Cardiovascular Clinical Trials in the Asia-Pacific Region.

This Viewpoint discusses the potential challenges to the operational conduct of clinical trials in the Asia-Pacific region, where there is a high rate of cardiovascular disease, and provides possible solutions.

Integrating Buprenorphine for Opioid Use Disorder into Rural, Primary Care Settings.

BACKGROUND: Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care. OBJECTIVE: Although challenges remain, some rural VA health care systems have begun offering opioid use disorder (OUD) treatment with buprenorphine in primary care. We conducted interviews with clinicians, leaders, and staff within these systems to understand how this outcome had been achieved. DESIGN: Using administrative data from the VA Corporate Data Warehouse (CDW), we identified rural VA health care systems that had improved their rate of primary care-based buprenorphine prescribing over the period 2015-2020. We conducted qualitative interviews (n = 30) with staff involved in implementing or prescribing buprenorphine in these systems to understand the processes that had facilitated implementation. PARTICIPANTS: Clinicians, staff, and leaders embedded within rural VA health care systems located in the Northwest, West, Midwest (2), South, and Northeast. APPROACH: Qualitative interviews were analyzed using a mixed inductive/deductive approach. KEY RESULTS: Interviews revealed the processes through which buprenorphine was integrated into primary care, as well as processes insufficient to enact change. Implementation was often initially catalyzed through a targeted hire. Champions then engaged clinicians and leaders one-on-one to "pitch" the case, describe concordance between buprenorphine prescribing and existing goals, and delineate the supportive role that they could provide. Sites were prepared for implementation by developing new clinical teams and redesigning clinical processes. Each of these processes was made possible with the active, instrumental support of leadership. CONCLUSIONS: Results suggest that rural systems seeking to improve buprenorphine accessibility in primary care may need to alter primary care structures to accommodate buprenorphine prescribing, whether through new hires, team development, or clinical redesign.

Germline prediction of immune checkpoint inhibitor discontinuation for immune-related adverse events.

Introduction: Immune checkpoint inhibitors (ICIs) can yield remarkable clinical responses in subsets of patients with solid tumors but can also often lead to immune-related adverse events (irAEs). Predictive features of clinically severe irAEs leading to cessation of ICIs have yet to be established. Using data from 1,327 patients with lung cancer treated with ICIs between 2009 and 2022 at four academic medical centers, we evaluated the association of a germline polygenic risk score for autoimmune disease and discontinuation of ICIs due to irAEs. Methods: Using Cox proportional hazards model, we assessed the association between a polygenic risk score for autoimmune disease (PRSAD) and cessation of ICI therapy due to irAEs. All models were adjusted for age at diagnosis, sex, lung cancer histology, type of therapy, recruiting center, and the first 5 principal components. To further understand the differential effects of type of therapy and disease stage on the association between PRSAD and cessation of ICI due to irAEs, we conducted stratified logistic regression analysis by type of ICI therapy and disease stage. Results: We found an association between PRSAD and ICI cessation due to irAEs (HR per SD = 1.18, 95% CI = 1.02 - 1.37, P = 0.03). This association was particularly strong in patients who had ICI cessation due to irAEs within three months of therapy initiation (HR per SD = 1.38, 95% CI = 1.08 - 1.78, P = 0.01). Individuals in the top 20th percentile of PRSAD had 7.2% ICI discontinuation for irAEs by three months, compared to 3.9% discontinuation by three months among patients in the bottom 80th percentile (log-rank P = 0.02). In addition, among patients who received combination PD-1/PD-L1 and CTLA-4 inhibitor therapy, PRSAD had an OR per SD of 1.86 (95% CI = 1.08 - 3.51, P = 0.04). Conclusions: We demonstrate an association between a polygenic risk score for autoimmune disease and early ICI discontinuation for irAEs, particularly among patients treated with combination ICI therapy. Our results suggest that germline genetics may be used as an adjunctive tool for risk stratification around ICI clinical decision-making in solid tumor oncology.

