A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

Transcrocetin Meglumine Salt Inhibits Spinal Glial Cell-Mediated Proinflammatory Cytokines and Attenuates Complete Freund's Adjuvant-Induced Inflammatory Pain.

INTRODUCTION: Inflammatory pain is a significant global clinical challenge that involves both unpleasant sensory and emotional experiences. The treatment of pain is imminent, and we are committed to seeking new analgesics for pain relief. Transcrocetin meglumine salt (TCMS), a saffron metabolite derived from the crocin apocarotenoids, has exhibited the ability to cross the blood-brain barrier and exert neuroprotective effects. In this study, we aimed to investigate whether TCMS could ameliorate complete Freund's adjuvant (CFA)-induced inflammatory pain in mice and elucidate its underlying mechanisms. METHODS: Here, we established an inflammatory pain model in mice by injecting CFA into the left hind paw. Three days later, we administered intraperitoneal injections of TCMS (10 mg/kg) or saline to the animals. We examined mechanical allodynia, thermal hypersensitivity, and anxiety behavior. Furthermore, the activation of glial cells and proinflammatory cytokines in the spinal cord were detected. RESULTS: Our results showed that TCMS significantly reversed the mechanical allodynia and thermal hypersensitivity in the CFA-injected mice. Furthermore, TCMS administration effectively inhibited the activation of microglia and astrocytes in the spinal cord induced by CFA. Additionally, TCMS suppressed the production and release of spinal proinflammatory cytokines, including TNF-α, IL-1ß, and IL-6, in CFA-injected mice. CONCLUSION: Taken together, our findings demonstrate that TCMS holds promise as an innovative analgesic due to its ability to ameliorate inflammatory reactions.

Patterns of use, effectiveness and safety of gadolinium contrast agents: a European prospective cross-sectional multicentre observational study.

BACKGROUND: The EU gadolinium-based contrast agents (GBCA) market has changed in recent years due to the European Medicines Agency decision to suspend the marketing authorisation of linear GBCA and the marketing authorisation of new generic macrocyclic GBCA. The study aims to understand the patterns of (GBCA) use, and to study the effectiveness and safety of GBCA in routine practice across Europe. METHODS: Prospective, cross-sectional, multicentre, observational study in patients undergoing contrast-enhanced magnetic resonance. Reported usage patterns included indication, referral and examination details. Assessment of effectiveness included changes in radiological diagnosis, diagnostic confidence and image quality. Safety data were collected by spontaneous patient adverse event (AE) reporting. RESULTS: 2118 patients were included from 8 centres across 5 European countries between December 2018 and November 2019. Clariscan, Dotarem (gadoteric acid), Gadovist (gadobutrol) and ProHance (gadoteridol) were utilised in 1513 (71.4%), 356 (16.8%), 237 (11.2%) and 12 (0.6%) patients, respectively. Most were performed in CNS-related indications (46.2%). Mean GBCA doses were 0.10 mmol/kg body weight, except for Gadovist (mean 0.12 mmol/kg). GBCA use increased confidence in diagnosis in 96.2% of examinations and resulted in a change in radiological diagnosis in 73.9% of patients. Image quality was considered excellent or good in 96.1% of patients and across all GBCA. Four patients reported AEs (0.19%), with only 1 (0.05%) considered serious. CONCLUSIONS: This European study confirmed that GBCAs are used appropriately in Europe for a wide range of indications. The study demonstrated a significant increase in diagnostic confidence after GBCA use and confirmed the good safety profile of GBCAs, with comparable results for all agents used.

[The results of phase III multicenter open randomized controlled study REM-Chol-III-16 in patients with intrahepatic cholestasis syndrome caused by chronic diffuse liver diseases].

