A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression.

Genome-wide association studies (GWASs) implicate the PHACTR1 locus (6p24) in risk for five vascular diseases, including coronary artery disease, migraine headache, cervical artery dissection, fibromuscular dysplasia, and hypertension. Through genetic fine mapping, we prioritized rs9349379, a common SNP in the third intron of the PHACTR1 gene, as the putative causal variant. Epigenomic data from human tissue revealed an enhancer signature at rs9349379 exclusively in aorta, suggesting a regulatory function for this SNP in the vasculature. CRISPR-edited stem cell-derived endothelial cells demonstrate rs9349379 regulates expression of endothelin 1 (EDN1), a gene located 600 kb upstream of PHACTR1. The known physiologic effects of EDN1 on the vasculature may explain the pattern of risk for the five associated diseases. Overall, these data illustrate the integration of genetic, phenotypic, and epigenetic analysis to identify the biologic mechanism by which a common, non-coding variant can distally regulate a gene and contribute to the pathogenesis of multiple vascular diseases.

The vagus nerve in cardiovascular physiology and pathophysiology: From evolutionary insights to clinical medicine.

The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we highlight vagal efferent and afferent innervation of the heart, with a focus on insights from comparative biology and advances in understanding the molecular and genetic diversity of vagal neurons, as well as interoception, parasympathetic dysfunction in heart disease, and the therapeutic potential of targeting the parasympathetic nervous system in cardiovascular disease.

Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve.

Spatially selective vagus nerve stimulation (sVNS) offers a promising approach for addressing heart disease with enhanced precision. Despite its therapeutic potential, VNS is limited by off-target effects and the need for time-consuming titration. Our research aimed to determine the spatial organization of cardiac afferent and efferent fibres within the vagus nerve of pigs to achieve targeted neuromodulation. Using trial-and-error sVNS in vivo and ex vivo micro-computed tomography fascicle tracing, we found significant spatial separation between cardiac afferent and cardiac efferent fibres at the mid-cervical level and they were localized on average on opposite sides of the nerve cross-section. This was consistent between both in vivo and ex vivo methods. Specifically, cardiac afferent fibres were located near pulmonary fibres, consistent with findings of cardiopulmonary convergent circuits and, notably, cardiac efferent fascicles were exclusive. These cardiac efferent regions were located in close proximity to the recurrent laryngeal regions. This is consistent with the roughly equitable spread across the nerve of the afferent and efferent fibres. Our study demonstrated that targeted neuromodulation via sVNS could achieve scalable heart rate decreases without eliciting cardiac afferent-related reflexes; this is desirable for reducing sympathetic overactivation associated with heart disease. These findings indicate that understanding the spatial organization of cardiac-related fibres within the vagus nerve can lead to more precise and effective VNS therapy, minimizing off-target effects and potentially mitigating the need for titration. KEY POINTS: Spatially selective vagus nerve stimulation (sVNS) presents a promising approach for addressing chronic heart disease with enhanced precision. Our study reveals significant spatial separation between cardiac afferent and efferent fibres in the vagus nerve, particularly at the mid-cervical level. Utilizing trial-and-error sVNS in vivo and micro-computed tomography fascicle tracing, we demonstrate the potential for targeted neuromodulation, achieving therapeutic effects such as scalable heart rate decrease without stimulating cardiac afferent-related reflexes. This spatial understanding opens avenues for more effective VNS therapy, minimizing off-target effects and potentially eliminating the need for titration, thereby expediting therapeutic outcomes in myocardial infarction and related conditions.

Impact of Pulmonary Complications on Outcomes and Resource Use After Elective Cardiac Surgery.

