24-h energy expenditure in people with type 1 diabetes: impact on equations for clinical estimation of energy expenditure.

BACKGROUND/OBJECTIVES: Type 1 diabetes (T1D) is associated with an increase in resting metabolic rate (RMR), but the impact of T1D on other components of 24-h energy expenditure (24-h EE) is not known. Also, there is a lack of equations to estimate 24-h EE in patients with T1D. The aims of this analysis were to compare 24-h EE and its components in young adults with T1D and healthy controls across the spectrum of body mass index (BMI) and derive T1D-specific equations from clinical variables. SUBJECTS/METHODS: Thirty-three young adults with T1D diagnosed ≥1 year prior and 33 healthy controls matched for sex, age and BMI were included in this analysis. We measured 24-h EE inside a whole room indirect calorimeter (WRIC) and body composition with dual x-ray absorptiometry. RESULTS: Participants with T1D had significantly higher 24-h EE than healthy controls (T1D = 2047 ± 23 kcal/day vs control= 1908 ± 23 kcal/day; P < 0.01). We derived equations to estimate 24-h EE with both body composition (fat free mass + fat mass) and anthropometric (weight + height) models, which provided high coefficients of determination (R2 = 0.912 for both). A clinical model that did not incorporate spontaneous physical activity yielded high coefficients of determination as well (R2 = 0.897 and R2 = 0.880 for body composition and anthropometric models, respectively). CONCLUSION: These results confirm that young adults with established T1D have increased 24-h EE relative to controls without T1D. The derived equations from clinically available variables can assist clinicians with energy prescriptions for weight management in patients with T1D.

A machine learning approach to predict mortality due to immune-mediated thrombotic thrombocytopenic purpura.

Background: Mortality due to immune-mediated thrombotic thrombocytopenic purpura (iTTP) remains significant. Predicting mortality risk may potentially help individualize treatment. The French Thrombotic Microangiopathy (TMA) Reference Score has not been externally validated in the United States. Recent advances in machine learning technology can help analyze large numbers of variables with complex interactions for the development of prediction models. Objectives: To validate the French TMA Reference Score in the United States Thrombotic Microangiopathy (USTMA) iTTP database and subsequently develop a novel mortality prediction tool, the USTMA TTP Mortality Index. Methods: We analyzed variables available at the time of initial presentation, including demographics, symptoms, and laboratory findings. We developed our model using gradient boosting machine, a machine learning ensemble method based on classification trees, implemented in the R package gbm. Results: In our cohort (n = 419), the French score predicted mortality with an area under the receiver operating characteristic curve of 0.63 (95% CI: 0.50-0.77), sensitivity of 0.35, and specificity of 0.84. Our gradient boosting machine model selected 8 variables to predict acute mortality with a cross-validated area under the receiver operating characteristic curve of 0.77 (95% CI: 0.71-0.82). The 2 cutoffs corresponded to sensitivities of 0.64 and 0.50 and specificities of 0.76 and 0.87, respectively. Conclusion: The USTMA Mortality Index was acceptable for predicting mortality due to acute iTTP in the USTMA registry, but not sensitive enough to rule out death. Identifying patients at high risk of iTTP-related mortality may help individualize care and ultimately improve iTTP survival outcomes. Further studies are needed to provide external validation. Our model is one of many recent examples where machine learning models may show promise in clinical prediction tools in healthcare.

Assessing ChatGPT's Responses to Otolaryngology Patient Questions.

