Thyroid Function Tests in Children and Adolescents With Trisomy 21
By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.
Summary
Definition of Syndrome-Specific Reference Ranges.
[Posted 13/Nov/2023]
AUDIENCE: Endocrinology, Pediatric, Family Medicine
KEY FINDINGS: By longitudinally assessing TFT in a wide pediatric DS population, we outlined the syndrome-specific reference nomograms for TSH, FT3, and FT4 and demonstrated a persistent upward shift of TSH compared to non-syndromic children.
BACKGROUND: The lack of syndrome-specific reference ranges for thyroid function tests (TFT) among pediatric patients with Down syndrome (DS) results in an overestimation of the occurrence of hypothyroidism in this population. Aim of this study is to (a) outline the age-dependent distribution of TFT among pediatric patients with DS; (b) describe the intraindividual variability of TFT over time; and (c) assess the role of elevated thyrotropin (TSH) in predicting the future onset of overt hypothyroidism.
DETAILS: In this retrospective, monocentric, observational analysis, authors included 548 patients with DS (0-18 years) longitudinally assessed between 1992 and 2022. Exclusion criteria were abnormal thyroid anatomy, treatments affecting TFT, and positive thyroid autoantibodies. Authors determined the age-dependent distribution of TSH, FT3, and FT4 and outlined the relative nomograms for children with DS. Compared with non-syndromic patients, median TSH levels were statistically greater at any age (P < .001). Median FT3 and FT4 levels were statistically lower than controls (P < .001) only in specific age classes (0-11 for FT3, 11-18 years for FT4). TSH levels showed a remarkable fluctuation over time, with a poor (23%-53%) agreement between the TSH centile classes at 2 sequential assessments. Finally, the 75th centile was the threshold above which TSH values predicted future evolution into overt hypothyroidism with the best statistical accuracy, with a satisfactory negative predictive value (0.91), but poor positive predictive value (0.15).
Our Most Popular Resources
Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
Source: Cattoni, A., Molinari, S., Capitoli, G., et al. (2023). Thyroid Function Tests in Children and Adolescents With Trisomy 21: Definition of Syndrome-Specific Reference Ranges. JCEM. 2023; 108(11): 2779-2788. Published: November, 2023. DOI: 10.1210/clinem/dgad333.
High-Quality Donor Kidneys Frequently Allocated to Adults Despite Pediatric Priority
Among deceased-donor kidneys with KDPI-10 below 35%, 23.4% were allocated to higher-priority adults. For ideal pediatric-quality kidneys, this proportion was 34.3%, with 77.5% received by multiorgan transplant recipients. KDPI-8 is unlikely to materially change pediatric access to ideal donor kidneys.
KEY FINDINGS: Despite pediatric allocation priority, a substantial proportion of high-quality donor kidneys continues to be allocated to adults with greater priority, predominantly multiorgan transplant recipients. The revised KDPI-8 calculation is not expected to materially alter the proportion of ideal pediatric-quality kidneys prioritized for children, although it changes the clinical composition of the donor pool by increasing the proportion of HCV-seropositive donors and reducing the proportion of donors after circulatory death. These findings highlight persistent limitations of KDPI-based allocation for pediatric candidates and support continued evaluation of policies that balance equity, donor-recipient matching, and long-term transplant outcomes.
BACKGROUND: Children receive allocation priority for deceased-donor kidneys with a kidney donor profile index (KDPI) <35%, although certain adult candidates retain higher priority. The recent transition from the 10-variable KDPI (KDPI-10) to the revised 8-variable KDPI (KDPI-8), which excludes donor race and hepatitis C virus (HCV) status, raised questions regarding its potential effect on pediatric access to high-quality donor kidneys.