OBJECTIVE: To characterize the impact of pulmonary complications (PCs) on mortality, costs, and readmissions after elective cardiac operations in a national cohort and to test for hospital-level variation in PC. BACKGROUND: PC after cardiac surgery are targets for quality improvement efforts. Contemporary studies evaluating the impact of PC on outcomes are lacking, as is data regarding hospital-level variation in the incidence of PC. METHODS: Adults undergoing elective coronary artery bypass grafting and/or valve operations were identified in the 2016-2019 Nationwide Readmissions Database. PC was defined as a composite of reintubation, prolonged (>24 hours) ventilation, tracheostomy, or pneumonia. Generalized linear models were fit to evaluate associations between PC and outcomes. Institutional variation in PC was studied using observed-to-expected ratios. RESULTS: Of 588,480 patients meeting study criteria, 6.7% developed PC. After risk adjustment, PC was associated with increased odds of mortality (14.6, 95% CI, 12.6-14.8), as well as a 7.9-day (95% CI, 7.6-8.2) increase in length of stay and $41,300 (95% CI, 39,600-42,900) in attributable costs. PC was associated with 1.3-fold greater hazard of readmission and greater incident mortality at readmission (6.7% vs 1.9%, P <0.001). Significant hospital-level variation in PC was present, with observed-to-expected ratios ranging from 0.1 to 7.7. CONCLUSIONS: Pulmonary complications remain common after cardiac surgery and are associated with substantially increased mortality and expenditures. Significant hospital-level variation in PC exists in the United States, suggesting the need for systematic quality improvement efforts to reduce PC and their impact on outcomes.

Machine Learning Based Prediction of Postoperative Pancreatic Fistula Following Pancreaticoduodenectomy.

OBJECTIVE: To develop a novel machine learning (ML) model to predict clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD). SUMMARY BACKGROUND DATA: Accurate prognostication of CR-POPF may allow for risk stratification and adaptive treatment strategies for potential PD candidates. However, antecedent models, such as the modified Fistula Risk Score (mFRS), are limited by poor discrimination and calibration. METHODS: All records entailing PD within the 2014-2018 ACS NSQIP were identified. Additionally, patients undergoing PD at our institution between 2013 and 2021 were queried from our local data repository. An eXtreme Gradient Boosting (XGBoost) model was developed to estimate the risk of CR-POPF using data from the ACS NSQIP and evaluated using institutional data. Model discrimination was estimated using the area under the receiver operating characteristic (AUROC) and precision recall curve (AUPRC). RESULTS: Overall, 12,281 and 445 patients undergoing PD were identified within the 2014-2018 ACS NSQIP and our institutional registry, respectively. Application of the XGBoost and mFRS scores to the internal validation dataset revealed that the former model had significantly greater AUROC (0.72 vs. 0.68, P<0.001) and AUPRC (0.22 vs. 0.18, P<0.001). Within the external validation dataset, the XGBoost model remained superior to the mFRS with an AUROC of 0.79 (95% CI 0.74-0.84) versus 0.75 (95% CI 0.70-0.80, P<0.001). In addition, AUPRC was higher for the XGBoost model, compared to the mFRS. CONCLUSIONS: Our novel ML model consistently outperformed the previously validated mFRS within internal and external validation cohorts, thereby demonstrating its generalizability and utility for enhancing prediction of CR-POPF.

The Presence of a Cost-Volume Relationship in Robotic-assisted Thoracoscopic Lung Resections.

OBJECTIVE: To characterize the relationship between institutional robotic-assisted pulmonary lobectomy volume and hospitalization costs. BACKGROUND: The high cost of robotic-assisted thoracoscopic surgery (RATS) is among several drivers of hesitation among nonadopters. Studies examining the impact of institutional experience on costs of RATS lobectomy are lacking. METHODS: Adults undergoing RATS lobectomy for primary lung cancers were identified from the 2016 to 2018 Nationwide Readmissions Database. A multivariable regression to model hospitalization costs was developed with the inclusion of hospital RATS lobectomy volume as restricted cubic splines. The volume corresponding to the inflection point of the spline was used to categorize hospitals as high- (HVH) or low-volume (LVH). We subsequently examined the association of HVH status with adverse events, length of stay, costs, and 30-day, nonelective readmissions. RESULTS: An estimated 14,756 patients underwent RATS lobectomy during the study period, with median cost of $23,000. Upon adjustment for patient and operative characteristics, hospital RATS volume was inversely associated with costs. Although only 17.2% of centers were defined as HVH, 51.7% of patients were managed at these centers. Patients at HVH and LVH had similar age, sex, and distribution of comorbidities. Notably, patients at HVH had decreased risk-adjusted odds of adverse events (adjusted odds ratio: 0.62, P <0.001), as well as significantly reduced length of stay (-0.8 d, P <0.001) and costs (-$3900, P <0.001). CONCLUSIONS: Increasing hospital RATS lobectomy volume was associated with reduced hospitalization costs. Our findings suggest the presence of streamlined care pathways at high-volume centers, which influence costs of care.

