Treatment guidelines can improve population health; however, their implementation within electronic health records (EHRs) can be challenging. We aimed to create an implementable framework using the American Diabetes Association (ADA) Standards of Care (SOC) for people with type 2 diabetes and cardiovascular or renal disease as an example.

A multidisciplinary team used agile methods to translate the text-based ADA SOC into structured elements within the EHR, including logic-driven algorithms and ontology groupers for diagnoses, laboratory values, and medications, leveraging standard terminologies such as SNOMED CT, LOINC, and RxNorm.

The structured elements were used to implement 3 tools in the EHR: a real-time patient registry and 2 clinical decision support (CDS) instruments. The real-time registry enables dynamic, ongoing identification of patients eligible for guideline-directed medical therapy, supports more advanced analytics, and can be filtered to evaluate treatment gaps at the population and individual provider levels. The CDS tools allow clinicians to address these gaps directly within their EHR workflows.

Transforming clinical guidelines into executable constructs within the EHR is feasible but remains complex and labor-intensive. Broader and more consistent implementation could be achieved if guideline organizations provided technical frameworks, regular updates (through addenda or shared interfaces), and collaborated with EHR vendors to support the distribution and maintenance of implementable algorithms.

The integration of executable logic into clinical guidelines, using deterministic frameworks such as Unified Modeling Language and standardized ontologies, would simplify guideline implementation across EHR platforms.

Uterine leiomyomas are a common benign neoplasm of the female reproductive tract. They are often asymptomatic and can be present during pregnancy without complication. When leiomyomas outgrow their blood supply, the tissue undergoes degeneration. This process is most often seen in pregnancy. A rare complication of this process is spontaneous rupture, which is a surgical emergency often resulting in intra-abdominal leakage, bleeding, and peritonitis. This report describes the case of a 36-year-old White woman (G1P0) at 35 weeks of gestation with a known enlarging anterior fundal leiomyoma with degeneration who presented with worsening abdominal pain and contractions in the setting of gestational diabetes mellitus. Imaging and clinical findings were concerning for rupture of a degenerating fibroid with intra-abdominal fluid leakage. This event resulted in threatened preterm labor. She underwent low transverse cesarean section, resulting in delivery of a viable neonate. Intraoperative findings included a broad-based fundal leiomyoma with a 1.5 cm defect and drainage of degenerative contents. Six months postpartum, the patient had persistent fibroid degeneration requiring robotic-assisted laparoscopic myomectomy. This case highlights the rare but serious complications of leiomyoma rupture in pregnancy and underscores the importance of close monitoring and appropriate surgical intervention for patients with degenerating leiomyomas.

Uric acid metabolism is associated with the development of type 2 diabetes mellitus (T2DM), cardiometabolic, and cardiovascular diseases. Additionally, T2DM patients often exhibit mild cognitive impairment (MCI). However, the underlying mechanisms remain unclear. This study aims to identify and validate biomarkers associated with uric acid metabolism in T2DM and MCI, with the goal of discovering potential diagnostic and therapeutic targets to improve the quality of life for T2DM patients. Transcriptomic data for T2DM, MCI and uric acid metabolism-related genes were sourced from public databases. Biomarkers were screened using machine learning and validated for expression. Subsequent analyses included functional enrichment, immune infiltration, subcellular localization, and drug prediction. Three biomarkers-HP, ITGB3, and SELP-were identified. All showed significantly elevated expression in the T2DM group (p < 0.05). HP and ITGB3 were primarily enriched in ribosome-related pathways, primary immunodeficiency, and adherens junction processes. Immune infiltration analysis revealed that immature B cells and plasmacytoid dendritic cells were significantly enriched in T2DM. HP showed the strongest positive correlation with plasmacytoid dendritic cells (cor = 0.65, FDR <0.05), while ITGB3 exhibited the strongest positive correlation with immature B cells (cor = 0.76, FDR <0.05). Several potential therapeutic drugs were predicted, including calcifediol (score = -99.93) and meclofenamic acid (score = -99.89). This study identified three candidate biomarkers co-dysregulated across T2DM and MCI transcriptomes and associated with uric acid metabolism. Given the exploratory sample sizes, these findings are considered hypothesis-generating and require validation in larger independent cohorts.

To assess the real-world associations of five glucagon-like peptide-1 receptor agonists (GLP-1RAs) with weight loss in a diverse US population of adults with obesity, with and without type 2 diabetes, and whether the relative ordering of weight loss observed in trials is mirrored in routine practice.

We conducted a retrospective, new-user, active-comparator cohort study using the National Institutes of Health All of Us Research Program. We included 14,046 adults with obesity (body mass index [BMI] ≥30 kg/m²) initiating exenatide, liraglutide, dulaglutide, semaglutide, or tirzepatide. Groups were compared after multivariable adjustment for baseline confounders. Participants were followed from the index date until the outcome, death, or loss to follow-up; percent weight and BMI change was assessed at 12 months (±45 days). Cox proportional hazards models estimated the relative likelihood over time of achieving weight-loss thresholds (≥5%, ≥10%, ≥15%) and ≥1 BMI-category reduction; linear regression assessed the magnitude of weight change, with liraglutide as reference.

