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Background Inconsistent nomenclature and anatomical descriptions of regional anesthetic techniques hinder scientific communication and engender confusion; this in turn has implications for research, education and clinical implementation of regional anesthesia. Having produced standardized nomenclature for abdominal wall, paraspinal and chest wall regional anesthetic techniques, we aimed to similarly do so for upper and lower limb peripheral nerve blocks. Methods We performed a three-round Delphi international consensus study to generate standardized names and anatomical descriptions of upper and lower limb regional anesthetic techniques. A long list of names and anatomical description of blocks of upper and lower extremities was produced by the members of the steering committee. Subsequently, two rounds of anonymized voting and commenting were followed by a third virtual round table to secure consensus for items that remained outstanding after the first and second rounds. As with previous methodology, strong consensus was defined as ≥75% agreement and weak consensus as 50%–74% agreement. Results A total of 94, 91 and 65 collaborators participated in the first, second and third rounds, respectively. We achieved strong consensus for 38 names and 33 anatomical descriptions, and weak consensus for five anatomical descriptions. We agreed on a template for naming peripheral nerve blocks based on the name of the nerve and the anatomical location of the blockade and identified several areas for future research. Conclusions We achieved consensus on nomenclature and anatomical descriptions of regional anesthetic techniques for upper and lower limb nerve blocks, and recommend using this framework in clinical and academic practice. This should improve research, teaching and learning of regional anesthesia to eventually improve patient care.

OBJECTIVE There is a high prevalence of cervical myelopathy that requires surgery; as such, it is important to identify how different groups benefit from surgery. The American Association of Neurological Surgeons launched the Quality Outcomes Database (QOD), a prospective longitudinal registry, that includes demographic, clinical, and patient-reported outcome data to measure the safety and quality of neurosurgical procedures. In this study, the authors assessed the impact of gender on patient-reported outcomes in patients who underwent surgery for cervical myelopathy. METHODS The authors analyzed 1152 patients who underwent surgery for cervical myelopathy and were included in the QOD cervical module. Univariate comparison of baseline patient characteristics between males and females who underwent surgery for cervical spondylotic myelopathy was performed. Baseline characteristics that significantly differed between males and females were included in a multivariate generalized linear model comparing baseline and 1-year postoperative Neck Disability Index (NDI) scores. RESULTS This study included 546 females and 604 males. Females demonstrated significantly greater improvement in NDI score 1 year after surgery (p = 0.036). In addition to gender, the presence of axial neck pain and insurance status were also significantly predictive of improvement in NDI score after surgery (p = 0.0013 and p = 0.0058, respectively). CONCLUSIONS Females were more likely to benefit from surgery for cervical myelopathy compared with males. It is important to identify gender differences in postoperative outcomes after surgery in order to deliver more personalized and patient-centric care.