Innervation and Neuronal Control of the Mammalian Sinoatrial Node a Comprehensive Atlas.

[Figure: see text].

Preoperative stents for the treatment of obstructing left-sided colon cancer: a national analysis.

BACKGROUND: Given the risks associated with urgent colectomy for large bowel obstruction, preoperative colonic stenting has been utilized for decompression and optimization prior to surgery. This study examined national trends in the use of colonic stenting as a bridge to resection for malignant large bowel obstruction and evaluated outcomes relative to immediate colectomy. METHODS: Adults undergoing colonic stenting or colectomy for malignant, left/sigmoid large bowel obstruction were identified in the 2010-2016 Nationwide Readmissions Database. Patients were classified as immediate resection (IR) or delayed resection (DR) if undergoing colonic stenting prior to colectomy. Generalized linear models were used to evaluate the impact of resection strategy on ostomy creation, in-hospital mortality, and complications. RESULTS: Among 9,706 patients, 9.7% underwent colonic stenting, which increased from 7.7 to 16.4% from 2010 to 2016 (p < 0.001). Compared to IR, the DR group was younger (63.9 vs 65.9 years, p = 0.04), had fewer comorbidities (Elixhauser Index 3.5 vs 3.9, p = 0.001), and was more commonly managed at high-volume centers (89.4% vs 68.1%, p < 0.001). Laparoscopic resections were more frequent among the DR group (33.1% vs 13.0%, p < 0.001), while ostomy rates were significantly lower (21.5% vs 53.0%, p < 0.001). After risk adjustment, colonic stenting was associated with reduced odds of ostomy creation (0.34, 95% confidence interval 0.24-0.46), but similar odds of mortality and complications. CONCLUSION: Colonic stenting is increasingly utilized for malignant, left-sided bowel obstructions, and associated with lower ostomy rates but comparable clinical outcomes. These findings suggest the relative safety of colonic stenting for malignant large bowel obstruction when clinically appropriate.

Impact of surgeon specialty on clinical outcomes following esophagectomy for cancer.

BACKGROUND: The impact of surgeon and hospital operative volume on esophagectomy outcomes is well-described; however, studies examining the influence of surgeon specialty remain limited. Therefore, we evaluated the impact of surgeon specialty on short-term outcomes following esophagectomy for cancer. METHODS: The 2016-2019 American College of Surgeons National Surgical Quality Improvement Project (ACS NSQIP) was queried to identify all patients undergoing esophagectomy for esophageal cancer. Surgeon specialty was categorized as general (GS) or thoracic (TS). Entropy balancing was used to generate sample weights that adjust for baseline differences between GS and TS patients. Weights were subsequently applied to multivariable linear and logistic regressions, which were used to evaluate the independent association of surgeon specialty with 30-day mortality, complications, and postoperative length of stay. RESULTS: Of 2657 esophagectomies included for analysis, 54.1% were performed by TS. Both groups had similar distributions of age, sex, and body mass index. TS patients more frequently underwent transthoracic esophagectomy, while GS patients more commonly received minimally invasive surgery. After adjustment, surgeon specialty was not associated with altered odds of 30-day mortality (adjusted odds ratio [AOR] 1.10 p = 0.73) or anastomotic leak (AOR 0.87, p = 0.33). However, TS patients exhibited a 40-min reduction in operative duration and faced greater odds of perioperative transfusion, relative to GS. CONCLUSION: Among ACS NSQIP participating centers, surgeon specialty influenced operative duration and blood product utilization, but not mortality and anastomotic leak. Our results support the relative safety of esophagectomy performed by select GS and TS.

