Spliced-vein Conduit Offers Better Patency and Limb Salvage Than Prosthetic Graft for Femoral-Tibial Bypasses in Critical Limb Threatening Ischemia.

BACKGROUND: Single-segment great saphenous vein (ssGSV) is the gold standard conduit for femoral-tibial bypasses in patients with critical limb-threatening ischemia (CLTI). In the absence of a good single-segment saphenous vein, alternative options are prosthetic grafts or spliced-vein conduits. Although spliced-vein conduits may provide better long-term patency/limb salvage, prosthetic grafts are more often the chosen conduit due to shorter operative and presumably better immediate postoperative outcomes; nevertheless, there is little data supporting this practice. In this study, we compared 30-day outcomes between spliced-vein and prosthetic conduits in CLTI bypass using a national registry. METHODS: CLTI patients who underwent lower extremity bypass using spliced vein (SpV) or prosthetic conduits only were selected from National Surgical Quality Improvement Program (NSQIP) targeted database. A 1:5 propensity-score matching was conducted between SpV and prosthetic groups to address preoperative differences. Thirty-day outcomes, including primary patency, reintervention, major amputation, mortality, major morbidity, transfusion, and wound complications, were compared between the two groups. RESULTS: There were 886 patients who underwent femoral-tibial bypass without ssGSV (104 SpV and 782 prosthetic grafts). All SpV patients were propensity-score matched to 445 prosthetic patients. SpV exhibited significantly better 30-day primary patency than prosthetic (87.5% vs 74.38%, P = 0.004). SpV was associated with significantly longer operative time (346 min vs 222 min, P < .001) and higher transfusion (43.3% vs 27.87%, P =0.003), but those did not translate into higher 30-day mortality or major systemic complications. There was no difference in wound complications or 30-day limb loss. CONCLUSION: Spliced-vein conduit affords significantly better 30-day primary patency than prosthetic grafts without increased mortality and morbidities. Therefore, despite greater procedural complexity and longer operative time, spliced-vein conduit should be considered when available. Future prospective studies are needed to investigate the long-term outcomes of these two conduits.

The meaning of mass extinctions and what the fossil record tells us about angiosperm survival at K-Pg: a reply to Hagen (2024).

Last year, we published research using phylogenetic comparative methods (PCMs) to reveal no phylogenetic evidence for elevated lineage-level extinction rates in angiosperms across K-Pg (Thompson JB, Ramírez-Barahona S. 2023 No phylogenetic evidence for angiosperm mass extinction at the Cretaceous-Palaeogene (K-Pg) boundary. Biol. Lett. 19, 20230314. (doi:10.1098/rsbl.2023.0314)), results that are in step with the global angiosperm fossil record. In a critique of our paper (Hagen ER. 2024 A critique of Thompson and Ramírez-Barahona (2023) or: how I learned to stop worrying and love the fossil record. EcoEvoRxiv. (doi:10.32942/X2631W)), simulation work is presented to argue we erred in our methodological choices and interpretations, and that we should have deferred to fossil evidence. In our opinion, underlying this critique are poor methodological choices on simulations and philosophical problems surrounding the definition of a mass extinction event, which leads to incorrect interpretations of both the fossil record and PCMs. We further argue that deferring to one source of evidence in favour of the other shuts the door to important evolutionary and philosophical questions.

Identifying the multiple drivers of cactus diversification.

Our understanding of the complexity of forces at play in the rise of major angiosperm lineages remains incomplete. The diversity and heterogeneous distribution of most angiosperm lineages is so extraordinary that it confounds our ability to identify simple drivers of diversification. Using machine learning in combination with phylogenetic modelling, we show that five separate abiotic and biotic variables significantly contribute to the diversification of Cactaceae. We reconstruct a comprehensive phylogeny, build a dataset of 39 abiotic and biotic variables, and predict the variables of central importance, while accounting for potential interactions between those variables. We use state-dependent diversification models to confirm that five abiotic and biotic variables shape diversification in the cactus family. Of highest importance are diurnal air temperature range, soil sand content and plant size, with lesser importance identified in isothermality and geographic range size. Interestingly, each of the estimated optimal conditions for abiotic variables were intermediate, indicating that cactus diversification is promoted by moderate, not extreme, climates. Our results reveal the potential primary drivers of cactus diversification, and the need to account for the complexity underlying the evolution of angiosperm lineages.