Scapular morphology does not predict supraspinatus tendon tear propagation following an individualised exercise therapy programme.

Purpose: To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size. Methods: Fifty-nine individuals aged 40-70 years with isolated symptomatic high-grade partial or full-thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12-week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three-dimensional subject-specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation. Results: The CSA was 30.0 ± 5.4°. Thirty-one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% (R 2 = 0.243) of variance in tear propagation (NS). Conclusions: CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme. Level of Evidence: II.

Physiological characteristics predictive of passing military physical employment standard tasks for ground close combat occupations in men and women.

Challenges for some women meeting the physical employment standards (PES) for ground close combat (GCC) roles stem from physical fitness and anthropometric characteristics. The purpose of this study was to identify the modifiable and nonmodifiable characteristics predictive of passing GCC-based PES tasks and determine the modifiable characteristics suitable to overcome nonmodifiable limitations. 107 adults (46 women) underwent multiday testing assessing regional and total lean mass (LM), percent body fat (BF%), aerobic capacity (V̇O2peak), strength, power, and PES performance. Predictors with p-value <0.200 were included in stepwise logistic regression analysis or binary logistic regression when outcomes among sexes were insufficient. Relative and absolute arm LM (OR: 4.617-8.522, p < 0.05), leg LM (OR: 2.463, p < 0.05), and upper body power (OR: 2.061, p < 0.05) predicted medicine ball chest throw success. Relative and absolute arm LM (OR: 3.734-11.694, p < 0.05), absolute trunk LM (OR: 2.576, p < 0.05), and leg LM (OR: 2.088, p < 0.05) predicted casualty drag success. Upper body power (OR: 3.910, p < 0.05), absolute trunk LM (OR: 2.387, p < 0.05), leg LM (OR: 2.290, p < 0.05), and total LM (OR: 1.830, p < 0.05) predicted maximum single lift success. Relative and absolute arm LM (OR: 3.488-7.377, p < 0.05), leg LM (OR: 1.965, p < 0.05), and upper body power (OR: 1.957, p < 0.05) predicted water can carry success. %BF (OR: 0.814, p = 0.007), V̇O2peak (OR: 1.160, p = 0.031), and lower body strength (OR: 1.059, p < 0.001) predicted repeated lift and carry success. V̇O2peak (OR: 1.540, p < 0.001) predicted 2-km ruck march success. Modifiable characteristics were the strongest predictors for GCC-based PES task success to warrant their improvement for enhancing PES performance for women.

Examining the "revisability" benefit of hip resurfacing arthroplasty.

BACKGROUND: Hip resurfacing arthroplasty (HRA) is an alternative to total hip arthroplasty (THA) that is typically reserved for young active patients because it preserves bone. However, the benefits of HRA only hold true if conversion THA after failed HRA provides acceptable outcomes. AIM: To compare patient reported outcomes for conversion THA after HRA failure to primary THA. METHODS: A retrospective review of 36 patients (37 hips) that underwent conversion THA for failed HRA between October 2006 and May 2019 by a single surgeon was performed. Patient reported outcomes [modified Harris Hip Score (mHHS), University of California Los Angeles (UCLA) activity score] were obtained via an email-based responder-anonymous survey. Outcomes were compared to normative data of a primary THA cohort with similar demographics. Subgroup analysis was performed comparing outcomes of conversion THA for adverse local tissue reaction (ALTR) vs all other causes for failure. RESULTS: The study group had a lower mHHS than the control group (81.7 ± 13.8 vs 90.2 ± 11.6, P < 0.01); however, both groups had similar UCLA activity levels (7.5 ± 2.3 vs 7.2 ± 1.6, P = 0.51). Patients that underwent conversion for non-ATLR causes had similar mHHS (85.2 ± 11.5 vs 90.2 ± 11.6, P = 0.11) and higher UCLA activity levels (8.5 ± 1.8 vs 7.2 ± 1.6, P < 0.01) compared to the control group. Patients that underwent conversion for ATLR had worse mHHS (77.1 ± 14.5 vs 90.2 ± 11.6, P < 0.01) and UCLA activity levels (6.1 ± 2.3 vs 7.2 ± 1.6, P = 0.05) when compared to the control group. CONCLUSION: Patient outcomes equivalent to primary THA can be achieved following HRA conversion to THA. However, inferior outcomes were demonstrated for ALTR-related HRA failure. Patient selection and perhaps further studies examining alternative HRA bearing surfaces should be considered.