Morbidity and Mortality Associated With Blood Transfusions in Elective Adult Cardiac Surgery.

OBJECTIVES: Perioperative transfusion thresholds have garnered increasing scrutiny as restrictive strategies have been shown to be noninferior. The study authors used data from a statewide academic collaborative to test the association between transfusion and 30-day mortality. DESIGN: All adult patients undergoing coronary artery bypass grafting (CABG) and/or valve surgeries between 2013 and 2019 in the authors' Academic Cardiac Surgery Consortium were examined. The relationship between the number of overall packed red blood cell (pRBC) and coagulation product (CP) (fresh frozen plasma, cryoprecipitate, platelets) transfusions on 30-day mortality was evaluated. Multivariate regression was used to evaluate predictors of transfusion and study endpoints. Machine learning (ML) models also were developed to predict 30-day mortality and rank transfusion-related features by relative importance. SETTING: At an Academic Cardiac Surgery Consortium of 5 institutions. PARTICIPANTS: Patients ≥18 years old undergoing CABG and/or valve surgeries. MEASUREMENTS AND MAIN RESULTS: Of the 7,762 patients (median hematocrit [HCT] 39%, IQR 35%-43%) who were included in the final study cohort, >40% were transfused at least 1 unit of pRBC or CP. In adjusted analyses, higher preoperative HCT was associated with reduced odds of mortality (adjusted odds ratio [aOR] 0.95, 95% CI 0.92-0.98), renal failure (aOR 0.95, 95% CI 0.92-0.98), and prolonged mechanical ventilation (aOR 0.97, 95% CI 0.95-0.99). In contrast, perioperative transfusions were associated with increased 30-day mortality after adjustment for preoperative HCT and other baseline features. The ML models were able to predict 30-day mortality with an area under the curve of 0.814-to-0.850, with perioperative transfusions displaying the highest feature importance. CONCLUSIONS: The present analysis found increasing HCT to be associated with a lower incidence of mortality. The study authors also found a direct dose-response association between transfusions and all study endpoints examined.

Association of Hospital Volume and Outcomes Following Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) has been used to mitigate the negative systemic effects of cardiopulmonary bypass. Recent consortium and single-institution studies suggest an association between operator experience and long-term survival. We thus aimed to ascertain the relationship between institutional OPCAB volume and outcomes using a contemporary nationwide all-payer database. METHODS: Adult admissions for elective isolated OPCAB were identified from the 2016-2019 Nationwide Readmissions Database. The primary outcome was major adverse events (MAE), defined as a composite of mortality, reoperation, prolonged mechanical ventilation, acute kidney injury requiring dialysis, or perioperative stroke during the index hospitalisation. Secondary outcomes included temporal trends, postoperative length of stay (pLOS), hospitalisation costs, non-home discharge, and 30-day readmission rate. High-volume hospitals (HVH) were defined to have annual caseloads >35 based on cubic spline analysis. RESULTS: Of an estimated 41,154 patients, 59.9% were treated at HVH. The proportion of coronary artery bypass grafting operations that were OPCAB significantly decreased from 21.1% in 2016 to 18.3% in 2019. After adjustment, HVH status was associated with lower adjusted odds of MAE (adjusted odds ratio [AOR] 0.78, 95% confidence interval [CI] 0.70-0.88), compared to others. HVH were also associated with shorter pLOS (ß -0.10, 95% -0.13, -0.07), reduced costs (ß -US$4,900, - US$6,300, - US$3,600), non-home discharge (AOR 0.54, 95% CI 0.45-0.64), and 30-day readmission (AOR 0.86, 95% CI 0.77-0.96). CONCLUSIONS: Our results suggest that OPCAB requires a distinct set of surgical expertise and institutional aptitude. As a result, centralisation of care to centres of excellence should be considered.

