radiography.

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.

Prevention of Allergic-like Reactions at Repeat CT: Steroid Pretreatment versus Contrast Material Substitution.

Background It is unclear whether steroid premedication is an effective means of preventing repeat allergic-like reactions in high-risk patients with a previous allergic-like reaction to iodinated contrast material (ICM). Purpose To compare the effectiveness of ICM substitution (ie, using iohexol in a patient with a previous iopromide reaction) with 12- and 2-hour steroid premedication for preventing repeat acute allergic-like reactions in high-risk patients. Materials and Methods This retrospective study identified all high-risk (ie, having a previous allergic-like reaction) adult and pediatric patients who underwent a contrast-enhanced CT examination at the institution from June 1, 2009, to May 9, 2017. Prophylactic treatments and repeat reactions were identified using chart review. The effectiveness of prophylactic treatments on repeat reaction rates was examined with multivariable regression models that used generalized estimating equations. Results A total of 1973 high-risk patients who underwent 4360 subsequent ICM-enhanced CT examinations were included. Of the 4360 examinations, a total of 280 allergic-like reactions occurred (6%) in 224 of the 1973 patients (11% of patients), with only 19 of 280 reactions (7%) that were more severe than the previous reaction being demonstrated. After adjustment, patients who received a different ICM with and without steroid premedication had a significantly lower rate of repeat reactions than did patients who received steroid premedication and the same ICM (same ICM and steroid premedication: 80 of 423 examinations [19%]; different ICM and no steroid premedication: 10 of 322 examinations [3%]; odds ratio [OR], 0.14 [95% CI: 0.06, 0.33]; P < .001; different ICM and steroid premedication: five of 166 patients [3%]; OR, 0.12 [95% CI: 0.04, 0.36]; P < .001). When examining the first scan only, patients who received the same ICM had a similar risk of repeat reactions regardless of whether they received steroid premedication (steroid premedication: 44 of 172 patients [26%] vs no premedication: 73 of 298 patients [25%]; OR, 1.00 [95% CI: 0.64, 1.57]; P = .99). Conclusion In this cohort, using an iodinated contrast material (ICM) substitution was more effective for preventing repeat allergic-like reactions than using steroid premedication and the same ICM that caused the previous reaction. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Davenport and Weinstein in this issue.

Prospective multicenter assessment of patient preferences for properties of gadolinium-based contrast media and their potential socioeconomic impact in a screening breast MRI setting.

OBJECTIVE: It is unknown how patients prioritize gadolinium-based contrast media (GBCM) benefits (detection sensitivity) and risks (reactions, gadolinium retention, cost). The purpose of this study is to measure preferences for properties of GBCM in women at intermediate or high risk of breast cancer undergoing annual screening MRI. METHODS: An institutional reviewed board-approved prospective discrete choice conjoint survey was administered to patients at intermediate or high risk for breast cancer undergoing screening MRI at 4 institutions (July 2018-March 2020). Participants were given 15 tasks and asked to choose which of two hypothetical GBCM they would prefer. GBCMs varied by the following attributes: sensitivity for cancer detection (80-95%), intracranial gadolinium retention (1-100 molecules per 100 million administered), severe allergic-like reaction rate (1-19 per 100,000 administrations), mild allergic-like reaction rate (10-1000 per 100,000 administrations), out-of-pocket cost ($25-$100). Attribute levels were based on published values of existing GBCMs. Hierarchical Bayesian analysis was used to derive attribute "importance." Preference shares were determined by simulation. RESULTS: Response (87% [247/284]) and completion (96% [236/247]) rates were excellent. Sensitivity (importance = 44.3%, 95% confidence interval = 42.0-46.7%) was valued more than GBCM-related risks (mild allergic-like reaction risk (19.5%, 17.9-21.1%), severe allergic-like reaction risk (17.0%, 15.8-18.1%), intracranial gadolinium retention (11.6%, 10.5-12.7%), out-of-pocket expense (7.5%, 6.8-8.3%)). Lower income participants placed more importance on cost and less on sensitivity (p < 0.01). A simulator is provided that models GBCM preference shares by GBCM attributes and competition. CONCLUSIONS: Patients at intermediate or high risk for breast cancer undergoing MRI screening prioritize cancer detection over GBCM-related risks, and prioritize reaction risks over gadolinium retention. KEY POINTS: • Among women undergoing annual breast MRI screening, cancer detection sensitivity (attribute "importance," 44.3%) was valued more than GBCM-related risks (mild allergic reaction risk 19.5%, severe allergic reaction risk 17.0%, intracranial gadolinium retention 11.6%, out-of-pocket expense 7.5%). • Prospective four-center patient preference data have been incorporated into a GBCM choice simulator that allows users to input GBCM properties and calculate patient preference shares for competitor GBCMs. • Lower-income women placed more importance on out-of-pocket cost and less importance on cancer detection (p < 0.01) when prioritizing GBCM properties.

