Citations

Abstract The radiation sensitivity index (RSI) and 12-chemokine gene expression signature (12CK GES) are two gene expression signatures (GES) that were previously developed to predict tumor radiation sensitivity or identify the presence of tertiary lymphoid structures in tumors, respectively. To advance the use of these GESs into clinical trial evaluation, their assays must be assessed within the context of the Clinical Laboratory Improvement Amendments (CLIA) process. Using HG-U133Plus2.0 arrays, we first established CLIA laboratory proficiency. Then the accuracy (limit of detection and macrodissection impact), precision (variability by time and operator), sample type (surgery vs. biopsy), and concordance with a reference laboratory were evaluated. RSI and 12CK GES were reproducible (RSI: 0.01 mean difference, 12CK GES: 0.17 mean difference) and precise with respect to time and operator. Taken together, the reproducibility analysis of the scores indicated a median RSI difference of 0.06 (6.47% of range) across samples and a median 12CK GES difference of 0.92 (12.29% of range). Experiments indicated that the lower limit of input RNA is 5 ng. Reproducibility with a second CLIA laboratory demonstrated reliability with the median RSI score difference of 0.065 (6% of full range) and 12CK GES difference of 0.93 (12% of observed range). Overall, under CLIA, RSI and 12CK GES were demonstrated by the Moffitt Cancer Center Advanced Diagnostic Laboratory to be reproducible GESs for clinical usage. Significance: The RSI and 12CK GES are two GESs that predict tumor radiation sensitivity or the presence of tertiary lymphoid structures in tumors, respectively. These GESs were assessed within the CLIA process for future clinical use. We established proficiency, reproducibility, and reliability characteristics for both signatures in a controlled setting, indicating these GESs are suitable for validation within future clinical trials.

BACKGROUND: Ventral rectopexy has become increasingly used in the surgical management of rectal prolapse. There is a need for a contemporary evaluation of the role of the procedure and a description of its use in clinical practice. OBJECTIVE: To create an international consensus on ventral rectopexy. DESIGN: An expert panel undertook a scoping review of the literature to identify subject domains of interest. Literature reviews were completed for each domain with subsequent development of evidence-based and practice-based statements. These statements were compiled and reviewed by the group over a total of 9 meetings. Once statements were confirmed, supportive text was finalized, and an anonymous vote was completed using Research Electronic Data Capture to record consensus. SETTING: An international expert panel comprising colorectal surgeons who perform ventral rectopexy in a high-volume center. MAIN OUTCOME MEASURES: Statements and associated expert consensus. RESULTS: Eleven experts identified 10 domains for review: indications, contraindications, assessment and planning, consent, operative details, prostheses, complications, follow-up, recurrence and reoperative surgery, and specific considerations. After round table review, there were 17 resultant statements for consideration. Experts agreed unanimously with 13 of the statements and their accompanying text, with different experts disagreeing regarding the remaining 4 statements (91% consensus each). LIMITATIONS: Paucity of high-quality data. CONCLUSIONS: This international group developed 17 statements with high consensus. These statements provide an up-to-date summary of the literature, identify key areas for research development, and provide a reference point for colon and rectal surgeons who undertake ventral rectopexy as part of their practice. See Video Abstract . RECTOPEXIA VENTRAL: CONSENSO DE UN PANEL INTERNACIONAL DE EXPERTOS Y REVISIÓN DE LA LITERATURA CONTEMPORÁNEA ANTECEDENTES: La rectopexia ventral se ha utilizado cada vez más en el tratamiento quirúrgico del prolapso rectal. Es necesario realizar una evaluación contemporánea del rol