Citations

Abstract Background: Alaska Native people are committed to increasing colorectal cancer (CRC) screening to reduce the high rate of CRC in this population. We conducted a community-level cluster randomized controlled trial (RCT) to evaluate the impact of multi-target stool DNA test introduction (mt-sDNA; Cologuard® Exact Sciences, Madison WI) on CRC screening in southwest Alaska Native communities using a mt-sDNA pre-processing lab in Anchorage, Alaska. Methods: A total of 32 rural/remote Alaska Native communities were evenly randomized to either high intensity patient navigation or medium intensity mailed health education compared to 14 communities receiving standard of care (screening recommendations at health care visits). The intervention was conducted from April 2021-February 2023. Outcome measures included CRC screening completion within 12 months and method used (mt-sDNA vs colonoscopy). Results: A total of 2032 Alaska Native participants (mean [SD] age, 56 [8.4] years; 817 women [40%]) were enrolled: 587 participants randomized to usual care, 696 participants randomized to the mailed education arm, and 749 participants randomized to the patient navigation arm. The mt-sDNA test was significantly preferred over colonoscopy by both mailed education participants (68%) and patient navigation participants (71%) (p<0.01). Mt-sDNA was somewhat more preferred by older participants ages 65-75 (79%) vs younger participants ages 45-54 (64%). Both men (71%) and women (68%) significantly preferred mt-sDNA compared with colonoscopy (p<0.01). Overall, 38% of those in the patient navigation intervention completed screening compared with 33% in the mailed education intervention and 10% in the usual care arm. No significant differences were observed in mt-sDNA completion between the patient navigation arm (154 participants [40%]) and the mailed education arm (100 participants [36%]) (p= 0.34). Colonoscopy completion (not including follow-up colonoscopies after abnormal stool tests) was higher in both the patient navigation arm (112 participants [44%]) and the mailed education arm (87 participants [43%]) compared with usual care (38 participants [14%]). Over 61% of kits sent to participants were completed and returned, however, 38% of the kits were not able to be processed, primarily because of mail transit time exceeding the manufacturer’s collection-to-processing limitation of 72 hrs. Conclusions: In this RCT among Alaska Native peoples who were not up to date with CRC screening recommendations, both a mailed education intervention and a patient navigator facilitated intervention were effective at increasing CRC screening compared with usual care. Participants overwhelmingly preferred mt-sDNA for screening but limitations in getting samples to the lab in time for analysis meant that about one-third of mt-sDNA samples were unable to be processed. These findings show that screening outreach and mt-sDNA use can substantially increase CRC screening, but shipping and weather issues remain to be addressed for expanding use of mt-sDNA in rural/remote Alaskan communities. Citation Format: Diana Redwood, Christie Flanagan, Lauren Jeffries, Peter Holck, Danika Bailie, Christine Desnoyers, Joseph Klejka, Lila Rutten, John Kisiel. Increase in colorectal cancer screening among rural and remote Alaska Native peoples using the multi-target stool DNA: A randomized controlled trial [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr A148.

The NCCN Guidelines for Non–Small Cell Lung Cancer (NSCLC) provide recommendations for the treatment of NSCLC. These NCCN Guidelines Insights discuss recent updates to the NCCN Guidelines, with a focus on systemic therapy options for the treatment of patients with nonmetastatic NSCLC and the corresponding molecular testing considerations.

Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

Background: A 21-question Lifestyle Medicine Assessment (LMA) tool was recently developed to quickly evaluate the lifestyle medicine domains (Avoidance of Substance Use, Nutrition, Connection, Movement, and Recovery). In this study, we used the LMA tool to complete a preliminary analysis of family medicine providers, a group that is known to face challenging lifestyle demands and burnout. Objective: The primary purpose was to assess the LMA domain scores and determine if significant differences exist (among the domains). The secondary purpose was to complete a correlation matrix for the LMA domain scores to better understand the strength of the relationships (among domains). Methods: The participants were 35 family medicine providers and all completed the LMA. The maximum LMA score is 50 (each of the five domains is scored 0-10 points). Pairwise comparisons were used to determine if there were significant differences among the five domain scores (P < .05) and Pearson correlation was used to assess correlations between domains. Results: The overall LMA score was moderate (34.68 ± 6.26). The Recovery domain score (4.71 ± 2.91) was significantly lower (P < 0.01) than the other domains (Connection = 6.94 ± 2.16; Nutrition = 7.41 ± 2.00; Movement = 6.26 ± 2.94; Avoidance of Substance Use = 9.35 ± 1.28). The Avoidance of Substance Use score was significantly higher than the other domains ( P < .01). Overall, the correlation scores among the domains were weak (all r-scores were ≤0.34). Conclusions: For this group of providers, there appears to be substantial room for improvement in four of the five domains. The domain of greatest concern appears to be Recovery. The weak correlation scores suggest that domain scores tend to be independent of each other, and that assessment results are unique to the individual.