Scalable and reversible axonal neuromodulation of the sympathetic chain for cardiac control.

Maladaptation of the sympathetic nervous system contributes to the progression of cardiovascular disease and risk for sudden cardiac death, the leading cause of mortality worldwide. Axonal modulation therapy (AMT) directed at the paravertebral chain blocks sympathetic efferent outflow to the heart and maybe a promising strategy to mitigate excess disease-associated sympathoexcitation. The present work evaluates AMT, directed at the sympathetic chain, in blocking sympathoexcitation using a porcine model. In anesthetized porcine (n = 14), we applied AMT to the right T1-T2 paravertebral chain and performed electrical stimulation of the distal portion of the right sympathetic chain (RSS). RSS-evoked changes in heart rate, contractility, ventricular activation recovery interval (ARI), and norepinephrine release were examined with and without kilohertz frequency alternating current block (KHFAC). To evaluate efficacy of AMT in the setting of sympathectomy, evaluations were performed in the intact state and repeated after left and bilateral sympathectomy. We found strong correlations between AMT intensity and block of sympathetic stimulation-evoked changes in cardiac electrical and mechanical indices (r = 0.83-0.96, effect size d = 1.9-5.7), as well as evidence of sustainability and memory. AMT significantly reduced RSS-evoked left ventricular interstitial norepinephrine release, as well as coronary sinus norepinephrine levels. Moreover, AMT remained efficacious following removal of the left sympathetic chain, with similar mitigation of evoked cardiac changes and reduction of catecholamine release. With growth of neuromodulation, an on-demand or reactionary system for reversible AMT may have therapeutic potential for cardiovascular disease-associated sympathoexcitation.NEW & NOTEWORTHY Autonomic imbalance and excess sympathetic activity have been implicated in the pathogenesis of cardiovascular disease and are targets for existing medical therapy. Neuromodulation may allow for control of sympathetic projections to the heart in an on-demand and reversible manner. This study provides proof-of-concept evidence that axonal modulation therapy (AMT) blocks sympathoexcitation by defining scalability, sustainability, and memory properties of AMT. Moreover, AMT directly reduces release of myocardial norepinephrine, a mediator of arrhythmias and heart failure.

Higher risk tumor features are not associated with higher nodal stage in patients with estrogen receptor-positive, node-positive breast cancer.

INTRODUCTION: Studies support omission of axillary lymph node dissection (ALND) for patients with sentinel node-positive disease, with ALND recommended for patients who present with clinically positive nodes. Here, we evaluate patient and tumor characteristics and pathologic nodal stage of patients with estrogen receptor-positive (ER +) breast cancer who undergo ALND to determine if differences exist based on nodal presentation. MATERIALS AND METHODS: Retrospective chart review from 2010 to 2019 defined three groups of patients with ER + breast cancer who underwent ALND for positive nodes: SLN + (positive node identified at SLN biopsy), cNUS (abnormal preoperative US and biopsy), and cNpalp (palpable adenopathy). Patients who received neoadjuvant chemotherapy or presented with axillary recurrence were excluded. RESULTS: Of 191 patients, 94 were SLN + , 40 were cNUS, and 57 were cNpalp. Patients with SLN + compared with cNpalp were younger (56 vs 64 years, p < 0.01), more often pre-menopausal (41% vs 14%, p < 0.01), and White (65% vs 39%, p = 0.01) with more tumors that were low-grade (36% vs 8%, p < 0.01). Rates of PR + (p = 0.16), levels of Ki67 expression (p = 0.07) and LVI (p = 0.06) did not differ significantly among groups. Of patients with SLN + disease, 64% had pN1 disease compared to 38% of cNUS (p = 0.1) and 40% of cNpalp (p = 0.01). On univariable analysis, tumor size (p = 0.01) and histology (p = 0.04) were significantly associated with pN1 disease, with size remaining an independent predictor on multivariable analysis (p = 0.02). CONCLUSION: Historically, higher risk features have been attributed to patients with clinically positive nodes precluding omission of ALND, but when restricting evaluation to patients with ER + breast cancer, only tumor size is associated with higher nodal stage.

