How Many Imaging Studies Do Patients With Neuromuscular Early Onset Scoliosis (EOS) Receive?

BACKGROUND: Children with neuromuscular early onset scoliosis (EOS) receive numerous radiographic studies both from orthopaedic and other specialties. Ionizing radiation doses delivered by computed tomography (CT) are reportedly 100 times higher than conventional radiography. The purpose of this study was to evaluate the number of radiographic studies ordered for neuromuscular EOS patients during their care. METHODS: Retrospective review at a tertiary children's hospital from January 2010 to June 2021 included all patients with neuromuscular EOS followed by an orthopaedic specialist for a minimum of 3 years. Patients were excluded if the majority of their nonorthopaedic care was provided by outside institutions. RESULTS: Eighteen patients met inclusion criteria with mean follow up of 6.4±2.3 years. A total of 1312 plain radiographs and 35 CT scans were performed. Of the plain radiographs, 34.7% were ordered by orthopaedic providers and 65.3% (857/1312) were ordered by other providers. Of the CT scans, 4 were ordered by orthopaedic providers, while 88.5% (21/35) were ordered by other providers. An average of 74.7 (range: 29 to 124) radiographs and 1.9 (range: 0 to 9) CT scans ordered over the course of each patient's treatment for an average of 13.0±6.0 radiographs and 0.3 CT scans per year. CONCLUSIONS: With an average of 75 radiographs and 1.9 CT scans performed per patient, consideration for steps to limit exposure to ionizing radiation should be made a particularly high priority in this unique subset of patients. This requires interdisciplinary coordination as 65% of the radiographs and over 80% of the CT scans were ordered by nonorthopaedic providers. LEVEL OF EVIDENCE: Level III.

Inter-Rater and Intra-Rater Agreement in Scoring Severity of Rodent Cardiomyopathy and Relation to Artificial Intelligence-Based Scoring.

We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists' ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen's kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen's kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies.

Which Ultrasound Characteristics Predict Lymphatic Spread of Papillary Thyroid Cancer?

INTRODUCTION: The 2015 American Thyroid Association guidelines recommend lymph node mapping US in patients with definitive cytological evidence of thyroid cancer. Suspicious lymph node features on imaging including enlarged size (>1 cm in any dimension), architectural distortion, loss of fatty hilum, and microcalcifications often prompt evaluation with fine needle aspiration. There is no universally agreed upon model for determining which ultrasound characteristics most strongly correlate with metastatic disease. METHODS: A retrospective review of patients with confirmed papillary thyroid cancer (PTC) undergoing lymph node mapping ultrasound from 2013 to 2019 was performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated for each individual ultrasound characteristic as well as for characteristic combinations. RESULTS: Data from 119 lymph nodes were included. Malignant lymph nodes were more likely to be enlarged (71% versus 61%, P < 0.001) and to have each individual suspicious feature. Loss of fatty hilum had the highest sensitivity (89%) but was not specific (19%) for metastatic disease. Architectural distortion was found to have the highest specificity (87%). A combination of the four features was found to have higher specificity (97%) and PPV (88%) than any individual feature or combination of two/three features. CONCLUSIONS: A combination of four sonographic features correlates with metastatic PTC to lymph nodes and has the highest specificity and PPV for malignancy. A risk stratification model based on these features may lead to better classification of ultrasound findings in PTC patients with concern for nodal metastases.

Understanding Variations in the Management of Displaced Distal Radius Fractures With Satisfactory Reduction.

BACKGROUND: The American Academy of Orthopaedic Surgeons has set forth Clinical Practice Guidelines (CPGs) to help guide management of closed, displaced distal radius fractures (DRFs). There still exists variation in practice regarding operative vs nonoperative decision-making. This study aims to identify which factors influence the decision to treat DRFs not indicated for surgery by the CPGs after initial closed reduction. METHODS: Fifteen sets of DRFs and clinical vignettes were distributed via email to over 75 orthopedic residency programs, Orthopaedic Trauma Association, and New York Society for Surgery of the Hand membership. A Qualtrics survey collected respondent demographics, choice of treatment, and rationale. RESULTS: Responses were received from 106 surgeons and resident trainees. The odds of selecting operative management for fractures with 5 or more radiographic instability signs versus 3 or 4 was 3.11 (P < .05). Age over 65, higher patient activity level, and dominant-hand injury were associated with greater odds of operative management (3.4, 30.28, and 2.54, respectively). In addition, surgeons with more years in practice and high-volume surgeons had greater odds of selecting operative management (2.43 and 2.11, respectively). CONCLUSIONS: Assessment of instability at the time of injury, patient age and activity level, as well as surgeon volume and time in practice independently affect the decision to manage well-reduced DRF with surgical or nonsurgical treatment. The source of heterogeneity in the treatment of these fractures is borne at least in part from a lack of formal direction on the importance of prereduction instability from the CPGs.