Transcriptional programs of Pitx2 and Tfap2a/Tfap2b controlling lineage specification of mandibular epithelium during tooth initiation.

How the dorsal-ventral axis of the vertebrate jaw, particularly the position of tooth initiation site, is established remains a critical and unresolved question. Tooth development starts with the formation of the dental lamina, a localized thickened strip within the maxillary and mandibular epithelium. To identify transcriptional regulatory networks (TRN) controlling the specification of dental lamina from the naïve mandibular epithelium, we utilized Laser Microdissection coupled low-input RNA-seq (LMD-RNA-seq) to profile gene expression of different domains of the mandibular epithelium along the dorsal-ventral axis. We comprehensively identified transcription factors (TFs) and signaling pathways that are differentially expressed along mandibular epithelial domains (including the dental lamina). Specifically, we found that the TFs Sox2 and Tfap2 (Tfap2a/Tfap2b) formed complimentary expression domains along the dorsal-ventral axis of the mandibular epithelium. Interestingly, both classic and novel dental lamina specific TFs-such as Pitx2, Ascl5 and Zfp536-were found to localize near the Sox2:Tfap2a/Tfap2b interface. To explore the functional significance of these domain specific TFs, we next examined loss-of-function mouse models of these domain specific TFs, including the dental lamina specific TF, Pitx2, and the ventral surface ectoderm specific TFs Tfap2a and Tfap2b. We found that disruption of domain specific TFs leads to an upregulation and expansion of the alternative domain's TRN. The importance of this cross-repression is evident by the ectopic expansion of Pitx2 and Sox2 positive dental lamina structure in Tfap2a/Tfap2b ectodermal double knockouts and the emergence of an ectopic tooth in the ventral surface ectoderm. Finally, we uncovered an unappreciated interface of mesenchymal SHH and WNT signaling pathways, at the site of tooth initiation, that were established by the epithelial domain specific TFs including Pitx2 and Tfap2a/Tfap2b. These results uncover a previously unknown molecular mechanism involving cross-repression of domain specific TFs including Pitx2 and Tfap2a/Tfap2b in patterning the dorsal-ventral axis of the mouse mandible, specifically the regulation of tooth initiation site.

Prophylactic muscle flaps in high-risk-for-poor-healing patients with prosthetic bypasses increases deep wound complications.

BACKGROUND: Incisional complications of groin after inflow or infrainguinal bypasses with prosthetic conduits can result in major morbidities that require reoperation, infected graft removal, and limb loss. Muscle flaps are typically performed to treat groin wound complications, but they are also done prophylactically at the time of index procedures in certain high-risk-for-poor-healing patients to mitigate anticipated groin wound complications. We used a nationwide multi-institutional database to investigate outcomes of prophylactic muscle flaps in high-risk patients who underwent prosthetic bypasses involving femoral anastomosis. METHODS: We utilized ACS-NSQIP database 2005-2021 to identify all elective inflow and infrainguinal bypasses that involve femoral anastomoses. Only high-risk patients for poor incisional healing who underwent prosthetic conduit bypasses were selected. A 1:3 propensity-matching was performed to obtain two comparable studied groups between those with (FLAP) and without prophylactic muscle flaps (NOFLAP) based on demographics and comorbidities. 30-day postoperative outcomes were compared. RESULTS: Among 35,011 NOFLAP, 990 of them were propensity-matched to 330 FLAP. There was no significant difference in 30-day mortality, MACE, pulmonary, or renal complications. FLAP was associated with higher bleeding requiring transfusion, longer operative time, and longer hospital stay. FLAP also had higher overall wound complications (15.2% vs. 10.6%; p = 0.03), especially deep incisional infection (4.9% vs. 2.4%; p = 0.04). CONCLUSION: Prophylactic muscle flap for prosthetic bypasses involving femoral anastomosis in high-risk-for-poor-healing patients does not appear to mitigate 30-day wound complications. Caution should be exercised with this practice and more long-term data should be obtained to determine whether prophylactic flaps decrease the incidence of graft infection.

Adaptations to a patient navigation program for follow-up colonoscopy in rural primary care practices.

