Citations

Objective We sought to characterize the frequency of postoperative opioid prescriptions in patients undergoing cleft lip repair (CLR). Design The NSQIP-P 2023 database was queried to identify patients undergoing CLR using CPT codes. Univariable analysis was conducted to identify factors associated with postoperative opioid prescription. Setting A multicenter sample from 157 participating sites. Patients/participants A total of 1497 cases (1215 unilateral CLR and 282 bilateral CLR) were identified. Main outcomes/measures The postoperative outcomes of interest were whether an opioid was prescribed to a patient at discharge and what factors were independently associated with opioid prescribing at discharge. Results A total of 44.6% of patients with a mean age of 5.1 ± 1.9 months were prescribed opioids at discharge, most commonly oxycodone (76.3%). Univariable analysis identified an increase in weight (kg) (OR: 1.09, 95% CI: 1.02-1.17, P = .03), American Society of Anesthesiologists (ASA) classification (ordinal) (OR: 1.25, 95% CI: 1.06-1.47, P = .01), anesthesia time (10 min) (OR: 1.02, 95% CI: 1.01-1.04, P = .03), and age (months) (OR: 1.06, 95% CI: 1.00-1.12, P = .04) as being associated with opioid prescription at discharge. Bilateral versus unilateral CLR ( P = .49) and outpatient versus inpatient operation ( P = .38) were not associated with opioid prescribing. Conclusion Opioid stewardship is important in pediatric care, with our results showing age, weight, anesthesia time, and ASA classifications are predictors of opioid prescription. Further research examining contributors to patient pain following CLR is necessary to optimize opioid prescribing without negatively impacting the patient.

Background/Objectives: Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) may report abnormalities in voice and speech; however, no formal research has been conducted in this area. Methods: An online mixed-methods survey was completed by 685 people with ME/CFS. A total of 302 respondents completed the qualitative component (44.09%). Questions assessed disease experience with ME/CFS and post-exertional malaise without prompting on specific symptoms. Within the qualitative results, a search of the terms “speech, voice,” “words,” and “speak” was conducted. Results: Excluding neurocognitive associations, colloquial phrases, and “speech therapy,” there were 38 mentions of the terms in the context of voice or speech changes across 28 unique qualitative survey responses (9.27%). Conclusions: A notable portion of respondents reported voice or speech changes when responding to open-ended qualitative questions about their disease experience. More research is needed regarding the implications of voice and speech anomalies in ME/CFS pathology and disease monitoring.

Features of new bleeding on conventional imaging in cerebral cavernous malformations (CCMs) often disappear after several weeks, yet the risk of rebleeding persists long thereafter. Increases in mean lesional quantitative susceptibility mapping (QSM) ≥ 6% on MRI during 1 year of prospective surveillance have been associated with new symptomatic hemorrhage (SH) during that period. The authors hypothesized that QSM at a single time point reflects features of hemorrhage in the prior year or potential bleeding in the subsequent year. Twenty-eight features were extracted from 265 QSM acquisitions in 120 patients enrolled in a prospective trial readiness project, and machine learning methods examined associations with SH and biomarker bleed (QSM increase ≥ 6%) in prior and subsequent years. QSM features including sum variance, variance, and correlation had lower average values in lesions with SH in the prior year (p < 0.05, false discovery rate corrected). A support-vector machine classifier recurrently selected sum average, mean lesional QSM, sphericity, and margin sharpness features to distinguish biomarker bleeds in the prior year (area under the curve = 0.61, 95% CI 0.52–0.70; p = 0.02). No QSM features were associated with a subsequent bleed. These results provide proof of concept that machine learning may derive features of QSM reflecting prior hemorrhagic activity, meriting further investigation. Clinical trial registration no.: NCT03652181 ( ClinicalTrials.gov )

Objective: To develop an artificial intelligence–based pipeline to assess and triage patient-submitted postoperative wound images. Background: The rise of outpatient surgeries, remote monitoring, and patient-submitted wound images via online portals has contributed to a growing administrative workload on clinicians. Early identification of surgical site infection (SSI) is essential for reducing postoperative morbidity. Methods: Patients ≥18 years old who underwent surgery at 9 affiliated Mayo Clinic hospitals (2019-2022) and were captured by the National Surgical Quality Improvement Program (NSQIP) were included. Eligibility required submission of one image via the patient portal within 30 days after surgery. Images were independently screened in duplicate to determine the presence of an incision. SSI outcomes were obtained from NSQIP. The developed model consisted of 2 stages: incision detection and SSI detection in images with incisions. Four pretrained architectures were evaluated using 10-fold cross-validation, with upsampling and data augmentation to mitigate class imbalance. An end-to-end pipeline, image quality assessment and sensitivity analysis stratified by race were also performed. Results: Among 6060 patients, the median age was 54 years (interquartile range: 40–65), 61.4% (n=3805) were female, and 92.5% (n=5731) identified as White. SSIs were confirmed in 6.2% (n=386) images. Vision Transformer outperformed all others, achieving an incision detection accuracy of 0.94 (area under the curve=0.98) and an SSI detection accuracy of 0.73 (area under the curve=0.81). In addition, it demonstrated strong performance in assessing image quality. Sensitivity analysis revealed comparable performance across racial subgroups. Conclusion: This artificial intelligence pipeline demonstrates promising performance in automating wound image assessment and SSI detection, reducing clinical workload and improving postoperative care.