Social media and anti-immigrant prejudice: a multi-method analysis of the role of social media use, threat perceptions, and cognitive ability.

Introduction: The discourse on immigration and immigrants is central to contemporary political and public discussions. Analyzing online conversations about immigrants provides valuable insights into public opinion, complemented by data from questionnaires on how attitudes are formed. Methods: The research includes two studies examining the expressive and informational use of social media. Study 1 conducted a computational text analysis of comments on Singaporean Facebook pages and forums, focusing on how social media is used to discuss immigrants. Study 2 utilized survey data to examine the use of social media at the individual level, testing the relationships between cognitive ability, perceptions of threat, negative emotions towards immigrants, and social media usage within the Integrated Threat Theory framework. Results: Study 1 found that discussions about immigrants on social media often involved negative emotions and concerns about economic impact, such as competition for jobs and crime. Complementing these findings about perceived economic threats, Study 2 showed that individuals with higher social media usage and greater perceptions of threat were more likely to have negative emotions towards immigrants. These relationships were mediated by perceptions of threat and were stronger in individuals with lower cognitive abilities. Discussion: The findings from both studies demonstrate the role of social media in shaping public attitudes towards immigrants, highlighting how perceived threats influence these attitudes. This research suggests the importance of considering how digital platforms contribute to public opinion on immigration, with implications for understanding the dynamics of attitude formation in the digital age.

Dedicated Early Morning Orthopaedic Trauma Operating Room Is Associated With Shorter Time to Surgery and Decreased Length of Hospital Stay for Children Undergoing Surgical Treatment of Supracondylar Humerus Fractures: A Retrospective Cohort Study.

INTRODUCTION: The purpose of this study was to investigate whether the use of a dedicated early morning orthopaedic trauma operating room (OR) resulted in shorter wait times, decreased surgical times, decreased length of stay (LOS), and decreased complications in children treated with urgent surgical intervention for supracondylar humerus fractures. METHODS: This retrospective comparative cohort study at a level I pediatric trauma center included patients younger than 12 years with supracondylar humerus fractures urgently treated with closed or open reduction and percutaneous pinning. Index surgical cases from April 28, 2013, to February 26, 2020, were included. Patients with prior humerus fracture, concomitant injuries, open fracture, pulseless supracondylar fracture, or missing data were excluded. Patients were analyzed based on the type of OR: dedicated early morning orthopaedic trauma OR or typical daytime orthopaedic OR. The primary outcome was time from presentation to surgery. Secondary outcomes included surgical time, complications, and LOS. RESULTS: A total of 401 patients with a mean age of 5 ± 2 (range: 1 to 11) years and a mean follow-up of 2.0 ± 2.1 (range: 0.5 to 25.0) months were included, of whom 137 patients (34%) underwent surgery in the early morning dedicated orthopaedic trauma OR. The dedicated early morning orthopaedic OR group had significantly less time from presentation to surgery (7.5 versus 9.4 hours; P = 0.0002) and shorter LOS (21.0 versus 24.0 hours; P = 0.004) compared with children treated in the typical daytime orthopaedic OR. Surgical time (31.1 versus 32.6 minutes; P = 0.40) and complication rates (5.8% versus 4.9%; P = 0.65) were similar between the groups. No revision surgery was required in either group. DISCUSSION: Surgical wait times were diminished with use of the dedicated early morning OR, as was LOS. Surgical times and complication rates were similar between groups. Institutions may consider adopting a dedicated early morning orthopaedic trauma OR to improve surgical wait times and decrease LOS. LEVEL OF EVIDENCE: III.

Human Motor Endplate Survival after Chronic Peripheral Nerve Injury.