del procedimiento y una descripción de su uso en la práctica clínica. OBJETIVO: Crear un consenso internacional sobre la rectopexia ventral. DISEÑO: Un panel de expertos realizó una revisión exhaustiva de la literatura para identificar los dominios temáticos de interés. Se completaron revisiones de la literatura para cada dominio con el desarrollo de declaraciones basadas en la evidencia y la práctica. Estas fueron compiladas y revisadas por el grupo a lo largo de un total de nueve reuniones. Una vez que se confirmaron las declaraciones, se finalizó el texto de apoyo y se completó una votación anónima utilizando REDCap para registrar el consenso. ESCENARIO: Un panel internacional de expertos compuesto por cirujanos colorrectales que realizan rectopexia ventral en un centro de alto volumen. PRINCIPALES MEDIDAS DE RESULTADOS: Declaraciones y consenso de expertos asociado. RESULTADOS: Once expertos identificaron diez dominios a revisar: indicaciones, contraindicaciones, evaluación y planificación, consentimiento, detalles operatorios, prótesis, complicaciones, seguimiento, recurrencia y cirugía reoperatoria y consideraciones específicas. Después de la revisión en mesa redonda, hubo 17 declaraciones resultantes para su consideración. Los expertos estuvieron de acuerdo unánimemente con trece de las declaraciones y su texto acompañante, y diferentes expertos estuvieron en desacuerdo con cuatro declaraciones (91% de consenso cada una). LIMITACIONES: Escasez de datos de alta calidad. CONCLUSIÓN: Este grupo internacional desarrolló 17 declaraciones con alto consenso. Estas declaraciones proporcionan un resumen actualizado de la literatura, identifican áreas claves para el desarrollo de la investigación y un punto de referencia para los cirujanos de colon y recto que realizan rectopexia ventral como parte de su práctica. (Traducción—Dr. Aurian Garcia Gonzalez )

Importance Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology. Objective To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia. Design, Setting, and Participants Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024. Main Outcomes and Measures Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms. Results In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI. Conclusions and Relevance Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumulation may commonly underlie depressive symptoms in late life.

ABSTRACTBackgroundThe self‐expanding, supra‐annular Evolut valve is an established platform for Transcatheter Aortic Valve Implantation (TAVI). Evolut PRO introduced an outer sealing wrap to mitigate paravalvular leakage. We evaluated the 3‐year clinical outcomes and valve performance of the Evolut PRO in standard clinical practice for severe aortic stenosis (AS) patients at intermediate or higher risk for surgery.MethodsThe FORWARD PRO prospective, single‐arm, multicentre, post‐market clinical study enrolled 638 patients with native aortic valve stenosis or failed surgical bioprosthetic aortic valve undergoing TAVI, at intermediate or high risk, with the Evolut PRO valve. Clinical and serial echocardiographic outcomes were followed‐up for 3 years.ResultsTAVI using Evolut PRO was attempted in 629 AS patients (implanted in 97%) (mean age 81.7 years; STS PROM score, 4.7%). At 3 years all‐cause mortality was 25.0%, disabling stroke 6.5% (all‐cause mortality or disabling stroke, 28.5%) and rate of new permanent pacemaker implantation 24.7%. Excellent valve haemodynamics were maintained (mean gradient 8.8 ± 4.7 mm Hg; mean effective orifice area 2.0 ± 0.5 cm2) at 3 years. In a paired analysis of patients with ≥ mild paravalvular leakage (PVL) at discharge, more than two‐thirds demonstrated improved PVL at 3 years. Patients with ≥ mild PVL at discharge had higher median total calcium volume than those with no/trace PVL (p < 0.001).ConclusionsIn clinical practice TAVI with the Evolut PRO valve is associated with favorable clinical outcomes and excellent haemodynamic performance out to 3 years. The observation of improvements in PVL over time warrants further research.