AIM: To assess the safety and efficacy of Remaxol, solution for infusion, compared with parenteral form of S-adenosyl-L-methionine, in the treatment of patients with intrahepatic cholestasis syndrome accompanying chronic diffuse liver diseases of various etiology. MATERIALS AND METHODS: In a multicenter open-label comparative study of the safety and efficacy of Remaxol (inosine + meglumine + methionine + nicotinamide + succinic acid) 317 patients aged 18 to 65 years were randomized into 2 groups: patients of the experimental group (n=168) received intravenous Remaxol, solution for infusion, 400 ml, and patients of the control group (n=149) Heptral (S-adenosyl-L-methionine) 800 mg. The duration of treatment was 10 days. The primary efficacy endpoint was the proportion of patients who responded to therapy, as demonstrated by dynamics of laboratory parameters of liver functional status: decrease in gamma glutamyl transpeptidase level by 40%, and/or alkaline phosphatase level by 30%, and/or decrease total bilirubin level by 30% from baseline by the end of the treatment course. RESULTS: The proportion of responders was 51% in the Remaxol group vs. 44.9% in the Heptral group (p=0.303); the lower limit of the one-sided 95% confidence interval for the difference in the proportions of responders was -4.01%, which exceeds the non-inferiority margin pre-defined by the study protocol, thus, the non-inferiority hypothesis was proven, i.e. Remaxol at a dose of 400 ml/day demonstrates similar efficacy to Heptral at a dose of 800 mg/day in patients with intrahepatic cholestasis syndrome associated with chronic diffuse liver diseases. Similar positive trends in the levels of transaminases, total bilirubin and the severity of pruritus were revealed in both treatment groups. We did not reveal statistically significant between-group differences in the frequency of adverse events definitely related to the study treatment. CONCLUSION: Administration of Remaxol as a part of the pathogenetic therapy of patients with intrahepatic cholestasis syndrome who need hepatoprotection is justified.

Observational study on the incidence of nephrogenic systemic fibrosis in patients with renal impairment following gadoterate meglumine administration: the NSsaFe study.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a rare life-threatening condition strongly associated with the administration of gadolinium-based contrast agents in patients with severe or endstage renal impairment. PURPOSE: To prospectively determine the incidence of NSF in patients with renal impairment after administration of gadoterate meglumine. STUDY TYPE: Prospective. POPULATION: In all, 540 patients with moderate, severe, or endstage renal impairment, scheduled to undergo a routine contrast-enhanced MRI with gadoterate meglumine. Mean age was 69.7 ± 12.7 years (range: 21-95) with 58.4% of males. FIELD STRENGTH/SEQUENCE: 1.5T or 3.0T, sequence according to each site practice. ASSESSMENT: Medical history, indication(s) for current MRI and adverse events were recorded for each patient. Patients were followed up over 2 years after administration with three visits separated by at least 3 months to detect any signs/symptoms suggestive of NSF. STATISTICAL TESTS: Descriptive. RESULTS: Renal impairment was graded as moderate for 69.4% of patients, severe for 16.0% and endstage for 12.1%; 2.6% had undergone a kidney transplant. Estimated glomerular filtration rate ranged from 4 to 59 mL/min/1.73 m2 except one value of 74 mL/min/1.73 m2 in a patient with kidney transplant. Central nervous system exploration was the main MRI indication (34.7%) and mean dose injected was 0.22 ± 0.09 mL/kg. Overall, 446 patients (82.6%) attended at least one follow-up visit and completed the NSF questionnaire and 329 (60.9%) attended the 2-year visit. No suspicion of NSF was reported in all 446 patients, including 119 patients with severe or endstage renal impairment. No deaths and no adverse events were reported during the MRI examination and the usual period of follow-up after gadoterate meglumine administration. DATA CONCLUSION: No cases of NSF were observed in the 446 patients with moderate to endstage renal impairment followed up over a maximum of 2 years after injection of gadoterate meglumine. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:607-614.

Does Gadoterate Meglumine Cause Gadolinium Retention in the Brain of Children? A Case-Control Study.