Abstract Disclosure: J.P. Frias: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.J. Auchus: Consulting Fee; Self; Corcept Therapeutics. Grant Recipient; Self; Corcept Therapeutics. Speaker; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. I. Bancos: None. L. Blonde: Advisory Board Member; Self; Corcept Therapeutics. Other; Self; Corcept Therapeutics. R.S. Busch: Consulting Fee; Self; Corcept Therapeutics. Speaker; Self; Bayer, Inc., Novo Nordisk, Amgen Inc, Eli Lilly & Company, AstraZeneca. J.B. Buse: Advisory Board Member; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Jansen Pharmaceuticals, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, GentiBio, Glycadia, Glyscend, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, Stability Health, Valo, Zealand Pharma. Consulting Fee; Self; AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Eli Lilly & Company, Janssen, Mannkind Corporation, Sanofi, Alkahest, Altimmune, Anji, Biomea Fusion Inc, CeQur, Cirius Therapeutics Inc, Dasman Diabetes Center (Kuwait), Fortress Biotech, GentiBio, Glycadia, Glyscend, Mediflix, Medscape, Mellitus Health, Moderna, Pendulum Therapeutics, Praetego, ReachMD, Stability Health, Valo, Zealand Pharma. Grant Recipient; Self; Novo Nordisk, Sanofi, VTV Therapeutics, Nanotype, NIH, NovaTarg, Tolerion, Dexcom. Stock Owner; Self; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio, Praetego, Stability Health. Other; Self; AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Novo Nordisk, Dasman Diabetes Institute, Zealand, Association for Clinical and Translational Science. R.A. DeFronzo: None. J.W. Findling: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. V. Fonseca: Advisory Board Member; Self; Corcept Therapeutics. Consulting Fee; Self; Corcept Therapeutics. O. Hamidi: Advisory Board Member; Self; Corcept Therapeutics, Lantheus, Recordati Rare Diseases, Neurocrine Biosciences, Amryt, Novo Nordisk, Strongbridge. Consulting Fee; Self; Corcept Therapeutics. Y. Handelsman: Consulting Fee; Self; Amgen Inc, Applied Therapeutic, AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Corcept Therapeutics, Esperion, Mannkind Corporation, Merck, Pfizer, Inc., Novartis Pharmaceuticals, Novo Nordisk, Sanofi, Vertis. Grant Recipient; Self; Amgen Inc, Applied Therapeutic, Ionis Pharmaceuticals Inc., Regor. Speaker; Self; AstraZeneca, Bayer, Inc., Esperion, Novo Nordisk, Vertis, Amarin. R.E. Pratley: Consulting Fee; Self; Bayer, Inc., Corcept Therapeutics, Gasherbrum Bio, Inc, Hanmi, Hengrui (USA) Ltd, Merck, Novo Nordisk, Pfizer, Inc., Rivus Pharmaceuticals Inc, Sun Pharmaceutical Industries, Sanofi, Scohia Pharma Inc, Dexcom. Grant Recipient; Self; Hanmi, Metavention, Novo Nordisk, Poxel SA. Speaker; Self; Novo Nordisk. J. Rosenstock: Advisory Board Member; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Consulting Fee; Self; Applied Therapeutics, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Novo Nordisk, Oramed, Sanofi, Structure Therapeutics, Zealand. Grant Recipient; Self; Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly & Company, Hanmi, Merck, Oramed, Novartis Pharmaceuticals, Novo Nordisk, Pfizer, Inc., Sanofi. I. Tudor: Employee; Self; Corcept Therapeutics. Stock Owner; Self; Corcept Therapeutics. A.G. Moraitis: Employee; Self; Corcept Therapeutics. D. Einhorn: Employee; Self; Corcept Therapeutics. Studies suggest that the prevalence of hypercortisolism in persons with difficult-to-control type 2 diabetes (T2D) is higher than is currently appreciated. A recently published meta-analysis suggests that the prevalence of hypercortisolism is higher in persons with T2D who require a greater number of antihyperglycemic agents and/or who have more comorbidities. To better understand the prevalence and whether treatment of hypercortisolism may result in better control of diabetes and other hypercortisolism-associated comorbidities, we describe a 2-part phase 4 study in adults with difficult-to-control T2D (HbA1c 7.5-11.5%) despite receiving multiple antihyperglycemic agents. The study will be conducted at approximately 30 sites in the United States. In Part 1, approximately 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test. Those responding with serum cortisol >1.8 µg/dL (50 nmol/L) and dexamethasone levels ≥140 ng/dL (3.6 nmol/L) will have adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, and cortisol measured in fasting blood samples obtained between 7-9 AM and a non-contrast adrenal computed tomography scan. Patients who may have ACTH-dependent hypercortisolism will be discontinued from the study and referred for further evaluation. The primary study endpoint is determining the prevalence of ACTH-independent hypercortisolism and will be evaluated in Part 1. Patients identified to have ACTH-independent hypercortisolism will advance to Part 2, a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of treatment with the glucocorticoid receptor antagonist mifepristone. Patients will be randomized 2:1 to mifepristone or placebo, stratified by the presence or absence of adrenal adenomas on CT, and receive treatment for 24 weeks. The mifepristone dose will be 300 mg once daily for 4 weeks, then increased to 600 mg daily for 20 weeks based on clinical assessment of tolerability and degree of improvement. There will be an option to increase to mifepristone 900 mg. Placebo will be titrated accordingly from 1 up to 3 tablets. Part 2 will assess the secondary endpoint of change in HbA1c from baseline to 24 weeks, as well as changes in hypercortisolism-related comorbidities (e.g., blood pressure, weight, waist circumference, quality of life). This will be the first prospective study to assess the prevalence of ACTH-independent hypercortisolism in persons with difficult-to-control T2D and the first prospective, randomized, placebo-controlled trial to assess the potential benefits and safety of treatment with mifepristone in this patient population. Presentation: Friday, June 16, 2023