PURPOSE: Patient navigation is a recommended practice to improve cancer screenings among underserved populations including those residing in rural areas with care access barriers. We report on patient navigation programme adaptations to increase follow-up colonoscopy rates after abnormal fecal testing in rural primary care practices. METHODS: Participating clinics delivered a patient navigation programme to eligible patients from 28 affiliated clinics serving rural communities in Oregon clustered within 3 Medicaid health plans. Patient navigation adaptations were tracked using data sources including patient navigation training programme reflections, qualitative interviews, clinic meetings, and periodic reflections with practice facilitators. FINDINGS: Initial, planned (proactive) adaptations were made to address the rural context; later, unplanned (reactive) adaptations were implemented to address the impact of the COVID-19 global pandemic. Initial planned adaptations to the patient navigation programme were made before the main trial to address the needs of the rural context, including provider shortages and geographic dispersion limiting both patient access to care and training opportunities for providers. Later unplanned adaptations were made primarily in response to COVID-19 care suspension and staff redeployments and shortages that occurred during implementation. CONCLUSION: While unplanned adaptations were implemented to address the contextual impact of the COVID-19 pandemic on care access patterns and staffing, the changes to training content and context were beneficial to the rural setting overall and should be sustained. Our findings can guide future efforts to optimise the success of such programmes in other rural settings and highlight the important role of adaptations in implementation projects.

Evaluating the Reach of a Patient Navigation Program for Follow-up Colonoscopy in a Large Federally Qualified Health Center.

Patient navigation (PN) has been shown to improve participation in cancer screening, including colorectal cancer screening, and is now a recommended practice by the Community Preventive Services Task Force. Despite the effectiveness of PN programs, little is known about the number of contacts needed to successfully reach patients or about the demographic and healthcare utilization factors associated with reach. PRECISE was an individual randomized study of PN versus usual care conducted as a partnership between two large health systems in the Pacific Northwest. The navigation program was a six-topic area telephonic program designed to support patients with an abnormal fecal test result to obtain a follow-up colonoscopy. We report the number of contact attempts needed to successfully reach navigated patients. We used logistic regression to report the demographic and healthcare utilization characteristics associated with patients allocated to PN who were successfully reached. We identified 1,200 patients with an abnormal fecal immunochemical test result, of whom 970 were randomized into the study (45.7% were female, 17.5% were Spanish-speaking, and the mean age was 60.8 years). Of the 479 patients allocated to the PN intervention, 382 (79.7%) were reached within 18 call attempts, and nearly all (n = 356; 93.2%) were reached within six contact attempts. Patient characteristics associated with reach were race, county of residence, and body mass index. Our findings can guide future efforts to optimize the reach of PN programs. Prevention Relevance: The findings from this large study can inform clinic-level implementation of future PN programs in Federally Qualified Health Centers to improve the reach of patients needing cancer screenings, optimize staff resources, and ultimately increase cancer screenings.

Engaging with Rural Communities for Colorectal Cancer Screening Outreach Using Modified Boot Camp Translation.

BACKGROUND: Colorectal cancer (CRC) incidence and mortality are disproportionately high among rural residents and Medicaid enrollees. OBJECTIVES: To address disparities, we used a modified community engagement approach, Boot Camp Translation (BCT). Research partners, an advisory board, and the rural community informed messaging about CRC outreach and a mailed fecal immunochemical test program. METHODS: Eligible rural patients (English-speaking and ages 50-74) and clinic staff involved in patient outreach participated in a BCT conducted virtually over two months. We applied qualitative analysis to BCT transcripts and field notes. RESULTS: Key themes included: the importance of directly communicating about the seriousness of cancer, leveraging close clinic-patient relationships, and communicating the test safety, ease, and low cost. CONCLUSIONS: Using a modified version of BCT delivered in a virtual format, we were able to successfully capture community input to adapt a CRC outreach program for use in rural settings. Program materials will be tested during a pragmatic trial to address rural CRC screening disparities.

The Reach of Calls and Text Messages for Mailed FIT Outreach in the PROMPT Stepped-Wedge Colorectal Cancer Screening Trial.