Center Volume Impacts Readmissions and Mortality after Congenital Cardiac Surgery.

OBJECTIVE: To characterize the relationship between surgical volume and postoperative outcomes in congenital heart surgery, we used a national cohort to assess the costs, readmissions, and complications in children undergoing cardiac operations. STUDY DESIGN: The Nationwide Readmissions Database was used to identify pediatric patients (≤18 years) undergoing congenital cardiac surgery from 2010 to 2017. Hospitals were categorized based on deciles and tertiles of annual caseload with high-volume categorized as the highest tertile of volume. Multivariable regression models adjusting for patient and hospital characteristics were used to study the impact of volume on 30-day nonelective readmission, mortality, home discharge, and resource use. RESULTS: Of an estimated 69 448 hospitalizations included for analysis, 56 672 (82%) occurred at high-volume centers. After adjustment for key clinical factors, each decile increase in volume was associated with a 25% relative decrease in the odds of mortality, a 14% decrease in the odds of nonhome discharge, and a 4% relative decrease in the likelihood of 30-day nonelective readmission. After risk adjustment, each incremental increase in volume decile was associated with a one-half-day decrease in the hospital length of stay, but did not alter costs of the index hospitalization. However, after including all readmissions within 30 days of the index discharge, high-volume centers were associated with significantly lower costs compared with low-volume hospitals. CONCLUSIONS: Increased congenital cardiac surgery volume is associated with improved mortality, reduced duration of hospitalization, 30-day readmissions, and resource use. These findings demonstrate the inverse relationship between hospital volume and resource use and may have implications for the centralization of care for congenital cardiac surgery.

Incidence and Outcomes of Laryngeal Complications Following Adult Cardiac Surgery: A National Analysis.

Laryngeal complications (LCs) following cardiac operations contribute to increased morbidity and resource utilization. Using a nationally representative cohort of cardiac surgical patients, we characterized the incidence of LC as well as its associated clinical and financial outcomes. All adults undergoing coronary artery bypass grafting and/or valvular operations were identified using the 2010-2017 Nationwide Readmissions Database. International Classification of Diseases 9th and 10th Revision diagnosis codes were used to identify LC. Trends were analyzed using a rank-based, non-parametric test (nptrend). Multivariable linear and logistic regressions were used to evaluate risk factors for LC, and its impact on mortality, complications, resource use and 30-day non-elective readmissions. Of an estimated 2,319,628 patients, 1.7% were diagnosed with perioperative LC, with rising incidence from 1.5% in 2010 to 1.8% in 2017 (nptrend < 0.001). After adjustment, female sex [adjusted odds ratio 1.08, 95% confidence interval (CI) 1.04-1.12], advancing age, and multi-valve procedures (1.51, 95% CI 1.36-1.67, reference: isolated CABG) were associated with increased odds of LC. Despite no risk-adjusted effect on mortality, LC was associated with increased odds of pneumonia (2.88, 95% CI 2.72-3.04), tracheostomy (4.84, 95% CI 4.44-5.26), and readmission (1.32, 95% CI 1.26-1.39). In addition, LC was associated with a 7.7-day increment (95% CI 7.4-8.0) in hospitalization duration and $24,200 (95% CI 23,000-25,400) in attributable costs. The present study found LC to be associated with increased perioperative sequelae and resource utilization. The development and application of active screening protocols for post-surgical LC are warranted to increase early detection and reduce associated morbidity.

Rapid measurement of cardiac neuropeptide dynamics by capacitive immunoprobe in the porcine heart.

