SAFARI Study Research Articles

Sacral nerve stimulation versus the magnetic sphincter augmentation device for adult faecal incontinence: the SaFaRI RCT.

Preliminary studies using the FENIX™ (Torax Medical, Minneapolis, MN, USA) magnetic sphincter augmentation device suggest that it is safe to use for the treatment of adult faecal incontinence, but efficacy data are limited. To compare FENIX with sacral nerve stimulation for the treatment of adult faecal incontinence in terms of safety, efficacy, quality of life and cost-effectiveness. Multicentre, parallel-group, unblinded, randomised trial comparing FENIX with sacral nerve stimulation in participants suffering moderate to severe faecal incontinence. Participants were randomised on an equal basis to either sacral nerve stimulation or FENIX. Follow-up occurred 2 weeks postoperatively and at 6, 12 and 18 months post randomisation. The primary outcome was success, defined as device in use and ≥ 50% improvement in Cleveland Clinic Incontinence Score at 18 months post randomisation. Secondary outcomes included complication rates, quality of life and cost-effectiveness. Between 30 October 2014 and 23 March 2017, 99 participants were randomised across 18 NHS sites (50 participants to FENIX vs. 49 participants to sacral nerve stimulation). The median time from randomisation to FENIX implantation was 57.0 days (range 4.0-416.0 days), and the median time from randomisation to permanent sacral nerve stimulation was 371.0 days (range 86.0-918.0 days). A total of 45 out of 50 participants underwent FENIX implantation and 29 out of 49 participants continued to permanent sacral nerve stimulation. The following results are reported, excluding participants for whom the corresponding outcome was not evaluable. Overall, there was success for 10 out of 80 (12.5%) participants, with no statistically significant difference between the two groups [FENIX 6/41 (14.6%) participants vs. sacral nerve stimulation 4/39 (10.3%) participants]. At least one postoperative complication was experienced by 33 out of 45 (73.3%) participants in the FENIX group and 9 out of 40 (22.5%) participants in the sacral nerve stimulation group. A total of 15 out of 50 (30%) participants in the FENIX group ultimately had to have their device explanted. Slightly higher costs and quality-adjusted life-years (incremental = £305.50 and 0.005, respectively) were observed in the FENIX group than in the sacral nerve stimulation group. This was reversed over the lifetime horizon (incremental = -£1306 and -0.23 for costs and quality-adjusted life-years, respectively), when sacral nerve stimulation was the optimal option (net monetary benefit = -£3283), with only a 45% chance of FENIX being cost-effective. The SaFaRI study was terminated in 2017, having recruited 99 participants of the target sample size of 350 participants. The study is, therefore, substantially underpowered to detect differences between the treatment groups, with significant uncertainty in the cost-effectiveness analysis. The SaFaRI study revealed inefficiencies in the treatment pathways for faecal incontinence, particularly for sacral nerve stimulation. The success of both FENIX and sacral nerve stimulation was much lower than previously reported, with high postoperative morbidity in the FENIX group. Further research is needed to clarify the treatment pathways for sacral nerve stimulation and to determine its true clinical and cost-effectiveness. Current Controlled Trials ISRCTN16077538. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 18. See the NIHR Journals Library website for further project information.

Abstract P3-08-55: Factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study

