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Abstract Objective: Numerous mobile health (mHealth) interventions are being developed to aid in management of complex chronic medical conditions. However, the acceptance of mHealth programs by low-income, bilingual populations has not yet been evaluated. The Trial to Examine Text-based mHealth for Emergency department patients with Diabetes (TExT-MED) program is a text message-based mHealth program designed specifically for resource-poor patients with diabetes. We conducted a prospective proof-of-concept trial to assess satisfaction and preliminary effectiveness of the TExT-MED program. Research Design and Methods: A consecutive sample of adult patients in the emergency department with diabetes and a text message-capable mobile phone was enrolled in the TExT-MED program. Participants received three text messages daily for 3 weeks in English or Spanish in the following domains: educational/motivational, medication reminders, healthy living challenges, diabetes trivia, and links to free diabetes management tools. Results: Twenty-three patients with diabetes (median hemoglobin A1c, 8.9%) were enrolled in TExT-MED. In the week before TExT-MED, 56.5% of subjects reported eating fruits/vegetables daily versus 83% after, 43.5% reported exercising before versus 74% after, and 74% reported performing foot checks before versus 85% after. Self-efficacy, measured by the Diabetes Empowerment Scale-Short Form, improved from 3.9 to 4.2. Scores on the Morisky Medication Adherence Scale improved more dramatically from 3.5 to 4.75. Ninety percent of participants indicated they would like to continue the program, and 100% would recommend the program to family or friends. Conclusions: This pilot trial of the TExT-MED program demonstrated increased healthy behaviors, improved diabetes self-efficacy and medication adherence, and received excellent satisfaction scores in resource-poor, inner city patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract Background Cervical cancer is the third most common cancer in women worldwide. The most common histopathological subtype is cervical squamous cell carcinoma (SCC, 75-80%), followed by adenocarcinoma (AC) and adenosquamous carcinoma (ASC; together 15-20%). Rising incidence rates of AC have been observed relative and absolute to SCC and evidence is accumulating that cervical AC is a distinct clinical entity. Cervical SCC, ASC, and AC are caused by a persistent infection with high-risk human papillomavirus (HPV) and failed control of the immune system plays a pivotal role in the carcinogenesis of all three histopathological subtypes. Human leukocyte antigen E (HLA-E), a non-classical HLA class Ib molecule, plays an important role in immune surveillance and immune escape of virally infected cells. In this study we investigated HLA-E expression in three well-defined cohorts of cervical AC, ASC, and SCC patients, and determined whether HLA-E expression was associated with histopathological parameters and patient survival. Methods and results HLA-E expression was assessed by immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections of 79 SCC, 38 ASC, and 75 AC patients. All patients included were International Federation of Gynaecology and Obstetrics stage I-II and underwent radical hysterectomy with lymphadenectomy as primary treatment. Significant differences between the histopathological subgroups were detected for age distribution, HPV positivity, HPV type distribution, tumour size, tumour infiltration depth, lymph-vascular space invasion, and adjuvant radiotherapy. High expression of HLA-E was found in 107/192 (56%) cervical carcinomas, with significantly more overexpression in cervical AC compared to SCC and ASC (37/79 SCC, 18/38 ASC, and 52/75 AC; P = 0.010). High HLA-E expression in cervical AC was associated with favourable long term disease-specific and recurrence-free survival (P = 0.005 and P = 0.001, respectively). Conclusion High expression of HLA-E occurred in the majority of all histopathological subtypes of cervical cancer; especially in cervical AC. High HLA-E expression in cervical AC was associated with improved patient survival. This study also highlights the importance of careful evaluation of cervical carcinomas to distinguish histopathological subtypes. In the future, insight into the biological behaviour and distinct molecular carcinogenetic processes of the AC, ASC, and SCC subtypes may contribute to the development of more tumour-specific treatment strategies.

Abstract: The number of people facing mental health issues continues to grow in the aftermath of COVID-19. Nurses are challenged with providing care for an increasing number of patients, including veterans, with complex mental health needs across healthcare settings. Of concern, many students transitioning into practice feel they lack the necessary confidence, education, and skills to competently care for patients with mental health illness. This article discusses an innovative mental health immersion experience strategically integrated within a new-nurse residency program., Competing Interests: The authors have declared no conflict of interest., (Copyright © 2024 National League for Nursing.)