BACKGROUND: Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening participation. We assessed the reach and effectiveness of adding notifications to mailed FIT programs. METHODS: We conducted secondary analyses of a stepped-wedge evaluation of an enhanced mailed FIT program (n = 15 clinics). Patients were stratified by prior FIT completion. Those with prior FIT were sent a text message (Group 1); those without were randomized 1:1 to receive a text message (Group 2) or live phone call (Group 3). All groups were sent automated phone call reminders. In stratified analysis, we measured reach and effectiveness (FIT completion within 6 months) and assessed patient-level associations using generalized estimating equations. RESULTS: Patients (n = 16,934; 83% Latino; 72% completed prior FIT) were reached most often by text messages (78%), followed by live phone calls (71%), then automated phone calls (56%). FIT completion was higher in patients with prior FIT completion versus without [44% (Group 1) vs. 19% (Group 2 + Group 3); P < 0.01]. For patients without prior FIT, effectiveness was higher in those allocated to a live phone call [20% (Group 3) vs. 18% (Group 2) for text message; P = 0.04] and in those who personally answered the live call (28% vs. 9% no call completed; P < 0.01). CONCLUSIONS: Text messages reached the most patients, yet effectiveness was highest in those who personally answered the live phone call. IMPACT: Despite the broad reach and low cost of text messages, personalized approaches may more successfully boost FIT completion.

Herbivore effects increase with latitude across the extent of a foundational seagrass.

Climate change is altering the functioning of foundational ecosystems. While the direct effects of warming are expected to influence individual species, the indirect effects of warming on species interactions remain poorly understood. In marine systems, as tropical herbivores undergo poleward range expansion, they may change food web structure and alter the functioning of key habitats. While this process ('tropicalization') has been documented within declining kelp forests, we have a limited understanding of how this process might unfold across other systems. Here we use a network of sites spanning 23° of latitude to explore the effects of increased herbivory (simulated via leaf clipping) on the structure of a foundational marine plant (turtlegrass). By working across its geographic range, we also show how gradients in light, temperature and nutrients modified plant responses. We found that turtlegrass near its northern boundary was increasingly affected (reduced productivity) by herbivory and that this response was driven by latitudinal gradients in light (low insolation at high latitudes). By contrast, low-latitude meadows tolerated herbivory due to high insolation which enhanced plant carbohydrates. We show that as herbivores undergo range expansion, turtlegrass meadows at their northern limit display reduced resilience and may be under threat of ecological collapse.

Polygenic Risk in Families With Spontaneous Coronary Artery Dissection.

Importance: Spontaneous coronary artery dissection (SCAD) is a poorly understood cause of acute coronary syndrome that predominantly affects women. Evidence to date suggests a complex genetic architecture, while a family history is reported for a minority of cases. Objective: To determine the contribution of rare and common genetic variants to SCAD risk in familial cases, the latter via the comparison of a polygenic risk score (PRS) with those with sporadic SCAD and healthy controls. Design, Setting, and Participants: This genetic association study analyzed families with SCAD, individuals with sporadic SCAD, and healthy controls. Genotyping was undertaken for all participants. Participants were recruited between 2017 and 2021. A PRS for SCAD was calculated for all participants. The presence of rare variants in genes associated with connective tissue disorders (CTD) was also assessed. Individuals with SCAD were recruited via social media or from a single medical center. A previously published control database of older healthy individuals was used. Data were analyzed from January 2022 to October 2023. Exposures: PRS for SCAD comprised of 7 single-nucleotide variants. Main Outcomes and Measures: Disease status (familial SCAD, sporadic SCAD, or healthy control) associated with PRS. Results: A total of 13 families with SCAD (27 affected and 12 unaffected individuals), 173 individuals with sporadic SCAD, and 1127 healthy controls were included. A total of 188 individuals with SCAD (94.0%) were female, including 25 of 27 with familial SCAD and 163 of 173 with sporadic SCAD; of 12 unaffected individuals from families with SCAD, 6 (50%) were female; and of 1127 healthy controls, 672 (59.6%) were female. Compared with healthy controls, the odds of being an affected family member or having sporadic SCAD was significantly associated with a SCAD PRS (where the odds ratio [OR] represents an increase in odds per 1-SD increase in PRS) (affected family member: OR, 2.14; 95% CI, 1.78-2.50; adjusted P = 1.96 × 10-4; sporadic SCAD: OR, 1.63; 95% CI, 1.37-1.89; adjusted P = 5.69 × 10-4). This association was not seen for unaffected family members (OR, 1.03; 95% CI, 0.46-1.61; adjusted P = .91) compared with controls. Further, those with familial SCAD were overrepresented in the top quintile of the control PRS distribution (OR, 3.70; 95% CI, 2.93-4.47; adjusted P = .001); those with sporadic SCAD showed a similar pattern (OR, 2.51; 95% CI, 1.98-3.04; adjusted P = .001). Affected individuals within a family did not share any rare deleterious variants in CTD-associated genes. Conclusions and Relevance: Extreme aggregation of common genetic risk appears to play a significant role in familial clustering of SCAD as well as in sporadic case predisposition, although further study is required.