Introduction ABBV-383 is a differentiated BCMA x CD3 bispecific antibody (fully humanized IgG4) T-cell engager composed of a bivalent BCMA binding domain with high avidity, a low-affinity CD3-binding domain, and a present but silenced-Fc tail retaining the FcRn binding allowing for an extended half-life and thereby, enabling dosing convenience. ABBV-383 monotherapy has shown promising activity and improved CRS safety profile with modified dexamethasone (Dex) premedication in patients (pts) with RRMM (NCT03933735; Rodriguez et al., JCO 2024;42[suppl 16]:7531). Here, ER and CRS PK/PD analyses supporting the selection of optimal SUD for ABBV-383 are reported. Methods ER-efficacy (N=286) and -safety (N=290) analyses were conducted using logistic regression methodology (R version 4.3.2) combining data from escalation (0.025-120 mg Q3W) and expansion (20, 40, 60 mg Q3W and 60 mg Q4W) cohorts of phase 1 study NCT03933735 and Arm A of phase 1b study NCT05650632 evaluating step-up dose (2 or 4 mg on Day 1) with a full dose (60 mg on Day 4) in pts with RRMM. Pts received modified Dex with full dose in expansion cohorts of 60 mg Q4W and 2/60 mg Q4W. In all other cohorts with or without SUD, pts received low Dex. Based on prior knowledge (JCO 2024;42[suppl 16]:7541), the safety endpoints (CRS: any-grade and ≥ G2) were modeled with Cycle 1 total (unbound + bound to soluble BCMA) Cmax, while objective response rate (ORR) was modeled with free (unbound + partially bound to soluble BCMA) Cavg. CRS ER models included a priori selected Dex (low vs. modified) and SUD (yes vs. no) as predictors. Relevant pt-specific covariates were tested in all models. CRS PK/PD analyses included total PK, IL-6, and CRS data (N=199) from the first 3 cycles of the above phase 1/1b studies. A semi-mechanistic indirect response PK/IL-6 model was developed to correlate total PK and IL-6 (NONMEM 7.5). Maximal IL-6 concentrations were derived using post hoc estimates from the PK/IL-6 model and correlated with CRS events (logistic regression; R version 4.3.2). The models included effects of time-dependent Dex (low vs. modified) and SUD (yes vs. no). The overall modeling approach was assessed by comparing observed and predicted CRS rates. Simulations were conducted for various dosing regimens, including one or two SUD and Dex premedication scenarios to support the selection of the optimal SUD. Results Consistent with clinical observations (separate abstract submission), any-grade CRS model predicted probabilities suggested two key outcomes: 1) premedication with modified Dex improves the CRS safety profile compared to the low Dex (42% vs 69% for 60 mg Q4W); 2) modified Dex with SUD further improves the CRS safety profile of ABBV-383 compared to low Dex with SUD (29% vs 43% for 2/60 mg Q4W). Consistent with prior work, no ER relationship was observed for ≥ G2 CRS (p &gt; 0.05). The ORR model resulted in a predicted probability of 68% ORR (closely matching with overall observed 64% ORR) with no impact of SUD and modified Dex. Only soluble BCMA was selected as a covariate in the ORR ER model. The final semi-mechanistic PK/IL-6 model well captured the observed IL-6 data, and the CRS rates (predicted by the logistic regression models) closely matched with the observed data. The CRS PK/PD analyses findings were consistent with the clinical observations and ER analyses key outcomes 1 and 2. The CRS PK/PD analyses predictions comparing the 1-SUD vs 2-SUD (untested) regimens with modified Dex suggested that 1) among the 2-SUD regimens with modified Dex, the 2/3/60 mg regimen would have the maximum reduction of 4% points in any-grade CRS compared to the 2/60 mg 1-SUD regimen, however, with substantial overlap of confidence intervals and with no decrease in ≥ G2 CRS (&lt; 0.5% point); 2) 4 mg as an intermediate SUD in a 2-SUD regimen would lead to higher any-grade and ≥ G2 CRS rates (~9% and 3% points higher, respectively), compared to the 2/60 mg Q4W regimen. Conclusions ER and CRS PK/PD analyses suggested that modified Dex and SUD improve the CRS safety profile of ABBV-383 with no impact on efficacy (ORR) in pts with RRMM. The CRS PK/PD predictions indicated that implementation of 2-SUDs provide minimal additional or no improvement in CRS safety profile compared to 1-SUD. Overall, the 1-SUD dosing regimen of 2 mg with modified premedication prior to the full dose of 60 mg Q4W showed promising results and can be considered for future evaluation and studies.

