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Expandable endoprostheses can be used to equalize limb length for pediatric patients requiring reconstruction following large bony oncologic resections. Outcomes of the Compress® Compliant Pre-Stress (CPS) spindle paired with an Orthopedic Salvage System expandable distal femur endoprosthesis have not been reported.We conducted a multi-institutional retrospective study of pediatric patients with distal femoral bone sarcomas reconstructed with the above endoprostheses. Statistical analysis utilized Kaplan-Meier survival technique and competing risk analysis.Thirty-six patients were included from five institutions. Spindle survivorship was 86.3% (95% confidence interval [CI], 67.7-93.5) at 10 years. Two patients had a failure of osseointegration (5.7%), both within 12 months. Twenty-two (59%) patients had 70 lengthening procedures, with mean expansions of 3.2 cm (range: 1-9) over 3.4 surgeries. The expandable mechanism failed in eight patients with a cumulative incidence of 16.1% (95% CI, 5.6-31.5) at 5 years. Twenty-nine patients sustained International Society of Limb Salvage failures requiring 63 unplanned surgeries. Periprosthetic joint infection occurred in six patients (16.7%). Limb preservation rate was 91% at 10 years.There is a high rate of osseointegration of the Compress® spindle among pediatric patients when coupled with an expandable implant. However, there is a high rate of expansion mechanism failure and prosthetic joint infections requiring revision surgery.Level IV, therapeutic study.

The tumor microenvironment contributes to tumorigenesis, disease progression, and response to therapy in soft tissue sarcomas (STSs). However, characterizing the malignant and stromal cells that make up STSs and correlating their abundance with clinical outcomes has proven difficult in fixed clinical specimens. We employed a machine learning framework called EcoTyper (Luca et al. Cell 2021) to identify cell type-specific transcriptional states and define tumor ecotypes consisting of co-occurring cell states from bulk transcriptomes. Analyzing 292 previously published STSs profiled by bulk RNA-sequencing (RNA-Seq), we identified 23 transcriptionally-defined sarcoma cell states in malignant, immune, and other stromal cells and validated the majority of these cell states using single cell RNA-Seq. Although sarcomas originate from mesenchymal tissues, we identified four epithelial-like sarcoma cell states and observed epithelial differentiation and expression of epithelial markers within malignant sarcoma cells across histologies. Cell states reflected known and novel cell phenotypes and many were strongly associated with patient outcomes in our RNA-Seq training cohort and an independent validation cohort of STSs profiled by microarray (n=309). By identifying co-occurring cell states across STSs, we discovered 3 sarcoma ecotypes associated with underlying genomic alterations and distinct clinical outcomes. On spatial transcriptomic analysis, we observed co-localization of cell states within the same sarcoma ecotypes and spatial aggregation of ecotypes within STSs, suggesting that sarcoma ecotypes represent distinct functional units within human sarcomas. One ecotype (sarcoma ecotype 3: SE3) defined by CLEC5A/SPP1+ M2-like immunosuppressive macrophages and MYC/MTORC1-activated epithelial-like malignant cells was associated with inferior progression-free survival (PFS) in the RNA-Seq training cohort (P=0.01) and inferior metastasis-free survival in the microarray validation cohort (P=0.002). Remarkably, SE3 was associated with improved PFS in patients with metastatic STSs treated with ipilimumab and nivolumab (n=38, P=0.003) but not patients treated with chemotherapy. Furthermore, SE3 outperformed previously reported predictors of immunotherapy response in STSs, PD-L1 expression and tertiary lymphoid structures (TLS), for predicting response to immunotherapy (AUCs: SE3 0.87; PD-L1 0.81; TLS 0.62). Finally, SE3 similarly predicted response to immunotherapy in an independent validation cohort (n=29, AUC 0.89). In summary, our findings provide a high-resolution cell atlas of STSs to guide the development of novel therapeutic strategies. In addition, we have identified a predictive biomarker of response to immune checkpoint inhibition that may enable personalization of systemic therapy in patients with advanced STSs. Citation Format: Ajay Subramanian, Neda Nemat-Gorgani, Timothy J. Ellis-Caleo, David G.P. van IJzendoorn, Timothy J. Sears, Anish Somani, Bogdan A. Luca, Maggie Y. Zhou, Martina Bradic, Ileana A. Torres, Eniola Oladipo, Christin New, Deborah E. Kenney, Raffi S. Avedian, Robert J. Steffner, Michael S. Binkley, David G. Mohler, William D. Tap, Sandra P. D’Angelo, Matt van de Rijn, Kristen N. Ganjoo, Nam Q. Bui, Gregory W. Charville, Aaron M. Newman, Everett J. Moding. Identification and validation of sarcoma cellular ecosystems associated with prognosis and predictive of immunotherapy response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5960.

Aim This study aimed to capture the experience of parents of youth with recent onset Type 1 diabetes who initiated use of continuous glucose monitoring (CGM) technology soon after diagnosis, which is a new practice. Methods Focus groups and individual interviews were conducted with parents of youth with Type 1 diabetes who had early initiation of CGM as part of a new clinical protocol. Interviewers used a semi-structured interview guide to elicit feedback and experiences with starting CGM within 30 days of diagnosis, and the benefits and barriers they experienced when adjusting to this technology. Groups and interviews were audio recorded, transcribed and analysed using content analysis. Results Participants were 16 parents (age 44.13 ± 8.43 years; 75% female; 56.25% non-Hispanic White) of youth (age 12.38 ± 4.15 years; 50% female; 50% non-Hispanic White; diabetes duration 10.35 ± 3.89 months) who initiated CGM 11.31 ± 7.33 days after diabetes diagnosis. Overall, parents reported high levels of satisfaction with starting CGM within a month of diagnosis and described a high level of reliance on the technology to help manage their child's diabetes. All participants recommended early CGM initiation for future families and were committed to continue using the technology for the foreseeable future, provided that insurance covered it. Conclusion Parents experienced CGM initiation shortly after their child's Type 1 diabetes diagnosis as a highly beneficial and essential part of adjusting to living with diabetes.