Effects of cyanoacrylate on leakage pressures of cooled canine cadaveric jejunal enterotomies.

OBJECTIVE: To compare the intraluminal initial and maximal pressures of enterotomies closed using three different techniques (single-layer appositional continuous closure; closure with cyanoacrylate; a single-layer appositional closure augmented with cyanoacrylate) in a cooled canine cadaveric jejunal model and to report the initial leak location in all samples. STUDY DESIGN: Experimental, ex-vivo study. SAMPLE POPULATION: Grossly normal chilled small intestine segments from three canine cadavers. METHODS: A total of 45 chilled jejunal segments (n = 15 segments/group) were assigned to a handsewn group (HSE), a cyanoacrylate only group (CE) and a handsewn and cyanoacrylate group (HS + CE). A 2 cm antimesenteric enterotomy was performed and closure with one of the above techniques. Initial leakage pressures (ILP), maximal intraluminal pressures (MIP) and initial leakage location were recorded by a single observer. RESULTS: Handsewn enterotomies leaked at higher ILP when augmented with cyanoacrylate (83.3 ± 4.6 mmHg, p < .001) compared to both the HSE group (43.8 ± 5.3 mmHg) and the CE group (18.6 ± 3.5 mmHg). Those sealed with cyanoacrylate only leaked at a lower MIP compared with the other groups (p < .001). Maximal intraluminal pressures did not differ between handsewn enterotomies, whether augmented or not (p = .19). CONCLUSION: Reinforcement of a sutured enterotomy closure with cyanoacrylate was easy to perform and resulted in significantly increased initial leak pressures in cadaveric jejunum. CLINICAL SIGNIFICANCE: The increased leakage pressures achieved by reinforcing enterotomies with cyanoacrylate could consequently reduce the incidence of postoperative intestinal leakage following an enterotomy and may result in reduced patient morbidity or mortality.

The recalibration and redevelopment of a model to calculate patients' probability of completing a colonoscopy following an abnormal fecal test.

OBJECTIVES: Fecal immunochemical testing (FIT) is an effective screening tool for colorectal cancer. If an FIT is abnormal, a follow-up colonoscopy is necessary to remove polyps or find cancers. We sought to develop a usable risk prediction model to identify patients unlikely to complete a colonoscopy following an abnormal FIT test. METHODS: We recalibrated and then redeveloped a prediction model in federally qualified health centers (FQHCs), using a retrospective cohort of patients aged 50-75 with an abnormal FIT test and clinical data. Logistic and Cox regressions were used to recalibrate and then redevelop the model. RESULTS: The initial risk model used data from eight FQHCs (26 clinics) including 1723 patients. When we applied the model to a single large FQHC (34 clinics, 884 eligible patients), the model did not recalibrate successfully (c-statistic dropped more than 0.05, from 0.66 to 0.61). The model was redeveloped in the same FQHC in a cohort of 1401 patients with a c-statistic of 0.65. CONCLUSIONS: The original model developed in a group of FQHCs did not adequately recalibrate in the single large FQHC. Health system, patient characteristics or data differences may have led to the inability to recalibrate the model. However, the redeveloped model provides an adequate model for the single FQHC.

Exercise is associated with younger methylome and transcriptome profiles in human skeletal muscle.

Exercise training prevents age-related decline in muscle function. Targeting epigenetic aging is a promising actionable mechanism and late-life exercise mitigates epigenetic aging in rodent muscle. Whether exercise training can decelerate, or reverse epigenetic aging in humans is unknown. Here, we performed a powerful meta-analysis of the methylome and transcriptome of an unprecedented number of human skeletal muscle samples (n = 3176). We show that: (1) individuals with higher baseline aerobic fitness have younger epigenetic and transcriptomic profiles, (2) exercise training leads to significant shifts of epigenetic and transcriptomic patterns toward a younger profile, and (3) muscle disuse "ages" the transcriptome. Higher fitness levels were associated with attenuated differential methylation and transcription during aging. Furthermore, both epigenetic and transcriptomic profiles shifted toward a younger state after exercise training interventions, while the transcriptome shifted toward an older state after forced muscle disuse. We demonstrate that exercise training targets many of the age-related transcripts and DNA methylation loci to maintain younger methylome and transcriptome profiles, specifically in genes related to muscle structure, metabolism, and mitochondrial function. Our comprehensive analysis will inform future studies aiming to identify the best combination of therapeutics and exercise regimes to optimize longevity.