Tirzepatide showed the highest likelihood of ≥15% weight loss (adjusted hazard ratio [aHR] 5.57; 95% CI, 3.66-8.49) and the greatest mean weight loss at 12 months (-13.0%), followed by semaglutide (aHR 1.77; 95% CI, 1.56-2.01; -5.9%); both were significantly greater than the older agents in adjusted analyses. Exenatide, dulaglutide, and liraglutide showed comparable, modest weight loss (approximately -4.0%). This ordering was consistent regardless of type 2 diabetes status, although weight loss was greater without diabetes for semaglutide but similar for tirzepatide.

In this large, diverse real-world cohort, tirzepatide and semaglutide were associated with significantly greater weight loss than older agents. These findings are consistent with the relative ordering reported in trials, though the observational design cannot confirm it. Residual confounding cannot be excluded, and the small tirzepatide sample (n=386) and limited follow-up warrant cautious interpretation.

HbA1c and blood glucose (BS) are routinely used in diabetic care, but they do not provide direct information about ongoing cellular pathogenic processes. Previous studies in diabetic animal models identified a CD106⁺TNFα⁺proinsulin⁺ subset within short-term hematopoietic stem/progenitor cell populations, termed diabetes stem cells, that was implicated in diabetic pathology. In this study, we examined peripheral blood from patients with type 2 diabetes mellitus (T2DM) (n = 12) and healthy volunteers (n = 10). The proportion of CD106⁺TNFα⁺proinsulin⁺CD34⁺ cells was significantly higher in patients with T2DM than in healthy controls and showed a significant positive correlation with HbA1c levels. These findings suggest that this aberrant peripheral blood CD34⁺ subset may represent a candidate cellular biomarker associated with T2DM and chronic glycemic status. Further studies in larger cohorts are required to evaluate its clinical utility.

Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy, with a continuously rising global prevalence. However, current diagnostic and therapeutic strategies are limited by delayed detection and insufficient targeting. Extracellular vesicles (EVs), as nanoscale messengers that mediate intercellular communication, have recently been implicated in GDM pathogenesis and exhibit dual potential as liquid biopsy biomarkers and drug delivery vehicles. This review systematically integrates research findings on EVs in GDM, constructs an EV-mediated multi-organ crosstalk network framework, and comparatively evaluates the diagnostic and therapeutic potential of EVs derived from the placenta, adipose tissue, blood, breast milk, and urine. And further discussed current challenges and future directions for clinical translation of EV-based strategies. It provides an integrative perspective on the pathogenesis, precision diagnosis, and treatment of GDM and offers critical guidance for advancing the clinical translation of EV-based strategies.

Post-transplant diabetes mellitus (PTDM) is common after orthotopic heart transplantation (OHT), but its long-term impact on myocardial function is unclear. We aimed to evaluate the effects of PTDM on left ventricular (LV) systolic function.

We prospectively studied 102 OHT recipients with echocardiographic follow-up at 1-, 3-, and 5-year post-transplant. Patients were classified according to PTDM status at 1 year. LV systolic function was assessed using ejection fraction (EF) and global longitudinal strain (GLS). Linear mixed-effects models were used to evaluate longitudinal associations, adjusting for age, sex, systolic blood pressure, and cardiac allograft vasculopathy (CAV).

PTDM was present in 36% of patients. At 1-year, EF and GLS were similar between groups. At 3 years, patients with PTDM exhibited significantly lower systolic function as assessed by GLS (-14.9±2.8 vs. -16.0±3.0%, p=0.022), and at 5 years, EF was also significantly lower (52±4 vs. 57±7%, p=0.002). In longitudinal analyses, PTDM was associated with persistently impaired GLS without a significant interaction with time (p=0.192). In contrast, EF demonstrated a significant PTDM×time interaction (p=0.039), reflecting a greater decline over time in patients with PTDM. These associations remained significant after adjustment for CAV, which was not independently associated with GLS or EF.

PTDM after OHT is associated with early and persistent impairment in myocardial deformation, followed by a progressive decline in systolic function. These findings suggest a metabolically mediated myocardial effect independent of chronic graft failure and highlight the importance of early detection and management of PTDM in heart transplant recipients.