Purpose: Health care systems have historically struggled to provide adequate care for patients with complex care needs that often result in overuse of hospital and emergency department resources. Patients with complex care needs generally have increased expenses, longer length of hospital stays, an increased need for care management resources during hospitalization, and high readmission rates. Mayo Clinic in Arizona aimed to ensure successful transitions for hospitalized patients with complex care needs to the community by developing a complex care transition team (CCTT) program. With typical care management models, patients are assigned to registered nurse case managers and social workers according to the inpatient nursing unit rather than patient care complexity. Patients with complex care needs may not receive the amount of time needed to ensure an efficient and effective transition to the community setting. Furthermore, after transitioning to the community, patients with complex care needs often do not have access to care management resources if further care coordination needs arise., Primary Practice Setting: Acute care hospital in the US Southwest., Methodology and Sample: The CCTT was composed of a registered nurse case manager, social worker, and care management assistant, with physician advisor support. The CCTT followed patients with complex care needs during their hospitalization and transition to the community for 90 days after discharge. The number of inpatient admissions and hospital readmission rates were compared between 6 months before and after enrollment in the CCTT program. Cost savings for decreased hospital length of stay, emergency department visits, and hospital readmissions were also determined., Results: The CCTT selected patients according to a complex care algorithm , which identified patients who required high use of the health care system. The CCTT then followed this cohort of patients for an average of 90 days after discharge. A total of 123 patients were enrolled in the CCTT program from July 1, 2019, to April 30, 2021, and 80 patients successfully graduated from the program. Readmission rates decreased from 51.2% at 6 months before the intervention to 22.0% at 6 months after the intervention. This reduced readmission rate resulted in a cost savings of more than $1 million., Implications for Case Management Practice: The outcomes resulting from implementation of the multidisciplinary CCTT highlight the need for a patient-specific approach to transitioning care to the outpatient setting. The patient social determinants of health that often contributed to overuse of health care resources included poor access to outpatient specialists, difficulty navigating the health care system due to illness or poor health literacy, and limited social support. The success of the CCTT program prompted the implementation of other specialty-specific pilot programs at Mayo Clinic in Arizona. The investment of time and resources, including dedicated personnel to follow patients with high hospital service usage, allows health care systems to reduce emergency department visits and hospital admissions and to provide patients with the best opportunity for success as they transition from the inpatient to outpatient setting., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The Glycemia Risk Index (GRI) was introduced as a single value derived from the ambulatory glucose profile that identifies patients who need attention. This study describes participants in each of the five GRI zones and examines the percentage of variation in GRI scores that is explained by sociodemographic and clinical variables among diverse adults with type 1 diabetes., Methods: A total of 159 participants provided blinded continuous glucose monitoring (CGM) data over 14 days (mean age [SD] = 41.4 [14.5] years; female = 54.1%, Hispanic = 41.5%). Glycemia Risk Index zones were compared on CGM, sociodemographic, and clinical variables. Shapley value analysis examined the percentage of variation in GRI scores explained by different variables. Receiver operating characteristic curves examined GRI cutoffs for those more likely to have experienced ketoacidosis or severe hypoglycemia., Results: Mean glucose and variability, time in range, and percentage of time in high, and very high, glucose ranges differed across the five GRI zones ( P values < .001). Multiple sociodemographic indices also differed across zones, including education level, race/ethnicity, age, and insurance status. Sociodemographic and clinical variables collectively explained 62.2% of variance in GRI scores. A GRI score ≥84.5 reflected greater likelihood of ketoacidosis (area under the curve [AUC] = 0.848), and scores ≥58.2 reflected greater likelihood of severe hypoglycemia (AUC = 0.729) over the previous six months., Conclusions: Results support the use of the GRI, with GRI zones identifying those in need of clinical attention. Findings highlight the need to address health inequities. Treatment differences associated with the GRI also suggest behavioral and clinical interventions including starting individuals on CGM or automated insulin delivery systems., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background : Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods : An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results : The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion : The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Context: People with clinically diagnosed type 2 diabetes (T2D) but positive anti-glutamic acid decarboxylase autoantibodies (GADA), referred to here as latent autoimmune diabetes in adults (LADA), may experience more rapid glycemic deterioration than those with T2D and may benefit from effective diabetes treatment with additional metabolic benefits., Objective: Assess glycated hemoglobin (HbA1c) and body weight (BW) changes associated with tirzepatide in GADA-positive versus GADA-negative participants with clinical T2D diagnosis., Design: Post hoc analyses based on pooled data from SURPASS 2-5, using mixed-model repeated measures from the efficacy analysis set, adjusting for study and baseline covariates including age, sex, baseline values, body mass index (BMI), and GADA status., Setting: N/A., Patients: N = 3791., Intervention: Tirzepatide (5, 10, 15 mg)., Main Outcome Measure(s): Change from baseline in HbA1c at Weeks 40 (SURPASS-2, -3, -5) and 42 (SURPASS-4)by GADA status., Results: In participants with confirmed GADA status, 3671 (96.8%) were GADA-negative and 120 (3.2%) were GADA-positive (76 [63.3%] with low and 44 [36.7%] with high GADA levels). Baseline characteristics were similar between groups, except for slightly lower BMI in GADA-positive versus GADA-negative participants (mean [SD] BMI 32.2 [6.1] versus 33.6 [6.3] kg/m2). At Week 40/42, both groups achieved robust reductions in HbA1c (-2.11% versus -2.32%) and BW (9.2 kg versus -9.6 kg) (p < 0.001, both groups). HbA1c reductions were greater in GADA-negative participants (estimated difference [95% CI]: 0.21% [0.03, 0.39]; p = 0.024) and BW reductions did not differ between groups (0.38 kg [-0.99, 1.75]; p = 0.588)., Conclusions: In this post hoc analysis, tirzepatide was associated with substantial reductions in HbA1c and BW irrespective of GADA status in adults diagnosed with T2D, suggesting that tirzepatide may improve glycemic control in individuals with LADA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: The Oncotype DX Breast RS test has been adopted in Scotland and has been the subject of a large population-based study by a Scottish Consensus Group to assess the uptake of the recurrence score (RS), evaluate co-variates associated with the RS and to analyse the effect it may have had on clinical practice., Materials & Methods: Pan-Scotland study between August 2018-August 2021 evaluating 833 patients who had a RS test performed as part of their diagnostic pathway. Data was extracted retrospectively from electronic records and analysis conducted to describe change in chemotherapy administration (by direct comparison with conventional risk assessment tools), and univariate/multivariate analysis to assess relationship between covariates and the RS., Results: Chemotherapy treatment was strongly influenced by the RS (p < 0.001). Only 30 % of patients received chemotherapy treatment in the intermediate and high risk PREDICT groups, where chemotherapy is considered. Additionally, 55.5 % of patients with a high risk PREDICT had a low RS and did not receive chemotherapy. There were 17 % of patients with a low risk PREDICT but high RS who received chemotherapy. Multivariate regression analysis showed the progesterone receptor Allred score (PR score) to be a strong independent predictor of the RS, with a negative PR score being associated with high RS (OR 4.49, p < 0.001). Increasing grade was also associated with high RS (OR 3.81, p < 0.001). Classic lobular pathology was associated with a low RS in comparison to other tumour pathology (p < 0.01). Nodal disease was associated with a lower RS (p = 0.012) on univariate analysis, with menopausal status (p = 0.43) not influencing the RS on univariate or multivariate analysis., Conclusions: Genomic assays offer the potential for risk-stratified decision making regarding the use of chemotherapy. They can help reduce unnecessary chemotherapy treatment and identify a subgroup of patients with more adverse genomic tumour biology. A recent publication by Health Improvement Scotland (HIS) has updated guidance on use of the RS test for NHS Scotland. It suggests to limit its use to the intermediate risk PREDICT group. Our study shows the impact of the RS test in the low and high risk PREDICT groups. The implementation across Scotland has resulted in a notable shift in practice, leading to a significant reduction in chemotherapy administration in the setting of high risk PREDICT scores returning low risk RS. There has also been utility for the test in the low risk PREDICT group to detect a small subgroup with a high RS. We have found the PR score to have a strong independent association with high risk RS. This finding was not evaluated by the key RS test papers, and the potential prognostic information provided by the PR score as a surrogate biomarker is an outstanding question that requires more research to validate., Competing Interests: Declaration of competing interest Dr Adam L Peters has received a travel grant to attend the Royal College of Radiology Clinical Oncology academic training day from the Beatson Cancer Charity. Miss Beatrix Elsberger has had an advisor role with Exact Sciences, and has received a travel grant to attend a meeting in London. The funds received were put back into the departmental pot to help fund a research nurse., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Objectives: To identify and distinguish between racial and socioeconomic disparities in age at hepatology care, diagnosis, access to surgical therapy, and liver transplant-free survival in patients with biliary atresia (BA)., Methods: Single-center retrospective cohort study of 69 BA patients from 2010 to 2021. Patients were grouped into White and non-White cohorts. The socioeconomic milieu was analyzed utilizing neighborhood deprivation index, a census tract-based calculation of six socioeconomic variables. The primary outcomes of this study were timing of the first hepatology encounter, surgical treatment with hepatic portoenterostomy (HPE), and survival with native liver (SNL) at 2 years., Results: Patients were 55% male and 72% White. White patients were referred at a median of 34 days (interquartile range [IQR]: 17-65) vs. 67 days (IQR: 42-133; p = 0.001) in non-White patients. White infants were more likely to undergo HPE (42/50 patients; 84%) compared to non-White (10/19; 53%), odds ratio (OR) 4.73 (95% confidence interval: 1.46-15.31; p = 0.01). Independent of race, patients exposed to increased neighborhood-level deprivation were less likely to receive HPE (OR: 0.49, p = 0.04) and achieve SNL (OR: 0.54, p = 0.02)., Conclusions: Racial and socioeconomic disparities are independently associated with timely BA diagnosis, access to surgical treatment, and transplant-free survival. Public health approaches to improve screening for pathologic jaundice in infants of diverse racial backgrounds and to test and implement interventions for socioeconomically at-risk families are needed., (© 2024 The Authors. Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Importance: The effect of testosterone replacement therapy (TRT) in men with hypogonadism on the risk of progression from prediabetes to diabetes or of inducing glycemic remission in those with diabetes is unknown., Objective: To evaluate the efficacy of TRT in preventing progression from prediabetes to diabetes in men with hypogonadism who had prediabetes and in inducing glycemic remission in those with diabetes., Design, Setting, and Participants: This nested substudy, an intention-to-treat analysis, within a placebo-controlled randomized clinical trial (Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men [TRAVERSE]) was conducted at 316 trial sites in the US. Participants included men aged 45 to 80 years with hypogonadism and prediabetes or diabetes who were enrolled in TRAVERSE between May 23, 2018, and February 1, 2022., Intervention: Participants were randomized 1:1 to receive 1.62% testosterone gel or placebo gel until study completion., Main Outcomes and Measures: The primary end point was the risk of progression from prediabetes to diabetes, analyzed using repeated-measures log-binomial regression. The secondary end point was the risk of glycemic remission (hemoglobin A1c level <6.5% [to convert to proportion of total hemoglobin, multiply by 0.01] or 2 fasting glucose measurements <126 mg/dL [to convert to mmol/L, multiply by 0.0555] without diabetes medication) in men who had diabetes., Results: Of 5204 randomized participants, 1175 with prediabetes (mean [SD] age, 63.8 [8.1] years) and 3880 with diabetes (mean [SD] age, 63.2 [7.8] years) were included in this study. Mean (SD) hemoglobin A1c level in men with prediabetes was 5.8% (0.4%). Risk of progression to diabetes did not differ significantly between testosterone and placebo groups: 4 of 598 (0.7%) vs 8 of 562 (1.4%) at 6 months, 45 of 575 (7.8%) vs 57 of 533 (10.7%) at 12 months, 50 of 494 (10.1%) vs 67 of 460 (14.6%) at 24 months, 46 of 359 (12.8%) vs 52 of 330 (15.8%) at 36 months, and 22 of 164 (13.4%) vs 19 of 121 (15.7%) at 48 months (omnibus test P = .49). The proportions of participants with diabetes who experienced glycemic remission and the changes in glucose and hemoglobin A1c levels were similar in testosterone- and placebo-treated men with prediabetes or diabetes., Conclusions and Relevance: In men with hypogonadism and prediabetes, the incidence of progression from prediabetes to diabetes did not differ significantly between testosterone- and placebo-treated men. Testosterone replacement therapy did not improve glycemic control in men with hypogonadism and prediabetes or diabetes. These findings suggest that TRT alone should not be used as a therapeutic intervention to prevent or treat diabetes in men with hypogonadism., Trial Registration: ClinicalTrials.gov Identifier: NCT03518034.

Introduction: Positional changes in intracranial pressure (ICP) have been described in humans when measured over minutes or hours in a static posture, with ICP higher when lying supine than when sitting or standing upright. However, humans are often ambulant with frequent changes in position self-generated by active movement., Research Question: We explored how ICP changes during movement between body positions., Material and Methods: Sixty-two patients undergoing clinical ICP monitoring were recruited. Patients were relatively well, ambulatory and of mixed age, body habitus and pathology. We instructed patients to move back and forth between sitting and standing or lying and sitting positions at 20 s intervals after an initial 60s at rest. We simultaneously measured body position kinematics from inertial measurement units and ICP from an intraparenchymal probe at 100 Hz., Results: ICP increased transiently during movements beyond the level expected by body position alone. The amplitude of the increase varied between participants but was on average ∼5 mmHg during sit-to-stand, stand-to-sit and sit-to-lie movements and 10.8 mmHg [95%CI: 9.3,12.4] during lie-to-sit movements. The amplitude increased slightly with age, was greater in males, and increased with median 24-h ICP. For lie-to-sit and sit-to-lie movements, higher BMI was associated with greater mid-movement increase (β = 0.99 [0.78,1.20]; β = 0.49 [0.34,0.64], respectively)., Discussion and Conclusion: ICP increases during movement between body positions. The amplitude of the increase in ICP varies with type of movement, age, sex, and BMI. This could be a marker of disturbed ICP dynamics and may be particularly relevant for patients with CSF-diverting shunts in situ., Competing Interests: This study was funded by the National Brain Appeal. MJB's research time was funded by the National Brain Appeal. EMM's research fellowship is sponsored by B. Braun. LD’A is supported by an 10.13039/501100000272NIHR Academic Clinical Fellowship and was the recipient of a research fellowship sponsored by B. Braun. LDW has received honoraria from and served on advisory boards for Medtronic, B. Braun and Codman. AKT's research time was supported by the 10.13039/501100000272National Institute for Health Research 10.13039/501100012621University College London Hospitals Biomedical Research Centre. The other authors have no disclosures to report., (© 2024 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Objectives: The Starzl Network for Excellence in Pediatric Transplantation identified optimizing immunosuppression (IS) as a priority practice improvement area for patients, families, and providers. We aimed to evaluate associations between clinical characteristics, early IS, and outcomes., Methods: We analyzed pediatric liver transplant (LT) data from 2013 to 2018 in the United Network for Organ Sharing (UNOS) and the Society of Pediatric Liver Transplantation (SPLIT) registries., Results: We included 2542 LT recipients in UNOS and 1590 in SPLIT. IS choice varied between centers with steroid induction and mycophenolate mofetil (MMF) use each ranging from 0% to 100% across centers. Clinical characteristics associated with early IS choice were inconsistent between the two data sets. T-cell depleting antibody use was associated with improved 1-year graft (hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.34-0.76) and patient (HR 0.40, 95% CI 0.20-0.79) survival in UNOS but decreased 1-year patient survival (HR 4.12, 95% CI 1.31-12.93) and increased acute rejection (HR 1.58, 95% CI 1.07-2.34) in SPLIT. Non-T-cell depleting antibody use was not associated with differential risk of survival nor rejection. MMF use was associated with improved 1-year graft survival (HR 0.73, 95% CI 0.54-0.99) in UNOS only., Conclusions: Variation exists in center choice of early IS regimen. UNOS and SPLIT data provide conflicting associations between IS and outcomes in multivariable analysis. These results highlight the need for future multicenter collaborative work to identify evidence-based IS best practices., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Aims: Patients with breast cancer who have positive lymph nodes are currently recommended axillary node clearance (ANC) or regional nodal irradiation (RNI). ANC is associated with complications such as lymphoedema, brachial plexopathy and shoulder stiffness. The AMAROS Group showed RNI to be non-inferior to ANC with regards to survival and recurrence, and with a better quality of life. We conducted a large real-world population study to show our centre's experience with the use of RNI and to contribute to the current discussion around the management of node-positive breast cancer., Materials and Methods: We evaluated patients who received RNI as opposed to ANC between 2006 and 2009 (n = 190). Patients had a range of cancer subtypes/grades. All had positive axillary disease, identified by axillary node sampling or sentinel lymph node biopsy. Systemic therapy was given as per standard protocol. Our data were compared with those of patients who had RNI (n = 681) in AMAROS. Patients were followed up retrospectively and overall survival, breast cancer-specific survival, distant metastasis-free survival, locoregional recurrence and toxicity were recorded, including lymphoedema, brachial plexopathy and shoulder stiffness. Survival analysis was performed on R via the Kaplan-Meier method. Univariate and multivariate analyses were also performed. Toxicity data were reported as percentages. Patients meeting POSNOC trial criteria (one to two positive sentinel lymph nodes, macrometastasis, receiving adjuvant chemotherapy) including if oestrogen receptor-positive (stratified POSNOC) were identified for subgroup analysis in the regression model., Results: Locoregional recurrence was 3.16% versus AMAROS RNI of 1.82%. Overall survival was slightly lower in our population, but cancer-specific survival was higher than AMAROS. Lymphoedema rates were 5.8% versus AMAROS 11% in RNI and 23% in ANC arms, respectively. Brachial plexopathy was 1.6% and arm/shoulder stiffness 7.4%. AMAROS conducted a quality of life survey pertaining to arm/shoulder stiffness, mobility and function, which seemed to affect about 18% in the RNI arm. Univariate analysis revealed POSNOC status, especially if also oestrogen receptor-positive, to be a low risk group with hazard ratio 0.42 (0.20-0.83, P = 0.015). Extracapsular extension of lymph node metastasis was a poor prognostic factor; hazard ratio 4.39 (1.45-14.0, P = 0.009)., Conclusion: We support the conclusion of the AMAROS trial with survival and recurrence following RNI being non-inferior to ANC, and with similarly favourable toxicity data. We support the continuing use of RNI as a treatment option for patients with node-positive breast cancer. Further research is required to answer the key questions regarding personalised management for node-positive breast cancer, with regards to de-escalation and also intensification for the patients exhibiting adverse tumour biology., (Copyright © 2023. Published by Elsevier Ltd.)

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data., Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation., Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals., Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

Objective: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years., Study Design: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021., Results: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively., Conclusions: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: While there is evidence that functioning, or ability to perform daily life activities, can be adversely influenced by type 1 diabetes, the impact of acute fluctuations in glucose levels on functioning is poorly understood., Research Design and Methods: Using dynamic structural equation modeling, we examined whether overnight glucose (coefficient of variation[CV], percent time <70 mg/dL, percent time >250 mg/dL) predicted seven next-day functioning outcomes (mobile cognitive tasks, accelerometry-derived physical activity, self-reported activity participation) in adults with type 1 diabetes. We examined mediation, moderation, and whether short-term relationships were predictive of global patient-reported outcomes., Results: Overall next-day functioning was significantly predicted from overnight CV (P = 0.017) and percent time >250 mg/dL (P = 0.037). Pairwise tests indicate that higher CV is associated with poorer sustained attention (P = 0.028) and lower engagement in demanding activities (P = 0.028), time <70 mg/dL is associated with poorer sustained attention (P = 0.007), and time >250 mg/dL is associated with more sedentary time (P = 0.024). The impact of CV on sustained attention is partially mediated by sleep fragmentation. Individual differences in the effect of overnight time <70 mg/dL on sustained attention predict global illness intrusiveness (P = 0.016) and diabetes-related quality of life (P = 0.036)., Conclusions: Overnight glucose predicts problems with objective and self-reported next-day functioning and can adversely impact global patient-reported outcomes. These findings across diverse outcomes highlight the wide-ranging effects of glucose fluctuations on functioning in adults with type 1 diabetes., (© 2023 by the American Diabetes Association.)

Analog insulins, insulin pumps, and continuous glucose monitors (CGM) have revolutionized type 1 diabetes (T1D) treatment over the last 50 years. Nevertheless, less than 20% of patients in the United States reach guideline-based HbA1c targets. The dysfunctional delivery of U.S. health care has further worsened glycemic outcomes among structurally disadvantaged groups such as non-Hispanic Black and low-income populations. Administrative complexities resulting from mixed insurance coverage and delivery systems, incongruity between effective policies and reimbursement, structural racism, and implicit biases have led to high diabetes care-related costs, provider scarcity and burnout, and patient diabetes distress. The Extension for Community Healthcare Outcomes (ECHO) Diabetes tele-education outreach model was created to increase self-efficacy among primary care providers through a combination of weekly didactic sessions led by a team of diabetes experts and access to community-based peer coaches. As an evolution of ECHO Diabetes, Blue Circle Health has been established as a philanthropically funded health care delivery system, using a whole-person, individualized approach to T1D care for adults living in underserved communities. The program will provide direct-to-patient telehealth services, including diabetes education, management, and related psychological care regardless of ability to pay. Community-based diabetes support coaches will serve as the primary point of contact, or guide on the "Blue Circle Health Member Journey." Access to needed insulins, supplies, and CGMs will be provided at no cost to the individual. Through a continuous learning and improvement model, a person-centered, equitable, accessible, and effective health care delivery model will be built for people living with T1D.