Abstract Rationale Inflammation is central to chronic obstructive pulmonary disease (COPD) pathogenesis but incompletely represented in COPD prognostic models. The neutrophil-to-lymphocyte ratio (NLR) is a readily available inflammatory biomarker. Objectives To explore the associations of NLR with smoking status, clinical features of COPD, and future adverse outcomes. Methods We analyzed NLR calculated from the complete blood count of participants who currently or formerly smoked (n = 2,624) and tobacco-naive control subjects (n = 187) in the SPIROMICS multicenter observational cohort study. We assessed the stability of NLR at 6 weeks and 1 year, the association with select blood biomarkers, and the impact of smoking on NLR and cell counts. We stratified participants by NLR quartiles to compare cross-sectional clinical features at enrollment, prospectively observed exacerbations at 1 year, and mortality during longitudinal follow up. Results Higher NLR quartiles were broadly associated with more severe clinical features of COPD. NLR values were repeatable at 6 weeks (intraclass correlation coefficient, 0.74) and 1 year (intraclass correlation coefficient, 0.62). The impact of smoking on NLR varied with the severity of airflow limitation, mediated by an interaction between smoking, forced expiratory volume in 1 second percent predicted, and neutrophil counts but not lymphocyte counts. The highest NLR quartile (&gt;3.11) was associated with an increased risk of exacerbation over 1 year (adjusted odds ratio, 1.51; 95% confidence interval, 1.18, 1.92) and increased risk of mortality (adjusted hazard ratio, 1.41; 95% confidence interval, 1.20, 1.66) compared with quartiles 1–3. Conclusions Elevated NLR in stable COPD is a widely available biomarker associated with increased risk for exacerbation and death. The impact of cigarette smoking on NLR varies with disease severity.

ABSTRACT Genital lymphedema presents significant challenges in surgical management, with limited effective interventions. This case report explores the use of contrast‐enhanced ultrasound (CEUS) with microbubble injection as an alternative adjunct technique for lymphatic mapping in lymphaticovenous anastomosis (LVA) surgery for genital lymphedema. A retrospective chart review approved by our institutional review board was performed for patients with genital lymphedema undergoing LVA surgery between 2020 and 2024. Intraoperative CEUS for lymphatic mapping was used with intradermal injection of microbubble suspension Lumason (Bracco Suisse, Monroe Township, NJ, USA). Data regarding demographics, comorbidities, clinical and operative characteristics, complications, and surgical outcomes were retrieved. Three patients with genital lymphedema who underwent LVA were identified. The first patient was a 34‐year‐old female with recurrent lymphangioma circumscriptum and vesicular drainage. She successfully underwent CEUS‐guided LVA followed by two debulking procedures. The second patient was a 16‐year‐old male with congenital scrotal and lower extremity lymphedema. He had two CEUS‐guided LVAs and subsequent debulking for anterior scrotal swelling, with long‐term reduction in edema. The third patient was a 31‐year‐old female with primary lymphedema of the right lower extremity and genital region. She underwent seven CEUS and indocyanine green lymphography (ICG) guided anastomoses targeting the mons and lower abdomen, resulting in substantial symptomatic and volumetric improvement. CEUS detected target lymphatic vessels in all cases, including cases where ICG imaging failed to identify candidate lymphatic vessels. CEUS with intradermal microbubble injection successfully identified target lymphatic vessels in the preoperative planning for LVA surgery in patients with genital lymphedema.