Objective: Degeneration of motor endplates (MEPs) in denervated muscle is thought to be a key factor limiting functional regeneration after peripheral nerve injury (PNI) in humans. However, there is currently no paradigm to determine MEP status in denervated human muscle to estimate likelihood of reinnervation success. Here, we present a quantitative analysis of MEP status in biopsies of denervated muscles taken during nerve repair surgery and ensuing functional recovery. Methods: This is a retrospective single-surgeon cohort study of patients (n=22) with upper extremity PNI confirmed with electromyography (EMG), treated with nerve transfers. Muscle biopsies were obtained intra-operatively from 10 patients for MEP morphometric analysis. Age at time of surgery ranged from 22-77 years and time from injury to surgery ranged from 2.5-163 months. Shoulder range of motion (ROM) and Medical Research Council (MRC) scores were recorded pre-op and at final follow-up. Results: Surviving MEPs were observed in biopsies of denervated muscles from all patients, even those greater than six months from injury. Average postoperative ROM improvement (assessed between 6-9 months post-surgery) was: forward flexion 84.3 ± 51.8°, abduction 62.5 ± 47.9°, and external rotation 25.3 ± 28.0°. Interpretation: While it is believed that MEP degeneration 6 months post-injury prevents reinnervation, this data details MEP persistence beyond this timepoint along with significant functional recovery after nerve surgery. Accordingly, persistence of MEPs in denervated muscles may predict the extent of functional recovery from nerve repair surgery.

All it takes is empathy: how virtual reality perspective-taking influences intergroup attitudes and stereotypes.

Research in the past decade has demonstrated the potential of virtual reality perspective-taking (VRPT) to reduce bias against salient outgroups. In the perspective-taking literature, both affective and cognitive mechanisms have been theorized and identified as plausible pathways to prejudice reduction. Few studies have systematically compared affective and cognitive mediators, especially in relation to virtual reality, a medium posited to produce visceral, affective experiences. The present study seeks to extend current research on VRPT's mechanisms by comparing empathy (affective) and situational attributions (cognitive) as dual mediators influencing intergroup attitudes (affective) and stereotypes (cognitive). In a between-subjects experiment, 84 participants were randomly assigned to embody a VR ingroup or outgroup waiting staff at a local food establishment, interacting with an impolite ingroup customer. Results indicated that participants in the outgroup VRPT condition reported significantly more positive attitudes and stereotypes towards outgroup members than those in the ingroup VRPT condition. For both attitudes and stereotypes, empathy significantly mediated the effect of VRPT, but situational attributions did not. Findings from this research provide support for affect as a key component of virtual experiences and how they shape intergroup perceptions. Implications and directions for further research are discussed.

Evolution of haploid and diploid populations reveals common, strong, and variable pleiotropic effects in non-home environments.

Adaptation is driven by the selection for beneficial mutations that provide a fitness advantage in the specific environment in which a population is evolving. However, environments are rarely constant or predictable. When an organism well adapted to one environment finds itself in another, pleiotropic effects of mutations that made it well adapted to its former environment will affect its success. To better understand such pleiotropic effects, we evolved both haploid and diploid barcoded budding yeast populations in multiple environments, isolated adaptive clones, and then determined the fitness effects of adaptive mutations in 'non-home' environments in which they were not selected. We find that pleiotropy is common, with most adaptive evolved lineages showing fitness effects in non-home environments. Consistent with other studies, we find that these pleiotropic effects are unpredictable: they are beneficial in some environments and deleterious in others. However, we do find that lineages with adaptive mutations in the same genes tend to show similar pleiotropic effects. We also find that ploidy influences the observed adaptive mutational spectra in a condition-specific fashion. In some conditions, haploids and diploids are selected with adaptive mutations in identical genes, while in others they accumulate mutations in almost completely disjoint sets of genes.

Small molecule screen identifies pyrimethamine as an inhibitor of NRF2-driven esophageal hyperplasia.

