Citations

Context.— Complexity of ordering and transfusing blood is particularly evident in the pediatric population. Simplification, clarification, and standardization of blood orders can decrease complexity and improve patient safety. Objective.— To improve patient safety by optimizing electronic ordering of blood components in pediatrics through a collaborative process improvement initiative. Design.— A multidisciplinary working group, formed as part of a value stream analysis to improve transfusion safety at Children’s Healthcare of Atlanta (Atlanta, Georgia), focused on decreasing variability and providing clarity when ordering, preparing, and transfusing blood using the electronic health record. Through benchmarking with other pediatric institutions and a collaborative design process with multiple local stakeholders, an extensive redesign in the existing orders and order sets occurred. Metrics were collected to determine if a change was an improvement. Results.— Nurse and laboratory informaticists, a pathology informaticist, and a transfusion medicine specialist built the new orders based on the design. The new orders focused on the following changes: standardization, introduction of logic, naming conventions, clarifying definitions, adding calculations, improving transparency of history and laboratory data, removing aliquots, clarifying communication, and implementing additional modules to inform the provider of necessary information about the patient. Metrics included a decrease in the number of orders changed within an hour, decreased calls from the blood bank to the provider to clarify the order, and an absence of overtransfusions and transfusion-related serious safety events for a year following implementation. Conclusions.— This collaborative initiative, using standard process improvement tools, resulted in standardized blood orders improving transfusion safety.

AbstractThe Enhanced EHR-facilitated Cancer Symptom Control (E2C2) Trial is a pragmatic trial testing a collaborative care approach for managing common cancer symptoms. There were challenges in identifying cancer site and metastatic status.This study compares three different approaches to determine cancer site and six strategies for identifying the presence of metastasis using EHR and cancer registry data.The E2C2 cohort included 50,559 patients seen in the medical oncology clinics of a large health system. SPPADE symptoms were assessed with 0 to 10 numeric rating scales (NRS). A multistep process was used to develop three approaches for representing cancer site: the single most prevalent International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) code, the two most prevalent codes, and any diagnostic code. Six approaches for identifying metastatic disease were compared: ICD-10 codes, natural language processing (NLP), cancer registry, medications typically prescribed for incurable disease, treatment plan, and evaluation for phase 1 trials.The approach counting the two most prevalent ICD-10 cancer site diagnoses per patient detected a median of 92% of the cases identified by counting all cancer site diagnoses, whereas the approach counting only the single most prevalent cancer site diagnosis identified a median of 65%. However, agreement among the three approaches was very good (kappa > 0.80) for most cancer sites. ICD and NLP methods could be applied to the entire cohort and had the highest agreement (kappa = 0.53) for identifying metastasis. Cancer registry data was available for less than half of the patients.Identification of cancer site and metastatic disease using EHR data was feasible in this large and diverse cohort of patients with common cancer symptoms. The methods were pragmatic and may be acceptable for covariates, but likely require refinement for key dependent and independent variables.