Sympathetic control of regional cardiac function occurs through postganglionic innervation from stellate ganglia and thoracic sympathetic chain. Whereas norepinephrine (NE) is their primary neurotransmitter, neuropeptide Y (NPY) is an abundant cardiac cotransmitter. NPY plays a vital role in homeostatic processes including angiogenesis, vasoconstriction, and cardiac remodeling. Elevated sympathetic stress, resulting in increased NE and NPY release, has been implicated in the pathogenesis of several cardiovascular disorders including hypertension, myocardial infarction, heart failure, and arrhythmias, which may result in sudden cardiac death. Current methods for the detection of NPY in myocardium are limited in their spatial and temporal resolution and take days to weeks to provide results [e.g., interstitial microdialysis with subsequent analysis by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), or mass spectrometry]. In this study, we report a novel approach for measurement of interstitial and intravascular NPY using a minimally invasive capacitive immunoprobe (C.I. probe). The first high-spatial and temporal resolution, multichannel measurements of NPY release in vivo are provided in both myocardium and transcardiac vascular space in a beating porcine heart. We provide NPY responses evoked by sympathetic stimulation and ectopic ventricular pacing and compare these to NE release and hemodynamic responses. We extend this approach to measure both NPY and vasoactive intestinal peptide (VIP) and show differential release profiles under sympathetic stimulation. Our data demonstrate rapid and local changes in neurotransmitter profiles in response to sympathetic cardiac stressors. Future implementations include real-time intraoperative determination of cardiac neuropeptides and deployment as a minimally invasive catheter.NEW & NOTEWORTHY The sympathetic nervous system regulates cardiac function through release of neurotransmitters and neuropeptides within the myocardium. Neuropeptide Y (NPY) acts as an acute cardiac vasoconstrictor and chronically to regulate angiogenesis and cardiac remodeling. Current methodologies for the measure of NPY are not capable of providing rapid readouts on a single-sample basis. Here we provide the first in vivo methodology to report dynamic, localized NPY levels within both myocardium and vascular compartments in a beating heart.

Impact of Payer Status on Delisting Among Liver Transplant Candidates in the United States.

Although socioeconomic disparities persist both pre- and post-transplantation, the impact of payer status has not been studied at the national level. We examined the association between public insurance coverage and waitlist outcomes among candidates listed for liver transplantation (LT) in the United States. All adults (age ≥18 years) listed for LT between 2002 and 2018 in the United Network for Organ Sharing database were included. The primary outcome was waitlist removal because of death or clinical deterioration. Continuous and categorical variables were compared using the Kruskal-Wallis and chi-square tests, respectively. Fine and Gray competing-risks regression was used to estimate the subdistribution hazard ratios (HRs) for risk factors associated with delisting. Of 131,839 patients listed for LT, 61.2% were covered by private insurance, 22.9% by Medicare, and 15.9% by Medicaid. The 1-year cumulative incidence of delisting was 9.0% (95% confidence interval [CI], 8.3%-9.8%) for patients with private insurance, 10.7% (95% CI, 9.9%-11.6%) for Medicare, and 10.7% (95% CI, 9.8%-11.6%) for Medicaid. In multivariable competing-risks analysis, Medicare (HR, 1.20; 95% CI, 1.17-1.24; P < 0.001) and Medicaid (HR, 1.20; 95% CI, 1.16-1.24; P < 0.001) were independently associated with an increased hazard of death or deterioration compared with private insurance. Additional predictors of delisting included Black race and Hispanic ethnicity, whereas college education and employment were associated with a decreased hazard of delisting. In this study, LT candidates with Medicare or Medicaid had a 20% increased risk of delisting because of death or clinical deterioration compared with those with private insurance. As more patients use public insurance to cover the cost of LT, targeted waitlist management protocols may mitigate the increased risk of delisting in this population.

Assessing the Burden of Nodal Disease for Breast Cancer Patients with Clinically Positive Nodes: Hope for More Limited Axillary Surgery.