DETAILS: This retrospective cohort study analyzed 60,587 deceased donors and their kidney recipients recorded in the Organ Procurement and Transplantation Network registry from January 1, 2018, through December 31, 2023. The investigators compared donor characteristics and kidney allocation patterns using KDPI-10 and KDPI-8. Ideal pediatric-quality donors were defined as donors with a KDPI <35%, donation after brain death, age <35 years, creatinine <=1.5 mg/dL, and no infectious risk, diabetes, or hypertension. Among kidneys from donors with KDPI-10 <35%, 23.4% were allocated to adults in categories with greater priority than pediatric candidates. Among ideal pediatric-quality kidneys, 34.3% were allocated to these higher-priority adult recipients, and 77.5% of these transplants were received by multiorgan transplant recipients. The proportion of donors meeting ideal pediatric-quality criteria was similar with KDPI-10 and KDPI-8 calculations (32.7% vs 33.5%). However, the KDPI-8 group included more Black donors (15.3% vs 9.9%) and HCV-seropositive donors (11.1% vs 3.6%) and fewer donors after circulatory death (12.7% vs 20.3%).
Our Most Popular Resources
Copyright © Skyscape. All rights reserved.
Source: Sonnenberg, E. M., Amaral, S., Zhang, S., et al. Allocation of Kidney Allografts From Donors With Kidney Donor Profile Index <35% and the Impact of Kidney Donor Profile Index Revisions on Access to Transplantation for Children. American Journal of Kidney Diseases. 2026; Published: August 22, 2026. DOI: 10.1053/j.ajkd.2026.02.643.
Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Ranitidine Cross-Contamination
Four nationwide-distributed lots of Cetirizine Hydrochloride Tablets USP 5 mg are being voluntarily recalled because of potential ranitidine cross-contamination. Patients with ranitidine hypersensitivity may be at risk for severe allergic reactions or anaphylaxis. No recall-related adverse events had been reported.
KEY FINDINGS: Unique Pharmaceutical Laboratories has initiated a voluntary nationwide recall of four lots of Cetirizine Hydrochloride Tablets USP 5 mg because of potential cross-contamination with ranitidine. The affected product was distributed nationwide in 100-count HDPE bottles under the Rising Pharma Holdings Inc. brand. Patients with hypersensitivity to ranitidine ingredients may be at risk for serious reactions, including severe hypersensitivity and life-threatening anaphylaxis. No adverse events related to the recalled product had been reported at the time of the announcement.
The recall was initiated after a pharmacy technician identified a discrepancy while counting tablets during dispensing. A product complaint described red dots and discoloration on some cetirizine tablets. The recalled lots are GY825029, GY825030, GY825031, and GY825032, each with an expiration date of 10/2028 and NDC 16571-401-10.
The manufacturer and distributor are arranging the return of the affected products. Clinicians should consider the recall when evaluating patients who may have received the affected medication and should assess and manage any suspected adverse reactions appropriately.
Our Most Popular Resources
Copyright © Skyscape. All rights reserved.
Source: Unique Pharmaceutical Laboratories (A Div. of J. B. Chemicals & Pharmaceuticals Ltd.) Issues Voluntary Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Cross Contamination with Ranitidine. FDA. Published: July 20, 2026.
Ambient Heat Significantly Elevates Hypoglycemia Risk in Type 1 Diabetes Patients
A study of 679 adults with T1DM using 33 million CGM readings identified a U-shaped risk curve between heat and hypoglycemia. Lowest risk was at 13C; at 25C temperature, the odds of hypoglycemia rose by 30%. Clinicians must advise dose adjustments in heat. Future automated insulin delivery systems should incorporate ambient temperature data to better predict and prevent hypoglycemic events.
KEY FINDINGS: Physicians should proactively educate patients with T1DM about the heightened risk of hypoglycemia during periods of increased ambient temperature. Managing glycemic levels in hot weather may require anticipatory reductions in insulin dosages to prevent dangerous declines. These findings also suggest that ambient temperature should be considered a dynamic variable within automated insulin delivery (AID) and hybrid closed-loop algorithms to optimize patient safety during seasonal heat waves.
BACKGROUND: As global temperatures continue to rise, understanding the impact of environmental factors on metabolic stability is increasingly critical for clinicians. Patients with Type 1 Diabetes (T1DM) often report seasonal fluctuations in glucose control, yet clinical guidelines remain ambiguous regarding whether high ambient temperatures primarily elevate the risk of hyperglycemia or hypoglycemia. This study was conducted to clarify the short-term relationship between outdoor temperature and the incidence of hypoglycemic events.