Screening for Unhealthy Alcohol Use Among Patients With Multiple Chronic Conditions in Primary Care.

Introduction: Unhealthy alcohol use increases the risk for and exacerbation of chronic health conditions. As such, screening, prevention, and management of unhealthy alcohol use is especially critical to improving health outcomes for patients with multiple chronic health conditions. It is unclear to what extent multiple chronic condition status is a barrier to screening for unhealthy alcohol use in the primary care setting. The authors hypothesized that patients with multiple chronic conditions would be at lower odds of being screened for unhealthy alcohol use than patients without multiple chronic conditions. Methods: The authors performed a secondary analysis of electronic health record data for patients from 67 primary care practices in Virginia (2020-2023). Using the Center for Medicare and Medicaid Services' chronic disease framework, they classified patients by multiple chronic condition status: no multiple chronic conditions, physical multiple chronic conditions, mental health multiple chronic conditions, and physical and mental health multiple chronic conditions. They used multiple logistic regressions with an added practice-level random effect to analyze the relationship between multiple chronic condition status and the odds of receiving an alcohol-related assessment, of being screened for unhealthy alcohol use with a U.S. Preventive Services Task Force-recommended instrument, and of screening positive for unhealthy alcohol use within the past 2 years. Results: Within a final cohort of n=11,789, a total of 6,796 patients (58%) had multiple chronic conditions (29% physical multiple chronic conditions, 4% mental health multiple chronic conditions, and 25% physical and mental health multiple chronic conditions). In all, 69% of patients were screened for unhealthy alcohol use, whereas 16% were screened with a U.S. Preventive Services Task Force-recommended instrument, and 7% screened positive for unhealthy alcohol use. Patients with physical and mental health multiple chronic conditions had 0.9 times lower odds of receiving any screening for unhealthy alcohol use than those with no multiple chronic conditions (95% CI=0.8, 1.0; p=0.0240), whereas patients with only physical multiple chronic conditions or only mental health multiple chronic conditions had similar odds. There was no difference in the odds of being screened with a U.S. Preventive Services Task Force-recommended instrument on the basis of multiple chronic condition status. Patients with mental health multiple chronic conditions and physical and mental health multiple chronic conditions had 1.8 and 1.5 times greater odds of screening positive for unhealthy alcohol use, respectively (95% CI=1.3, 2.7; p=0.0014 and 95% CI=1.2, 1.8; p=0.0003). Conclusions: Although patients with chronic mental health conditions were more likely to screen positive for unhealthy alcohol use than patients without multiple chronic conditions, Virginia primary care patients with physical and mental health multiple chronic conditions were less likely to receive an alcohol-related assessment during the past 2 years. Given the overall modest rate of screening with a U.S. Preventive Services Task Force-recommended instrument, further efforts are needed to create the conditions for high-quality alcohol-related preventive service delivery in primary care, particularly for patients with high complexity and/or mental health conditions.

The effect of pleural drainage on pulse oximetry in a post-operative thoracic surgery population.