Advances in next-generation sequencing have expanded the identification of hereditary cancer patients, which account for approximately 10% of all cancer diagnoses. Precision medicine has profoundly reshaped the landscape of oncology, particularly in the management of hereditary cancer syndromes, through the convergence of germline genetics and targeted therapeutics. Disruption of homologous recombination repair genes such as BRCA1/2 and PALB2 confers synthetic lethal sensitivity to Poly ADP-ribose polymerase inhibitors and combination strategies targeting replication stress or cell-cycle checkpoints. Mismatch repair deficiency results in microsatellite instability and an increased neoantigen load, enabling durable responses to immune checkpoint blockade and supporting organ-preserving approaches in selected localized settings. Germline VHL inactivation induces a constitutive pseudohypoxic state that can be therapeutically exploited with HIF2α inhibitors in von Hippel-Lindau-associated neoplasms, illustrating interception of a lineage-agnostic metabolic axis. Activating germline RET pathogenic variants in hereditary medullary thyroid carcinoma demonstrate how highly selective kinase inhibitors can achieve superior efficacy-toxicity profiles compared with earlier multikinase agents. In patients with neurofibromatosis type 1, dysfunction of the neurofibromin GTPase-activating protein leads to RAS pathway hyperactivation, defining a rational therapeutic target. This evolving paradigm underscores the expanding role of germline testing beyond individuals with strong personal or family histories of cancer. Timely and equitable access to genetic results is essential to ensure that patients benefit from precision therapies without unnecessary delays. This review provides an integrative framework for bridging hereditary cancer and precision oncology.

Women with breast cancer face many barriers to returning to work (RTW) after their treatment. The Facilitating and Sustaining the Return to Work After Breast Cancer (FASTRACS) intervention aims to facilitate and sustain functional RTW.

The main objective of the RECOVA-FASTRACS (Realist Collaborative Evaluation of a Work Disability Prevention Program for Breast Cancer Survivors) study is to evaluate the processes using a realist approach that analyzes what works, how, for whom, and under what circumstances.

The RECOVA-FASTRACS study uses a mixed methods design to assess the implementation, context, and impact mechanisms of the FASTRACS intervention. The qualitative analysis will include 2 main components: a trajectory analysis and a focus group assessment. The trajectory analysis will examine the experiences of women who participated in the intervention and key individuals involved in their RTW process. We will use semistructured interviews according to the multiple-case study method. Additionally, to explore organizational and professional practices, focus groups will be conducted with professionals who deliver the intervention. To analyze the trajectories, embedded and iterative integration will combine the qualitative findings with relevant quantitative data from the FASTRACS randomized controlled trial for 5 domains: personal situation, professional situation, RTW, care pathway, intervention tool use, and perceived usefulness.

The RECOVA-FASTRACS study received funding in 2022. Recruitment and qualitative data collection began in month 6. Final analyses are expected to be completed by the end of 2026, with dissemination of the main findings anticipated in late 2027.

Our mixed methods realist evaluation will provide a detailed analysis of the intervention processes, helping to identify impact mechanisms within specific contexts. This approach is meant to ensure a more informed and realist deployment of the intervention by professionals following the study.

Introduction Basal cell markers and prostate lineage markers are routinely used as diagnostic adjuncts in prostatic epithelial lesions. High-molecular-weight cytokeratin (HMWCK/34βE12) highlights basal cells, whereas NKX3.1 is a prostate-restricted nuclear transcription factor with established diagnostic value in prostatic adenocarcinoma. The present study evaluated the diagnostic expression pattern of HMWCK and NKX3.1 and assessed whether NKX3.1 expression was associated with adverse clinicopathological parameters. Materials and methods This prospective observational study included 58 evaluable prostatic epithelial neoplasms received over 24 months at a tertiary care institute. HMWCK and NKX3.1 immunohistochemistry were performed on formalin-fixed paraffin-embedded tissue. NKX3.1 was scored as 0 (0% positive tumor cells), 1 (1-50%), and 2 (51-100%). Statistical analysis included chi-square/Fisher's exact tests, Mann-Whitney U test, Spearman correlation, and logistic regression. Serum prostate-specific antigen (PSA) values were available for analysis in 42 adenocarcinoma cases. Results The final cohort included 57 prostatic adenocarcinomas and one high-grade prostatic intraepithelial neoplasia. Among carcinoma cases, the mean age was 68.09 ± 8.04 years. HMWCK was absent in all adenocarcinoma cases, while NKX3.1 was positive in 55/57 cases (96.5%). NKX3.1 scores were 0 in two cases (3.5%), 1 in 30 cases (52.6%), and 2 in 25 cases (43.9%). Worst Gleason Grade Group showed a weak but significant inverse correlation with NKX3.1 score (Spearman rho = -0.286, p = 0.031). Perineural invasion (PNI) showed the strongest association with NKX3.1 expression; reduced NKX3.1 expression was present in 20/22 PNI-positive tumors compared with 12/35 PNI-negative tumors (p < 0.001; OR 19.17). Serum PSA also correlated inversely with NKX3.1 score among cases with available values (rho = -0.367, p = 0.017), and core involvement percentage correlated inversely with NKX3.1 score (rho = -0.365, p = 0.006). Conclusions HMWCK and NKX3.1 showed complementary diagnostic utility in prostatic adenocarcinoma. HMWCK supported invasive adenocarcinoma by demonstrating basal cell loss, while NKX3.1 was retained in most carcinomas as a sensitive prostatic lineage marker. Reduced NKX3.1 expression was associated with higher worst Grade Group, PNI, serum PSA, tumor core involvement, and adverse clinical status. The strongest association was observed between PNI and reduced NKX3.1 expression.