DETAILS: Researchers employed a case time series analysis using 33 million continuous glucose monitoring (CGM) data points collected between 2017 and 2024. The study cohort included 679 adults with T1DM residing in Sussex, UK. The primary exposure was the daily mean outdoor temperature at the participants' residential postcodes. Hypoglycemia was defined as a sensor glucose reading below 3.9 mmol/L (70 mg/dL) for a minimum of 15 minutes. The analysis revealed a non-linear, U-shaped association between ambient temperature and hypoglycemia risk. The lowest risk was observed at a daily mean temperature of 13°C. Risk significantly increased at temperature extremes, with the strongest effect seen during hotter weather. Specifically, at a daily mean temperature of 25°C, the odds of experiencing hypoglycemia were approximately 30% higher compared to the reference temperature of 13°C.
Our Most Popular Resources
Copyright © Skyscape. All rights reserved.
Source: Daultrey, H. E., Oliver, N. S., Chakera, A. J., et al. The Association Between Ambient Temperature and Hypoglycemia in People Living With Type 1 Diabetes: A Case Time Series Analysis Using Real-Time Continuous Glucose Monitoring. Diabetes Care. 2026; 49(8):1323-1329. Published: August, 2026. DOI: 10.2337/dc25-2383
Fluocinolone Acetonide Implant as Baseline Therapy for Diabetic Macular Edema
This randomized Phase 4 study found that a fluocinolone acetonide implant-based treatment strategy maintained visual and retinal anatomical outcomes comparable with aflibercept monotherapy while significantly reducing overall injection burden. Although the primary endpoint was not met, the findings suggest that sustained corticosteroid therapy may offer a treatment-burden advantage in appropriately selected patients, with careful monitoring for cataract formation and intraocular pressure elevation.
Summary
Results from the Phase 4 NEW DAY Study
[Posted 16/Jul/2026]
AUDIENCE: Ophthalmology, Internal Medicine
KEY FINDINGS: This randomized Phase 4 study demonstrated that baseline treatment with the fluocinolone acetonide implant achieved visual and anatomic outcomes comparable to aflibercept monotherapy while reducing the total number of intravitreal injections by more than half over 18 months. Although steroid-associated cataract and IOP events occurred more frequently, the overall safety profile was consistent with previous studies, supporting the FAc implant as a potential early treatment strategy for selected patients with DME.
BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy remains the standard treatment for diabetic macular edema (DME), but the need for frequent injections and clinic visits can create a substantial treatment burden. The fluocinolone acetonide (FAc) 0.19-mg intravitreal implant provides sustained corticosteroid delivery and has demonstrated efficacy in persistent DME. The Phase 4 NEW DAY study evaluated whether using the FAc implant as baseline therapy, supplemented with aflibercept only when needed, could reduce injection burden while maintaining visual and anatomic outcomes comparable with aflibercept monotherapy.
DETAILS: NEW DAY was a prospective, randomized, single-masked, active-controlled, multicenter, 18-month Phase 4 trial conducted at 42 sites in the United States. A total of 517 participants were screened, and 306 adults with type 1 or type 2 diabetes and center-involving DME were randomized to receive either a 0.19-mg FAc implant (n = 154) followed by rescue aflibercept injections as needed or aflibercept (n = 152) administered as five loading doses every four weeks followed by rescue treatment when required. The primary endpoint was the mean number of rescue supplemental aflibercept injections during the study. Secondary outcomes included total intravitreal injections, time to first rescue injection, best-corrected visual acuity (BCVA), central subfield thickness (CST), cataract procedures, and intraocular pressure (IOP)-related safety outcomes. The primary endpoint was not met, with a similar mean number of rescue aflibercept injections in the FAc and aflibercept groups (2.4 ± 3.2 vs. 2.5 ± 3.1; P = 0.76). However, the FAc strategy substantially reduced overall treatment burden, requiring fewer total injections than aflibercept monotherapy (3.4 ± 3.2 vs. 7.2 ± 3.4; nominal P < 0.001). Time to first rescue injection was significantly longer with the FAc implant (185.4 ± 97.9 days vs. 132.8 ± 94.0 days; nominal P < 0.001). Approximately one-third of participants in both groups required no rescue injections throughout the study (32.5% vs. 30.3%; nominal P = 0.68). Improvements in visual acuity and retinal anatomy were comparable between groups, with mean BCVA changes of 1.8 letters and 5.5 letters (nominal P = 0.08) and mean CST reductions of -119 ± 112 µm and -114 ± 103 µm (nominal P = 0.71) in the FAc and aflibercept groups, respectively. Cataract procedures occurred more frequently with the FAc implant (27.9% vs. 6.6%), and increased IOP was reported in 15.6% of FAc-treated participants compared with 3.3% receiving aflibercept. Despite these steroid-related adverse events, incisional IOP procedures were uncommon, and no new safety signals were identified.