OBJECTIVE: This study aims to evaluate ChatGPT's performance in addressing real-world otolaryngology patient questions, focusing on accuracy, comprehensiveness, and patient safety, to assess its suitability for integration into healthcare. METHODS: A cross-sectional study was conducted using patient questions from the public online forum Reddit's r/AskDocs, where medical advice is sought from healthcare professionals. Patient questions were input into ChatGPT (GPT-3.5), and responses were reviewed by 5 board-certified otolaryngologists. The evaluation criteria included difficulty, accuracy, comprehensiveness, and bedside manner/empathy. Statistical analysis explored the relationship between patient question characteristics and ChatGPT response scores. Potentially dangerous responses were also identified. RESULTS: Patient questions averaged 224.93 words, while ChatGPT responses were longer at 414.93 words. The accuracy scores for ChatGPT responses were 3.76/5, comprehensiveness scores were 3.59/5, and bedside manner/empathy scores were 4.28/5. Longer patient questions did not correlate with higher response ratings. However, longer ChatGPT responses scored higher in bedside manner/empathy. Higher question difficulty correlated with lower comprehensiveness. Five responses were flagged as potentially dangerous. CONCLUSION: While ChatGPT exhibits promise in addressing otolaryngology patient questions, this study demonstrates its limitations, particularly in accuracy and comprehensiveness. The identification of potentially dangerous responses underscores the need for a cautious approach to AI in medical advice. Responsible integration of AI into healthcare necessitates thorough assessments of model performance and ethical considerations for patient safety.

Adolescents and young adults (AYA) with cancer: the clinical course of COVID-19 infections.

Adolescents and Young Adults (AYAs: 15-39 y) with cancer face unique vulnerabilities, yet remain under-represented on clinical trials, including adult registries of COVID-19 in cancer (AYAs: 8-12%). Thus, we leveraged the Pediatric Oncology COVID-19 Case Report (POCC) to examine the clinical course of COVID-19 among AYAs with cancer. POCC collects de-identified clinical and sociodemographic data regarding 0-39yo with cancer (AYAs = 37%) and COVID-19 from >100 institutions. Between 04/01/2020-11/28/2023, 191 older AYAs [22-39y] and 640 younger AYAs [15-21y] were captured. Older AYAs were less often hospitalized (p < .001), admitted to the intensive care unit (ICU, p = .02), and/or required respiratory support (p = .057). In multivariable analyses, older AYAs faced 80% lower odds of ICU admission but 2.3-times greater odds of changes to cancer-directed therapy. Unvaccinated patients had 5.4-times higher odds of ICU admission. Among AYAs with cancer, the COVID-19 course varies by age. These findings can inform pediatric/adult oncology teams surrounding COVID-19 management and prevention.

Estimating the Impact of Rurality in Disparities in Cancer Mortality.

PURPOSE: Estimation of the independent effect of rurality on cancer mortality requires causal inference methodology and consideration of area-level socioeconomic status and rural designations. METHODS: Using SEER data, we identified key incident cancers diagnosed between 2000 and 2016 at age ≥20 years (N = 3,788,273), examining a 20% random sample (n = 757,655). Standardized competing risk and survival models estimated the association between rural residence, defined by Rural-Urban Continuum Codes, and cancer-specific and all-cause mortality, controlling for age at cancer diagnosis, sex, race/ethnicity, year of diagnosis, and Area Deprivation Index (ADI). We estimated the attributable fraction (AF) of rurality and high ADI (ADI > median) to the probability of mortality. Finally, we examined county measurement issues contributing to mortality rates discordant from hypothesized rates. RESULTS: The 5-year standardized failure probability for cancer mortality for rural patients was 33.9% versus 31.56% for urban. The AF for rural residence was 1.04% at year 1 (0.89% by year 5), the highest among local stage disease (Y1 2.1% to Y5 1.9%). The AF for high ADI was 3.33% in Y1 (2.87% in Y5), while the joint effect of rural residence and high ADI was 4.28% in Y1 (3.71% in Y5). Twenty-two percent of urban counties and 30% of rural were discordant. Among discordant urban counties, 30% were only considered urban because of adjacency to metro area. High ADI was associated with urban discordance and low ADI with rural discordance. CONCLUSION: Rural residence independently contributes to cancer mortality. The rural impact is the greatest among those with localized disease and in high deprivation areas. Rural-urban county designations may mask high-need urban counties, limiting eligibility to state and federal resources dedicated to rural areas.

Nutritional Status, Dietary Intake, and Nutrition-Related Interventions Among Older Adults With Type 1 Diabetes: A Systematic Review and Call for More Evidence Toward Clinical Guidelines.

There is an emerging population of older adults (≥65 years) living with type 1 diabetes. Optimizing health through nutrition during this life stage is challenged by multiple and ongoing changes in diabetes management, comorbidities, and lifestyle factors. There is a need to understand nutritional status, dietary intake, and nutrition-related interventions that may maximize well-being throughout the life span in type 1 diabetes, in addition to nutrition recommendations from clinical guidelines and consensus reports. Three reviewers used Cochrane guidelines to screen original research (January 1993-2023) and guidelines (2012-2023) in two databases (MEDLINE and CENTRAL) to characterize nutrition evidence in this population. We found limited original research explicitly focused on nutrition and diet in adults ≥65 years of age with type 1 diabetes (six experimental studies, five observational studies) and meta-analyses/reviews (one scoping review), since in the majority of analyses individuals ≥65 years of age were combined with those age ≥18 years, with diverse diabetes durations, and also individuals with type 1 and type 2 diabetes were combined. Further, existing clinical guidelines (n = 10) lacked specificity and evidence to guide clinical practice and self-management behaviors in this population. From a scientific perspective, little is known about nutrition and diet among older adults with type 1 diabetes, including baseline nutrition status, dietary intake and eating behaviors, and the impact of nutrition interventions on key clinical and patient-oriented outcomes. This likely reflects the population's recent emergence and unique considerations. Addressing these gaps is foundational to developing evidence-based nutrition practices and guidelines for older adults living with type 1 diabetes.

Bullet holes: A novel model to identify the most impactful gaps in the firearm homicide prevention laws of each state.

BACKGROUND: Firearm homicides (FH) are a major cause of mortality in the United States (US). Firearm law implementation is variable across states, and legislative gaps may represent opportunities for FH prevention. For each state, we sought to identify which firearm law category would have been most effective if implemented and how effective it would have been. METHODS: We conducted a retrospective cohort study examining the effects of firearm laws on FH rates in the 48 contiguous US states 2010-2019. Data were obtained from the CDC WONDER and FBI UCR databases, State Firearm Law Database, and US Census. Firearm laws were grouped into 14 categories. We assessed the association between the presence of each law category and FH rate as an incidence rate ratio (IRR) using a Poisson regression accounting for state population characteristics and laws of surrounding states. We estimated the IRR for each state that did not have a given law category present and determined which of these missing law categories would have been associated with the greatest reduction in FH rate. RESULTS: FH rates varied widely across states and increased from a mean of 3.2 (SD = 1.7) to 4.2 (SD = 2.9) FH per 100,000. All law categories were significantly associated with decreased FH rate (p < 0.05), with IRR ranging from 0.25-0.85. The most effective missing law category differed between states but was most commonly child access prevention (34.09% of states), assault weapons and large-capacity magazines (15.91%), preemption (15.91%), and concealed carry permitting (13.64%). In total across 2010-2019, we estimated that 129,599 fewer FH would have occurred with enactment of the most effective missing law category in each state. CONCLUSIONS: Modeling firearm law prevention of FH with regard to state legislative and population characteristics can identify the highest impact missing law categories in each state. These results can be used to inform efforts to reduce FH. LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological.

Variation in coupling across neural and cardiac systems of regulation is linked to markers of anxiety risk in preschool.

Both cortical and parasympathetic systems are believed to regulate emotional arousal in the service of healthy development. Systemic coordination, or coupling, between putative regulatory functions begins in early childhood. Yet the degree of coupling between cortical and parasympathetic systems in young children remains unclear, particularly in relation to the development of typical or atypical emotion function. We tested whether cortical (ERN) and parasympathetic (respiratory sinus arrhythmia [RSA]) markers of regulation were coupled during cognitive challenge in preschoolers (N = 121). We found no main effect of RSA predicting ERN. We then tested children's typical and atypical emotion behavior (context-appropriate/context-inappropriate fear, anxiety symptoms, neuroendocrine reactivity) as moderators of early coupling in an effort to link patterns of coupling to adaptive emotional development. Negative coupling (i.e., smaller ERN, more RSA suppression or larger ERN, less RSA suppression) at age 3 was associated with greater atypical and less typical emotion behaviors, indicative of greater risk. Negative age 3 coupling was also visible for children who had greater Generalized Anxiety Disorder symptoms and blunted cortisol reactivity at age 5. Results suggest that negative coupling may reflect a maladaptive pattern across regulatory systems that is identifiable during the preschool years.

Advances in Automated Insulin Delivery with the Medtronic 780G: The Australian Experience.

Aim: To assess the real-world performance of MiniMed™ 780G for Australians with type 1 diabetes (T1D) following advanced hybrid closed loop (AHCL) activation and to evaluate the effect of changing from MiniMed 670/770G to 780G. Methods: We analyzed deidentified Carelink™ continuous glucose monitoring (CGM) data from Australian users from January 2020 to December 2022, including the proportion attaining three major consensus targets: Glucose management indicator (GMI <7.0%), time in range (TIR 70-180 mg/dL >70%), and time below range (TBR 70 mg/dL <4%). Results: Comparing 670/770G users (n = 5676) for mean ± standard deviation 364 ± 244 days with 780G users (n = 3566) for 146 ± 145 days, the latter achieved a higher TIR (72.6% ± 10.6% vs. 67.3% ± 11.4%; P < 0.001), lower time above range (TAR) (25.5% ± 10.9% vs. 30.6% ± 11.7%; P < 0.001), and lower GMI (6.9% ± 0.4% vs. 7.2% ± 0.4%; P < 0.001) without compromising TBR (1.9% ± 1.8% vs. 2.0% ± 1.8%; P = 0.0015). Of 1051 670/770G users transitioning to 780G, TIR increased (70.0% ± 10.7% to 74.0% ± 10.2%; P < 0.001), TAR decreased (28.1% ± 10.9% to 24.0% ± 10.7%; P < 0.001), and TBR was unchanged. The percentage of users attaining all three CGM targets was higher in 780G users (50.1% vs. 29.5%; P < 0.001). CGM metrics were stable at 12 months post-transition. Conclusion: Real-world data from Australia shows that a higher proportion of MiniMed 780G users meet clinical targets for CGM consensus metrics compared to MiniMed 670/770G users and glucose control was sustained over 12 months.

Femoral Neck Anteversion: Which Distal Femur Landmark Matters?

Background: Femoral neck anteversion has traditionally been measured by the angle between the distal femur posterior condylar axis (PCA) and a line drawn through the center of the femoral head and neck. While less common, the transepicondylar axis (TEA) has also been used to reference femoral neck anteversion. The purpose of this study was to compare femoral neck version of the PCA vs the TEA using computerized tomography (CT). Methods: A total of 1507 femoral CTs were included. Precise bony landmarks were established: lateral epicondyle, medial epicondyle, posteromedial condyle, posterolateral condyle, center of the femoral neck, and center of the femoral head. Femoral version was calculated between the head and neck axis and either the PCA or TEA. Differences between sex and ethnicity were evaluated. Results: The mean femoral anteversion was 12.7° ± 9.1° based on the PCA and 11.5° ± 7.9° based on the TEA (mean difference 1.2° ± 1.9°, P < .001). Males were less anteverted than females (9.8° ± 7.6° vs 13.5° ± 7.8°, P < .001). African Americans had less anteversion than other groups (8.1° ± 9.2° vs 11.5° ± 7.8°, P = .04), while Asians were more anteverted than other groups (12.1° ± 9.0° vs 11.2° ± 7.3°, P = .04). These values were referenced on the TEA. Conclusions: In this series of over 1500 femoral CT scans, the mean difference between anteversion measurements referencing the PCA and TEA was 1.2°. Native femoral version varied widely between gender and ethnic groups. Extreme femoral version, defined as <0° or >30°, was present in 11.8% of patients referencing the PCA.

A Single Arm Phase 2 Trial of Trametinib in Patients With Locally Advanced or Metastatic Epithelioid Hemangioendothelioma.

PURPOSE: Epithelioid hemangioendothelioma (EHE) is a rare vascular cancer with pathogenic TAZ-CAMTA1 operating as an oncogenic driver through activation of MAPK pathway. Trametinib is an inhibitor of MEK, a critical kinase in the MAPK pathway. We sought to evaluate the effect of trametinib in patients with EHE. PATIENTS AND METHODS: A phase 2 trial of trametinib was conducted in patients with locally advanced or metastatic EHE. Eligibility requirements included evidence of tumor progression or presence of EHE-related pain requiring opiates for management prior to enrollment. The primary endpoint was objective response rate (ORR) per RECIST1.1 in cases with TAZ-CAMTA1 confirmed by fusion-FISH. Secondary objectives were to estimate ORR for all patients, median PFS, 2-year OS rate, patient safety, and change in patient-reported global health and pain scores per PROMIS questionnaires. RESULTS: 44 patients enrolled and 42 started trametinib. TAZ-CAMTA1 was detected in 27 tumor samples. The ORR was 3.7% (95% CI: 0.094, 19.0), median PFS was 10.4 months (95% CI: 7.1, NA), and 2-year OS rate was 33.3% (95% CI: 19.1, 58.2) in the target population. Median pain intensity and interference scores improved significantly after 4 weeks of trametinib in patients using opiates. Common AEs related to trametinib were rash, fatigue, nausea/vomiting, diarrhea/constipation, alopecia and edema; one Grade 5 ARDS/pneumonitis was related to trametinib. CONCLUSIONS: Trametinib was associated with reduction in EHE-related pain and median PFS of more than 6 months providing palliative benefit in patients with advanced EHE, but the trial did not meet the ORR goal.

Codesigning enhanced models of care for Northern Australian Aboriginal and Torres Strait Islander youth with type 2 diabetes: study protocol.

INTRODUCTION: Premature onset of type 2 diabetes and excess mortality are critical issues internationally, particularly in Indigenous populations. There is an urgent need for developmentally appropriate and culturally safe models of care. We describe the methods for the codesign, implementation and evaluation of enhanced models of care with Aboriginal and Torres Strait Islander youth living with type 2 diabetes across Northern Australia. METHODS AND ANALYSIS: Our mixed-methods approach is informed by the principles of codesign. Across eight sites in four regions, the project brings together the lived experience of Aboriginal and Torres Strait Islander young people (aged 10-25) with type 2 diabetes, their families and communities, and health professionals providing diabetes care through a structured yet flexible codesign process. Participants will help identify and collaborate in the development of a range of multifaceted improvements to current models of care. These may include addressing needs identified in our formative work such as the development of screening and management guidelines, referral pathways, peer support networks, diabetes information resources and training for health professionals in youth type 2 diabetes management. The codesign process will adopt a range of methods including qualitative interviews, focus group discussions, art-based methods and healthcare systems assessments. A developmental evaluation approach will be used to create and refine the components and principles of enhanced models of care. We anticipate that this codesign study will produce new theoretical insights and practice frameworks, resources and approaches for age-appropriate, culturally safe models of care. ETHICS AND DISSEMINATION: The study design was developed in collaboration with Aboriginal and Torres Strait Islander and non-Indigenous researchers, health professionals and health service managers and has received ethical approval across all sites. A range of outputs will be produced to disseminate findings to participants, other stakeholders and the scholarly community using creative and traditional formats.

The development and diversity of religious cognition and behavior: Protocol for Wave 1 data collection with children and parents by the Developing Belief Network.

The Developing Belief Network is a consortium of researchers studying human development in diverse social-cultural settings, with a focus on the interplay between general cognitive development and culturally specific processes of socialization and cultural transmission in early and middle childhood. The current manuscript describes the study protocol for the network's first wave of data collection, which aims to explore the development and diversity of religious cognition and behavior. This work is guided by three key research questions: (1) How do children represent and reason about religious and supernatural agents? (2) How do children represent and reason about religion as an aspect of social identity? (3) How are religious and supernatural beliefs transmitted within and between generations? The protocol is designed to address these questions via a set of nine tasks for children between the ages of 4 and 10 years, a comprehensive survey completed by their parents/caregivers, and a task designed to elicit conversations between children and caregivers. This study is being conducted in 39 distinct cultural-religious groups (to date), spanning 17 countries and 13 languages. In this manuscript, we provide detailed descriptions of all elements of this study protocol, give a brief overview of the ways in which this protocol has been adapted for use in diverse religious communities, and present the final, English-language study materials for 6 of the 39 cultural-religious groups who are currently being recruited for this study: Protestant Americans, Catholic Americans, American members of the Church of Jesus Christ of Latter-day Saints, Jewish Americans, Muslim Americans, and religiously unaffiliated Americans.

Passaged Articular Chondrocytes From the Superficial Zone and Deep Zone Can Regain Zone-Specific Properties After Redifferentiation.

BACKGROUND: Bioengineered cartilage is a developing therapeutic to repair cartilage defects. The matrix must be rich in collagen type II and aggrecan and mechanically competent, withstanding compressive and shearing loads. Biomechanical properties in native articular cartilage depend on the zonal architecture consisting of 3 zones: superficial, middle, and deep. The superficial zone chondrocytes produce lubricating proteoglycan-4, whereas the deep zone chondrocytes produce collagen type X, which allows for integration into the subchondral bone. Zonal and chondrogenic expression is lost after cell number expansion. Current cell-based therapies have limited capacity to regenerate the zonal structure of native cartilage. HYPOTHESIS: Both passaged superficial and deep zone chondrocytes at high density can form bioengineered cartilage that is rich in collagen type II and aggrecan; however, only passaged superficial zone-derived chondrocytes will express superficial zone-specific proteoglycan-4, and only passaged deep zone-derived chondrocytes will express deep zone-specific collagen type X. STUDY DESIGN: Controlled laboratory study. METHODS: Superficial and deep zone chondrocytes were isolated from bovine joints, and zonal subpopulations were separately expanded in 2-dimensional culture. At passage 2, superficial and deep zone chondrocytes were seeded, separately, in scaffold-free 3-dimensional culture within agarose wells and cultured in redifferentiation media. RESULTS: Monolayer expansion resulted in loss of expression for proteoglycan-4 and collagen type X in passaged superficial and deep zone chondrocytes, respectively. By passage 2, superficial and deep zone chondrocytes had similar expression for dedifferentiated molecules collagen type I and tenascin C. Redifferentiation of both superficial and deep zone chondrocytes led to the expression of collagen type II and aggrecan in both passaged chondrocyte populations. However, only redifferentiated deep zone chondrocytes expressed collagen type X, and only redifferentiated superficial zone chondrocytes expressed and secreted proteoglycan-4. Additionally, redifferentiated deep zone chondrocytes produced a thicker and more robust tissue compared with superficial zone chondrocytes. CONCLUSION: The recapitulation of the primary phenotype from passaged zonal chondrocytes introduces a novel method of functional bioengineering of cartilage that resembles the zone-specific biological properties of native cartilage. CLINICAL RELEVANCE: The recapitulation of the primary phenotype in zonal chondrocytes could be a possible method to tailor bioengineered cartilage to have zone-specific expression.

Contribution of County Characteristics to Disparities in Rural Mortality After Cancer Diagnosis.

INTRODUCTION: Rural disparities in cancer outcomes have been widely evaluated, but limited evidence is available to describe what characteristics of rural environments contribute to the increased risk of poor outcomes. Therefore, this manuscript sought to assess the mediating effects of county characteristics on the relationship between urban/rural status and mortality among patients with cancer, characterize county profiles, and determine at-risk county profiles alongside rural settings. METHODS: Patients diagnosed with cancer between 2000 and 2016 were assessed using Surveillance, Epidemiology and End Results data linked to the 2010 Rural-Urban Commuting Codes and 2010 County Health Rankings. There were 757,655 patients representing 596 counties (of 3,143 in the U.S.) and 12 states. Mediation analyses, conducted in 2023, estimated the direct contribution of rurality to 5-year all-cause survival and the contribution of the rural effect indirectly through County Health Ranking domains. Latent class analysis and survival models identified county groupings and estimated the hazard of mortality associated with class membership. RESULTS: Rankings for premature death, clinical care, and physical environment resulted in rural patients having 17.9%-20.2% less survival time than urban patients. Of this, 4.1%-12.6% of the total excess risk was mediated by these characteristics. Patients living in rural and high-risk county classes saw higher all-cause mortality than those in urban lower-risk counties (hazard ratio=1.04, 95% CI=1.01, 1.08 and 1.07, 95% CI=1.03, 1.11). CONCLUSIONS: Counties with poorer health rankings had increased mortality risks regardless of rurality; however, the poor rankings, notably health behaviors and social and economic factors, elevated the risk for rural counties.

Improved Glycemic Outcomes With Diabetes Technology Use Independent of Socioeconomic Status in Youth With Type 1 Diabetes.

OBJECTIVE: Technology use in type 1 diabetes (T1D) is impacted by socioeconomic status (SES). This analysis explored relationships between SES, glycemic outcomes, and technology use. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of HbA1c data from 2,822 Australian youth with T1D was undertaken. Residential postcodes were used to assign SES based on the Index of Relative Socio-Economic Disadvantage (IRSD). Linear regression models were used to evaluate associations among IRSD quintile, HbA1c, and management regimen. RESULTS: Insulin pump therapy, continuous glucose monitoring, and their concurrent use were associated with lower mean HbA1c across all IRSD quintiles (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA1c (P = 0.624), reflecting a similar association of lower HbA1c with technology use across all IRSD quintiles. CONCLUSIONS: Technology use was associated with lower HbA1c across all socioeconomic backgrounds. Socioeconomic disadvantage does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.

Pre-exercise protein intake is associated with reduced time in hypoglycaemia among adolescents with type 1 diabetes.

AIM: Secondary analyses were conducted from a randomized trial of an adaptive behavioural intervention to assess the relationship between protein intake (g and g/kg) consumed within 4 h before moderate-to-vigorous physical activity (MVPA) bouts and glycaemia during and following MVPA bouts among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: Adolescents (n = 112) with T1D, 14.5 (13.8, 15.7) years of age and 36.6% overweight/obese, provided measures of glycaemia using continuous glucose monitoring [percentage of time above range (>180 mg/dl), time in range (70-180 mg/dl), time below range (TBR; <70 mg/dl)], self-reported physical activity (previous day physical activity recalls), and 24 h dietary recall data at baseline and 6 months post-intervention. Mixed effects regression models adjusted for design (randomization assignment, study site), demographic, clinical, anthropometric, dietary, physical activity and timing covariates estimated the association between pre-exercise protein intake on percentage of time above range, time in range and TBR during and following MVPA. RESULTS: Pre-exercise protein intakes of 10-19.9 g and >20 g were associated with an absolute reduction of -4.41% (p = .04) and -4.83% (p = .02) TBR during physical activity compared with those who did not consume protein before MVPA. Similarly, relative protein intakes of 0.125-0.249 g/kg and ≥0.25 g/kg were associated with -5.38% (p = .01) and -4.32% (p = .03) absolute reductions in TBR during physical activity. We did not observe a significant association between protein intake and measures of glycaemia following bouts of MVPA. CONCLUSIONS: Among adolescents with T1D, a dose of ≥10 g or ≥0.125 g/kg of protein within 4 h before MVPA may promote reduced time in hypoglycaemia during, but not following, physical activity.