Importance Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD). Objective To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes. Design, Setting, and Participants Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024. Cognitively unimpaired individuals and patients with a clinical diagnosis of mild cognitive impairment (MCI), AD dementia, or other neurodegenerative disorders were included. Exposures Tau PET with flortaucipir F 18, amyloid-β (Aβ) PET, and clinical examinations. Tau PET scans were visually rated as positive according to a US Food and Drug Administration– and European Medicines Agency–approved method, designed to indicate the presence of advanced neurofibrillary tangle pathology (Braak stages V-VI). Main Outcomes and Measures Frequency of tau PET positivity and absolute risk of clinical progression (eg, progression to MCI or dementia). Results Among the 6514 participants (mean age, 69.5 years; 50.5% female), median follow-up time ranged from 1.5 to 4.0 years. Of 3487 cognitively unimpaired participants, 349 (9.8%) were tau PET positive; the estimated frequency of tau PET positivity was less than 1% in those aged younger than 50 years, and increased from 3% (95% CI, 2%-4%) at 60 years to 19% (95% CI, 16%-24%) at 90 years. Tau PET positivity frequency estimates increased across MCI and AD dementia clinical diagnoses (43% [95% CI, 41%-46%] and 79% [95% CI, 77%-82%] at 75 years, respectively). Most tau PET–positive individuals (92%) were also Aβ PET positive. Cognitively unimpaired participants who were positive for both Aβ PET and tau PET had a higher absolute risk of progression to MCI or dementia over the following 5 years (57% [95% CI, 45%-71%]) compared with both Aβ PET–positive/tau PET–negative (17% [95% CI, 13%-22%]) and Aβ PET–negative/tau PET–negative (6% [95% CI, 5%-8%]) individuals. Among participants with MCI at the time of the tau PET scan, an Aβ PET–positive/tau PET–positive profile was associated with a 5-year absolute risk of progression to dementia of 70% (95% CI, 59%-81%). Conclusions and Relevance In a large convenience sample, a positive tau PET scan occurred at a nonnegligible rate among cognitively unimpaired individuals, and the combination of Aβ PET positivity and tau PET positivity was associated with a high risk of clinical progression in both preclinical and symptomatic stages of AD. These findings underscore the potential of tau PET as a biomarker for staging AD pathology.

Background: The use of validated risk stratification tools for the workup of suspected pulmonary embolism (PE) is a recommendation of the American Society of Hematology and the American College of Emergency Physicians. Methods: We designed and implemented electronic clinical pretest probability (PTP) tools for use in emergency departments (ED). Overall, 38 EDs (tertiary and regional EDs) in the United States were involved across three health systems. PTP use was analyzed between September 12, 2022 and January 11, 2023 in 270,247 ED visits. PTP use was examined in terms of the percentage of visits for which patients underwent computed tomography pulmonary angiography (CTPA). Each site chose the 3-tier Wells’ score for implementation and Site 2 designed a combined Wells’, pulmonary embolism rule-out criteria (PERC), and YEARS score. Results: At Site 3, forced use resulted in documented PTP scores in 49–53% of ordered CTPAs. At Sites 1 and 2, where PTP scores were optional, documented PTP scores occurred in 2–3% and 1–3% of CTPA orders, respectively. At Site 1, the use of PTP increased slightly over the study period, with signs that PE yield on imaging was also increasing (3.4–5.9%). At Site 2, PE yield on imaging was 9–10%, and it remained similar, with similar use of PTP tools over the study period. PE yield (6–8%) on imaging also remained similar throughout the study at Site 3. Conclusions: Guideline-endorsed PTP scores for PE at three independent health systems in the United States did not increase PE yield on imaging. Novel implementation strategies involving interdisciplinary teams are urgently needed.

For over a century, scientists reported the disruption of normal nuclear shape and size in cancer. These changes have long been used as tools for diagnosis and staging of malignancies. However, to date, the mechanisms underlying these aberrant nuclear phenotypes and their biological significance remain poorly understood. Using a model of pancreatic ductal adenocarcinoma (PDAC), the major histological subtypes of pancreatic cancer, we found that oncogenic mutant KRAS reduces nuclear size. Transcriptomic and protein expression analysis of mutant KRAS–expressing PDAC cells revealed differential levels of several nuclear envelope–associated genes. Further analysis demonstrated the nuclear lamina protein, Emerin (EMD), acted downstream of KRAS to mediate nuclear size reduction in PDAC. Analysis of human PDAC samples showed that increased EMD expression associates with reduced nuclear size. Finally, in vivo genetic depletion of EMD in a mutant KRAS–driven PDAC model resulted in increased nuclear size and a reduced incidence of poorly differentiated PDAC. Thus, our data provide evidence of a potentially novel mechanism underlying nuclear size regulation and its effect in PDAC carcinogenesis.