BACKGROUND: Accumulation of macrocyclic gadolinium agents in children's brains remain to be determined. PURPOSE: To demonstrate whether there is an intracranial macrocyclic gadolinium deposition after multiple contrast-enhanced MRI with gadoterate meglumine in a pediatric population. STUDY TYPE: Retrospective case-control. POPULATION: In all, 45 children (age range: 5-17 years; mean, 13.7 ± 3.4 years) for the study group and 45 healthy children (age range: 5-17 years; mean, 13.7 ± 3.4 years) for the control group. FIELD STRENGTH/SEQUENCE: T1 - and T2 -weighted axial images on a 1.5T scanner. ASSESSMENT: Children with at least three enhanced brain MRIs and an age- and sex-matched control group with an unenhanced brain MRIs were compared in terms of T1 signal intensity (SI). All patients in the study group received gadoterate meglumine intravenously (0.1 mmol/kg). SI measurements were made by drawing six regions of interest (ROIs): dentate nuclei (DN), pons, globus pallidi (GP), frontal white matter (FWM), thalamus (T), clivus, and cerebrospinal fluid (CSF) for both groups on unenhanced T1 -weighted images. STATISTICAL TESTS: Student's t-test was used for comparison of SI. The Pearson correlation was calculated for the correlation between the SI and the number of gadolinium administrations. RESULTS: A significant difference was detected between two groups for DN/CSF, pons/CSF, GP/CSF, thalamus/CSF, and FWM/CSF (P < 0.001, P < 0.001, P = 0.002, P = 0.002, P = 0.024, respectively). There was no significant difference between the two groups for clivus/CSF (P = 0.15). A good correlation between the number of gadoterate meglumine administrations and the SI for DN/CSF, pons/CSF, GP/CSF, and T/CSF (r = 0.80, r = 0.73, r = 0.91, and r = 0.90, respectively) was found. DATA CONCLUSION: A significant T1 SI increase reflecting gadolinium retention in the brain was detected for children with at least three gadoterate meglumine administrations in this series. The number of administrations correlated well with the increased SI. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2020;51:1471-1477.

Baseline characteristics, diagnostic efficacy, and peri-examinational safety of IV gadoteric acid MRI in 148,489 patients.

BACKGROUND: Magnetic resonance imaging (MRI) examinations with intravenous (IV) contrast are performed worldwide in routine daily practice. In order to detect and enumerate even rare adverse events (AE) and serious adverse events (SAE), and to relate them with patients' baseline characteristics and diagnostic effectiveness, high quantity sample size is necessary. PURPOSE: To assess safety, diagnostic effectiveness, and baseline characteristics of patients undergoing IV gadoteric acid (Dotarem®) MRI in routine practice. MATERIAL AND METHODS: Data from two observational post-marketing surveillance (PMS) databases compiled by 139 and 52 German centers in 2004-2011 and 2011-2013, respectively, were pooled, yielding data on a total of 148,489 patients examined over a 10-year period. Radiologists used a standardized questionnaire to report data including patient demographics, characteristics of MR examinations, and results in terms of diagnosis and patient safety. RESULTS: Overall, 712 AEs were reported in 467 (0.3%) patients, mainly nausea (n = 224, 0.2%), vomiting (n = 29, <0.1%), urticaria (n = 20, <0.1%), and feeling hot (n = 13, <0.1%). AEs were considered related to gadoteric acid in 362 (0.2%) patients. Higher frequencies of AEs were observed among patients with a previous reaction to a contrast agent (2.0%), liver dysfunction (0.7%), bronchial asthma (0.7%), and a history of allergies (0.6%). There were 49 SAEs in 18 (<0.1%) patients, including two children. No fatal SAE was reported. Examinations were diagnostic in 99.8% of all patients, and image quality was excellent or good in 97.7% of the patients. CONCLUSION: Gadoteric acid is a safe peri-examinational and effective contrast agent for MRI in routine practice.

Safety of gadoterate meglumine in children younger than 2 years of age.

BACKGROUND: Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age. OBJECTIVE: To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration. MATERIALS AND METHODS: Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. RESULTS: One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. CONCLUSION: No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

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.

Gadoxetate Disodium versus Gadoterate Meglumine: Quantitative Respiratory and Hemodynamic Metrics by Using Compressed-Sensing MRI.