BACKGROUND: Pleural effusions in post-operative thoracic surgery patients are common. Effusions can result in prolonged hospitalizations or readmissions, with prior studies suggesting mixed effects of pleural drainage on hypoxia. We aimed to define the impact of pleural drainage on pulse oximetry (SpO2) in post-thoracic surgery patients. METHODS: A retrospective study of post-operative thoracic surgery patients undergoing pleural drainage was performed. SpO2 and supplemental oxygen (FiO2) values were recorded at pre- and post-procedure. The primary outcome was difference in pre-procedural and post-procedural SpO2. RESULTS: We identified 95 patients with a mean age of 65 (SD - 13.8) years undergoing 122 pleural drainage procedures. Mean drainage volume was 619 (SD-423) mL and the majority of procedures (88.5 %) included a drainage of <1000 mL. SpO2 was associated with an increase from 94.0 % (SD-2.6) to 97.3 % (SD-2.0) at 24-h (p < 0.0001). FiO2 was associated with a decrease from 0.31 (SD-0.15) to 0.29 (SD-0.12) at 24-h (p = 0.0081). SpO2/FiO2 was associated with an increase from 344.5 (SD-99.0) to 371.9 (SD-94.7) at 24-h post-procedure (p < 0.0001). CONCLUSIONS: Pleural drainage within post-operative thoracic surgery patients offers statistically significant improvements in oxygen saturation by peripheral pulse oximetry and oxygen supplementation; however the clinical significance of these changes remains unclear. Pleural drainage itself may be requested for numerous reasons, including diagnostic (fevers, leukocytosis, etc.) or therapeutic (worsening dyspnea) evaluation. However, pleural drainage may offer minimal clinical impact on pulse oximetry in post-operative thoracic surgery patients.

Radiopaque FeMnN-Mo composite drawn filled tubing wires for braided absorbable neurovascular devices.

Flow diverter devices are small stents used to divert blood flow away from aneurysms in the brain, stagnating flow and inducing intra-aneurysmal thrombosis which in time will prevent aneurysm rupture. Current devices are formed from thin (∼25 µm) wires which will remain in place long after the aneurysm has been mitigated. As their continued presence could lead to secondary complications, an absorbable flow diverter which dissolves into the body after aneurysm occlusion is desirable. The absorbable metals investigated to date struggle to achieve the necessary combination of strength, elasticity, corrosion rate, fragmentation resistance, radiopacity, and biocompatibility. This work proposes and investigates a new composite wire concept combining absorbable iron alloy (FeMnN) shells with one or more pure molybdenum (Mo) cores. Various wire configurations are produced and drawn to 25-250 µm wires. Tensile testing revealed high and tunable mechanical properties on par with existing flow diverter materials. In vitro degradation testing of 100 µm wire in DMEM to 7 days indicated progressive corrosion and cracking of the FeMnN shell but not of the Mo, confirming the cathodic protection of the Mo by the FeMnN and thus mitigation of premature fragmentation risk. In vivo implantation and subsequent µCT of the same wires in mouse aortas to 6 months showed meaningful corrosion had begun in the FeMnN shell but not yet in the Mo filament cores. In total, these results indicate that these composites may offer an ideal combination of properties for absorbable flow diverters.

Ocean warming and acidification adjust inter- and intra-specific variability in the functional trait expression of polar invertebrates.

Climate change is known to affect the distribution and composition of species, but concomitant alterations to functionally important aspects of behaviour and species-environment relations are poorly constrained. Here, we examine the ecosystem ramifications of changes in sediment-dwelling invertebrate bioturbation behaviour-a key process mediating nutrient cycling-associated with near-future environmental conditions (+ 1.5 °C, 550 ppm [pCO2]) for species from polar regions experiencing rapid rates of climate change. We find that responses to warming and acidification vary between species and lead to a reduction in intra-specific variability in behavioural trait expression that adjusts the magnitude and direction of nutrient concentrations. Our analyses also indicate that species behaviour is not predetermined, but can be dependent on local variations in environmental history that set population capacities for phenotypic plasticity. We provide evidence that certain, but subtle, aspects of inter- and intra-specific variation in behavioural trait expression, rather than the presence or proportional representation of species per se, is an important and under-appreciated determinant of benthic biogeochemical responses to climate change. Such changes in species behaviour may act as an early warning for impending ecological transitions associated with progressive climate forcing.

Patterns of 12-Month Post-Myocardial Infarction Medication Use According to Revascularisation Strategy: Analysis of 15,339 Admissions in Victoria, Australia.