Disease response and progression assessment in multiple myeloma (MM) is based on various measurements of monoclonal protein (serum and urine protein electrophoresis, serum free light chain (FLC, and or quantitative immunoglobulins). Currently, the IMWG consensus response criteria require two sequential assessments of any one marker made at any time before confirmation of disease progression and the institution of any new therapy. However, this can be cumbersome in clinical trials. Herein, we hypothesized that if two markers meet the progression criteria simultaneously, a repeat of either will not be necessary for confirmation. We retrospectively studied all sequential patients with myeloma enrolled in clinical trials at Mayo Clinic. We identified 583 episodes of confirmed progression in our study. Among the 583 progression episodes, nearly 70% (sensitivity of the simultaneous criteria) met the two simultaneous variable criteria at the first testing, indicating progression. Conversely, among 413 patients who met progression criteria by two simultaneous values, 98% (specificity of the simultaneous criteria) of patients subsequently had confirmed progression by sequential values. In summary, for patients with two disease burden markers meeting the simultaneous progression criteria, sequential assessment either one for confirmation may not be necessary to determine disease progression.

OBJECTIVE Reports of surgical outcomes for Cushing’s disease are mostly limited to single-center experiences by expert surgeons. Therefore, no generalizable surgical outcome metrics for endoscopic endonasal Cushing’s disease surgery are available for practitioners to guide quality-improvement efforts. This is potentially problematic, given the high morbidity and excess mortality observed in patients who do not achieve remission. This study proposes a bundle of evidence-based metrics for low-risk patients with Cushing’s disease, for whom optimal outcomes would be expected, that focus on the cost efficiency of care and surgical outcomes from multicenter collaboration of US pituitary centers. METHODS The steering committee of the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) consortium proposed the metrics based on available data from 12 US pituitary centers. A benchmarking population of low-risk patients undergoing first-time surgery was identified. Patient characteristics and outcomes were aggregated and analyzed by a data coordinating center. Metrics were reported using 2 approaches. RESULTS A total of 431 patients from 12 centers who underwent primary endoscopic transsphenoidal surgery from January 1, 2006, to December 31, 2022, were included. There were 227 patients in the low-risk cohort (age < 70 years, BMI < 50, microadenoma, and Knosp grade 0–2). For the cost-efficiency metrics, the mean (SD) length of stay was 3.8 (4.8) midnights, and the percentage of patients readmitted was 11.1%. The rate of disposition to a skilled nursing facility was 2.2%. For surgical outcomes, the rate of postoperative CSF leakage was 1.3%, and the rate of 1-year sustained surgical remission was 81.2%. The rates of permanent and temporary arginine vasopressin deficiencies were 1.8% and 11.9%, respectively. The 75th percentile performance by center was 3.0 midnights for length of stay, 6.3% for 90-day unplanned readmission, < 1% for disposition to a skilled nursing facility, < 1% for CSF leakage, and 92.2% for 1-year sustained remission. The 75th percentile was < 1% for both permanent and temporary arginine vasopressin deficiencies. CONCLUSIONS An evidence-based bundle of metrics in a Cushing’s disease patient population at low risk who underwent first-time endoscopic pituitary surgery is proposed. Surgeons can use these metrics to assess and improve the quality of their clinical pathways.

Abstract Background Radiofrequency ablation (RFA) of neuromas has emerged as a potential treatment option for refractory neuroma‐associated postamputation pain (PAP). Objective To evaluate the feasibility of using internally cooled radiofrequency ablation (C‐RFA) for treating neuroma‐associated PAP. Design Prospective single‐arm pilot study. Setting Tertiary academic medical center. Participants Eight participants with neuroma‐associated PAP (mean age 56.5 [ interquartile range, 50.5–68.5] years; mean body mass index 30.2 [ interquartile range, 26.3–34.8] kg/m 2 ). Intervention Participants were recruited and treated with C‐RFA between 2019 and 2023. Main Outcome Measures Pain and functional outcomes were assessed at 1, 3, 6, and 12 months after C‐RFA using Numeric Rating Scale (NRS), Groningen Activity Restriction Scale (GARS), Patient Global Impression of Change (PGIC), and Medication Quantification Scale III (MQS‐III). Responder definitions for each outcome measure were ≥50% NRS reduction, ≥30% GARS improvement, ≥6 on PGIC, and ≥6.8‐point MQS‐III reduction. Results NRS responder rates at 1, 3, 6, and 12 months were 25.0% (95% CI, 7.0%–59.1%), 50.0% (95% CI, 21.5%–78.5%), 37.5% (95% CI, 13.7%–69.4%), and 50.0% (95% CI, 21.5%–78.5%), respectively. Responder rates for GARS were 25.0% (95% CI, 7.1%–59.1%) at 1 month and 12.5% (95% CI, 2.2%–47.1%) at 3, 6, and 12 months. The proportion of PGIC responders was 37.5% (95% CI, 13.7%–69.4%) at 1 and 3 months and 12.5% (95% CI, 2.2%–47.1%) at 6 and 12 months. MQS‐III responder rates were 25.0% (95% CI, 7.1%–59.1%) at 1 month, 12.5% (95% CI, 2.2%–47.1%) at 3 months, and 37.5% (95% CI, 13.7%–69.4%) at 6 and 12 months. There were no complications associated with the C‐RFA procedure. Conclusions These findings indicate the feasibility of neuroma C‐RFA as a treatment for refractory neuroma‐associated PAP but also suggest that further patient selection and C‐RFA technique optimization are warranted before investigating this treatment paradigm in a larger prospective study.

