Twelve-Month Follow-up from a Randomized Controlled Trial of Simplified Meal Announcement Versus Precise Carbohydrate Counting in Adolescents with Type 1 Diabetes Using the MiniMed™ 780G Advanced Hybrid Closed-Loop System.

Background and Aims: Carbohydrate counting is a well-established tool for self-management of type 1 diabetes (T1D) and can improve glycemic control and potentially reduce long-term complication risk. However, it can also be burdensome, error-prone, and complicated for the patient. A randomized controlled trial was conducted to investigate glycemic control with carbohydrate counting ("flex") versus simplified meal announcement ("fix") in adolescents with T1D using the MiniMed™ 780G system. The present study reports follow-up data to 12 months. Methods: Adolescents with T1D were randomly assigned 1:1 to use the MiniMed™ 780G system alongside the flex versus fix approaches. Participants were followed for 12 months with outcomes recorded at 3, 6, 9, and 12 months. The primary endpoint was the difference in time-in-range (TIR), and secondary endpoints included glycated hemoglobin (HbA1c) and other glucose and insulin metrics. Results: At 12 months, TIR (proportion of time with sensor glucose 70-180 mg/dL) was significantly lower in the fix versus flex group (72.9% vs. 80.1%, respectively; P = 0.001). There was no significant difference in HbA1c between the fix (6.8% ± 0.5%) and flex groups (6.5% ± 0.5%) at 12 months (P = 0.092), and mean HbA1c was below 7% at all time points in both arms. Conclusions: Glycemic control with simplified meal announcement was maintained over 12 months. On average, the international consensus targets were met in both arms for all time points. The simplified approach represents a viable alternative to carbohydrate counting, particularly in people who find the latter burdensome; however, carbohydrate counting resulted in superior TIR. This study is registered with ClinicalTrials.gov, number NCT05069727.

An Automated Insulin Delivery System with Automatic Meal Bolus Based on a Hand-Gesturing Algorithm.

Background: Carbohydrate counting (CC) and meal announcements, before eating, introduce a significant burden for individuals managing type 1 diabetes (T1D). An automated insulin delivery system with automatic bolusing that eliminates the need for CC and premeal bolusing (i.e., a hands-free closed-loop [HFCL] system) was assessed in a feasibility trial of adults with T1D. Methods: The system included the MiniMed™ 780G pump and a smartphone-paired smartwatch with the Klue application (Klue, Inc.) that detects eating and drinking gestures. A smartphone algorithm converted gestures into carb amounts that were transmitted to the pump for automatic bolusing. For 5 days, participants (N = 17, 18-75 years of age) used the system at home with meal announcements based on traditional CC, with the Klue application disabled (Home-stay phase). Thereafter, participants moved to a supervised hotel setting, where the Klue application was enabled for 5 days and meals were not announced (Hotel-stay phase). Participants consumed the same eight test meals (six solid and two liquid) of varying caloric and carb size at the same time and day of the week for both phases, and glycemic metrics were compared. Otherwise, there were no other meal restrictions. Results: The overall time in range (70-180 mg/dL) was 83.4% ± 7.0% and 80.6% ± 6.7% for the Home-stay and Hotel-stay, respectively (P = 0.08). The average time at <70 mg/dL was 3.1% and 3.0% (P = 0.9144), respectively, and the average time at >180 mg/dL was 13.5% and 16.3% (P = 0.1046), respectively. Postprandial glycemia following low-carb test meals was similar between the two phases. The system's ability to accommodate high-carb meals was somewhat limited. There were no episodes of severe hypoglycemia or diabetic ketoacidosis. Conclusion: Preliminary findings show that a HFCL system was safe and maintained overall glycemic control, similar to that observed with traditional CC and manual meal bolusing. By eliminating these daily T1D burdens, a HFCL system may improve quality of life for individuals with T1D. ClinicalTrials.gov number: NCT04964128.

Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Longitudinal Femoral Cartilage T2 Relaxation Time and Thickness Changes with Fast Sequential Radiographic Progression of Medial Knee Osteoarthritis-Data from the Osteoarthritis Initiative (OAI).