AIM: Clinical guidelines recommend secondary prevention medications following myocardial infarction (MI) regardless of revascularisation strategy. Studies suggest that there is variation in post-MI medication use following percutaneous coronary intervention (PCI) and coronary artery bypass grafts (CABG). We investigated initial dispensing and 12-month patterns of medication use according to revascularisation strategy following non-ST-elevation MI (NSTEMI). METHOD: We included all public and private hospital admissions for NSTEMI for patients aged ≥30 years in Victoria, Australia, between July 2012 and June 2017. We investigated initial dispensing of P2Y12 inhibitors (P2Y12i), statins (total and high intensity), angiotensin-converting-enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), and beta blockers within 60 days after discharge. Twelve-month post-MI medication use was estimated as the proportion of days covered (PDC) over a 12-month period from the date of hospital discharge. Analyses were performed using adjusted regression models, stratified by revascularisation strategy. RESULTS: There were 15,399 admissions for NSTEMI: 11,754 with PCI and 3,645 with CABG. Following adjustments, predicted probability of initial dispensing in the PCI and CABG groups, respectively, was 0.94 (95% confidence interval 0.93-0.95) vs 0.17 (0.13-0.21) for P2Y12i; 0.69 (0.66-0.71) vs 0.42 (0.37-0.48) for ACEi/ARB; 0.59 (0.57-0.62) vs 0.69 (0.64-0.74) for beta blockers; 0.89 (0.87-0.91) vs 0.89 (0.85-0.92) for statins; and 0.60 (0.57-0.62) vs 0.69 (0.63-0.73) for high intensity statins. The 12-month PDC in the PCI and CABG groups, respectively, was 0.82 (0.80-0.83) vs 0.12 (0.09-0.15) for P2Y12i; 0.62 (0.60-0.65) vs 0.43 (0.39-0.48) for ACEi/ARB; 0.53 (0.51-0.55) vs 0.632 (0.58-0.66) for beta blockers; 0.79 (0.78-0.81) vs 0.78 (0.74-0.81) for statins; and 0.49 (0.47-0.51) vs 0.55 (0.50-0.59) for high intensity statins. CONCLUSIONS: Post-discharge dispensing of secondary prevention medications differed with respect to revascularisation strategy from 2012 to 2017, despite clear evidence of benefit during this period. Interventions may be needed to address possible clinician and patient uncertainty about the benefits of secondary prevention medications, regardless of revascularisation strategy.

Comparative single-cell transcriptional and proteomic atlas of clinical-grade injectable mesenchymal source tissues.

Bone marrow aspirate concentrate (BMAC) and adipose-derived stromal vascular fraction (ADSVF) are the most marketed stem cell therapies to treat a variety of conditions in the general population and elite athletes. Both tissues have been used interchangeably clinically even though their detailed composition, heterogeneity, and mechanisms of action have neither been rigorously inventoried nor compared. This lack of information has prevented investigations into ideal dosages and has facilitated anecdata and misinformation. Here, we analyzed single-cell transcriptomes, proteomes, and flow cytometry profiles from paired clinical-grade BMAC and ADSVF. This comparative transcriptional atlas challenges the prevalent notion that there is one therapeutic cell type present in both tissues. We also provide data of surface markers that may enable isolation and investigation of cell (sub)populations. Furthermore, the proteome atlas highlights intertissue and interpatient heterogeneity of injected proteins with potentially regenerative or immunomodulatory capacities. An interactive webtool is available online.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

BACKGROUND: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3, 4, 5, 8, and 10 cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio (PVR) was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3D printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT, both received 2 fractions. RESULTS: Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. PVRs were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses on both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS: We report commissioning results, treatment processes, and the first two patients treated with MBRT using a clinical orthovoltage unit. While demonstrating feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.

THE CLASSIFICATION OF HIATAL SHAPES AND ITS USE AS A MARKER FOR COMPLEXITY, OPERATIVE INTERVENTIONS, AND RECURRENCE.

BACKGROUND: Diaphragmatic reconstruction is a vital, but challenging component of hiatal hernia and anti-reflux surgery. Results are optimized by minimizing axial tension along the esophagus, assessed with intra-abdominal length, and radial tension across the hiatus, which has not been standardized. We categorized hiatal openings into four shapes, as a surrogate for radial tension, to correlate their association with operative interventions and recurrence. METHODS: We retrospectively reviewed all primary hiatal hernias (≥3cm) repaired at a single center between 2010-2020. Patients with intra-operative hiatal photos with at least one year of follow up were included. The hiatal openings were classified into four shapes: slit, inverted teardrop, "D", and oval and ordered in this manner of hypothesized increased complexity and tension. RESULTS: A total of 239 patients were studied, with 113 (47%) having a recurrence. Age (p<0.001), proportion of paraesophageal hernias (p<0.001), hernia axial length (p<0.001), and hiatal width (p<0.001) all increased as shape progressed from slit to inverted teardrop to 'D" to oval. Mesh (p=0.003) and relaxing incisions (p<0.001) were more commonly employed in more advanced shapes, "D" and ovals. However, recurrence (p=0.88) did not correlate with hiatal shape. CONCLUSION: Four different hiatal shapes are commonly seen during hernia repair. These shapes represent a spectrum of hernia chronicity and complexity necessitating increased use of operative measures but not correlating with recurrence. While failing to be a direct marker for recurrence risk, hiatal shape may serve as an intra-operative tool to inform surgeons of the potential need for additional hiatal interventions.

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

Inhalational exposure history is associated with differential sinonasal gene expression profiles and clinical outcomes in chronic rhinosinusitis patients: A pilot study.

KEY POINTS: Inhalational exposure (IE) history assessment is important and may guide chronic rhinosinusitis disease management. Combined exposure status was the most significant factor across differential gene expression analyse IE history was associated with pro-inflammatory transcriptome changes and worse clinical outcomes.

Improving access to buprenorphine for rural veterans in a learning health care system.

OBJECTIVE: To describe a learning health care system research process designed to increase buprenorphine prescribing for the treatment of opioid use disorder (OUD) in rural primary care settings within U.S. Department of Veterans Affairs (VA) treatment facilities. DATA SOURCES AND STUDY SETTING: Using national administrative data from the VA Corporate Data Warehouse, we identified six rural VA health care systems that had improved their rate of buprenorphine prescribing within primary care from 2015 to 2020 (positive deviants). We conducted qualitative interviews with leaders, clinicians, and staff involved in buprenorphine prescribing within primary care from these sites to inform the design of an implementation strategy. STUDY DESIGN: Qualitative interviews to inform implementation strategy development. DATA COLLECTION/EXTRACTION METHODS: Interviews were audio-recorded, transcribed verbatim, and coded by a primary coder and secondary reviewer. Analysis utilized a mixed inductive/deductive approach. To develop an implementation strategy, we matched clinical needs identified within interviews with resources and strategies participants had utilized to address these needs in their own sites. PRINCIPAL FINDINGS: Interview participants (n = 30) identified key clinical needs and strategies for implementing buprenorphine in rural, primary care settings. Common suggestions included the need for clinical mentorship or a consult service, buprenorphine training, and educational resources. Building upon interview findings and in partnership with a clinical team, we developed an implementation strategy composed of an engaging case-based training, an audit and feedback process, and educational resources (e.g., Buprenorphine Frequently Asked Questions, Rural Care Model Infographic). CONCLUSIONS: We describe a learning health care system research process that leveraged national administrative data, health care provider interviews, and clinical partnership to develop an implementation strategy to encourage buprenorphine prescribing in rural primary care settings.

Combining Nuclear Medicine With Other Modalities: Future Prospect for Multimodality Imaging.

This meeting report summarizes a consultants meeting that was held at International Atomic Energy Agency Headquarters, Vienna, in July 2022 to provide an update on the development of multimodality imaging by combining nuclear medicine imaging agents with other nonradioactive molecular probes and/or biomedical imaging techniques.