Introduction: Sickle cell disease (SCD) is prevalent in sub-Saharan Africa. Phenotypic diversity in patients with similar SCD genotypes may result from genetic and environmental factors. Nigeria has the highest SCD prevalence, with homozygous SCD (HbSS) being the most severe form. Stroke affects about 11% of children under 20 years with SCD (Ohene-Frempong, Weiner, et al. 1998), primarily ischemic, involving medium to large intracranial arteries. Specific single nucleotide polymorphisms have been linked to ischemic stroke risk in some populations. (Earley, Kelly et al. 2023). This study aimed to identify genetic factors associated with early-age large-vessel stroke in SCD using whole-exome sequencing (WES) in a Nigerian cohort. Methods: The protocol was approved by the IRBs of TJU, Nemours, and 3 Nigerian sites. Subjects with SCD who experienced large vessel stroke early in life (16 years or less) were enrolled, along with controls (SCD patients without stroke). Subjects were recruited from 3SCD clinics in Kano Metropolis, Nigeria. Inclusion criteria were confirmed SCD diagnosis (SS and Sβ0 thalassemia genotypes), abnormal transcranial doppler (TCD) measurements, and clinical evidence of stroke confirmed by MRI by age 16. Controls included SCD patients (SS and Sβ0) aged 16-26 years without clinical stroke and at least one normal TCD. All cases underwent Magnetic Resonance Angiography (MRA) to establish arteriopathy. Immediate family members of subjects &gt;16 years (siblings and parents) were used per best practice trio analysis to annotate variants with appropriate Mendelian inheritance patterns. WES was performed using SureSelect XT HS (Agilent) and Human All Exon V7 Rev B capture probes for library preparation on all samples. Libraries were sequenced on a NextSeq 550 to 50M paired-end 150bp reads. Variants were called using the GATK suite of algorithms following best practice guidelines and annotated using the VarSeq algorithm, including AlphaMissense annotations. Results: The control group had a median age of 21 years, and the stroke group had a median age of 9 years. The stroke group had a higher proportion of males (60%) compared to controls (30%) (p &lt; 0.05). Fifty percent of the stroke group and 73% of the controls had a history of acute chest syndrome. History of avascular necrosis (7.5%), heart disease (2.5%), and splenic sequestration (1.3%) were present only in controls. Malaria (1.3%), sepsis (2.5%), and hand-foot syndrome (59%) affected the stroke group. History of priapism (6.3%) and leg ulcers (10%) had similar rates in both groups. Using AlphaMissense annotations, nine genes were identified to have more damaging mutations in the stroke cohort compared to the control cohort (odds ratio &gt; 1 and p &lt; 0.05). Pathway enrichment analysis utilizing genes prioritized with an odds ratio &gt; 1 identified cadherin signaling, cellular junction/adhesion, and WNT signaling as significant (p &lt; 0.05). The role of cellular adhesion has been previously described in SCD stroke subjects (Oni, Brito et al. 2024). The genes that we found that showed significance in our analysis include ADAMTSL2, ADCY9, OR3A1, OR3A2, XRRA1, ABTB2, CLDN18, CPNE7, EIF3A, SLC7A6, UBA7, PDE6A, GLOD5, and PCDHA1. Conclusion: Genes in the ADCY9 and ADAMSL2 families have been reported in previous studies to be associated with ischemic stroke. Though the small sample size limits this study, it offers preliminary insights into the genetic and clinical determinants of stroke in SCD patients in Northern Nigeria. The identified candidate genes potentially hold biological significance for the stroke phenotype; however, additional research with a larger sample size is required to validate these associations. These findings underscore the need for further whole-exome sequencing studies in Nigerian patients with the stroke/arteriopathy phenotype, which may augment our understanding of this severe complication. An in-depth examination of the genetic modifiers associated with stroke in SCD could lead to enhanced predictive models and targeted preventive interventions, reducing the burden of stroke in affected individuals. Our team has identified additional datasets in the United States to help validate molecular signatures of interest, inspiring us to continue our work in this important field.