Abstract Background: To evaluate the survival risk is an important factor to decide or treatment options for recurrent breast cancer patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 negative (HER2−), though there are not enough supporting reports from large-scale databases. The Safari study (UMIN000015168) is a newly conducted retrospective, multicenter cohort study including 1072 ER+ advanced breast cancer Japanese patients treated with fulvestrant 500 mg mostly as a second or later line hormonal therapy. The follow-up data of Safari study is evaluated to focus on any relationship between clinicopathological factors and post-recurrence survival (PRS) in ER+ HER2− recurrent breast cancer patients. Methods: PRS was defined as the duration from the date of initial treatment for recurrent breast cancer to death. The Cox hazards model was used to evaluate the relationship between the clinical factors and PRS. We also performed multivariate analysis on PRS using factors that showed a statistical difference (p < 0.15) in univariate analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) and p-values are described. All tests were two-sided and p<0.05 was considered statistically significant. Results: The main analysis was performed for 1031 cases (96.2%). Ninety four patients with HER2+ status and 53 patients with unknown HER2 status were excluded from this analysis. One hundred seventy-four cases with de novo metastatic or unresectable locally advanced disease were also excluded. Seven hundred ten patients were eligible for the PRS analysis. Median PRS was 7.0 years (95% CI: 6.4-7.6 years). In univariate analysis, the following factors were defined as associated with significantly longer PRS; younger age, earlier treatment line, longer the time from recurrent diagnosis to fulvestrant use, lower nuclear or histological grade (G1/G2/G3), no central nerve metastasis, chemotherapy as initial palliative systemic therapy, longer time to initial palliative chemotherapy, no prior perioperative chemotherapy, no prior perioperative hormonal therapy, and longer period after perioperative hormonal therapy to the diagnosis of recurrence. Recurrence cases after over 1-year perioperative hormonal therapy had better PRS than those after less than 1-year therapy. In multivariate analysis, the following factors were identified to be correlated with longer PRS (median 7.0 years); younger age (< 65 years; p = 0.0002), longer time (≥ 3 years) from recurrent breast cancer diagnosis to fulvestrant treatment (p< 0.001), low nuclear or histological grade (1/3; p< 0.001), chemotherapy as an initial palliative systemic treatment (p = 0.01), longer time to initial palliative chemotherapy (p< 0.0001), and no perioperative chemotherapy (p = 0.02). Kaplan-Meier curve showed that a longer time (≥ 1 year) to subsequent chemotherapy correlated positively with prolonged PRS (median PRS: 10.7 years, 95% CI 8.5-12.3 years vs. 6.3 years, 95% CI 5.9-6.8 years; p < 0.0001). Conclusions: In ER+ HER2− recurrent breast cancer patients who received fulvestrant as their initial or second line palliative treatment, the longer duration to initiate a subsequent chemotherapy positively correlated with longer PRS. Citation Format: Kenjiro Aogi, Hidetoshi Kawaguchi, Norikazu Masuda, Takahiro Nakayama, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-55.

Abstract P5-11-13: Outcomes of fulvestrant therapy among Japanese women with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of the JBCRG-C06 safari study