OBJECTIVE: NRF2 is a master transcription factor that regulates the stress response. NRF2 is frequently mutated and activated in human esophageal squamous cell carcinoma (ESCC), which drives resistance to chemotherapy and radiation therapy. Therefore, a great need exists for NRF2 inhibitors for targeted therapy of NRF2high ESCC. DESIGN: We performed high-throughput screening of two compound libraries from which hit compounds were further validated in human ESCC cells and a genetically modified mouse model. The mechanism of action of one compound was explored by biochemical assays. RESULTS: Using high-throughput screening of two small molecule compound libraries, we identified 11 hit compounds as potential NRF2 inhibitors with minimal cytotoxicity at specified concentrations. We then validated two of these compounds, pyrimethamine and mitoxantrone, by demonstrating their dose- and time-dependent inhibitory effects on the expression of NRF2 and its target genes in two NRF2Mut human ESCC cells (KYSE70 and KYSE180). RNAseq and qPCR confirmed the suppression of global NRF2 signaling by these two compounds. Mechanistically, pyrimethamine reduced NRF2 half-life by promoting NRF2 ubiquitination and degradation in KYSE70 and KYSE180 cells. Expression of an Nrf2E79Q allele in mouse esophageal epithelium (Sox2CreER;LSL-Nrf2E79Q/+) resulted in an NRF2high phenotype, which included squamous hyperplasia, hyperkeratinization, and hyperactive glycolysis. Treatment with pyrimethamine (30 mg/kg/day, p.o.) suppressed the NRF2high esophageal phenotype with no observed toxicity. CONCLUSION: We have identified and validated pyrimethamine as an NRF2 inhibitor that may be rapidly tested in the clinic for NRF2high ESCC.

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study.

Up to 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory to or relapse after first-line therapy, highlighting the need for better treatments. Mosunetuzumab is a CD20 × CD3 bispecific antibody that engages and redirects T cells to eliminate malignant B cells. In this phase 2, open-label study (NCT03677141), 40 patients (52.5% with international prognostic index ≥3) with previously untreated DLBCL initiated 6 cycles of IV mosunetuzumab with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Mosunetuzumab was administered in cycle 1 as step-up doses to mitigate cytokine release syndrome [CRS], and a dose of 30 mg was given on day 1 of cycles 2-6. Efficacy end points included objective and complete response rates, as determined by the investigator, via positron emission tomography-computed tomography, using Lugano 2014 criteria (87.5% and 85.0%, respectively). At a median follow-up of 32.0 months, the estimated 2-year progression-free survival and event-free survival rates were 65.4% (95% confidence interval [CI], 49.5-81.4) and 60.4% (95% CI, 44.7-76.1), respectively. CRS occurred in 60.0% of patients; all events were grade 1 (45.0%) or grade 2 (15.0%) and occurred primarily in cycle 1. Mosunetuzumab-related grade ≥3 neurologic adverse events (AEs) potentially consistent with immune effector cell-associated neurotoxicity syndrome occurred in 1 patient (2.5%). Grade 5 AEs were reported in 2 patients. Neutropenia occurred in 70.0% of patients, mostly during cycle 1 and was of short duration. These findings demonstrate promising activity and a manageable safety profile for mosunetuzumab-CHOP and warrant further investigation of mosunetuzumab in first-line combination regimens for DLBCL.

A chloroplast protein atlas reveals punctate structures and spatial organization of biosynthetic pathways.

Chloroplasts are eukaryotic photosynthetic organelles that drive the global carbon cycle. Despite their importance, our understanding of their protein composition, function, and spatial organization remains limited. Here, we determined the localizations of 1,034 candidate chloroplast proteins using fluorescent protein tagging in the model alga Chlamydomonas reinhardtii. The localizations provide insights into the functions of poorly characterized proteins; identify novel components of nucleoids, plastoglobules, and the pyrenoid; and reveal widespread protein targeting to multiple compartments. We discovered and further characterized cellular organizational features, including eleven chloroplast punctate structures, cytosolic crescent structures, and unexpected spatial distributions of enzymes within the chloroplast. We also used machine learning to predict the localizations of other nuclear-encoded Chlamydomonas proteins. The strains and localization atlas developed here will serve as a resource to accelerate studies of chloroplast architecture and functions.

Bat ASC2 suppresses inflammasomes and ameliorates inflammatory diseases.

Bats are special in their ability to live long and host many emerging viruses. Our previous studies showed that bats have altered inflammasomes, which are central players in aging and infection. However, the role of inflammasome signaling in combating inflammatory diseases remains poorly understood. Here, we report bat ASC2 as a potent negative regulator of inflammasomes. Bat ASC2 is highly expressed at both the mRNA and protein levels and is highly potent in inhibiting human and mouse inflammasomes. Transgenic expression of bat ASC2 in mice reduced the severity of peritonitis induced by gout crystals and ASC particles. Bat ASC2 also dampened inflammation induced by multiple viruses and reduced mortality of influenza A virus infection. Importantly, it also suppressed SARS-CoV-2-immune-complex-induced inflammasome activation. Four key residues were identified for the gain of function of bat ASC2. Our results demonstrate that bat ASC2 is an important negative regulator of inflammasomes with therapeutic potential in inflammatory diseases.