Our Most Popular Resources
Copyright © Skyscape. All rights reserved.
Source: Singer, M. A., Wykoff, C. C., Riemann, C. D., et al. Fluocinolone Acetonide Implant as a Baseline Therapy for Diabetic Macular Edema. American Academy of Ophthalmology. 2026; 133(7): 837-851. Published: June 22, 2026. DOI: 10.1016/j.ophtha.2026.03.019.
Gadolinium-Based Contrast Agents: Reassessing Safety Beyond Nephrogenic Systemic Fibrosis
This review highlights that gadolinium-based contrast agents continue to play a critical role in diagnostic MRI, but their use should be guided by careful patient selection and individualized risk assessment. Although the risk of nephrogenic systemic fibrosis has declined considerably, further research is needed to clarify the clinical significance of gadolinium retention and its long-term safety.
KEY FINDINGS: This review emphasizes that GBCAs remain indispensable for diagnostic MRI but should be used following an individualized benefit-risk assessment, particularly in patients with chronic kidney disease or acute kidney injury. Although modern practice has substantially reduced the incidence of NSF, uncertainties remain regarding gadolinium retention, long-term toxicity, and persistent symptoms after exposure. Continued research into the mechanisms of gadolinium-associated injury, along with transparent patient counseling and evidence-based imaging policies, will be essential to optimize both patient safety and diagnostic care.
BACKGROUND: Gadolinium-based contrast agents (GBCAs) have been widely used to enhance magnetic resonance imaging (MRI) since the 1980s because of their favorable diagnostic performance and generally low incidence of acute adverse reactions. However, concerns regarding nephrogenic systemic fibrosis (NSF), gadolinium retention, and potential long-term toxicity have prompted ongoing debate about their safety, particularly in patients with kidney disease. This review examines current evidence on GBCA-associated complications, mechanisms of toxicity, and considerations for balancing diagnostic benefits with potential risks.
DETAILS: This narrative review synthesizes published evidence on the clinical safety of GBCAs, including acute hypersensitivity reactions, nephrotoxicity, NSF, gadolinium retention, and emerging concepts such as gadolinium-associated symptoms. The authors discuss differences between linear and macrocyclic GBCAs, proposed mechanisms of tissue deposition and fibrosis, the role of kidney dysfunction in gadolinium elimination, current American College of Radiology (ACR) recommendations, and unresolved questions regarding long-term toxicity. Experimental and clinical data addressing tissue retention, dialysis, and mechanistic pathways underlying gadolinium-induced injury are also reviewed. The review highlights that the incidence of NSF has declined substantially following the adoption of risk-based prescribing practices and updated clinical guidelines. Nevertheless, available evidence indicates that gadolinium retention can occur in multiple tissues, including the brain, even in individuals without severe renal impairment. The authors emphasize that tissue retention and toxicity are not fully explained by current GBCA classifications and that macrocyclic agents, although generally considered more stable, do not completely eliminate potential risk. Evidence reviewed also suggests that gadolinium may contribute to acute kidney injury, persistent tissue deposition, rare cases of encephalopathy, and symptoms associated with gadolinium exposure. Current data do not establish a definitive exposure threshold for toxicity, and the benefit of prophylactic hemodialysis after GBCA administration remains uncertain. While observational studies have estimated the risk of NSF with group II agents to be below 0.07%, the review notes that the true absolute risk remains difficult to define because of limitations in available evidence and confounding factors.
Our Most Popular Resources
Specialty: