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Accessing pediatric surgical care is challenging for rural families given long travel distances, financial burden, and logistical barriers. Appalachia is a rural, socioeconomically distressed region with poor health outcomes. This study assessed barriers to care among Appalachian families attending appointments at a centralized Main Campus (MC) versus a decentralized Close to Home (CTH) clinic in Appalachia. Stakeholder-guided surveys were administered to families from Appalachian ZIP codes at MC (12/2023-9/2024) and a CTH pediatric surgery clinic in southeastern Ohio (11/2024-8/2025) upon check-in. Family experience and barriers to care, including distance traveled, travel time, financial strain, missed work/lost wages, and comfort with travel, parking, and locating the clinic, were compared by clinic location using chi-squared tests. Among 276 families approached, 79% participated (n=193 MC, n=41 CTH). Across both sites, most families traveled >1 hour (86.2%), spent >$20 on travel (77.3%), and missed work (70.1%) and wages (52.6%) to attend the appointment. Travel burden >1 hour (92.2% vs 37.5%, p< 0.001) and travel costs >$20 (81.8% vs 41.7%, p< 0.001) were more common among those attending MC than CTH appointments. Those attending the CTH clinic had significantly decreased perceived burden of accessing care including comfort in traveling to the appointment, navigating the campus, and finding the clinic (p&#x2264;0.003 for all comparisons). Overall, 76.5% preferred CTH clinic appointments, including 95.8% of CTH clinic attendees. Rural families seeking pediatric surgical care face notable logistical and financial barriers. A new Appalachian CTH clinic is well-received by families, significantly improving perceived accessibility. IV.

Peripheral arterial disease (PAD) is a progressive vascular disorder among older adults that is associated with significant disability and elevated cardiovascular mortality. However, national mortality trends and disparities among US adults aged &#x2265;65 years with PAD listed on death certificates have not been fully characterized. This study evaluated national mortality trends and demographic disparities among US adults aged &#x2265;65 years with PAD or selected peripheral vascular/arterial conditions. Using the CDC WONDER Multiple Cause of Death database (1999-2020), we conducted a retrospective population-based analysis. ICD-10 codes for peripheral vascular and arterial diseases were used to identify deaths in which PAD or associated peripheral arterial/vascular conditions were listed as an underlying or contributing cause of death. Age-adjusted mortality rates (AAMR) per 100,000 population were calculated using the 2000&#x2009;US standard population. We used joinpoint regression to estimate annual percent change (APC) and average annual percent change (AAPC), with P values < 0.05 considered statistically significant. A total of 1,738,432 PAD-related deaths occurred among adults aged &#x2265;65 years. The overall AAMR declined from 245.14 in 1999 to 145.82 in 2020. Mortality was higher among males than females (282.70 vs 215.26 in 1999; 173.84 vs 117.10 in 2020). Non-Hispanic Black individuals had the highest mortality burden (319.28; 179.12), whereas non-Hispanic Asian or Pacific Islander individuals had the lowest (116.56; 77.52). Adults aged &#x2265;85 years exhibited the highest mortality (836.30; 473.61). Nonmetropolitan areas demonstrated higher mortality than metropolitan areas (268.35 vs 239.55 in 1999; 160.15 vs 142.88 in 2020). Regionally, the Midwest had the highest AAMR (265.61; 148.99), while the Northeast had the lowest (203.99; 127.07). State-level variation ranged from 281.89 in Ohio to 114.82 in Hawaii. Most deaths occurred in medical facilities (39.1%). Mortality among older adults with PAD or selected peripheral vascular/arterial conditions listed on death certificates declined overall. However, demographic and geographic disparities persisted, with recent increases observed after 2018. Targeted prevention, early detection, and modification of risk factors are needed for high-risk older populations.

Bovine &#x3b2;-casomorphin-7 (b-BCM7) is a bioactive peptide released during the digestion of A1 and A2 &#x3b2;-casein, with reported possible effects on gastrointestinal and neurological functions. We aimed to determine how the geographical origin of Colombian commercial UHT milks influences the release of b-BCM7 during a static in vitro gastrointestinal digestion. Using a validated LC-MS/MS analytical method combined with the standardized INFOGEST in vitro digestion model, we observed 2 distinct phase-dependent release patterns. Milks from high-tropic regions showed an early release of b-BCM7 during the gastric phase, reaching concentrations from 14.5 to 49.9 ng/mL, whereas low-tropic milks exhibited minimal gastric release (5.0-5.5 ng/mL). In contrast, intestinal digestion resulted in substantially higher b-BCM7 concentrations in low-tropic samples (658-1,050 ng/mL) compared with high-tropic samples (30.5-292 ng/mL). These findings reveal a phase-dependent release pattern in which geographical origin, likely reflecting differences in breed composition CSN2 allele frequency, modulates the timing and magnitude of peptide liberation Understanding these mechanisms enhances our knowledge of milk bioactivity and provides insight for developing differentiated dairy products with potential nutritional and functional value in tropical production systems.

Mumps was a common childhood viral illness before the implementation of the measles, mumps, and rubella (MMR) vaccination in 1967. There was a significant decrease in mumps cases in the postvaccine era; however, there has been an increase in outbreaks in the United States over the past two decades. Complications of mumps can lead to hospitalization and require a high index of suspicion to diagnose. Early recognition and adequate infection control measures are imperative in outbreak management. Additional studies to inform public health guidelines are needed, including data on the efficacy of a third MMR vaccine in adults.

Postoperative sinus tachycardia is a poorly understood complication following the Fontan procedure. The molecular signaling cascades triggering acute tachycardia remain uncharacterized, limiting therapeutic innovation. Here, we present a retrospective study leveraging serum proteomics and machine learning to identify the molecular drivers of postoperative Fontan sinus tachycardia. We integrated a clinically relevant ovine Fontan model with continuous telemetric heart rate monitoring and human patient data. Serum proteomics coupled with least absolute shrinkage and selection operator and Boruta machine learning algorithms were used to identify protein panels predictive of postoperative sinus tachycardia. Cross-species validation was performed by comparing proteomic signatures from sheep and pediatric patients undergoing Glenn or Fontan surgery. Ovine Fontan animals demonstrated significant heart rate elevation beginning on postoperative day 1, peaking at postoperative day 3 (159.4&#xb1;11.7&#x2009;bpm versus preoperative, 105.3&#xb1;10.5&#x2009;bpm; P=0.0002), before trending toward baseline by postoperative day 10. This pattern was mirrored in human patients with a more modest magnitude. Surgical controls did not exhibit tachycardia. The principal component most correlated with heart rate (principal component 1: r=0.78, P=2.2&#xd7;10-4) was enriched for inflammatory and neural pathways. The Boruta algorithm identified an 11-protein panel with strong predictive power (area under the receiver operating characteristic curve, 0.963). Cross-species comparison demonstrated that angiotensinogen, angiotensin-converting enzyme, and pentraxin 3 were similarly dysregulated in both species postoperatively. This study provides molecular evidence implicating a dysregulated neurohormonal-inflammatory axis in acute postoperative Fontan sinus tachycardia and establishes a foundation for developing targeted diagnostics and therapeutics for this complication.

In 2021, the American College of Gastroenterology and Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America released guidelines for Clostridioides difficile infection (CDI) management, with conflicting recommendations. We surveyed US gastroenterologists (GIs), infectious disease (ID) specialists, and primary care physicians (PCPs) on their use of clinical guidelines and attitudes toward gut microbial therapies for CDI. We conducted an online survey of 302 physicians (n = 101 GIs, 101 IDs, 100 PCPs; February 24 to March 13, 2023). Included GIs and IDs saw a minimum of 3 to 4 patients and PCPs 1 to 2 patients with CDI per month. Physicians working in hospital/academic settings were more familiar with CDI guidelines than those working in independent/group practices. Half of GIs used American College of Gastroenterology guidelines; 98% of IDs followed Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines. More PCPs reported that their institutions did not have set guidelines (40%). More GIs (51%) and IDs (74%) used the recommended multistep algorithm for CDI testing; PCPs were more likely to use a single diagnostic test (49%). GIs and IDs more often prescribed vancomycin taper (93% and 98%, respectively) and fidaxomicin (87% and 97%, respectively); PCPs were more likely to prescribe metronidazole (84%). Less than 10% of physicians felt very knowledgeable about donor-derived microbiome therapies. While 60% of GIs, 53% of IDs, and 50% of PCPs agreed donor-derived microbiome therapies are essential for CDI management, more than 50% cited the need for real-world evidence of safety and efficacy. Education around CDI guidelines and standardized diagnostic and treatment algorithms are needed to ensure consistent CDI management.

Binary metal oxide nanoparticles (biMO-NPs) combining transition and main-group metals with well-organized atomic architectures have unique potential as robust and economical heterogeneous catalysts. Herein, metal oxide nanoparticles (CoAlxOy) using cobalt and aluminum were synthesized, and their structure, morphology, and chemical composition were investigated using various characterization techniques. The biMO-NPs, which had a Gaussian-type size distribution (&#x223c;6&#xa0;nm), were assembled on plain silicon substrates modified chemically with linker molecules bearing suitable end groups. Surface analysis revealed an ordered, uniform, close-packed arrangement of biMO-NPs forming a monolayer architecture with nanoscale thickness (&#x223c;12&#xa0;nm), high surface uniformity, and negligible defects. The nanoparticle monolayer film (NP-MF) was employed as a catalyst to grow carbon nanotube (CNT) forests via the thermal chemical vapor deposition (CVD) method, similar to those grown from catalyst thin films deposited by physical vapor deposition. Structural characterization confirmed the growth of a dense, uniform, high-quality vertically aligned carbon nanotube (VA-CNT) forest with a length of &#x223c;125&#xa0;&#xb5;m, which is comparable to the VA-CNTs grown from expensive thin films. Thus, CNT growth was successfully catalyzed by the biMO-NPs, highlighting a simple and inexpensive alternative for catalyst deposition. In this innovative wet-chemistry approach, the catalyst and catalyst support are combined within a single nanoparticle before NP-MF assembly. Interestingly, this approach provides a scalable and cost-effective pathway for CNT growth, eliminating the need for expensive thin deposition techniques.

Endoscopic ultrasound-guided biliary drainage with lumen-apposing metal stents (LAMS) is an effective alternative for the management of malignant biliary obstruction. Despite its effectiveness, the procedure carries risks including rare but severe vascular complications. We report the first case of a ruptured pseudoaneurysm of the right hepatic artery as an immediate complication of LAMS placement and subsequent covered self-expanding metal stent (cSEMS) placement. A 63-year-old female with unresectable metastatic pancreatic adenocarcinoma was admitted to our hospital with worsening abdominal pain and jaundice. Imaging revealed biliary ductal dilation and a pancreatic mass involving major vascular structures. Owing to failed endoscopic retrograde cholangiopancreatography, EUS-guided choledochoduodenostomy with LAMS placement was performed. Immediately after LAMS deployment, massive bleeding occurred, which was controlled with an additional cSEMS. Despite the initial stabilization, subsequent gastrointestinal bleeding was observed. Computed tomography angiography (CTA) revealed a right hepatic artery pseudoaneurysm that required emergent arterial embolization. This case highlights a super rapid pseudoaneurysm formation following rescue cSEMS placement for the bleeding caused by LAMS placement.

Fructose high-salt (FHS) diets increase blood pressure (BP). The mineralocorticoid receptor (MR), regulates Na+ reabsorption by the aldosterone-sensitive distal nephron (ASDN). The MR can be transactivated by glucocorticoids, including those locally produced by 11&#x3b2;-HSD1. The epithelial sodium channel (ENaC) is a key transporter regulated by the MR. We hypothesized that fructose-induced salt-sensitive hypertension depends in part on abnormal activation of MRs in the ASDN with consequent increases in ENaC expression. We found that aldosterone-upregulated genes in mice ASDN, significantly overlapped with 74 genes upregulated by FHS in the rat kidney cortex (13/74; p&#x2264;1x10-8), and that these 74 genes are prominently expressed in rat ASDN cells. Additionally, the average z-score expression of mice-aldosterone-upregulated genes is highly correlated with FHS compared to glucose high-salt (GHS) in the rat kidney cortex (Pearson correlation; r=0.75; p&#x2264;0.005). FHS and GHS suppressed serum aldosterone to similar levels; however, 11&#x3b2;-HSD1/11&#x3b2;-HSD2 ratio in the kidney cortex at both transcripts (&#x2206;32&#xb1;13%; p&#x2264;0.03; n=6) and protein levels (&#x2206;61&#xb1;27%; p&#x2264;0.05; n=6) was increased in FHS. FHS also increased BP by 23&#xb1;6 mmHg compared to GHS, and blocking MRs with eplerenone prevented this increase. Additionally, inhibiting ENaC with amiloride significantly reduced BP in FHS from 148&#xb1;6 to 134&#xb1;5 mmHg (p&#x2264;0.019). Compared to GHS, FHS increased total and cleaved &#x3b1;ENaC protein by 89&#xb1;14 % (p&#x2264;0.03) and 47&#xb1;16 % (p&#x2264;0.01) respectively. FHS did not change &#x3b2;- or &#x3b3;-subunit expression. These results suggest that fructose-induced salt-sensitive hypertension depends, in part, on abnormal Na+ retention by ENaC, resulting from the activation of MRs by glucocorticoids.

The introduction of calcitonin gene-related peptide antagonists has transformed migraine care. Zavegepant, a third-generation intranasal gepant, offers a nonoral treatment option for acute migraine. Although clinical trials support its efficacy and safety, real-world data are limited. This study reports patient-reported outcomes of zavegepant at a tertiary care center using the Migraine Treatment Optimization Questionnaire-5 (MTOQ-5) and additional survey questions. In this single-center, descriptive, cross-sectional survey study of a retrospectively identified real-world cohort, data were collected from patients prescribed 10&#x2009;mg intranasal zavegepant at the Cleveland Clinic between July 1, 2023, and December 31, 2024. Surveys were administered from January 2025 to March 2025. Eligible patients completed the MTOQ-5 and additional questions assessing dosage frequency, pain freedom, freedom from the most bothersome symptom, adverse events, and willingness to reuse zavegepant. Demographics including race, ethnicity, sex, age, body mass index, monthly migraine days, headache-free days, and number of preventive and rescue therapies prescribed prior to zavegepant use were also recorded. Of 99 patients surveyed, 60 responded and met inclusion criteria and were included in the analysis. Among 60 included patients who used at least two doses, 27 of 60 (45%) patients reported pain freedom within 2&#x2009;h of most attacks half the time or more, 17 of 60 (28%) reported less than half the time, and 16 of 60 (27%) reported never achieving pain freedom within 2&#x2009;h. After zavegepant administration, 38 of 60 (63%) patients reported pain freedom within 2&#x2009;h, and 10 of 60 (17%) patients reported pain freedom within 30&#x2009;min of use. One dose of zavegepant relieving headache for at least 24&#x2009;h was reported half the time or more in 26 of 60 (43%) patients. Following zavegepant use, 36 of 60 patients (60%) reported being able to return to normal activities half the time or more, and 43 of 60 (72%) felt comfortable planning daily activities half the time or more with zavegepant. Zavegepant was well-tolerated half the time or more in 41 of 60 (68%) patients. Dysgeusia was the most common adverse event reported. Overall, 43 of 60 (72%) patients would use zavegepant again. This study represents the first retrospective, real-world, patient-reported outcome study on the use of zavegepant using the validated MTOQ-5. These findings suggest that intranasal zavegepant may be a useful acute migraine treatment option in clinical practice, with patient-reported improvement in pain, most bothersome symptom, function, tolerability, and willingness to reuse. However, the descriptive single-arm design and exclusion of single dose or nonusers limit interpretation and preclude comparative conclusions. Further real-world follow up with larger sample sizes is warranted to validate these findings. This study aimed to understand how well intranasal zavegepant works for acute migraine treatment in a real&#x2010;world setting by surveying patients about their overall experience using the medication. We collected data from 60 patients treated with zavegepant, asking about pain relief, symptom improvement, daily functioning, and tolerability. The findings indicate that many patients experienced fast migraine relief and good tolerability, and that most were willing to use zavegepant again, suggesting it may be an effective and well&#x2010;tolerated option for acute migraine treatment in clinical practice.

Researchers have emphasized the need to integrate patients into medical education, specifically advocating for patient-based assessments within medical curricula. However, there is a critical gap in understanding how patient involvement is conceptualized and operationalized within assessment practices. Thus, we aimed to gain a deeper understanding of the current discourses surrounding the integration of real patients in the assessment of medical trainees. We performed a Discourse Analysis using Hodges' empirical discourse methodology. Coding of the 54 included articles initially focused on "conceptualization," "ways patients participate," "opportunities created," "challenges," and detailed aspects of "assessment," including content, development, validation, and format. The team iteratively discussed the codes and themes until they reached a consensus about the data interpretation. We identified three distinct-yet not always mutually exclusive-discourses: (1) patients as survey-fillers, (2) patients as feedback providers, and (3) patients as part of programmatic assessment. By illuminating these discourses, this study deepens our understanding of why patient involvement takes the forms it does and suggests that moving toward positioning patients as part of programmatic assessment may offer a more meaningful basis for patient partnership in the assessment of medical trainees.

Nonradiative electron-hole recombination driven by nonadiabatic coupling (NAC) between band-edge states is the primary bottleneck limiting carrier lifetime and thus the power conversion efficiency (PCE) of photovoltaic and photocatalytic materials. In this work, we demonstrate that NAC in lead-free Ruddlesden-Popper (RP) perovskites can be substantially reduced by identifying and suppressing the electron-phonon (e-ph) coupling in the specific atomic layer that contributes most strongly to carrier recombination, which we term the target layer. Taking Y2Ti2O5S2 as a model system, we show that its rock-salt [Y2S2]2+ layer is the dominant source of e-ph coupling. By tuning the spatial distribution of the band-edge states to eliminate their overlap within this target layer, the NAC of Ti-based (and Zr-based) RP perovskites is reduced to 0.18 meV, comparable to that of lead halide perovskites (0.16 meV). Time-dependent density functional theory (TDDFT) simulations yield a carrier lifetime of &#x223c;0.8 &#x3bc;s for the designed material Ba3Zr2O5S2 at room temperature, surpassing that of c-CsPbI3 (&#x223c;0.4 &#x3bc;s). This strategy of controlling NAC through target-layer engineering provides new insight into carrier dynamics and offers a practical guideline for designing lead-free perovskites with improved PCE.

Residual major adverse cardiovascular event (MACE) risk persists despite successful prevention of cardiovascular disease (CVD) with statin therapy among people with HIV (PWH). Identifying key biomarkers related to residual cardiovascular risk is critical for PWH. The objective of the current analysis was to assess the association of immune, inflammatory, cardiac, and lipid-related biomarkers among contemporary antiretroviral therapy-treated PWH in the REPRIEVE global primary cardiovascular prevention trial in residual risk analyses. We assessed relationships of baseline inflammatory, cardiac, and lipid-related biomarkers to incident MACE using Cox models adjusted for randomized statin treatment and atherosclerotic CVD risk. Population attributable fractions (PAFs) were assessed for biomarkers. Of the 7769 REPRIEVE participants, 7,005 (90%) had biomarker data available at baseline, with the median follow-up of 5.6 years. Relatively high percentages of participants had elevated inflammatory (high-sensitivity C-reactive protein >3 mg/L [49%], interleukin [IL]-6 &#x2265;3.3 pg/mL [33%]) and cardiac markers (high-sensitivity troponin &#x2265;6 ng/L [35%], N-terminal pro-B-type natriuretic peptide &#x2265;50 pg/mL [33%]). Inflammatory biomarkers showed minimal correlation with cardiac or lipid biomarkers (apolipoprotein B-100, oxidized low-density lipoprotein, and lipoprotein(a)). Individual biomarkers were related to MACE in analyses adjusted for PCE and statin randomization, with the largest HRs for IL-6 (HR: 2.2; 95% CI: 1.3-3.9) and high-sensitivity troponin (HR: 2.2; 95% CI: 1.2-4.1) comparing those with highest vs lowest biomarker levels. PAFs were highest for IL-6, 18.6% (95% CI: 7.4%-30.5%) and high-sensitivity C-reactive protein 17.2% (95% CI: 1.6%-32.9%). Among PWH with low-moderate predicted CVD risk and well-controlled HIV, persistent inflammation, innate immune activation, and subclinical cardiac dysfunction are common, and strongly relate to residual MACE risk, accounting for a large PAF. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290.

Respiratory viral infections cause significant mortality. Pre-existing atopy has demonstrated protection from virus-induced death. Atopic mice with house dust mite (HDM) extract survive normally lethal parainfluenza (Sendai virus, SeV) and influenza A (IAV) infection. Neuregulin-1 (NRG1), markedly elevated in airways of atopic mice, has been shown to significantly attenuate mortality to SeV and IAV in non-atopic mice. Hypothesizing that atopy and NRG1 mediate protection from death through similar mechanisms, we anazlyed single-cell RNA sequencing data from CD45+ (hematopoietic) and CD45- (structural) lung cells prior to infection. Both treatments reduced alveolar macrophages, lymphatic endothelial cells, airway smooth muscle cells, and pericytes, while increasing alveolar type 2 cells. However, atopy led to increased fibroblasts with reduced club cells compared to NRG1 treatment. Further, in the hematopoietic cell compartment, atopy drove an increase in more inflammatory cells than NRG1 and associated with significant upregulation of immune cell signaling pathways, something not seen with NRG1 administration. Moreover, NRG1 knockdown did not reverse the protection from virus-induced death in mice with pre-existing atopy. Taken together, these data strongly suggest that atopy and NRG1 mediate increased survival from a respiratory viral infection through disparate mechanisms.

We present a solid-state reactive processing (SSRP) route that enables in situ formation and uniform dispersion of metallic Fe nanoparticles within an aluminum matrix through controlled nanothermitic reactions. Using friction-assisted plastic deformation of an Al-Mg alloy embedded with a small fraction (&#x223c;4 wt %) of Fe3O4 particles, localized heat and shear deformation promote concurrent mechanical mixing, thermal activation, and chemical reduction. The reaction between Fe3O4 and Al/Mg produces Fe cores encapsulated by MgO and Al2O3-rich shells, effectively suppressing the formation of brittle Fe-Al intermetallics that typically hinder Fe-reinforced Al systems. The resulting microstructure exhibits fine-scale dispersion of core-shell nanoparticles and significant matrix refinement, leading to enhanced hardness and electrical resistivity. This proof-of-concept demonstrates that multistimuli coupling during solid-state processing can activate in situ controlled thermite reactions at moderate temperatures, providing a new pathway for fabricating lightweight, multifunctional metal-oxide nanocomposites.

Analgesic medications are sometimes taken prior to vaccination to prevent local and systemic adverse reactions. Although studies have examined the association between postvaccination analgesic use and immunogenicity, few have evaluated the effects of prevaccination analgesic use. This analysis assessed antibody response, influenza-like illness (ILI), and influenza infection among adults with and without analgesic use before influenza vaccination. The Pragmatic Assessment of Influenza Vaccine Effectiveness in the DoD (PAIVED) study was an open-label, randomized trial evaluating the effectiveness of FDA-licensed influenza vaccines during 4 influenza seasons in adult military healthcare beneficiaries. PAIVED participants with data on analgesic use within 24&#x2005;hours before vaccination were included in this analysis if they either provided prevaccination and postvaccination venous blood samples or participated in weekly ILI surveillance. Among 684 PAIVED participants with prevaccination and postvaccination antibody titers, 10.4% (n = 71) reported analgesic use before influenza vaccination. Multivariable analyses showed no association between analgesic use and geometric mean titer fold change. There was a modest association between acetaminophen use and increased seroconversion to influenza A/H3N2 compared with no analgesic use (aIRR = 1.37; P = .022); however, this association was not significant in sensitivity analyses adjusting for multiple comparisons. Among 10 723 PAIVED participants with ILI surveillance data, 10.6% (n = 1140) reported prevaccination analgesic use. Multivariable analyses revealed no association between analgesic use and incidence of ILI or odds of influenza infection. These findings suggest acetaminophen and/or nonsteroidal anti-inflammatory analgesic use within 24&#x2005;hours before influenza vaccination does not reduce vaccine immunogenicity or effectiveness in adults.

Posterior cruciate ligament (PCL) with tibial avulsion injuries commonly occur following high-energy trauma. While the posteromedial approach is traditionally favored for fixation, emerging evidence suggests that a direct posterior approach may be a safe and effective alternative for select fracture patterns. We report the case of a 26-year-old polytrauma patient with no significant prior medical or surgical history who presented after a motorcycle accident with a PCL tibial avulsion injury resulting in posterolateral and tibial intercondylar eminence fracture with a central articular posterior rim involvement. We performed a direct posterior approach, as described by Abbott-Carpenter. Fixation was achieved with FiberWire sutures for the ligamentous avulsion and cannulated screws for the bony fragments. The post-operative recovery was notable for a transient tibial nerve neuropraxia that resolved before discharge, and the patient progressed well in rehabilitation with favorable clinical outcomes at follow-up. PCL tibial avulsion injuries associated with posterior rim fracture commonly result from hyperflexion mechanisms, classically described as dashboard-type injuries. The fracture morphology and ligamentous involvement determine the optimal surgical approach. This case highlights a less commonly reported fixation strategy using FiberWire sutures and cannulated screws through a direct posterior approach. Our findings contribute to the growing body of evidence that the direct posterior approach to repairing PCL tibial avulsion injury is safe and effective with minimal complications.

Arterial thrombosis is a leading cause of death and disability worldwide. Administration of tissue plasminogen activator (tPA) remains the current noninvasive clinical gold standard but is ineffective for many patients. Von Willebrand factor (VWF) is mechanistically critical in arterial thrombosis and has been studied as an alternative target for thrombolytic therapy. This study utilizes a microfluidic system of arterial thrombosis to evaluate VWF-A1 domain inhibitor aptamer (BB-031), aiming to understand VWF-mediated recanalization (vessel reopening) and compare efficacy of BB-031 to Alteplase and Tenecteplase. Thrombotic occlusion is simulated in a microfluidic device, and thrombi are allowed to retract and remodel for up to 6&#x2009;hr. During a subsequent 2&#x2009;h treatment reperfusion period (not disruptive to the original thrombus), thrombus morphology, composition, and channel patency (openness) are analyzed. Thrombi substantially remodel post-occlusion. BB-031 treatment results in an inability to maintain thrombus and significantly improves microfluidic patency compared to vehicle and tPA. Acute ischemic stroke patient samples demonstrate improved microfluidic patency with BB-031 compared to vehicle. Here we establish an in vitro/ex vivo platform to study arterial occlusion, clot retraction, drug delivery, and recanalization/patency, and implement this platform to demonstrate BB-031 could be a safe and efficacious therapeutic alternative to tPA.

Multiple clinical trials have failed to show benefit of anticoagulation over antiplatelets in preventing recurrent stroke among patients with embolic stroke of undetermined source (ESUS). However, there are limited data on antithrombotic prescribing patterns and clinical outcomes in a real-world setting. This is a subgroup analysis of a multicenter retrospective observational cohort of consecutive adults with ESUS (admitted between 2015 and 2023). Patients were categorized according to antithrombotic initiation by day 7 after stroke or discharge, whichever was sooner: single antiplatelet therapy (SAPT), combination antiplatelet therapy (CAPT) without anticoagulation (AC), or AC with or without antiplatelet therapy (AP) initiated within the first 7 days of index stroke. Differences in treatment strategies were compared between patients admitted between 2015-2018 and 2019-2023 approximating the publication of RESPECT ESUS and NAVIGATE ESUS trials. The primary composite outcome of recurrent ischemic stroke, major bleeding, intracerebral hemorrhage, or death was assessed using unadjusted and adjusted Cox proportional hazards regression. Of the 2,328 included patients, 1,537 (66.0%) were prescribed SAPT, 561 (24.1%) CAPT, and 230 (9.9%) AC &#xb1; AP. Compared with other treatment groups, patients treated with CAPT were less likely to be female, but more likely to have atherosclerotic risk factors and presented with milder symptoms. Patients treated with AC &#xb1; AP were younger, more likely to have a prior stroke, a higher NIHSS, a large vessel occlusion, and reduced left ventricular ejection fraction. Compared with patients admitted from 2015 to 2018, those admitted between 2019 and 2023 were more frequently prescribed AC &#xb1; AP (11.3% vs 5.9%) or CAPT (26.7% vs 17.2%) and less frequently prescribed SAPT (62.0% vs 76.9%, p < 0.001). Compared with SAPT, neither CAPT nor AC were associated with any significant difference in the primary composite outcome. Of the secondary outcomes, CAPT was associated with lower risk of death vs SAPT in unadjusted and adjusted models (aHR 0.69, 95%CI, 0.48-0.98). In this large multicenter cohort study, there was an increased frequency of discharge on AC in ESUS patients after the publication of ESUS randomized trials. Treatment with CAPT or AC &#xb1; AP was not associated with a reduced risk of recurrent stroke compared with SAPT. The study is registered on ClinicalTrials.gov (NCT06398366).