Preoperative Muscle Biopsy to Assess Motor End Plate Integrity as a Predictor for Successful Nerve Transfer: A Case Report.

CASE: A 60-year-old right-hand-dominant man was referred for persistent right deltoid weakness, lateral shoulder numbness, and severe functional deficit 3 months after undergoing proximal humerus open reduction and internal fixation with plate and fibular strut allograft. Deltoid muscle biopsy demonstrated motor end plate (MEP) degeneration. After partial radial-to-axillary nerve transfer, repeat deltoid muscle biopsy revealed successful regeneration of MEPs with reinnervation of deltoid confirmed with postnerve transfer electromyography. CONCLUSION: Selective nerve transfer can successfully rescue a denervated target muscle from further degeneration by restoration of healthy MEPs.

Balancing medical innovation and affordability in the new healthcare ecosystem in China: Review of pharmaceutical pricing and reimbursement policies.

The China Basic Medical Insurance Program was created in 1999 with three objectives: equal accessibility, affordability, and quality. Today, it has become the biggest medical insurance program in the world, covering 95% of China's population. Since 2015, China's healthcare ecosystem has been reshaped by increasing innovation, which has in turn been driven by regulatory reform, enhancement of research and development capability, and capital market development. There has also been improved regulatory efficiency to reduce lags in launching drugs. In 2022, nearly 20% of novel active substances launched globally were from China. China has also risen to become the second biggest contributor to innovation in terms of pipelines. Using a "fast-follow" strategy, many locally developed innovative drugs can compete with products from multinational companies in their quality and pricing. However, China's pharmaceutical and biotechnology industry will continue to face challenges in pricing and reimbursement, as well as a shortened product lifecycle with rapid price erosion. The government has already accelerated the timeline for updating the drug reimbursement list and is willing to create a high-quality medical insurance program. However, some obstacles are hard to overcome, including reimbursement for advanced therapies, limited funding and an increasing burden of disease due to an aging population. This article reviews the trajectory of medical innovation in China, including the challenges. Looking forward, balancing affordability and innovation will be critical for China to continue the trajectory of growth. The article also offers some suggestions for future policy reform, including optimizing reimbursement efficiency with a focus on high-quality solutions, enhancing the value assessment framework, payer repositioning from "value buyer" to "strategic buyer", and developing alternative market access pathways for innovative drugs.

SARS-CoV-2 Omicron variant emerged under immune selection.

The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.

Case Report: Neuroblastoma-Like Schwannoma in a Domestic Short-Haired Cat.

An axillary mass was detected in a 6-year-old, neutered, male, domestic short-haired cat during a wellness exam. Gross examination following surgical removal revealed a discrete, deep subcutaneous, discoid mass that was between 0.5- and 0.7-cm-in-diameter and diffusely firm and white. Histologically, the mass was well-demarcated, partially encapsulated, and expanded the panniculus carnosus. It was composed of tightly packed, giant rosettes of radially arranged fusiform cells stacked in one to 10 layers with peripherally palisading nuclei and with centrally oriented, fibrillary, cytoplasmic processes, and collagenous fibers. Laminin immunoreactivity and ultrastructural examination highlighted a continuous basal lamina outside the plasma membrane of each neoplastic cell. Neoplastic cells were immunoreactive for GFAP, S100, periaxin, and Sox-10 and were immunonegative for synaptophysin, smooth muscle actin, and pancytokeratin. Collective findings were consistent with a diagnosis of neuroblastoma-like schwannoma. This is the first veterinary report of this rare variant of benign schwannoma.

Posttraumatic Ulnar Translocation of the Carpus: A Case Report and Brief Review of the Literature.

We report a case of posttraumatic ulnar translocation of the carpus, which resulted after a fall from a six-foot ladder. This patient presented with multiple injuries to the skull bones, face, and limbs. A diagnosis of ulnar translocation of the carpus was missed on initial radiographs. Ulnar translocations require a high clinical index of suspicion and should be considered in the context of any high-impact injury to the wrist. A volar fleck just distal to the radial articular surface represents evidence of ligamentous disruption and should alert physicians that a more severe injury may be present. Nonsurgical and surgical treatment options are reviewed.