BACKGROUND: Omission of axillary lymph node dissection (ALND) is accepted for patients with one or two positive sentinel nodes, and studies are focusing on clinically node-positive patients who have been downstaged with neoadjuvant chemotherapy (NAC). Evidence is lacking for patients with positive nodes who undergo surgery upfront. These patients are assumed to have a higher burden of nodal disease such that ALND remains the standard of care. METHODS: Patients who underwent ALND for breast cancer between 2010 and 2019 at the authors' institution were retrospectively identified. Those with clinical N1 disease were included in the study. Patients who received NAC and those who had surgery for sentinel node positive disease or axillary recurrence were excluded. Clinical and pathologic factors associated with nodal stage were evaluated. RESULTS: Of 111 patients who met the inclusion criteria, 61.3% had a palpable node on exam, and 41.4% ultimately had pN1 disease. Most of the tumors were estrogen receptor (ER)-positive (91.5%), and 21.7% of the tumors were invasive lobular cancers. Lobular histology, tumor size, and metastasis size were associated with higher nodal stage. In the multivariable analysis, the patients with nodal metastasis larger than 10 mm had significantly lower odds of having pN1 disease (odds ratio 0.12; 95% confidence interval 0.02-0.69; p = 0.02). In a subset analysis of patients with palpable nodes, tumor size and histology remained significantly associated with nodal stage. CONCLUSION: More than 40% of breast cancer patients with clinically positive nodes had minimal nodal disease (pN1) at surgery. Additionally, palpable nodes on exam did not predict higher nodal stage. A subset of patients with clinically positive nodes may be identified who can potentially be spared the morbidity of ALND.

Clinical and Financial Outcomes of Necrotizing Soft-Tissue Infections in Safety-Net Hospitals.

Background Prior work has demonstrated inferior outcomes for a multitude of medical and surgical conditions at hospitals with high burdens of underinsured patients (safety-net). The present study aimed to evaluate trends in incidence, clinical outcomes and resource utilization in the surgical management of necrotizing soft-tissue infections (NSTI) at safety-net hospitals. Materials and methods Adults requiring surgical debridement/amputation following NSTI-related hospitalizations were identified in the 2005-2018 National Inpatient Sample. Safety-net status (SNH) was assigned to institutions in the top tertile for annual proportion of underinsured patients. Logistic multivariable regression was utilized to evaluate the association of SNH with mortality, hospitalization duration (LOS), costs and discharge disposition. Results Of an estimated 212,692 patients, 76,719 (36.1%) were managed at SNH. The annual incidence of NSTI admissions increased overall while associated mortality declined. After adjustment, SNH status was associated with greater odds of mortality (adjusted odds ratios: 1.14, 95% CI: 1.03-1.26), LOS (ß: +1.8 d, 95% CI: 1.3-2.2) and costs (ß: +$4,400, 95% CI: 2,900-5,800). SNH patients had similar rates of amputation but lower likelihood of care facility or home health discharge. Conclusion With a rising incidence and overall reduction in mortality, safety-net hospitals persistently exhibit greater mortality and resource use for surgical NSTI admissions. Variation in access, disease presentation and timeliness of operative intervention may explain the observed findings.

Association of donor hypertension and outcomes in orthotopic heart transplantation.

The present study examined the impact of donor hypertension on recipient survival and offer acceptance practices in the United States. This was a retrospective study of all patients undergoing OHT from 1995 to 2019 using the United Network for Organ Sharing and Potential Transplant Recipient file databases. Hypertensive donors were stratified by Short (0-5 years) and Prolonged (> 5 years) hypertension. Multivariable logistic regression was used to analyze offer acceptance practices while Cox proportional-hazards models were used to compare mortality across groups. Of 38,338 heart transplants meeting study criteria, 5662 were procured from hypertensive donors (69% Short and 31% Prolonged). After adjustment, Prolonged donor hypertension was associated with increased mortality (hazard ratio, HR, 1.31, 95% confidence interval, CI, 1.04-1.64), while recipients of Short donors experienced no decrement in post-transplant survival. Both Short and Prolonged hypertension were independently associated with decreased odds of offer acceptance (odds ratio, OR .92 95%CI: .88-.96 and OR .93 95%CI: .88-.99, respectively). While prolonged untreated hypertension in OHT donors is associated with a slight decrement in recipient survival, donors with ≤5 years of hypertension yielded similar outcomes. Donor hypertension was associated with reduced organ offer acceptance, highlighting a potential source of organ underutilization.