e19545 Background: Cytogenetic abnormalities (CA) at diagnosis are important prognostic factors in multiple myeloma (MM), but there is limited information on how these abnormalities evolve at first relapse and their significance. Methods: This retrospective study included patients aged ≥18 years, with a confirmed diagnosis of MM who experienced at least one disease relapse and had fluorescence in situ hybridization analysis within six months of both diagnosis and relapse. Data on CA and clinical outcomes were collected. High-risk (HR) secondary CA were defined as the presence of deletion of chromosome 17p (del17p) or gain or amplification of chromosome 1q. The primary objective was to evaluate changes in HR secondary CA at first relapse, while the secondary objective was to assess the impact of the cytogenetic changes on overall survival (OS) from diagnosis. Based on the presence or absence of HR secondary CA, patients who were tested for HR secondary CA at both time points were classified into four groups: 1) persistent absence of HR secondary CA, 2) emergence of HR secondary CA at relapse, 3) persistent presence of HR secondary CA, and 4) loss of HR secondary CA at relapse. Results: A total of 233 patients diagnosed between 2004 and 2023 were included. HR secondary CA were tested in 98.7% (n= 230) of patients at diagnosis, with 24.8% (n=57) testing positive. At first relapse, testing for HR secondary CA was performed in 97.4% (n=227) of patients, of whom 23.8% (n=54) tested positive. Del17p was evaluated in 98.3% (n=229) of patients at baseline and 95.7% (n=223) at relapse, with positivity increasing from 10.9% (n=25) to 15.3% (n=34). Gain or amplification of chromosome 1q was evaluated in 49.4% (n=115) at baseline and 25.5% (n=60) at relapse, with positivity rate rising from 28.7% (n=33) to 38.3% (n=23). There were no differences in overall response rate or very-good-partial-response-or-better rates to the initial therapy at diagnosis between the groups. (Table) Emergence/persistence of HR CA were associated with lower OS from diagnosis. Conclusions: Emergence of HR secondary CA at first relapse in MM has prognostic significance. These findings highlight the importance of serial cytogenetic testing for risk stratification. Response rate to initial line of therapy and overall survival from diagnosis among patients tested for HR secondary CA both at diagnosis and first relapse (n=224). Outcome Persistent absence of HR secondary CA(n=142) Emergence of HR secondary CA at relapse (n=25) Persistent presence of HR secondary CA (n=27) Loss of HR secondary CA at relapse(n=30) p-value Overall response rate a 75% (106) 76% (19) 63% (17) 67% (20) 0.5 b Very-good-partial response or better response rate 43% (61) 36% (9) 44% (12) 40% (12) >0.9 b Median (95% CI) OS from diagnosis in years 11.3 (9.7-13.4) 7.5 (5.1-12.1) 6.1 (4.2-9.4) 10.1 (6.5-14.1) <0.0001 c a Partial response or better; b Chi-square test; c Log-rank test.