This study tested for longitudinal changes in femoral cartilage T2 relaxation time and thickness in fast-progressing medial femorotibial osteoarthritis (OA). From the Osteoarthritis Initiative (OAI) database, nineteen knees fulfilled the inclusion criteria, which included medial femorotibial OA and sequential progression from Kellgren-Lawrence grade (KL) 1 to KL2 to KL3 within five years. Median T2 value and mean thickness were calculated for six condylar volumes of interest (VOIs; medial/lateral anterior, central, posterior) and six sub-VOIs (medial/lateral anterior external, central, internal). T2 value and thickness changes between severity timepoints were tested using repeated statistics. T2 values increased between KL1 and KL2 and between KL1 and KL3 in the medial compartment (p ≤ 0.02), whereas both increases and decreases were observed between the same timepoints in the lateral compartment (p ≤ 0.02). Cartilage thickness decreased in VOI/subVOIs of the medial compartment from KL1 to KL2 and KL3 (p ≤ 0.014). Cartilage T2 value and thickness changes varied spatially over the femoral condyles. While all T2 changes occurred in the early radiographic stages of OA, thickness changes occurred primarily in the later stages. These data therefore support the use of T2 relaxation time analyses in methods of detecting disease-related change during early OA, a valuable period for therapeutic interventions.

Mid- and long-term outcome of Salter's, Pemberton's and Dega's osteotomy for treatment of developmental dysplasia of the hip: a systematic review and meta-analysis.

INTRODUCTION: Early diagnosis and early treatment have become the gold standard for management of developmental dysplasia of the hip. Surgery is required in case of failed initial treatment. Innominate pelvic osteotomy of Salter (SIO), Pemberton's pericapsular osteotomy (PPO) and Dega's acetabuloplasty (DA) are among the most used procedures.We performed a systematic review and meta-analysis of the past 57 years in order to assess the mid- and long-term outcome of these techniques. METHODS: Studies met inclusion criteria if they: (1) reported at least 5 cases treated by 1 of the abovementioned surgical techniques; (2) included children aged between 1 and 8 years; (3) surgical indication was late detected DDH or a failed initial treatment; (4) presented a minimal follow-up of 24 months; (5) reported the radiological score of Severin and/or the clinical score of McKay.Clinical and radiological outcomes were dichotomised into favourable and unfavourable outcome and weighted summary rates were determined using meta-analysis models. RESULTS: From a total of 7391 articles, 48 level of evidence grade IV articles were included in our review. A total of 2143 cases with a mean follow up of 112.4 months were included.Pooled Severin score indicated a statistically better outcome for PPO and DA compared to SIO (p = 0.0003 and p = 0.002, respectively). By dichotomising the results in favourable and unfavourable outcome, PPO showed the best results (p = 0.0002 vs. SIO, p = 0.01 vs. DA).Pooled McKay score showed a statistically better outcome for PPO and DA compared to SIO (p < 0.0001 and p = 0.03, respectively) as well as better outcomes for PPO compared to DA (p = 0.01). By dichotomising the results in favourable and unfavourable, PPO showed the best results. CONCLUSIONS: Even if our review demonstrates slightly better radiological and clinical results with the PPO, the currently available and limited data do not allow for clear recommendation towards one of these techniques.

Modifying Stride Length in Isolation and in Combination With Foot Progression Angle and Step Width Can Improve Knee Kinetics Related to Osteoarthritis; A Preliminary Study in Healthy Subjects.

The purpose of this study was to determine the effects of modifying stride length (SL) on knee adduction and flexion moments, two markers of knee loading associated with medial-compartment knee osteoarthritis (OA) progression. This study also tested if SL modifications, in addition to foot progression angle (FP) and step width (SW) modifications, provide solutions in more subjects for reducing knee adduction moment (KAM) without increasing knee flexion moment (KFM), potentially protecting the joint. Fourteen healthy subjects (six female) were enrolled in this preliminary study. Walking trials were collected first without instructions, and then following foot placement instructions for 50 combinations of SL, FP, and SW modifications. Repeated measures analysis of variance was used to detect group-average effects of footprint modifications on maximum KAM and KFM and on KAM impulse. Subject-specific dose-responses between footprint modifications and kinetics changes were modeled with linear regressions, and the models were used to identify modification solutions, per subject, for various kinetics change conditions. Shorter SL significantly decreased the three kinetics measures (p < 0.01). Potential solutions for 10% reductions in maximum KAM and KAM impulse without increasing maximum KFM were identified for five subjects with FP and SW modifications. A significantly higher proportion of subjects had solutions when adding SL modifications (11 subjects, p = 0.04). In conclusion, SL is a valuable parameter to modify, especially in combination with FP and SW modifications, to reduce markers of medial knee loading. Future work is needed to extend these findings to osteoarthritic knees.

Comprehensive description of T2 value spatial variations in non-osteoarthritic femoral cartilage using three-dimensional registration of morphological and relaxometry data.