Aim: To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium-glucose co-transporters 1 and 2, in adults with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3)., Materials and Methods: This phase 3, randomized, placebo-controlled trial evaluated sotagliflozin 200 and 400 mg in 787 patients with T2D and an estimated glomerular filtration rate of 30-59 ml/min/1.73m 2 . The primary objective was superiority of week 26 HbA1c reductions with sotagliflozin versus placebo. Secondary endpoints included changes in other glycaemic and renal endpoints overall and in CKD3 subgroups., Results: At 26 weeks, the placebo-adjusted mean change in HbA1c (from a baseline of 8.3% ± 1.0%) was -0.1% (95% CI: -0.2% to 0.05%; P = .2095) and -0.2% (-0.4% to -0.09%; P = .0021) in the sotagliflozin 200 and 400 mg groups, respectively. Significant reductions in fasting plasma glucose and body weight, but not systolic blood pressure, were observed. Among patients with at least A2 albuminuria at week 26, the urine albumin-creatinine ratio (UACR) was reduced with both sotagliflozin doses relative to placebo. At week 52, UACR was reduced with sotagliflozin 200 mg in the CKD3B group. Adverse events (AEs), including serious AEs, were similar between the treatment groups., Conclusions: After 26 weeks, HbA1c was significantly reduced with sotagliflozin 400 but not 200 mg compared with placebo in this CKD3 cohort. UACR in patients with at least A2 albuminuria was reduced with each of the two doses at 26 weeks, but changes were not sustained at week 52. The safety findings were consistent with previous reports (NCT03242252)., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Pulmonary complications of blood transfusion, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload (TACO), and transfusion-associated dyspnea, are generally underdiagnosed and under-reported. The international TRALI and TACO definitions have recently been updated. Currently, no standardized pulmonary transfusion reaction reporting form exists and most of the hemovigilance forms have not yet incorporated the updated definitions. We developed a harmonized reporting form, aimed at improved data collection on pulmonary transfusion reactions for hemovigilance and research purposes by developing a standardized model reporting form and flowchart., Materials and Methods: Using a modified Delphi method among an international, multidisciplinary panel of 24 hemovigilance experts, detailed recommendations were developed for a standardized model reporting form for pulmonary complications of blood transfusion. Two Delphi rounds, including scoring systems, took place and several subsequent meetings were held to discuss issues and obtain consensus. Additionally, a flowchart was developed incorporating recently published redefinitions of pulmonary transfusion reactions., Results: In total, 17 participants completed the first questionnaire (70.8% response rate) and 14 participants completed the second questionnaire (58.3% response rate). According to the results from the questionnaires, the standardized model reporting form was divided into various subcategories: general information, patient history and transfusion characteristics, reaction details, investigations, treatment and supportive care, narrative, and transfused product., Conclusion: In this article, we present the recommendations from a global group of experts in the hemovigilance field. The standardized model reporting form and flowchart provide an initiative that may improve data collected to address pulmonary transfusion reactions., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Time spent in glycemic target range (time in range [TIR]; plasma glucose 70-180 mg/dL [3.9-10.0 mmol/L]) as a surrogate endpoint for long-term diabetes-related outcomes requires validation. This post hoc analysis investigated the association between TIR, derived from 8-point glucose profiles (derived TIR [dTIR]) at 12 months, and time to cardiovascular or severe hypoglycemic episodes in people with type 2 diabetes in the DEVOTE trial. At 12 months, dTIR was significantly negatively associated with time to first major adverse cardiovascular event ( P  = 0.0087), severe hypoglycemic episode ( P  < 0.0001), or microvascular event ( P  = 0.024). A nonsignificant trend was seen toward association between 12-month hemoglobin A1c (HbA1c) and these outcomes, but this was no longer seen after addition of dTIR to the model. The results support targeting TIR >70% and suggest dTIR could be used in addition to, or in some instances in place of, HbA1c as a clinical biomarker. Trial registration details: ClinicalTrials.gov, NCT01959529.