Clinical Outcomes with MiniMedTM 780G Advanced Hybrid Closed-Loop Therapy in 2- to 6-Year-Old Children with Type 1 Diabetes.

Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.

The Actin Cytoskeleton as a Regulator of Proteoglycan 4.

OBJECTIVE: The superficial zone (SZ) of articular cartilage is responsible for distributing shear forces for optimal cartilage loading and contributes to joint lubrication through the production of proteoglycan 4 (PRG4). PRG4 plays a critical role in joint homeostasis and is chondroprotective. Normal PRG4 production is affected by inflammation and irregular mechanical loading in post-traumatic osteoarthritis (PTOA). THe SZ chondrocyte (SZC) phenotype, including PRG4 expression, is regulated by the actin cytoskeleton in vitro. There remains a limited understanding of the regulation of PRG4 by the actin cytoskeleton in native articular chondrocytes. The filamentous (F)-actin cytoskeleton is a potential node in crosstalk between mechanical stimulation and cytokine activation and the regulation of PRG4 in SZCs, therefore developing insights in the regulation of PRG4 by actin may identify molecular targets for novel PTOA therapies. MATERIALS AND METHODS: A comprehensive literature search on PRG4 and the regulation of the SZC phenotype by actin organization was performed. RESULTS: PRG4 is strongly regulated by the actin cytoskeleton in isolated SZCs in vitro. Biochemical and mechanical stimuli have been characterized to regulate PRG4 and may converge upon actin cytoskeleton signaling. CONCLUSION: Actin-based regulation of PRG4 in native SZCs is not fully understood and requires further elucidation. Understanding the regulation of PRG4 by actin in SZCs requires an in vivo context to further potential of leveraging actin arrangement to arthritic therapeutics.

The Hip-spine Assessment of a Novel Surgical Planning Software Provides Acetabular Component Targets That Are Reliable and in Agreement With Current Clinical Recommendations.

Background: Spinopelvic immobility has been reported to increase dislocation risk following total hip arthroplasty. Surgically placing acetabular components in a functional orientation has been shown to mitigate risk. The aim of this study was to evaluate the validity and reliability of novel surgical planning software to generate clinically recommended cup targets. Methods: Hip-spine assessments were performed retrospectively on 40 patients. Five reviewers, including 3 arthroplasty-trained surgical fellows and 2 clinical research scientists performed the assessments. Hip-spine assessments consisted of measuring anterior pelvic plane tilt, sacral slope, pelvic incidence, and lumbar lordosis on standing anteroposterior pelvis and lateral standing and seated hip-spine images. Generated cup targets and a control group (40°/20° relative to the anterior pelvic plane) were compared to clinically recommended cup targets. Agreement was defined as a cup position within the recommended range or within 3° of a specific target (eg, 40° inclination) when no range was provided. Intraclass correlation coefficients were used to assess interrater and intrarater reliability, and McNemar's chi-square test was used to measure success relative to the control group. Results: The intraclass correlation coefficient was 0.88 for delta sacral slope and 0.92 for pelvic incidence-lumbar lordosis mismatch. For patients with spinopelvic risk factors, the generated targets matched the clinical recommendations in 81% of patients compared to only 16% in the control group. Conclusions: Excellent interrater and intrarater reliability was achieved using the novel surgical planning software. The resultant target values agreed with clinical recommendations to a greater extent than the control group.