Acute Reactions to Gadolinium-Based Contrast Agents in a Pediatric Cohort: A Retrospective Study of 16,237 Injections.

BACKGROUND. Incidences and risk factors for acute reactions to gadolinium-based contrast agents (GBCAs) are not fully understood, particularly in pediatric patients. OBJECTIVE. The purpose of this study was to retrospectively examine allergiclike and physiologic acute reactions in pediatric patients who receive GBCAs for MRI examinations. METHODS. The study cohort consisted of all pediatric patients (age < 18 years old) who underwent an MRI examination with a GBCA at our institution from June 1, 2009, to May 9, 2017. Acute reactions were identified by medical record review and classified by severity using the American College of Radiology guidelines. Potential risk factors for reactions were examined using generalized estimating equation methods accounting for rare events. RESULTS. A total of 16,237 GBCA injections (10,141 gadodiamide injections, 4880 gadobutrol injections, and 1216 gadobenate dimeglumine injections) were administered to a study cohort of 10,190 patients (49% [7982/16,237] girls and 51% [8255/16,237] boys). Incidences of 0.10% (17/16,237) for allergiclike and 0.14% (23/16,237) for physiologic reactions were observed. No severe reactions occurred. Allergiclike reaction incidences were significantly higher with gadobenate compared with gadodiamide (0.49% vs 0.04%; p < .001) and in patients who underwent abdominal or pelvic MRI examinations (0.38%) or cardiac examinations (0.55%) compared with head examinations (0.05%; p < .001 and p = .006, respectively). Physiologic reaction incidences were significantly higher in older patients (0.25% in patients 12-17 years old vs 0.03% in patients 2 to < 12 years old; p < .001) and in patients who underwent abdominal or pelvic examinations compared with head examinations (0.38% vs 0.10%; p = .002). Of 16 MRI examinations performed in patients with a prior allergiclike reaction to GBCAs, only one resulted in a repeat reaction. CONCLUSION. In this pediatric cohort, GBCA type, patient age, and MRI type were risk factors for acute reactions. Repeat reactions were rare. CLINICAL IMPACT. Providers must weigh the risks and benefits when choosing a particular GBCA to use in their practices and must consider multiple, potentially disparate risks associated with each GBCA.

Emergency Presentations for Gastrostomy Complications Are Similar in Adults and Children.

ABSTRACT: Gastrostomy tube (GT) complications are often managed in the Emergency Department (ED). We aimed to characterize and compare the pattern of ED presentations of GT complications in adults and children. A retrospective chart review of patients with GT complications presenting to 3 Australian EDs in 2 years was undertaken. ED visits for GT complications occurred in 70 GT patients (36 adults, 34 children) with 122 presentations. When comparing adults to children, infections occurred in 21% versus 36%, respectively; P = 0.08, mechanical issues in 48% versus 52%; P = 0.86, vomiting in 23% versus 8%; P = 0.02, and other issues in 7% versus 5%; P = 0.7. Presentation to ED within 28 days of initial GT insertion occurred in 3 (8%) adults and 3 (9%) children, predominantly with tube dislodgement. GT complications seen in ED are predominantly infectious and mechanical in nature, with an increased frequency of vomiting in adults when compared with children.

Asymptomatic macrocephaly: to scan or not to scan.

BACKGROUND: Macrocephaly is a common finding in infants and is often idiopathic or familial. In the absence of clinical signs and symptoms, it can be difficult to determine when concern for underlying pathology is justified. OBJECTIVES: The objectives of this study were to determine the utility of screening head ultrasound (US) in asymptomatic infants with macrocephaly and to identify clinical factors associated with significant US findings. MATERIALS AND METHODS: A 20-year retrospective review was performed of infants undergoing head US for macrocephaly or rapidly increasing head circumference. Data collected included age, gender, head circumference at birth and at the time of US, specialty of the ordering physician, US findings, computed tomography (CT) or magnetic resonance imaging (MRI) findings, and clinical course including interventions. RESULTS: Four hundred and forty infants met inclusion criteria. Two hundred and eighty studies (64%) were found to be normal, 137 (31%) had incidental findings, 17 (3.8%) had indeterminate but potentially significant findings, and 6 (1.4%) had significant findings. Twenty of the 23 infants with indeterminate or significant findings had subsequent CT or MRI. This confirmed significant findings in eight infants (1.8%): three subdural hematomas, two intracranial tumors, two aqueductal stenoses, and one middle fossa cyst. Five of the eight infants required surgical procedures. The only statistically significant association found with having a significant finding on head US was head circumference at birth. CONCLUSION: Ultrasound is a useful initial study to evaluate infantile macrocephaly, identifying several treatable causes in our study and, when negative, effectively excluding significant pathology.

Imaging pediatric acute appendicitis during the coronavirus disease 2019 (COVID-19) pandemic: collateral damage is variable.

BACKGROUND: Since coronavirus disease 2019 (COVID-19) was declared a worldwide pandemic in March 2020, many authors have noted the collateral damage on non-COVID-19-related illnesses. These indirect effects of the pandemic have resulted in people presenting later and with more severe stages of disease, even if their diagnoses are not directly related to SARS-CoV-2, the virus that causes COVID-19. OBJECTIVE: We studied these indirect effects of COVID-19 on the imaging workup and outcomes for pediatric patients at our center who had acute appendicitis during the pandemic. MATERIALS AND METHODS: We performed a retrospective review of cases in children ≤18 years who were evaluated for acute appendicitis during the same period, March 1 to May 31, in both 2019 and 2020. We compared demographic and clinical data as well as surgical and pathological findings, and we graded imaging findings according to severity. Differences in patient outcomes were assessed using the Wilcoxon rank sum test and the Pearson chi-square test. RESULTS: The total number of pediatric patients evaluated with imaging for acute appendicitis dropped by 43% between 2019 and 2020 (298 vs. 169), but the total number of children treated remained similar (59 vs. 51). There was proportionate use of US and CT in each timeframe but a higher percentage of positive imaging findings in 2020 (50/169, 29.6% vs. 56/298, 18.7% in 2019, P=0.04). There were more imaging examinations with features of complicated appendicitis among positive cases (9/51, 18% vs. 5/59, 8% in 2019, P=0.08) and more pathologically proven perforated cases during the pandemic (14/51, 27% vs. 6/59, 10% in 2019, P=0.11), although these results did not reach statistical significance. There were no changes in surgical management, vital signs, laboratory values, length of stay or complication rates. CONCLUSION: There was a large drop in the number of pediatric patients imaged for acute appendicitis during the acute phase of the COVID-19 pandemic despite similar numbers of patients treated. The utilization trends of US vs. CT remained stable between time periods. The differences in imaging findings and perforation rates were less pronounced compared to other published studies.

Gadolinium retention within multiple rat organs after intra-articular administration of gadolinium-based contrast agents.

OBJECTIVE: To characterize the extent of retention and biodistribution of gadolinium (Gd) following intra-articular (IA) injection of linear and macrocyclic gadolinium-based contrast agents (GBCAs) into the knee joint of a rat model. MATERIALS AND METHODS: Fifteen Wistar rats were divided into five groups and underwent fluoroscopically-guided injections of both knee joints of (1) clinical 1:200 dilution (low dose, LD) gadodiamide (linear GBCA), (2) LD gadobutrol (macrocyclic GBCA), (3) undiluted (high dose, HD) gadodiamide, (4) HD gadobutrol, and (5) saline. Gd concentrations were quantified by inductively coupled plasma mass spectrometry in (1) blood and urine samples obtained over a 72 h period and (2) knee joint tissues, brain, kidney, and bone marrow at 3 days post-injection. RESULTS: Both HD and LD gadodiamide and gadobutrol were rapidly absorbed from the joint with peak serum and urine concentration at 1 h post-injection, with relatively faster clearance of gadobutrol. All GBCA-exposed groups had detectable levels of Gd in the joint tissues, bone marrow, and/or kidneys (median tissue gadolinium range: 0.1-71 µg Gd/g tissue), with higher amounts observed with gadodiamide versus gadobutrol. Retention within brain tissues was only detected following HD gadodiamide administration but not LD gadodiamide nor HD or LD gadobutrol. CONCLUSION: There was rapid systemic absorption, redistribution, and widespread multi-organ retention of Gd following IA injection of both linear and macrocyclic GBCAs, despite substantial amounts of urinary excretion. Higher concentrations of Gd were observed with administration of gadodiamide compared to gadobutrol in most tissues and biofluids.

The diversity of population responses to environmental change.

The current extinction and climate change crises pressure us to predict population dynamics with ever-greater accuracy. Although predictions rest on the well-advanced theory of age-structured populations, two key issues remain poorly explored. Specifically, how the age-dependency in demographic rates and the year-to-year interactions between survival and fecundity affect stochastic population growth rates. We use inference, simulations and mathematical derivations to explore how environmental perturbations determine population growth rates for populations with different age-specific demographic rates and when ages are reduced to stages. We find that stage- vs. age-based models can produce markedly divergent stochastic population growth rates. The differences are most pronounced when there are survival-fecundity-trade-offs, which reduce the variance in the population growth rate. Finally, the expected value and variance of the stochastic growth rates of populations with different age-specific demographic rates can diverge to the extent that, while some populations may thrive, others will inevitably go extinct.

Acute Adverse Events Following Gadolinium-based Contrast Agent Administration: A Single-Center Retrospective Study of 281 945 Injections.

Background Acute allergic-like and physiologic reactions occur following administration of gadolinium-based contrast agents (GBCAs) for MRI examinations. Because these reactions are uncommon, it is challenging to compare reaction rates between GBCAs and to determine risk factors. Purpose To compare reaction rates between the four GBCAs gadodiamide, gadobutrol, gadobenate dimeglumine, and gadoterate meglumine, and to determine potential risk factors for reactions. Materials and Methods This retrospective study identified all intravenous GBCA injections for MRI examinations performed at a single institution from June 1, 2009, to May 9, 2017. Reactions were identified by reviewing records from the MRI technologist, MRI nursing staff, radiologist, emergency department, and provider. Reactions were classified as allergic-like or physiologic and as mild, moderate, or severe by using American College of Radiology criteria. GBCA reaction rates and other potential risk factors were examined by using multivariable regression models with generalized estimating equations. Results Analysis included a total of 158 100 patients (median age, 55 years [interquartile range, 40-67 years], 51% women) who received a total of 281 945 GBCA injections (140 645 gadodiamide, 94 109 gadobutrol, 39 138 gadobenate, and 8053 gadoterate). At multivariate analysis, gadobenate or gadobutrol had higher rates of allergic-like reactions compared with gadodiamide (gadobenate: odds ratio [OR], 3.9 [95% confidence interval {CI}: 3.0, 5.1]; P < .001; gadobutrol: OR, 2.3 [95% CI: 1.8, 2.9]; P < .001) or gadoterate (gadobenate: OR, 4.8 [95% CI: 1.0, 23]; P = .049; gadobutrol: OR, 2.8 [95% CI: 0.6, 14]; P = .20). Physiologic reactions were more frequently observed with gadoterate (OR, 7.7 [95% CI: 2.3, 25; P = .001), gadobenate (OR, 1.8 [95% CI: 1.3, 2.5; P < .001), and gadobutrol (OR, 1.6 [95% CI: 1.3, 2.1; P < .001) administration compared with gadodiamide. Six severe allergic-like reactions (three gadobutrol, three gadobenate) occurred requiring hospitalization. Patient age (P values .025 to < .001), sex (P < .001), location (P = .006), and MRI type (P = .003 and P = .006) were associated with acute reactions. Conclusion Gadobenate and gadobutrol are associated with higher rates of allergic-like reactions compared with gadodiamide or gadoterate, and gadoterate, gadobenate, and gadobutrol are associated with higher rates of physiologic reactions compared with gadodiamide. Patient sex, age, location, and MRI type correlate with acute reaction rates. © RSNA, 2019 Online supplemental material is available for this article.

Periprocedural Major Bleeding Risk of Image-Guided Percutaneous Chest Tube Placement in Patients with an Elevated International Normalized Ratio.

PURPOSE: To evaluate the incidence of major hemorrhage after image-guided percutaneous chest tube placement in patients with an abnormal international normalized ratio (INR) measured before the procedure. MATERIALS AND METHODS: Between January 2013 and September 2017, 49 image-guided percutaneous chest tubes were placed in 45 adult patients who had an elevated INR of greater than 1.6. Data collected included routine serum pre-procedure coagulation studies, indication for chest tube placement, insertion technique, size of chest tube, and presence of complications after drain placement. Major bleeding complications were defined using the Society of Interventional Radiology classification system. RESULTS: Mean patient age was 62 years (range, 22-94 years), with median American Society of Anesthesiologists score of 4. Mean INR was 2.1 (range, 1.7-3), with 21 (43%) procedures with an INR between 1.7 and 1.9, 20 (41%) procedures with an INR between 2.0 and 2.4, and 8 (16%) procedures with an INR between 2.5 and 3.0. Computed tomography guidance was used for 27 (55%) procedures; ultrasound guidance was used for 22 (45%) procedures. Median size of chest tube was 10 Fr (range, 8-14 Fr) used in 27 (55%) procedures. No major bleeding complications were observed. There was a small, significant decrease in mean hemoglobin after the procedure (mean = 0.9g/dL; P < .0001), which correlated to increasing chest tube size (P = .0269). CONCLUSIONS: No major bleeding complications were observed after image-guided percutaneous chest tube placement in patients with an elevated INR. Major bleeding complications in these patients may be safer than initially considered, and this study encourages the conduct of larger trials for further evaluation.