Background: Tacrolimus (TAC)-mediated renal disease occurs in up to 70% of pediatric liver transplant (LT) recipients. The safety and efficacy of renal-sparing immunosuppression using anti-thymocyte globulin (ATG) induction and delayed TAC administration has not been studied in children. We evaluated the safety and efficacy of ATG induction on preserving renal function in children within the first year (Y1) post-LT in a single-center retrospective cohort study., Methods: Children under age 18 years of who received isolated LT from 2008 to 2020 with a GFR < 70 received renal-sparing (RS) protocol consisting of ATG with methylprednisolone (MP), delayed TAC administration, lower initial TAC trough goals, and mycophenolate mofetil (MMF). The RS group was matched 1:2 by age and LT indication with standard immunosuppression (SI) group. Changes in renal function as well as adverse events within Y1 post-LT were compared., Results: Forty-four pediatric patients were included in the analysis, of which 13 received RS. As expected, the RS group had significantly lower mean TAC trough levels at 30 days (10.3 vs. 13.2, p = .001) post-LT. Renal function was significantly preserved at 6 (-0.26 vs. 0.21, p = .004) and 12 months (-0.33 vs. 0.11, p = .003) post-LT in the RS versus SI group as measured by mean change in serum creatinine, with similar trends observed in eGFR and cystatin C. ACR, sepsis, viremia, graft loss and mortality occurred at similar rates in both RS and SI groups., Conclusion: Induction immunosuppression with ATG and delayed TAC administration in children with renal impairment is safe and effectively preserves renal function during Y1 post-LT., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Background: Late acute cellular rejection (ACR) is associated with donor-specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T-cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR. To test the hypothesis that the inflammatory milieu is associated with delayed response (DR) to rejection therapy, we performed a single-center retrospective case-control study of pediatric late liver ACR using multiparameter immunofluorescence for CD4, CD8, CD68, CD20, and CD138 to identify immune cell subpopulations., Methods: Pediatric liver transplant recipients transplanted at <17 years of age and treated for biopsy-proven late ACR between January 2014 and 2019 were stratified into rapid response (RR) and DR based on alanine aminotransferase (ALT) normalization within 30 days of diagnosis. All patients received IV methylprednisolone as an initial rejection treatment. Immunofluorescence was performed on archived formalin-fixed paraffin embedded (FFPE) liver biopsy tissue., Results: Liver biopsies from 60 episodes of late ACR in 54 patients were included in the analysis, of which 33 were DR (55%). Anti-thymocyte globulin was only required in the DR group. The frequency of liver-infiltrating CD20 + and CD8 + lymphocytes and the prevalence of autoantibodies were higher in the DR group. In univariate logistic regression analysis, serum gamma-glutamyl transpeptidase (GGT) level at diagnosis, but not ALT, Banff score or presence of DSA, predicted DR., Conclusions: Higher serum GGT level, presence of autoantibodies, and increased CD8 + T-cell infiltration portends DR in late ACR treatment in children., (© 2023 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Objective: Automated insulin delivery (AID) has rarely been studied in adults with type 2 diabetes. We tested the feasibility of using AID for type 2 diabetes with the Omnipod 5 System in a multicenter outpatient trial., Research Design and Methods: Participants previously were using either basal-only or basal-bolus insulin injections, with or without the use of a continuous glucose monitor (CGM), and had a baseline HbA1c ≥8% (≥64 mmol/mol). Participants completed 2 weeks of CGM sensor data collection (blinded for those not previously using CGM) with their standard therapy (ST), then transitioned to 8 weeks of AID. Participants who previously used basal-only injections used the AID system in manual mode for 2 weeks before starting AID. Antihyperglycemic agents were continued at clinician discretion. Primary safety outcomes were percentage of time with sensor glucose ≥250 mg/dL and <54 mg/dL during AID. Additional outcomes included HbA1c and time in target range (TIR) (70-180 mg/dL)., Results: Participants (N = 24) had a mean (± SD) age of 61 ± 8 years, baseline HbA1c of 9.4% ± 0.9% (79 ± 10 mmol/mol), and diabetes duration of 19 ± 9 years. Percentage of time with sensor glucose ≥250 mg/dL decreased with AID by 16.9% ± 16.2% (P < 0.0001), whereas percentage of time at <54 mg/dL remained low during both ST and AID (median [interquartile range] 0.0% [0.00%, 0.06%] vs. 0.00% [0.00%, 0.03%]; P = 0.4543). HbA1c (± SD) decreased by 1.3% ± 0.7% (14 ± 8 mmol/mol; P < 0.0001) and TIR increased by 21.9% ± 15.2% (P < 0.0001) without a significant change in total daily insulin or BMI with AID., Conclusions: Findings from this feasibility trial of AID in adults with type 2 diabetes with suboptimal glycemic outcomes justify further evaluation of this technology in this population., (© 2023 by the American Diabetes Association.)

Labeling of platelets (PLTs) is essential for research purposes, in order to measure the recovery and survival of transfused PLTs in vivo. Biotinylation is a promising new alternative to the gold standard of radioactive labeling. This review highlights 4 key publications that provide significant insights into biotin-labeled PLTs (bioPLTs). Stohlawetz et al. established that transfusion of bioPLTs in human recipients is possible. De Bruin et al. developed a standardized, reproducible protocol for biotinylation of PLTs as a promising method to trace and isolate transfused PLTs in vivo, with reduced levels of PLT activation markers. Muret et al. developed a nonwashing biotin labeling method to implement in a blood bank environment. Finally, in a preclinical study, Ravanat et al. showed that different densities of biotin can be used to concurrently monitor multiple populations of human PLTs in the circulation of the same subject. These studies have made major contributions to the development of bioPLTs as a viable option for use in human research, and indicate that bioPLTs can be safely administered, preferably at a low density of biotin., Competing Interests: Conflict of interest The authors have no conflict of interest to disclose in relation to the submitted review., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Regular physical activity improves cardiometabolic and musculoskeletal health, helps with weight management, improves cognitive and psychosocial functioning, and is associated with reduced mortality related to cancer and diabetes mellitus. However, turnover rates of glucose in the blood increase dramatically during exercise, which often results in either hypoglycaemia or hyperglycaemia as well as increased glycaemic variability in individuals with type 1 diabetes mellitus (T1DM). A complex neuroendocrine response to an acute exercise session helps to maintain circulating levels of glucose in a fairly tight range in healthy individuals, while several abnormal physiological processes and limitations of insulin therapy limit the capacity of people with T1DM to exercise in a normoglycaemic state. Knowledge of the acute and chronic effects of exercise and regular physical activity is critical for the formulation of clinical strategies for the management of insulin and nutrition for active patients with T1DM. Emerging diabetes-related technologies, such as continuous glucose monitors, automated insulin delivery systems and the administration of solubilized glucagon, are demonstrating efficacy for preserving glucose homeostasis during and after exercise in this population of patients. This Review highlights the beneficial effects of regular exercise and details the complex endocrine and metabolic responses to different types of exercise for adults with T1DM. An overview of basic clinical strategies for the preservation of glucose homeostasis using emerging technologies is also provided., (© 2022. Springer Nature Limited.)