Abstract Background: After the CONFIRM trial, fulvestrant 500 mg (F500) became a standard treatment for patients with estrogen receptor positive (ER+) advanced/metastatic breast cancer (AMBC). The JBCRG-C06 Safari study (UMIN 000015168) showed that earlier F500 use, a longer time from diagnosis to F500 use, and no prior chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with ER+ and HER2-negative AMBC (Kawaguchi H, et al. Breast Cancer Res Treat, 2017; Kawaguchi H, et al. Curr Med Res Opin, 2018). We had carried out subgroup analyses on real world data from the Safari study focusing on ER+ and HER2+ AMBC with the objective to examine further on potential interactions between TTF and the following: F500 single treatment or F500 with anti-HER2 therapy; presence or absence of visceral metastasis; progesterone receptor (PgR) status; and prior chemotherapy for AMBC. Material & methods: The Safari study was a retrospective, multicenter cohort study, conducted in 1072 patients at 16 sites in Japan for ER+ AMBC. Patients starting treatment with F500 between Nov 2011 and Dec 2014 were registered. After the data cleaning through the central review, 94 patients (9.6%) has been included in this sub-analysis among the 978 patients in which HER2 status was confirmed by the documentation. The relationship between baseline clinical/pathological factors, treatment line, and TTF (time from start to cessation of F500 treatment for any reason, including toxicity and death) were analyzed using Kaplan-Meier methods. Univariate analysis of TTF data was performed by Cox hazards model using: age, histological type, histological/nuclear grade, visceral-metastases, stage, PgR, period from AMBC diagnosis to F500 use, treatment line of F500, prior chemotherapy. Results: Median age at diagnosis of AMBC was 57.5yrs (33-85); 59(33-85) and 56.5(39-75) for F500 with/ without anti-HER2 therapy. Median age of fulvestrant start was 61yrs (35-96). 21.3% had de novo metastatic disease; 78.7% recurrent disease; 37.2% visceral metastases. All patients’ ER status was positive, and PgR status was positive in 65.9%, negative 25.5% respectively. HER2 IHC 3+ patients accounted for 44.7%, IHC 2+/1+ for 38.3%. In the case of IHC 2+/1+, HER2-positivity was confirmed by FISH. F500 alone was administered in 52 patients, while F500 with anti-HER2 therapy in 42 patients. At median follow up of 3.9 years, median TTF was 4.4m (95% CI: 3.3-5.7); 3.7m (95% CI: 2.9-5.9), 5.1m(95% CI: 3.6-6.4) for the F500 alone group, F500 with anti-HER2 therapy group respectively (p = 0.5973). F500 with/ without anti-HER2 therapy was administered in 1stor 2nd-line in 20 (21.3%), and ≥3rd-line in 74(78.7%) patients. Median TTF was 6.6m (95% CI: 4.6-8.5) and 3.7m (95% CI: 2.8-5.2) in the 1stor 2nd-line and ≥3rd-line respectively (p value:0.0145). Although no statistically significant difference was found, TTF tended to be shorter in the group receiving chemotherapy prior to F500 (median TTF: 3.7m vs 5.5m). No other clinical parameters including age, PgR status, metastatic sites were associated with the effectiveness. The median OS was 7.8-years (95% CI: 5.9-9.5), which had not been influenced by with/ without anti-HER2 therapy. The toxicity profile we observed was similar to that in the registration trial. Conclusions: Our findings suggest that F500 with/without anti-HER2 therapy appears to be effective also in the ER+ and HER2-positive ABMC setting which is consistent with the limited results previously published. Earlier line use of F500 use may be useful in HER2-positive patients as well as HER2-negative patients. Citation Format: Misato Hagi, Hidetoshi Kawaguchi, Norikazu Masuda, Shigehira Saji, Yutaka Yamamoto, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Daisuke Yotsumoto, Satoshi Morita, Masakazu Toi, Shinji Ohno. Outcomes of fulvestrant therapy among Japanese women with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of the JBCRG-C06 safari study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-13.

Factors associated with prolonged overall survival in patients with postmenopausal estrogen receptor-positive advanced breast cancer using real-world data: a follow-up analysis of the JBCRG-C06 Safari study

BackgroundAssessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients.MethodsOS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study.ResultsA total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age (< 60 years), longer time from ABC diagnosis to fulvestrant use (≥ 3 years), no prior palliative chemotherapy before fulvestrant use, and progesterone receptor (PgR) negativity (PgR−) were significantly correlated with prolonged OS (median 7.0 years). For cases with histological or nuclear grade data, lower histological or nuclear grades were also correlated with longer OS. In recurrent metastatic cases, long disease-free interval (DFI) was not correlated with longer OS.ConclusionsIn ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR−, and lower histological or nuclear grade correlated positively with prolonged OS.

Sleep apnoea screening for patients with atrial fibrillation: Results of the SAFARI study

Sleep apnoea screening for patients with atrial fibrillation: Results of the SAFARI study

Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study

Background/AimsProspective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect...

2093-P: Acanthosis Nigricans as a Composite Marker of Cardiometabolic Risk and Its Complex Association with Obesity and Insulin Resistance in Mexican-American Children