Abstract Background Alcohol biomarkers including ethyl glucuronide (EtG) and phosphatidylethanol (PEth) are ordered frequently in clinical and forensic settings including solid organ transplantation. PEth provides a long detection window but can be insensitive to light drinking. In contrast, EtG and ethyl sulfate (EtS) can be elevated after light alcohol consumption and might complement PEth testing. Methods Urine EtG/EtS and whole blood PEth results were evaluated from all clinically-ordered testing between 2014 and 2024. PEth and EtG/EtS confirmation were performed by liquid chromatography tandem mass spectrometry at two reference laboratories, using cutoffs: Lab A, PEth 20 ng/ml, EtG and EtS 500 and 250 ng/ml; Lab B, PEth 10 ng/ml, EtG and EtS 250 and 100 ng/ml. Only Lab B performed EtG screening by immunoassay, using a 500 ng/ml cutoff. Results Phosphatidylethanol was positive in 1269 (15.6%) of 8131 samples, compared to 769 (6.7%) confirmed EtG/EtS positives from 11 555 samples. EtG screening (n = 9668) was positive in 743 (7.7%) samples, of which 30 (4.0%) confirmed negative (false positives); the screen was indeterminate in 267 (2.8%) samples, 66 of which confirmed positive and 172 negative. Of 3132 paired PEth and EtG samples, 2887 (92.2%) were concordant, 224 (7.2%) were PEth-positive, and 21 (0.7%) were EtG-positive. PEth was significantly more sensitive in paired samples (P &lt; .001), even after accounting for potential confounders such as transfusion. Limiting testing to PEth would have correctly identified alcohol consumption in 331 of 373 (88.7%) instances versus EtG/EtS in 149 (39.9%), and reduced charges by &gt;$720 000 USD. Discussion Phosphatidylethanol outperformed EtG/EtS in detecting alcohol consumption in a predominantly abstinent transplant population. Compared to PEth, EtG/EtS had lower overall positivity and poorer sensitivity in paired samples; additionally, EtG screening demonstrated false positives and indeterminate results. EtG testing provided little added value beyond PEth in this population, and did not warrant the increased cost of performing both tests.

Abstract Hereditary adult-onset ataxias are a heterogeneous group of phenotypically overlapping conditions, often caused by pathogenic expansions of short tandem repeats. Currently, 18 repeat disorders with a core phenotype of adult-onset ataxia are known. Diagnosis typically relies on sequential PCR-based methods, which are labour-intensive and lack precision. Long-read sequencing (LRS) has the potential to overcome these limitations and is currently implemented and validated in clinical genetics. Using clinical nanopore Cas9-targeted sequencing (Clin-CATS) for parallel in-depth repeat analysis, we evaluated a diagnostic cohort of 513 adult-onset ataxia patients, determining frequencies of all known repeat-associated ataxias except Spinocerebellar ataxia 4 (SCA4), as well as the carrier frequencies for autosomal-recessive disorders, RFC1 spectrum disorder and Friedreich’s ataxia (FRDA). Additionally, phenotypes of patients with established genetic diagnoses were characterized, especially those of patients living with RFC1 spectrum disorder and SCA27B. Repeat-associated ataxias were confirmed in 33.3% of cases, including rare ataxias, such as SCA10, SCA36 and SCA37, alongside as the most prevalent conditions SCA27B and RFC1 spectrum disorder. Potentially pathogenic expansions in FGF14 were identified in an additional 4.7% of patients. Testing of another 347 patients for ZFHX3 expansions linked to SCA4 did not identify any cases. Dual diagnoses were frequent, occurring in 6.4% of patients with repeat-associated ataxia. We confirmed a high RFC1 spectrum disorder carrier frequency (7.2%) and reclassified certain FXN expansions as likely non-pathogenic, resulting in a lower than estimated carrier frequency for FRDA of 0.8%. We also identified novel repeat configurations in several loci and illustrated the high heterogeneity of repeat expansions in RFC1, highlighting it as a potential source of false results when using PCR-based methods. This study underscores the diagnostic advantages of LRS for comprehensive repeat analysis and recommends its adoption as a standard in clinical genetics, replacing Southern blot and PCR-based approaches. Furthermore, based on our findings in a large patient cohort a re-evaluation of existing phenotype-genotype correlations is recommended as well as evaluating additional parameters alongside the repeat length to improve diagnostic precision of repeat analysis.

Abstract Objectives Effective communication is crucial in healthcare, and for patients with a non-English language preference (NELP), professional interpreters are recognized as the gold standard in supporting bidirectional communication. However, interpreters are not always readily available, prompting the exploration of other options for translation and interpretation. The recent developments in artificial intelligence-based neural network translation tools, namely neural machine translation (NMT) may enable robust interpretation and translation. Materials and Methods We conducted a systematic review (SR) to evaluate the literature on NMT for this purpose. We did a comprehensive search of several databases with guidance from a professional librarian. The search was limited to the year 2000 onwards and English language. Title and abstract screening and full-text review were independently conducted by two reviewers with conflicts resolved by a third reviewer Results 2867 studies were identified with 10 studies included in the final analysis. Among these, six evaluated interpretation in real or simulated clinical settings and four examined translation of discharge materials. Google Translate and ChatGPT were assessed in several studies. Accuracy differed by language, with low-resource languages performing worse. Discussion NMT technologies in healthcare have several advantages including broad language accessibility and potential cost savings for institutions. Despite improved accuracy of these novel tools, due to possible critical errors NMT tools are not yet ready for widespread clinical use. Conclusion Future studies should focus on optimizing evaluation methods as well as how best to integrate these technologies into real-time clinical settings.