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialised for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organisations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organisation has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonisation of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organisations for confirmation., (© 2022. American Diabetes Association and the European Association for the Study of Diabetes.)

Objectives: To assess risk factors and incidence of diabetes complications in women with type 1 diabetes (T1D) based on parity., Research Design/methods: Data were collected from women (16-40 years old) in the T1D Exchange completing pregnancy/childbirth questionnaires during 2011-2013 and 2016-2018. Incidence of risk factors and diabetes complications were compared between women with a first pregnancy at/within 1-year of enrollment ( n  = 28) and never pregnant women by year 5 ( n  = 469)., Results: There was a trend for lower HbA1c (adjusted p  = .14) and higher rates of overweight/obesity, triglyceride/HDL > 2, log (triglyercide/HDL), and hypertension among parous women compared with nulliparous women. There were no significant differences in rates of advanced nephropathy, albuminuria or cardiovascular disease., Conclusions: Four-5 years after delivery, parous women with T1D tended to have lower HbA1c levels despite higher body mass indices and more frequent adverse lipid profiles and hypertension compared with nulliparous women. Further studies based on these trends are warranted.

A technological solution for the management of diabetes in people who require intensive insulin therapy has been sought for decades. The last 10 years have seen substantial growth in devices that can be integrated into clinical care. Driven by the availability of reliable systems for continuous glucose monitoring, we have entered an era in which insulin delivery through insulin pumps can be modulated based on sensor glucose data. Over the past few years, regulatory approval of the first automated insulin delivery (AID) systems has been granted, and these systems have been adopted into clinical care. Additionally, a community of people living with type 1 diabetes has created its own systems using a do-it-yourself approach by using products commercialized for independent use. With several AID systems in development, some of which are anticipated to be granted regulatory approval in the near future, the joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association has created this consensus report. We provide a review of the current landscape of AID systems, with a particular focus on their safety. We conclude with a series of recommended targeted actions. This is the fourth in a series of reports issued by this working group. The working group was jointly commissioned by the executives of both organizations to write the first statement on insulin pumps, which was published in 2015. The original authoring group was comprised by three nominated members of the American Diabetes Association and three nominated members of the European Association for the Study of Diabetes. Additional authors have been added to the group to increase diversity and range of expertise. Each organization has provided a similar internal review process for each manuscript prior to submission for editorial review by the two journals. Harmonization of editorial and substantial modifications has occurred at both levels. The members of the group have selected the subject of each statement and submitted the selection to both organizations for confirmation., (© 2022 by the American Diabetes Association and the European Association for the Study of Diabetes.)

Background: Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusion that is thought of as a two-hit event: first the underlying patient condition (e.g., sepsis), and then the transfusion. Transfusion factors include human leukocyte antigen antibodies or biologic response modifiers (BRMs) accumulating during storage. Preclinical studies show an increased TRALI risk with longer stored platelets, clinical studies are conflicting. We aim to discover whether longer platelet concentrate (PC) storage time increases TRALI risk in a controlled human experiment., Study Design and Methods: In a randomized controlled trial, 18 healthy male volunteers received a first hit of experimental endotoxemia (2 ng/kg lipopolysaccharide), and a second hit of fresh (2-day old) or aged (7-day old) autologous PC, or physiological saline. After 6 h, changes in TRALI pathways were determined using spirometry, chest X-ray, and bronchoalveolar lavage (BAL)., Results: All subjects reacted adequately to lipopolysaccharide infusion and satisfied SIRS criteria (increased pulse [>90/min] and temperature [>38°C]). There were no differences between the saline, fresh, and aged PC groups in BAL-fluid protein (95 ± 33 μg/ml; 83 ± 21 μg/ml and 104 ± 29 μg/ml, respectively) and relative neutrophil count (1.5 ± 0.5%; 1.9 ± 0.8% and 1.3 ± 0.8%, respectively), nor in inflammatory BAL-fluid BRMs (Interleukin-6, CXCL8, TNFα , and myeloperoxidase), clinical respiratory parameters, and spirometry results. All chest X-rays were normal., Conclusions: In a human endotoxemia model of autologous platelet transfusion, with an adequate first hit and platelet storage lesion, transfusion of 7-day-old PC does not increase pulmonary inflammation compared with 2-day-old PC., (© 2022 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)