Acanthosis nigricans (AN) is highly prevalent in Mexican Americans (MAs). It is a strong correlate of obesity, and is considered a marker of insulin resistance (IR). AN is associated with various other cardiometabolic risk factors (CMF). However, the direct causal relationship of IR with AN in obesity has been recently questioned. Therefore, we aimed to assess its genetic and environmental correlations with CMFs and examine the complex causal relationships among the troika of AN, obesity, and IR in MA, using a mediation analysis. As part of our SAFARI Study, we obtained data from 670 nondiabetic MA children, aged 6-17 years (49% girls), BMI percentile median 87 (IQR 60, 97). AN (prevalence 33%) severity scores (range 0-5) were used as a quasi-quantitative trait for analysis. We used the program SOLAR for partitioning phenotypic correlations between AN and CMFs (BMI, HOMA-IR, lipids, blood pressure, hs-C-Reactive Protein (hs-CRP), and Harvard physical fitness score (PFS)). The matrices of genetic and environmental correlations were subsequently used in mediation (direct, indirect and partial) analysis using AMOS program. We computed standardized beta values for effect measurement and goodness-of-fit indices (AIC and BCC) for model comparisons. Heritability of AN was 0.75 (p&amp;lt;0.0001), and it was positively and significantly (p&amp;lt;0.05) correlated with traits such as BMI, HOMA-IR, and hs-CRP, and negatively correlated with HDL-C and PFS. Of the models tested, indirect mediation analysis of BMI -&amp;gt; HOMA-IR -&amp;gt; AN yielded lower goodness-of-fit than a partial mediation model where BMI explained the relationship with both HOMA-IR and AN simultaneously. Using complex models, BMI was associated with AN and IR mediating most of the CMFs; but no relationship between IR and AN. In conclusion, our models suggest that obesity explains the presence of AN and IR, but no causal relationship between IR and AN in Mexican American children. Disclosure J.C. Lopez-Alvarenga: None. R. Arya: None. G. Chittoor: None. S.F. Paul: None. S.R. Puppala: None. V.S. Farook: None. S.P. Fowler: None. R.G. Resendez: None. A. Diaz-Badillo: None. D. Lehman: None. S. Mummidi: None. C. Jenkinson: None. J.L. Lynch: Board Member; Self; American Academy of Pediatrics. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Daiichi Sankyo Company, Limited, National Institutes of Health, Novo Nordisk Inc., Pediatric Diabetes Consortium. R.A. DeFronzo: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Elcelyx Therapeutics, Inc., Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk Inc. J. Blangero: None. D.E. Hale: None. R. Duggirala: None. Funding National Institutes of Health (R01HD049051, HD041111, DK053889, DK042273, K01DK064867, P01HL045522, DK047482, MH059490, M01-RR-01346)

25(OH) vitamin D and functional outcomes in older adults admitted to rehabilitation units: the safari study.

Vitamin D (25(OH)D) deficiency is highly prevalent in older people, and it is associated with poor muscular strength and physical performance. Its impact on functional outcomes during geriatric rehabilitation has been poorly studied. We aim to analyze the association between 25(OH)D and functional recovery in geriatric rehabilitation units. We conducted a prospective multi-center cohort study including patients ≥ 65years old admitted to 3 geriatric rehabilitation units in Italy and Spain, after orthopedic events or stroke. Outcomes were absolute functional gain (AFG, discharge-admission Barthel index) and ability to walk (AW) at 3months after admission. The association between 25(OH)D quartiles (Q1-Q2-Q3-Q4) and outcomes was explored using linear or logistic regression models. We included 420 patients (mean age = 81.2years [SD = 7.7], 66.4% females, mean 25(OH)D concentration = 13.5ng/ml [SD = 8.7]) (to convert to nmol/l multiply by 2.496). A non-linear relationship between 25(OH)D and AFG was found, with a stronger association for 25(OH)D levels < 16ng/ml. Compared to Q1 (25(OH)D ≤ 6ng/ml), participants in Q3 (25(OH)D 11.5-18.2ng/ml) had the best AFG and AW (mean AFG [SD], Q1 = 28.9 [27.8], Q2 = 32.5 [23.5], Q3 = 43.1 [21.9], Q4 = 34.5 [29.3], R2 = 7.3%; AW, Q1-Q2 = 80%, Q3 = 91%, Q4 = 86%). Regression models adjusted for potential confounders confirmed these results (AGF Q2, β = 2.614, p = 0.49; Q3, β = 9.723, p < 0.01; Q4, β = 4.406, p = 0.22; AW Q2, OR [95% CI] = 1.84 [0.67-5.33]; Q3, OR [95% CI] = 4.01 [1.35-13.48]; Q4, OR [95% CI] = 2.18 [0.81-6.21]). In our study, 25(OH)D concentration showed a positive association with functional outcomes at 3months. The association is stronger below the usual cutoff for "deficiency." Dosage of 25(OH)D concentration may help identify geriatric rehabilitation patients at risk for a worse functional recovery.

Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study

Objective: The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2−) cases.Methods: The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2−.Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months).Conclusions: In ER+/HER2− patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

Sleep apnoea screening for patients with atrial fibrillation: interim results from the SAFARI study

Sleep apnoea screening for patients with atrial fibrillation: interim results from the SAFARI study

Patient-Reported Treatment Satisfaction with Rivaroxaban for Stroke Prevention in Atrial Fibrillation. A French Observational Study, the SAFARI Study.

BackgroundFor antithrombotic treatments, Patient Reported Outcomes (PRO) and patient satisfaction with treatment are essential data for physicians because of the strong relationship between patient satisfaction and adherence to treatment. The impact of rivaroxaban on patient satisfaction and quality of life was not sufficiently documented in phase III studies. There is a need for further data in this field especially in real life conditions.MethodsThe SAFARI study is composed of patients with non-valvular atrial fibrillation (AF), previously treated with vitamin K antagonist (VKA) and switched to rivaroxaban. Patient satisfaction with anticoagulant therapy was measured by the Anti-Clot Treatment Scale (ACTS), a validated 15-item patient-reported scale including a 12-item ACTS Burdens scale and a 3-item ACTS Benefits scale. Satisfaction of medication was compared between baseline and 1, 3 and 6 months.ResultsStudy population was composed of 405 patients. Mean age was 74.8 (standard deviation = 9.0) years and 63.0% were male. Mean CHA2DS2-VASc score was 3.4 (1.5) and mean HAS-BLED score was 2.9 (1.0). After 3 months of treatment with rivaroxaban, patient satisfaction improved compared with VKA: mean ACTS burdens scores significantly increased by 8.3 (8.9) points (p<0.0001) and ACTS benefits scale by 0.4 (2.9) (p<0.001). Compared with baseline, the improvement in ACTS burdens and benefits became apparent at 1 month (46.5 vs. 53.6 p<0.001 and 10.4 vs. 10.7, p<0.05 respectively) and persisted at 6 months (46.5 vs. 54.76 p<0.001 and 10.4 vs. 10.8 p = 0.02 respectively). Rivaroxaban persistence was 88.7% at 6 months.ConclusionsSAFARI data support a good risk-benefit balance for rivaroxaban, with a good safety profile and encourage PRO design studies. The switch from VKA to rivaroxaban improved patient satisfaction at 1, 3 and 6 months after rivaroxaban initiation among patients with AF, particularly in reducing patient-reported anticoagulation burden.

Genetic epidemiology of cardiometabolic risk factors and their clustering patterns in Mexican American children and adolescents: the SAFARI Study

Pediatric metabolic syndrome (MS) and its cardiometabolic components (MSCs) have become increasingly prevalent, yet little is known about the genetics underlying MS risk in children. We examined the prevalence and genetics of MS-related traits among 670 non-diabetic Mexican American (MA) children and adolescents, aged 6-17years (49% female), who were participants in the San Antonio Family Assessment of Metabolic Risk Indicators in Youth study. These children are offspring or biological relatives of adult participants from three well-established Mexican American family studies in San Antonio, TX, at increased risk of type 2 diabetes. MS was defined as ≥3 abnormalities among 6 MSC measures: waist circumference, systolic and/or diastolic blood pressure, fasting insulin, triglycerides, HDL-cholesterol, and fasting and/or 2-h OGTT glucose. Genetic analyses of MS, number of MSCs (MSC-N), MS factors, and bivariate MS traits were performed. Overweight/obesity (53%), pre-diabetes (13%), acanthosis nigricans (33%), and MS (19%) were strikingly prevalent, as were MS components, including abdominal adiposity (32%) and low HDL-cholesterol (32%). Factor analysis of MS traits yielded three constructs: adipo-insulin-lipid, blood pressure, and glucose factors, and their factor scores were highly heritable. MS itself exhibited 68% heritability. MSC-N showed strong positive genetic correlations with obesity, insulin resistance, inflammation, and acanthosis nigricans, and negative genetic correlation with physical fitness. MS trait pairs exhibited strong genetic and/or environmental correlations. These findings highlight the complex genetic architecture of MS/MSCs in MA children, and underscore the need for early screening and intervention to prevent chronic sequelae in this vulnerable pediatric population.