Introduction Patients (pts) with multiple myeloma (MM) eventually become refractory to current treatments. There is an unmet need for new therapies with durable efficacy, favorable safety, and simplified dosing schedules. ABBV-383 is a unique BCMA x CD3 bispecific antibody T-cell engager comprising bivalent high-avidity BCMA binding domains, a low-affinity CD3-binding domain designed to minimize cytokine release and the risk for cytokine release syndrome (CRS), and a silenced Fc tail for extended half-life enabling dosing convenience. In an ongoing first-in-human (FIH) study (NCT03933735) in heavily pretreated pts with relapsed or refractory (RR) MM, ABBV-383 monotherapy (60 mg Q4W) resulted in deep and durable responses. Introduction of a modified dexamethasone (Dex) premedication (premed) schedule in cycle (C) 1 lowered incidence and severity of CRS (43% overall; 5% grade ≥2) vs pts treated with low Dex (71% overall; 20% grade ≥2) (JCO 2024;42[suppl 16]:7531). We now report results of Arm A of the open-label, phase 1b study (NCT05650632) evaluating 1 step-up dose (SUD) of ABBV-383 as a strategy to mitigate the risk of severe CRS and further assess ABBV-383 activity in pts with RRMM. Methods This study is enrolling pts with RRMM, ECOG performance status ≤2, and documented evidence of progression during or after the last treatment. Pts must have received ≥3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Arm A consists of a dose-optimization (DO) and a dose-expansion (DE) part. During DO, pts received a single SUD of intravenous ABBV-383 (2/4 mg) on C1 day (D) 1, followed by the target dose of 60 mg on D4. In the DE, based on DO findings, pts received the recommended ABBV-383 SUD on C1D1, followed by 60 mg on D4. The modified premed schedule that lowered incidence and severity of CRS in the FIH study was also introduced prior to target dose on C1D4. After C1, pts received 60 mg ABBV-383 Q4W on D1 of each cycle for DO and DE until disease progression, withdrawal, or discontinuation. Primary endpoint was grade ≥2 CRS events during C1. Other endpoints included any grade CRS events, treatment-emergent adverse events (TEAEs), immune pharmacodynamics, and clinical activity. Results As of April 2024, 70 pts were enrolled in Arm A: 47 in DO (2 mg SUD, n=26; 4 mg SUD, n=21) and 23 in DE. Median age was 69 years (range: 40-84), 59% were male, and 76% were triple-class refractory. Median prior lines of therapy was 4 (range: 3-10). Median follow-up time (months [mo]) was 6.5, 7.5, and 2.8 for 2 mg DO, 4 mg DO, and DE, respectively. Any grade CRS was reported in 10 (39%) and 11 (52%) pts during DO at 2 and 4 mg SUD; CRS grade ≥2 occurred in 3 (12%) pts in the 2 mg SUD and in 6 (29%) pts in the 4 mg SUD, leading to selection of 2 mg SUD for DE. In the DE, 7 (30%) pts experienced CRS; 1 (4%) pt experienced grade 2 CRS, there were no grade ≥3 events, and only 2 (9%) pts received tocilizumab to treat CRS. Overall, median time to CRS onset and resolution was 14.7 and 9 hours, respectively; no pts had CRS after C1. Immune effector cell-associated neurotoxicity syndrome occurred in 7 (10%) pts (grade 1: 4%; grade 2: 6%; grade 3: 4%). Most common TEAEs were CRS (40%), neutropenia (37%), diarrhea (29%), anemia (24%), and fatigue (20%); most common grade 3/4 TEAEs were neutropenia (31%), anemia (19%), thrombocytopenia (13%), and leukopenia (11%). Grade 5 TEAEs occurred in 5 pts; 1 event was deemed possibly related to ABBV-383 (COVID-19 pneumonia). In the efficacy-evaluable population (n=68), the objective response rate was 62% (95% CI: 49.2, 73.3); 35 (52%) pts had a VGPR or better. Median time to response was 1.1 mo (range: 1-4) and median duration of follow-up was 5.8 mo (range: 1-12). Response rates are expected to improve with longer follow-up. Maximum reduction in peak levels of CRS-related cytokines, including IL-6, were observed in DE compared with DO and 60 mg Q4W without SUD (FIH study). Peak activation and proliferation of CD8 T cells was comparable with ABBV-383 in DO, DE, and 60 mg Q4W-treated pts. Conclusions Introduction of 1 SUD of 2 mg on D1 followed by full dose of 60 mg on D4 in C1 combined with modification to the Dex premed schedule reduced the incidence and severity of CRS in pts with RRMM, further optimizing the safety profile of ABBV-383. Preliminary efficacy data show early and high response rates, consistent with outcomes from other ABBV-383 studies.