PURPOSE: The aim of this study was to develop and assess a method of quantifying cartilage T2 relaxation times in a series of volumes of interest (VOIs) covering the entire cartilage of the femoral condyles. Subsequently, the method was used to test for T2 spatial variations in non-osteoarthritic (OA) knees. METHODS: Ten non-OA subjects (five female, average 30 years) were enrolled after informed consent. Three-dimensional bone and cartilage models were created by double echo steady state (DESS) morphological magnetic resonance image (MRI) segmentation, and the models were semi-manually registered with multi-slice, multi-echo (MSME) T2 MRI. Mean T2 values were calculated for 12 VOIs derived from cartilage thickness literature and their respective superficial and deep layers. RESULTS: Analyses showed that intra- and inter-rater reliabilities of the presented method were "good" to "excellent" in more than 90% of the VOIs. Additionally, several spatial differences in T2 values were observed, including, for the medial condyle, higher T2 values in the anterior and central VOIs versus in the posterior VOI (p < .05). T2 values were also generally higher in the superficial versus deep layers (p < .05). CONCLUSIONS: The presented MRI T2 analysis method is reliable and provides a comprehensive quantification of spatial heterogeneity of healthy cartilage compositional properties. This method can be further applied to better understand knee OA pathophysiology and potentially define clinically relevant diagnostic features of the disease.

Alterations in knee kinematics after partial medial meniscectomy are activity dependent.

BACKGROUND: Alterations in knee kinematics after partial meniscectomy have been linked to the increased risk of osteoarthritis in this population. Understanding differences in kinematics during static versus dynamic activities of increased demand can provide important information regarding the possible underlying mechanisms of these alterations. HYPOTHESIS: Differences in the following 2 kinematics measures will increase with activity demand: (1) the offset toward external tibial rotation for the meniscectomized limb compared with the contralateral limb during stance and (2) the difference in knee flexion angle at initial foot contact between the meniscectomized and contralateral limbs. STUDY DESIGN: Controlled laboratory study. METHODS: This study compared side-to-side differences in knee flexion and rotation angles during static and dynamic activities. Thirteen patients (2 female) were tested in a motion capture laboratory at 6 ± 2 months after unilateral, arthroscopic, partial medial meniscectomy during a static reference pose and during 3 dynamic activities: walking, stair ascent, and stair descent. RESULTS: The meniscectomized limb demonstrated more external tibial rotation compared with the contralateral limb during dynamic activities, and there was a trend that this offset increased with activity demand (repeated-measures analysis of variance [ANOVA] for activity, P = .07; mean limb difference: static pose, -0.1° ± 3.3°, P = .5; walking, 1.2° ± 3.8°, P = .1; stair ascent, 2.0° ± 3.2°, P = .02; stair descent, 3.0° ± 3.5°, P = .005). Similarly, the meniscectomized knee was more flexed at initial contact than the contralateral limb during dynamic activities (repeated-measures ANOVA for activity P = .006; mean limb difference: reference pose, 1.0° ± 2.5°, P = .09; walking, 2.0° ± 3.9°, P = .05; stair ascent, 5.9° ± 5.3°, P = .009; stair descent, 3.5° ± 4.0°, P = .004). CONCLUSION: These results suggest both a structural element and a potential muscular element for the differences in kinematics after partial medial meniscectomy and highlight the importance of challenging the knee with activities of increased demands to detect differences in kinematics from the contralateral limb. CLINICAL RELEVANCE: With further investigation, these findings could help guide clinical rehabilitation of patients with torn meniscus tissue, especially in the context of the patients' increased risk of joint degeneration.

The role of inflammation in the initiation of osteoarthritis after meniscal damage.

Meniscal damage and meniscectomy lead to subsequent osteoarthritis (OA) of the knee joint through multiple and diverse mechanisms, yet the interaction of these mechanisms remains unknown. Therefore, the aim of this review is to suggest the multi-scale, multi-faceted components involved between meniscal injury or meniscectomy and the initiation of OA. There is evidence of structural, mechanical, and biological changes after meniscal damage, all of which can be greatly affected by the presence of local or systemic inflammation. Meniscal damage or resection causes changes in knee mechanics during walking, resulting in altered cartilage loading. Because cartilage is mechanically sensitive, these loading changes can initiate a catabolic effect, culminating in tissue degeneration. The evidence suggests that the addition of elevated inflammation at the time of meniscal damage or meniscectomy results in an accelerated progression toward cartilage degradation. Initial cartilage degradation produces inflammation and pain in conjunction with structural changes to the joint, thus perpetuating the cycle of altered cartilage loading and subsequent degradation. Furthermore, the inflammation secondary to obesity and aging introduces an increased risk of developing OA following meniscal injury. Therefore, an overall route between meniscal damage or resection and OA is presented here in a manner that considers two distinct pathways; these pathways reflect the absence or presence of conditions that cause elevated inflammation.