Developing Patient-Refined Messaging for Follow-Up Colonoscopy After Abnormal Fecal Testing in Hispanic Communities: Key Learnings from Virtual Boot Camp Translation.

Colorectal cancer (CRC) is a leading cause of cancer death in the US. Screening by fecal immunochemical test (FIT) is a strategy to lower CRC rates. Unfortunately, only half of patients with an abnormal FIT result complete the follow-up colonoscopy, an essential component of screening. We used virtual Boot Camp Translation (BCT), to elicit input from partners to develop messaging/materials to motivate patients to complete a follow-up colonoscopy. Participants were Hispanic, ages 50 to 75 years, and Spanish-speaking. All materials were developed in English and Spanish. The first meeting included expert presentations that addressed colorectal health. The two follow-up sessions obtained feedback on messaging/materials developed based on themes from the first meeting. Ten participants attended the first meeting and eight attended the follow-up sessions. The two key barriers to follow-up colonoscopy after abnormal FIT noted by participants were (a) lack of colonoscopy awareness and (b) fear of the colonoscopy procedure. We learned that participants valued simple messaging to increase knowledge and alleviate concerns, patient-friendly outreach materials, and increased access to health information. Using virtual BCT, we included participant feedback to design culturally relevant health messages to promote follow-up colonoscopy after abnormal fecal testing among Hispanic patients served by community clinics.

No phylogenetic evidence for angiosperm mass extinction at the Cretaceous-Palaeogene (K-Pg) boundary.

The Cretaceous-Palaeogene mass extinction event (K-Pg) witnessed upwards of 75% of animal species going extinct, most notably among these are the non-avian dinosaurs. A major question in macroevolution is whether this extinction event influenced the rise of flowering plants (angiosperms). The fossil record suggests that the K-Pg event had a strong regional impact on angiosperms with up to 75% species extinctions, but only had a minor impact on the extinction rates of major lineages (families and orders). Phylogenetic evidence for angiosperm extinction dynamics through time remains unexplored. By analysing two angiosperm mega-phylogenies containing approximately 32 000-73 000 extant species, here we show relatively constant extinction rates throughout geological time and no evidence for a mass extinction at the K-Pg boundary. Despite high species-level extinction observed in the fossil record, our results support the macroevolutionary resilience of angiosperms to the K-Pg mass extinction event via survival of higher lineages.

Effectiveness and Cost of an Enhanced Mailed Fecal Test Outreach Colorectal Cancer Screening Program: Findings from the PROMPT Stepped-Wedge Trial.

BACKGROUND: Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening rates, yet little is known about how to optimize these programs for effectiveness and cost. METHODS: PROMPT was a pragmatic, stepped-wedge, cluster-randomized effectiveness trial of mailed FIT outreach. Participants in the standard condition were mailed a FIT and received live telephone reminders to return it. Participants in the enhanced condition also received a tailored advance notification (text message or live phone call) and two automated phone call reminders. The primary outcome was 6-month FIT completion; secondary outcomes were any colorectal cancer screening completion at 6 months, implementation, and program costs. RESULTS: The study included 27,585 participants (80% ages 50-64, 82% Hispanic/Latino; 68% preferred Spanish). A higher proportion of enhanced participants completed FIT at 6 months than standard participants, both in intention-to-treat [+2.8%, 95% confidence interval (CI; 0.4-5.2)] and per-protocol [limited to individuals who were reached; +16.9%, 95% CI (12.3-20.3)] analyses. Text messages and automated calls were successfully delivered to 91% to 100% of participants. The per-patient cost for standard mailed FIT was $10.84. The enhanced program's text message plus automated call reminder cost an additional $0.66; live phone calls plus an automated call reminder cost an additional $10.82 per patient. CONCLUSIONS: Adding advance notifications and automated calls to a standard mailed FIT program boosted 6-month FIT completion rates at a small additional per-patient cost. IMPACT: Enhancements to mailed FIT outreach can improve colorectal cancer screening participation. Future research might test the addition of educational video messaging for screening-naïve adults.