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Background Rhabdomyosarcoma (RMS) is an aggressive soft tissue sarcoma that most often develops in children. Chemoradiation therapy is a standard treatment modality; however, the detrimental long-term skeletal muscle consequences of this therapy in juvenile cancer survivors include muscle atrophy and fibrosis resulting in decreased physical performance. Using a novel model of murine resistance and endurance exercise training, we investigate its role in preventing the long-term effects of juvenile RMS plus therapy. Methods Four-week-old male (n = 10) and female (n = 10) C57Bl/6J mice were injected with M3-9-M RMS cell into the left gastrocnemius with the right limb serving as an internal control (CON). Mice received a systemic vincristine injection and then five doses of 4.8 Gy of gamma radiation localized to the left hindlimb (RMS + Tx). Mice were then randomly divided into either sedentary (SED) or resistance and endurance exercise training (RET) groups. Changes in exercise performance, body composition, myocellular adaptations and the inflammatory/fibrotic transcriptome were assessed. Results RET improved endurance performance (P < 0.0001) and body composition (P = 0.0004) compared to SED. RMS + Tx resulted in significantly lower muscle weight (P = 0.015) and significantly smaller myofibre cross-sectional area (CSA) (P = 0.014). Conversely, RET resulted in significantly higher muscle weight (P = 0.030) and significantly larger Type IIA (P = 0.014) and IIB (P = 0.015) fibre CSA. RMS + Tx resulted in significantly more muscle fibrosis (P = 0.028), which was not prevented by RET. RMS + Tx resulted in significantly fewer mononuclear cells (P < 0.05) and muscle satellite (stem) cells (MuSCs) (P < 0.05) and significantly more immune cells (P < 0.05) than CON. RET resulted in significantly more fibro-adipogenic progenitors (P < 0.05), a trend for more MuSCs (P = 0.076) than SED and significantly more endothelial cells specifically in the RMS + Tx limb. Transcriptomic changes revealed significantly higher expression of inflammatory and fibrotic genes in RMS + Tx, which was prevented by RET. In the RMS + Tx model, RET also significantly altered expression of genes involved in extracellular matrix turnover. Conclusions Our study suggests that RET preserves muscle mass and performance in a model of juvenile RMS survivorship while partially restoring cellular dynamics and the inflammatory and fibrotic transcriptome.

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OBJECTIVE To evaluate glycemic outcomes in youth (aged 13–25 years) with type 1 diabetes and high-risk glycemic control (HbA1c ≥8.5% [69 mmol/mol]) on multiple daily injection (MDI) therapy after transitioning to advanced hybrid closed loop (AHCL) therapy. RESEARCH DESIGN AND METHODS This prospective, 3-month, single-arm, dual-center study enrolled 20 participants, and all completed the study. RESULTS HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol), and time spent in target range 70–180 mg/dL (3.9–10.0 mmol/L) increased from 27.6 ± 13.2% at baseline to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. CONCLUSIONS AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI therapy.

Background: Open-source automated insulin delivery (AID) is a user-driven treatment modality used by thousands globally. Healthcare professionals' (HCPs) ability to support users of this technology is limited by a lack of knowledge of these systems. Aims: To describe the challenges experienced by HCPs supporting participants' use of open-source automated insulin delivery in the Community deRivEd AuTomatEd insulin delivery (CREATE) study. Methods: Data were collected prospectively from the study team's fortnightly meetings and Slack Workspace (Slack Technologies, Ltd. 2018) during the first 4 months of the trial. Key topics were identified from minutes of meetings. Slack conversations were categorised by topic, with the number of posts per conversation, number of sites per conversation and involvement of experts in open-source AID being recorded. Results: In the first 4 months of the trial, there were 254 conversations in Slack with a mean of 5.2 (±4.25) posts per conversation. The most frequent learning challenge was insulin pump and cannula problems relating to the DANA-i TM insulin pump, which totalled 24.0% of all conversations. Experts on open-source AID use were involved in 83.3% of conversations. Conclusions: A significant proportion of challenges related to specific devices, rather than AID. Challenges relating to the functioning of open-source AID were more likely to involve input from experts in open-source AID. This is the first report of challenges experienced by a multidisciplinary team in a supported opensource environment that may inform expectations in routine clinical care.

Purpose Open-source automated insulin delivery (AID) is used by thousands of people with type 1 diabetes (T1D), but has unknown generalisability to marginalised ethnic groups. This study explored experiences of Indigenous Māori participants in the CREATE trial with use of an open-source AID system to identify enablers/barriers to health equity. Methods The CREATE randomised trial compared open-source AID (OpenAPS algorithm on an Android phone with a Bluetooth-connected pump) to sensor-augmented pump therapy. Kaupapa Māori Research methodology was used in this sub-study. Ten semi-structured interviews with Māori participants (5 children, 5 adults) and whānau (extended family) were completed. Interviews were recorded and transcribed, and data were analysed thematically. NVivo was used for descriptive and pattern coding. Results Enablers/barriers to equity aligned with four themes: access (to diabetes technologies), training/support, operation (of open-source AID), and outcomes. Participants described a sense of empowerment, and improved quality of life, wellbeing, and glycaemia. Parents felt reassured by the system’s ability to control glucose, and children were granted greater independence. Participants were able to use the open-source AID system with ease to suit whānau needs, and technical problems were manageable with healthcare professional support. All participants identified structures in the health system precluding equitable utilisation of diabetes technologies for Māori. Conclusion Māori experienced open-source AID positively, and aspired to use this therapy; however, structural and socio-economic barriers to equity were identified. This research proposes strength-based solutions which should be considered in the redesign of diabetes services to improve health outcomes for Māori with T1D. Trial Registration: The CREATE trial, encompassing this qualitative sub-study, was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000034932p) on the 20th January 2020.

<p>  </p> <p>Objective: To evaluate glycemic outcomes in youth (aged 13–25 years) with type 1 diabetes and high-risk glycemic control [HbA1c ≥ 8.5% (69 mmol/mol)] on multiple daily injections (MDI) after transitioning to advanced hybrid closed-loop (AHCL) therapy. </p> <p>Research Design and Methods: This prospective 3-month single-arm, dual-center study enrolled 20 participants, and all completed the study. </p> <p>Results: HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol) and time spent in target range 70–180 mg/dL (3.9–10.0 mmol/L) increased from 27.6 ± 13.2% at baseline, to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. </p> <p>Conclusions: AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI.</p>

<p>  </p> <p>Objective: To evaluate glycemic outcomes in youth (aged 13–25 years) with type 1 diabetes and high-risk glycemic control [HbA1c ≥ 8.5% (69 mmol/mol)] on multiple daily injections (MDI) after transitioning to advanced hybrid closed-loop (AHCL) therapy. </p> <p>Research Design and Methods: This prospective 3-month single-arm, dual-center study enrolled 20 participants, and all completed the study. </p> <p>Results: HbA1c decreased from 10.5 ± 2.1% (91.2 ± 22.8 mmol/mol) at baseline to 7.6 ± 1.1% (59.7 ± 11.9 mmol/mol) and time spent in target range 70–180 mg/dL (3.9–10.0 mmol/L) increased from 27.6 ± 13.2% at baseline, to 66.5 ± 9.8% after 3 months of AHCL. Two episodes of diabetic ketoacidosis attributed to infusion set failure occurred. </p> <p>Conclusions: AHCL has the potential to improve suboptimal glycemia in youth with type 1 diabetes previously on MDI.</p>