Assessing COVID-19 risk with temporal indices and geographically weighted ordinal logistic regression in US counties.

PURPOSE: Research on the novel coronavirus diseases 2019 (COVID-19) mainly relies on cross-sectional data, but this approach fails to consider the temporal dimension of the pandemic. This study assesses three temporal dimensions of the COVID-19 infection risk in US counties, namely probability of occurrence, duration of the pandemic, and intensity of transmission, and investigate local patterns of the factors associated with these risks. METHODS: Analyzing daily data between January 22 and September 11, 2020, we categorize the contiguous US counties into four risk groups-High-Risk, Moderate-Risk, Mild-Risk, and Low-Risk-and then apply both conventional (i.e., non-spatial) and geographically weighted (i.e., spatial) ordinal logistic regression model to understand the county-level factors raising the COVID-19 infection risk. The comparisons of various model fit diagnostics indicate that the spatial models better capture the associations between COVID-19 risk and other factors. RESULTS: The key findings include (1) High- and Moderate-Risk counties are clustered in the Black Belt, the coastal areas, and Great Lakes regions. (2) Fragile labor markets (e.g., high percentages of unemployed and essential workers) and high housing inequality are associated with higher risks. (3) The Monte Carlo tests suggest that the associations between covariates and COVID-19 risk are spatially non-stationary. For example, counties in the northeastern region and Mississippi Valley experience a stronger impact of essential workers on COVID-19 risk than those in other regions, whereas the association between income ratio and COVID-19 risk is stronger in Texas and Louisiana. CONCLUSIONS: The COVID-19 infection risk levels differ greatly across the US and their associations with structural inequality and sociodemographic composition are spatially non-stationary, suggesting that the same stimulus may not lead to the same change in COVID-19 risk. Potential interventions to lower COVID-19 risk should adopt a place-based perspective.

Evaluation of Extended Infusion Set Performance in Adults with Type 1 Diabetes: Infusion Set Survival Rate and Glycemic Outcomes from a Pivotal Trial.

Background: Standard insulin infusion sets (IISs) are to be replaced every 2 to 3 days to avoid complications and diabetic ketosis due to set failure. This pivotal trial evaluated the safety and performance of a new extended-wear infusion set (EIS) when used for 7 days by adults with type 1 diabetes (T1D). Methods: This single-arm, nonrandomized trial enrolled adults (18-80 years of age) with T1D, who used their own MiniMed™ 670G system with insulin lispro or insulin aspart and the EIS for up to 7 days, across 12 consecutive wears. Safety endpoints included incidence of serious adverse events (SAEs), serious adverse device effects (SADEs), unanticipated adverse device effects (UADEs), severe hypoglycemia (SevHypo), severe hyperglycemia (SevHyper), diabetic ketoacidosis (DKA), and skin infection. The EIS failure rate due to unexplained hyperglycemia (i.e., suspected occlusion), the overall EIS survival rate, glycemic control outcomes (i.e., A1C, mean sensor glucose and time spent in established glucose ranges), total daily insulin delivered, and satisfaction with the EIS were determined. Results: The intention to treat population (n = 259, 48% men, 45.0 ± 14.1 years) wore a total of 3041 EIS devices. No SADE, UADE, or DKA events was reported. Overall rates of SAEs, SevHypo, SevHyper, and skin infection were 3.8, 2.5, 104.1, and 20.1 events per 100 participant-years. The rate of EIS failure due to unexplained hyperglycemia at the end of day 7 was 0.1% (95% confidence interval [CI]: 0.03-0.51) and 0.4% (95% CI: 0.16-1.00) for insulin lispro and aspart use, respectively. Overall EIS survival rate at the end of day 7 was 77.8% (95% CI: 76.2-79.3), glycemic control did not change, and participants reported greater satisfaction with the EIS compared with standard IISs worn before the study (P < 0.001). Conclusions: This investigation demonstrates that the EIS, when worn for up to 7 days, was safe and rated with high satisfaction, without adversely affecting glycemic control in adults with T1D. Clinical Trial Registration number: NCT04113694 (https://clinicaltrials.gov/ct2/show/NCT04113694).