Spinal cord stimulation for motor recovery after spinal cord injury is a popular research intervention, though off-target effects are a concern. Using continual blood pressure and heart rate recordings during passive spinal cord stimulation parameter testing, we identified frequent episodes of autonomic dysreflexia that were rarely associated with symptoms. This presents a previously unrecognized risk of spinal cord stimulation and appropriate vigilance in targeted monitoring is urged to maintain participant safety.

Abstract Aims To assess the reproducibility of interpreting hypoattenuated thickening (HAT) and peridevice leak (PDL) using cardiac computed tomography (CT) imaging following Watchman FLX left atrial appendage closure (LAAC). Methods and results In this multicentre retrospective reproducibility study, 100 anonymized post-LAAC cardiac CT scans were evaluated within the same cardiac phase by an experienced and a novice rater blinded to prior evaluations. All scans were evaluated twice by each rater, assessing overall HAT and PDL categories as well as specific associated findings based on suggested algorithms for post-LAAC interpretation. Inter- and intra-rater agreement and reliability were evaluated using absolute agreement, Cohen’s kappa, and Kendall’s tau for categorical variables, and mean difference, Bland–Altman plots, limits of agreement (lower and upper), and intra-class correlation coefficients (ICCs) for continuous variables. Within overall categories of both HAT and PDL, substantial agreement (kappa ≥0.61) and reliability (Kendall’s tau-b ≥ 0.75) were observed. Specifically, identifying high-grade HAT (kappa ≥0.78) and distal patency (kappa ≥0.85) displayed the highest agreement within HAT and PDL interpretation. Meanwhile, measuring the height of the proximal screw hub cove represented the least reliable HAT assessment among both inter- and intra-rater comparisons (ICC &lt; 0.75), while suspected leak mechanism represented the least reproducible PDL measure. Conclusion Despite only minimal training of one rater, overall high levels of inter- and intra-rater agreement and reliability were observed across the chosen algorithms for interpretation of HAT and PDL following Watchman FLX LAAC. The prognostic implications of the included variables are to be explored in future trials and registries.

ABSTRACT Background Creatinine-based equations are the most used to estimate glomerular filtration rate (eGFR). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), the re-expressed Lund-Malmö Revised (r-LMR) and the European Kidney Function Consortium (EKFC) equations are the most validated. The EKFC and r-LMR equations have been suggested to have better performances in young adults, but this is debated. Methods We collected data (GFR) measured by clearance of an exogenous marker (reference method), serum creatinine, age and sex from 2366 young adults (aged between 18 and 25 years) both from Europe and the USA. Results In the European cohorts (n = 1892), the bias (in mL/min/1.73 m²) was systematically better for the EKFC and r-LMR equations compared with the CKD-EPI equation [2.28, 95% confidence interval (1.59; 2.91), –2.50 (–3.85; –1.76), 17.41 (16.49; 18.47), respectively]. The percentage of estimated GFR within 30% of measured GFR (P30) was also better for EKFC and r-LMR equations compared with the CKD-EPI equation [84.4% (82.8; 86.0), 87.2% (85.7; 88.7) and 65.4% (63.3; 67.6), respectively]. In the US cohorts (n = 474), the bias for the EKFC and r-LMR equations was better than for the CKD-EPI equation in the non-Black population [0.97 (–1.69; 3.06), –2.62 (–5.14; –1.43) and 7.74 (5.97; 9.63), respectively], whereas the bias was similar in Black US individuals. P30 results were not different between the three equations in US cohorts. Analyses in sub-populations confirmed these results, except in individuals with high GFR levels (GFR ≥120 mL/min/1.73 m²) for whom the CKD-EPI equation might have a lower bias. Conclusions We demonstrated that both the EKFC and r-LMR creatinine-based equations have a better performance than the CKD-EPI equation in a young population. The only exception might be in patients with hyperfiltration.