Background Gadoxetate disodium has been associated with various respiratory irregularities at arterial imaging MRI. Purpose To measure the relationship between gadolinium-based contrast agent administration and irregularities by comparing gadoxetate disodium and gadoterate meglumine at free breathing. Materials and Methods This prospective observational cohort study (January 2015 to May 2017) included consecutive abdominal MRI performed with either gadoxetate disodium or gadoterate meglumine enhancement. Participants underwent dynamic imaging by using the golden-angle radial sparse parallel sequence at free breathing. The quantitative assessment evaluated the aortic contrast enhancement, the respiratory hepatic translation, and the k-space-derived respiratory pattern. Analyses of variance compared hemodynamic metrics, respiratory-induced hepatic motion, and respiratory parameters before and after respiratory gating. Results A total of 497 abdominal MRI examinations were included. Of these, 338 participants were administered gadoxetate disodium (mean age, 59 years ± 15; 153 women) and 159 participants were administered gadoterate meglumine (mean age, 59 years ± 17; 85 women). The arterial bolus of gadoxetate disodium arrived later than gadoterate meglumine (19.7 vs 16.3 seconds, respectively; P < .001). Evaluation of the hepatic respiratory translation showed respiratory motion occurring in 70.7% (239 of 338) of participants who underwent gadoxetate-enhanced examinations and in 28.9% (46 of 159) of participants who underwent gadoterate-enhanced examinations (P < .001). The duration of motion irregularities was longer for gadoxetate than for gadoterate (19.2 seconds vs 17.2 seconds, respectively) and the motion irregularities were more severe (P < .001). Both the respiratory frequency and amplitude were shorter for participants administered gadoxetate from the prebolus phase to the late arterial phase compared with gadoterate (P < .001). Conclusion The administration of two different gadolinium-based contrast agents, gadoxetate and gadoterate, at free-breathing conditions potentially leads to respiratory irregularities with differing intensity and onset. © RSNA, 2019 Online supplemental material is available for this article.

Gadolinium-Induced Fibrosis.

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

Notice of Withdrawal: No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney Disease.

The authors have requested to withdraw this manuscript from publication because the study was not conducted in full accordance with the relevant institutional IRB protocol. © RSNA, 2018.

Reactions to Both Nonionic Iodinated and Gadolinium-Based Contrast Media: Incidence and Clinical Characteristics.

OBJECTIVE: The objective or our study was to assess the incidence rate and clinical characteristics of allergiclike reactions in patients who received both nonionic iodinated contrast medium (ICM) and gadolinium-based contrast medium (GBCM). MATERIALS AND METHODS: Acute allergiclike reactions in patients who received both ICM and GBCM to nonionic ICM or GBCM injections during a 5-year period were analyzed. Allergy preparation was not administered when patients received a different type of contrast material. Acute allergiclike reactions to both ICM and GBCM were evaluated. RESULTS: Of 302,858 contrast injections (155,234 ICM and 147,624 GBCM) during a 5-year period, 1006 (752 ICM and 254 GBCM) acute allergiclike contrast reactions were reported. The overall rate of reaction to ICM was 0.48% (95% CI, 0.45-0.52%), and the overall rate of reaction to GBCM was 0.17% (95% CI, 0.15-0.19%). A total of 19,237 patients received at least one ICM injection and one GBCM injection, with a total of 56,310 injections (19,237 initial injections and 37,073 subsequent injections). Nine patients had reactions to both ICM and GBCM with the primary reaction rate of 9/19,237 (incidence rate, 0.047%; 95% CI, 0.044-0.050%), and the secondary reaction rate of 9/37,073 (incidence rate, 0.024%; 95% CI, 0.023-0.026%). All secondary reactions in patients who had a reaction to both ICM and GBCM were mild. None of the patients required medication for the treatment of the secondary reaction. CONCLUSION: An allergiclike reaction to both nonionic ICM and GBCM was an extremely rare event that presented as a mild acute reaction without significant clinical consequences despite the fact that an allergy preparation was not administered.

Non-clinical assessment of safety and gadolinium deposition after cumulative administration of gadobenate dimeglumine (MultiHance®) to neonatal and juvenile rats.

To determine the impact of single and cumulative doses of MultiHance on toxicity, pharmacokinetics, tissue gadolinium presence, behavior and neurological function in juvenile rats. Juvenile male and female rats received either physiological saline or MultiHance at 0.6, 1.25 or 2.5 mmol/kg bodyweight. Animals received either single or six consecutive MultiHance administrations and were sacrificed the day after the last administration or after a 60-day treatment-free period. Animals were assessed for behavior, cognitive function, grip strength, gait, pupillary reflex, and auditory reflex, as well as for physical development, sexual maturation and histopathology. Gadolinium presence in brain, femur, kidneys, liver and skin was determined using inductively coupled plasma-mass spectrometry (ICP-MS). No effects of MultiHance on behavior, cognitive function or any other parameter were noted, even for the highest administered cumulative dose (15 mmol/kg). Gadolinium presence was variable across tissues and decreased during the 60-day treatment-free period. The highest levels were noted in the femur and the lowest levels in the brain. Gadolinium presence in juvenile rat brain following single or repeated MultiHance administrations was minimal and non-impactful.

Half-dose versus full-dose macrocyclic gadolinium at 3-T magnetic resonance imaging in paediatric bone and soft-tissue disease.

BACKGROUND: Given the recent concerns about gadolinium-based contrast agent safety, dose reduction strategies are being investigated. OBJECTIVE: To compare half-dose and standard full-dose gadoterate meglumine at 3-tesla (T) MRI in paediatric bone and soft-tissue diseases. MATERIALS AND METHODS: We prospectively enrolled 45 children (age range 2.7 months to 17.5 years, median age 8.7 years, 49 total anatomical segments) with bone and soft-tissue diseases (neoplastic, inflammatory/infectious, ischaemic and vascular) imaged at 3-T MRI. Two consecutive half-doses of gadoterate meglumine (0.05 mmol/kg body weight) were administered. Two sets of post-contrast T1-weighted images were obtained, one after the first half dose and the other after the second half dose. For qualitative analysis, three radiologists, masked to the gadolinium dose, compared the diagnostic quality of the images. For quantitative analysis, we compared signal-to-noise ratio and contrast-to-noise ratio at half and full doses. RESULTS: Signal-to-noise ratio and contrast-to-noise ratio did not vary significantly between the two groups. Qualitative analysis yielded excellent image quality in both post-contrast image datasets (Cohen κ=0.8). CONCLUSION: In paediatric bone and soft-tissue 3-T MRI, it is feasible to halve the standard dose of gadoterate meglumine without losing image quality.

Meglumine antimoniate intralesional infiltration for localised cutaneous leishmaniasis: a single arm, open label, phase II clinical trial.

BACKGROUND: Cutaneous leishmaniasis (CL) is a world-wide health problem which currently lacks effective, affordable and easy to use therapy. Recently, the meglumine antimoniate (MA) intralesional infiltration was included among the acceptable therapies for New World leishmaniasis. While this approach is attractive, there is currently little evidence to support its use in Americas. OBJECTIVES: The aim of this study was to provide information about effectiveness and safety of a standardised MA intralesional infiltration technique for the treatment of CL. METHODS: It is a single-arm phase II clinical trial conducted at a Brazilian referral centre. CL cases with parasitological confirmation presenting a maximum of three CL-compatible skin lesions were treated with weekly MA intralesional infiltration by using a validated technique, up to a maximum of eight infiltrations. RESULTS: A total of 53 patients (62 lesions) were included. Overall, patients received a median of seven infiltrations (IQR25-75% 5-8) over a median treatment period of 43 days (IQR25-75% 28-52 days). The definitive cure rate at D180 was 87% (95% CI:77-96%). The majority of adverse events were local, with mild or moderate intensity. Bacterial secondary infection of the lesion site was observed in 13% of the treated patients, beside two intensity-three adverse events (hypersensitivity reactions).

Observational study on the safety profile of gadoterate meglumine in 35,499 patients: The SECURE study.

PURPOSE: To investigate the safety of gadoterate meglumine and identify the incidence of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: An international prospective observational study was conducted from November 2008 to June 2013. A total of 35,499 adults and children who were scheduled to undergo contrast-enhanced MRI using gadoterate meglumine were analyzed (female, 53.1%; mean age: 49.5 years; range: 0-98 years). At least 3-month follow-up was planned for patients with an estimated creatinine clearance or glomerular filtration rate <60 mL/min (/1.73 m2) to detect any suspicion or occurrence of NSF. Adverse events (AEs) were prospectively recorded. Demographic data, risk factors, indications for MRI examinations, characteristics of gadoterate meglumine administration, and efficacy were documented. RESULTS: MRI examinations were mainly for central nervous system (61%). The most frequent risk factor was renal insufficiency (14.7%). Seventy AEs were observed in 44 patients (0.12%). Among the 70 AEs, 38 in 32 patients (0.09% of all patients) were considered related to gadoterate meglumine and classified as adverse drug reaction (ADR).The most frequent ADRs were urticaria (9 patients, 0.03%), nausea (7 patients, 0.02%), and vomiting (4 patients, 0.01%). Within the pediatric population (1,629 patients), only one AE (vomiting) was observed. Nine adult patients (0.03%) experienced serious AEs. Moderate to severe renal insufficiency at inclusion was reported in 514 patients (1.5%). Among them, 476 (92.6%) were followed-up. No patients were suspected of having NSF and no cases of NSF were observed. CONCLUSION: Our study confirms the excellent safety profile of gadoterate meglumine in routine practice. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:988-997.

An Investigation of Transient Severe Motion Related to Gadoxetic Acid-enhanced MR Imaging.

PURPOSE: To investigate the cause of imaging artifacts observed during gadoxetic acid-enhanced arterial phase imaging of the liver. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board. Data were collected prospectively at two sites (site A, United States; site B, Japan) from patients undergoing contrast material-enhanced MR imaging with gadoxetic acid (site A, n = 154, dose = 0.05 mmol/kg; site B, n = 130, 0.025 mmol/kg) or gadobenate dimeglumine (only site A, n = 1666) from January 2014 to September 2014 at site A and from November 2014 to January 2015 at site B. Detailed comparisons between the two agents were made in the patients with dynamic liver acquisitions (n = 372) and age-, sex-, and baseline oxygen saturation (Spo2)-matched pairs (n = 130) at site A. Acquired data included self-reported dyspnea after contrast agent injection, Spo2, and breath-hold fidelity monitored with respiratory bellows. RESULTS: Self-reported dyspnea was more frequent with gadoxetic acid than with gadobenate dimeglumine (site A, 6.5% [10 of 154] vs 0.1% [two of 1666], P < .001; site B, 1.5% [two of 130]). In the matched-pair comparison, gadoxetic acid, as compared with gadobenate dimeglumine, had higher breath-hold failure rates (site A, 34.6% [45 of 130] vs 11.7% [15 of 130], P < .0001; site B, 16.2% [21 of 130]) and more severe artifacts during arterial phase imaging (site A, 7.7% [10 of 130] vs 0% [none of 130], P < .001; site B, 2.3% [three of 130]). Severe imaging artifacts in patients who received gadoxetic acid were significantly associated with male sex (P = .023), body mass index (P = .021), and breath-hold failure (P < .001) but not with dyspnea or Spo2 decrease. CONCLUSION: Severe motion-related artifacts in the arterial phase of gadoxetic acid-enhanced liver MR imaging are associated with breath-hold failure but not with subjective feelings of dyspnea or a substantial decrease in blood Spo2. Subjective feelings of dyspnea are not necessarily associated with imaging artifacts. The phenomenon, albeit at a lower rate, was confirmed at a second site in Japan.

Topical liposomal azithromycin in the treatment of acute cutaneous leishmaniasis.

Cutaneous leishmaniasis (CL) treatment is based on pentavalant antimony (sbv) drugs which are accompanied by many side effects and are facing ever-increasing resistance. Topical treatment of CL is an attractive alternative avoiding toxicities of parenteral therapy while being administered through a simple painless route. The liposomal formulations of different drugs have recently been increasingly used in the treatment of several types of leishmaniasis. The efficacy of a topical liposomal azithromycin formulation was compared with intralesional meglumine antimoniate (glucantime) in the treatment of CL. Sixty-six patients with 97 lesions who met our inclusion criteria were randomly divided into two groups. One group was administered with the topical liposomal form of azithromycin twice daily. The other group was treated by weekly intralesional injections of glucantime with a volume of 0.5-2 cm3 into each lesion till complete blanching of the lesion occurred. Clinical evaluations were performed weekly during the treatment course (8 weeks) by a single dermatologist for both groups. Per-protocol analysis showed no statistically significant difference between the two groups (p = 0.84, 95% confidence interval (CI) = 0.764 (0.714-0.821). Serious drug side effects were not observed in either group. Topical liposomal azithromycin has the same efficacy as intralesional glucantime in the treatment of CL.