Background. Ex vivo machine perfusion (MP) has transformed organ preservation, offering significant benefits in liver transplantation (LT), particularly with high-risk donor grafts. However, adoption in the United States has been limited. We aimed to examine early adoption trends, surgeon perceptions, and barriers to implementing MP in the United States after Food and Drug Administration approval of MP platforms. Methods. A 23-question electronic survey was distributed to members of the American Society of Transplant Surgeons between October and November 2022, capturing attitudes and practices related to MP adoption. Responses from 96 surgeons representing 77 LT centers across 11 Organ Procurement and Transplantation Network regions were analyzed. Results. Forty-four respondents (48%) reported having an MP program at their institution. Adoption of MP was significantly more common in high-volume centers and those performing ≥20 donation after circulatory death (DCD) transplants annually (P < 0.001). MP utilization received strong support, with 88% endorsing its use for DCD liver allografts and 82% for donation after brain death allografts. Respondents cited MP’s ability to reduce ischemic cholangiopathy, enable graft repair, and facilitate viability assessment as key benefits. Normothermic MP was preferred for high-risk donor profiles, including DCD grafts, older donors, and steatotic livers, and was associated with an increased willingness to accept medically complex grafts compared with static cold storage. Barriers to MP utilization included program costs, personnel demands, and logistical complexities. Centers with higher proportions of privately insured patients were more likely to adopt MP. Despite these challenges, 84% of respondents expressed interest in future MP adoption. Conclusions. MP enhances graft utilization and outcomes, particularly for complex and high-risk donor livers, but widespread US adoption requires addressing financial and logistical barriers. Future efforts should focus on refining cost-effectiveness analyses, collaboration with organ procurement organizations and device companies, and developing standardized training to optimize MP integration and maximize its clinical impact on LT.

In REACH3 (ClinicalTrials.gov identifier: NCT03112603 ), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

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.

Abstract P2x purinoreceptor 7 (P2RX7), an ATP-gated ion channel, is known to play pivotal roles in the progression of Alzheimer’s disease (AD), although its cell type-specific pathological mechanisms have yet to be elucidated. Here, we show that genetic deletion of P2rx7 mitigates brain atrophy, tau accumulation and cognitive impairment in PS19 tauopathy mice. Specific deletion of P2rx7 in microglia, but not astrocytes, significantly suppresses tau propagation from the entorhinal cortex to CA1 in the hippocampus, an early event in AD pathology. Single-cell (sc)-RNA sequencing of mouse brains revealed specific P2rx7 expression in microglia, inducing inflammatory changes accompanied by elevated extracellular vesicles (EVs) secretion in PS19 mice. Brain-derived EVs (BDEVs) proteome demonstrated that P2RX7 increases EV cargo loading of tau and mitochondrial molecules in BDEVs from PS19 mice, which was further validated by single-molecule super-resolution. Notably, following the injection of BDEVs isolated from PS19 mice with or without P2rx7 deficiency, the microglial transcriptome of recipient mice revealed enriched DNA-sensing and type II interferon signaling in response to BDEVs from PS19 mice, which was diminished in the group injected with P2rx7-deficient BDEVs. Thus, our results indicate that P2RX7 regulates EV-mediated tau and mitochondrial transfer and inflammatory activation in microglia with increased EV secretion, thereby contributing to tauopathy and neurodegeneration, highlighting the therapeutic potential of targeting the P2RX7-EV axis in AD.

Objective: Diabetes is a defining disease of the 21st century because of its rising prevalence, association with obesity, and enormous health impact. Abundant evidence shows that lifestyle interventions can delay or prevent type 2 diabetes (T2D) in adults, offer relief, and sometimes achieve complete remission. Despite this empowering message, there are no clinical practice guidelines that focus primarily on lifestyle interventions as first-line management of prediabetes and T2D. Our objective, therefore, is to offer pragmatic, trustworthy, and evidence-based guidance for clinicians in using the 6 pillars of lifestyle medicine—nutrition, physical activity, stress management, sleep, social connectedness, avoidance of risky substances—for managing adults with T2D and in preventing T2D in adults with prediabetes or a history of gestational diabetes mellitus. Methods: We used well-established, peer-reviewed guideline methodology to develop evidence-based key action statements (recommendations) that facilitate quality improvement in clinical practice. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. Recommendation strength was based on the aggregate evidence supporting a key action statement plus a comparison of associated benefits vs harms/costs. Multiple literature searches, conducted by an information specialist, identified 8 relevant guidelines, 118 relevant systematic reviews, and 112 randomized clinical trials. The guideline underwent extensive internal, external, and public review and comment prior to publication. Results: We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Conclusions: There is robust research evidence supporting the efficacy of lifestyle interventions in preventing, treating, and achieving remission of T2D in adults. Our multidisciplinary guideline development group successfully synthesized this evidence into 14 key action statements that can be used by clinicians and other healthcare professionals to improve quality of care for adults with, or at-risk for, T2D. Despite the research gaps and implementation challenges we highlight in the guideline we believe strongly that our recommendations have immediate relevance and can help raise awareness and shift the paradigm of T2D management towards optimal use of lifestyle interventions.