CGM use is associated with lower HbA1c in people with T1D. We hypothesize early CGM initiation will improve longer term HbA1c. Youth with newly diagnosed T1D from July 2018 to May 2019 (pilot cohort, n=65), were offered CGM initiation in the 1st month of T1D diagnosis with 62 initiating CGM. We compared HbA1c outcomes in this pilot cohort with those diagnosed in 2014-2016 (control cohort, n=272) with follow-up duration restricted to 15 months. HbA1c trajectories were visualized using locally estimated scatter plot smoothing (Figure 1) and compared using a generalized mixed effects regression model adjusted for baseline characteristics (HbA1c at onset, age, sex, race and insurance type). Mean HbA1c at diagnosis was higher in the pilot cohort (12.0% vs. 10.7%). Over the first 15 months of T1D, CGM was initiated in 95% of the pilot cohort (78.5% within 30 days), whereas 56% initiated in the control cohort (1.8% within 30 days). Adjusting for baseline characteristics, mean HbA1c levels were 0.5% lower (95%CI: -1.0, -0.1) in the pilot cohort at 3 months and 1.7% lower (95% CI: -2.6, -0.8) at 6 months compared to the control cohort. Differences beyond 6 months were also in the expected direction and statistically significant at the 0.05 level. Early initiation of CGM in the new onset period was associated with lower HbA1c compared to historic controls. These data suggest that early CGM initiation should be considered a part of standard new onset T1D care. Disclosure P. Prahalad: None. V. Ding: None. A. Addala: None. C. New: None. B.P. Conrad: None. A. Chmielewski: None. E. Geels: None. J. Leverenz: None. A. Martinez-Singh: None. P. Sagan: None. J. Senaldi: None. A. Freeman: None. D. Scheinker: None. K.K. Hood: Research Support; Self; Dexcom, Inc. Speaker’s Bureau; Self; LifeScan, Inc., MedIQ. M. Desai: None. D.M. Maahs: Advisory Panel; Self; Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk A/S. Consultant; Self; Abbott, Sanofi. Research Support; Self; Bigfoot Biomedical, Dexcom, Inc., Roche Diabetes Care, Tandem Diabetes Care.

Objective US Hispanics bear a disproportionate burden of excess body weight and associated morbidity, making obesity prevention and control in this population a public health priority. Development of culturally appropriate weight loss interventions requires understanding the influence of acculturation on attitudes and behavior related to obesity and weight loss. Design and Methods Using data from the National Health and Nutrition Examination Survey (2001–2004), we analyzed the associations of country of birth and language usage with weight perception, weight dissatisfaction, intention to lose weight, and intended weight loss of clinical significance among obese Hispanic adults (>20 years of age; unweighted n = 675) in multivariable logistic regression analyses. Results US birth was significantly associated with correct weight perception (odds ratio [OR], 4.45; 95% confidence interval [CI], 2.16–9.17) and weight dissatisfaction (OR = 2.95; 95% CI = 1.63–5.35). Compared with Spanish-speaking only, obese Hispanics, bilingual, obese Hispanics were more likely to attempt weight loss (OR = 2.78; 95% CI = 1.43–5.40) and achieve clinically significant weight loss (OR = 3.94; 95% CI = 1.51–10.3). Conclusions The findings suggest that lack of acculturation as measured by foreign birth and limited English proficiency may contribute to within-ethnicity health inequality among obese Hispanics, even after controlling for a variety of sociodemographic characteristics, including education and income, differential healthcare access and use, and health status. Further studies should examine the underlying mechanisms, thereby informing culturally competent intervention strategies targeted at obese US Hispanics.

US Hispanics bear a disproportionate burden of excess body weight and associated morbidity, making obesity prevention and control in this population a public health priority. Development of culturally appropriate weight loss interventions requires understanding the influence of acculturation on attitudes and behavior related to obesity and weight loss.Using data from the National Health and Nutrition Examination Survey (2001-2004), we analyzed the associations of country of birth and language usage with weight perception, weight dissatisfaction, intention to lose weight, and intended weight loss of clinical significance among obese Hispanic adults (20 years of age; unweighted n = 675) in multivariable logistic regression analyses.US birth was significantly associated with correct weight perception (odds ratio [OR], 4.45; 95% confidence interval [CI], 2.16-9.17) and weight dissatisfaction (OR = 2.95; 95% CI = 1.63-5.35). Compared with Spanish-speaking only, obese Hispanics, bilingual, obese Hispanics were more likely to attempt weight loss (OR = 2.78; 95% CI = 1.43-5.40) and achieve clinically significant weight loss (OR = 3.94; 95% CI = 1.51-10.3).The findings suggest that lack of acculturation as measured by foreign birth and limited English proficiency may contribute to within-ethnicity health inequality among obese Hispanics, even after controlling for a variety of sociodemographic characteristics, including education and income, differential healthcare access and use, and health status. Further studies should examine the underlying mechanisms, thereby informing culturally competent intervention strategies targeted at obese US Hispanics.