Introduction: Genome-wide association studies (GWAS) have discovered >300 associations for CAD. Few loci are functionally characterized and may represent new mechanisms of disease. Hypothesis: Can an unbiased transcriptional screen for the >2000 candidate GWAS genes in endothelial cells (ECs) identify causal genes and disease-relevant pathways at CAD GWAS loci. Methods: We applied CRISPRi-Perturb-seq to knock down expression of genes within 500 Kb of coronary artery disease GWAS loci (2,300 genes in total) and measure their transcriptomic effects using single-cell RNA-seq. Validation of candidate causal genes was conducted in primary human ECs and zebrafish. Results: We identified 50 programs of co-expressed genes, which represent core cellular pathways (i.e. ribosome biogenesis) and 13 EC-specific pathways such as flow response and angiogenesis. The EC-specific programs show the greatest contribution to CAD heritability. 5 EC-specific programs have the greatest number of GWAS candidate genes. We find that 43 of 306 CAD GWAS signals converge onto these 5 gene programs, and all are regulated by genes in the cerebral cavernous malformations (CCM) pathway—which coordinates KLF2/4 transcriptional responses in endothelial cells, but has not been linked to CAD risk. The strongest regulator of these programs is TLNRD1 , which we show is a new CAD gene and novel regulator of the CCM pathway. TLNRD1 loss-of-function alters actin organization and barrier function in endothelial cells in vitro , and heart development in zebrafish in vivo . Conclusions: High-throughput functional analysis of 2,300 genes proximal to CAD GWAS loci prioritized pathways—such as angiogenesis and EC migration—that are regulated by multiple risk SNPs. Our study identifies new genes that likely influence risk for CAD, identifies convergence of CAD genes into certain pathways in endothelial cells, and prioritizes study of genes in the CCM-signaling pathway for contribution to CAD risk.

OBJECTIVE The authors sought to compare 3-level anterior with posterior fusion surgical procedures for the treatment of multilevel cervical spondylotic myelopathy (CSM). METHODS The authors analyzed prospective data from the 14 highest enrolling sites of the Quality Outcomes Database CSM module. They compared 3-level anterior cervical discectomy and fusion (ACDF) and posterior cervical laminectomy and fusion (PCF) surgical procedures, excluding surgical procedures crossing the cervicothoracic junction. Rates of reaching the minimal clinically important difference (MCID) in patient-reported outcomes (PROs) were compared at 24 months postoperatively. Multivariable analyses adjusted for potential confounders elucidated in univariable analysis. RESULTS Overall, 199 patients met the inclusion criteria: 123 ACDF (61.8%) and 76 PCF (38.2%) patients. The 24-month follow-up rates were similar (ACDF 90.2% vs PCF 92.1%, p = 0.67). Preoperatively, ACDF patients were younger (60.8 ± 10.2 vs 65.0 ± 10.3 years, p < 0.01), and greater proportions were privately insured (56.1% vs 36.8%, p = 0.02), actively employed (39.8% vs 22.8%, p = 0.04), and independently ambulatory (14.6% vs 31.6%, p < 0.01). Otherwise, the cohorts had equivalent baseline modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), numeric rating scale (NRS)–arm pain, NRS–neck pain, and EQ-5D scores (p > 0.05). ACDF patients had reduced hospitalization length (1.6 vs 3.9 days, p < 0.01) and a greater proportion had nonroutine discharge (7.3% vs 22.8%, p < 0.01), but they had a higher rate of postoperative dysphagia (13.5% vs 3.5%, p = 0.049). Compared with baseline values, both groups demonstrated improvements in all outcomes at 24 months (p < 0.05). In multivariable analyses, after controlling for age, insurance payor, employment status, ambulation status, and other potential clinically relevant confounders, ACDF was associated with a greater proportion of patients with maximum satisfaction on the North American Spine Society Patient Satisfaction Index (NASS) (NASS score of 1) at 24 months (69.4% vs 53.7%, OR 2.44, 95% CI 1.17–5.09, adjusted p = 0.02). Otherwise, the cohorts shared similar 24-month outcomes in terms of reaching the MCID for mJOA, NDI, NRS–arm pain, NRS–neck pain, and EQ-5D score (adjusted p > 0.05). There were no differences in the 3-month readmission (ACDF 4.1% vs PCF 3.9%, p = 0.97) and 24-month reoperation (ACDF 13.5% vs PCF 18.6%, p = 0.36) rates. CONCLUSIONS In a cohort limited to 3-level fusion surgical procedures, ACDF was associated with reduced blood loss, shorter hospitalization length, and higher routine home discharge rates; however, PCF resulted in lower rates of postoperative dysphagia. The procedures yielded comparably significant improvements in functional status (mJOA score), neck and arm pain, neck pain–related disability, and quality of life at 3, 12, and 24 months. ACDF patients had significantly higher odds of maximum satisfaction (NASS score 1). Given comparable outcomes, patients should be counseled on each approach’s complication profile to aid in surgical decision-making.

AbstractPatients with viral myocarditis are at risk of sudden death and may progress to dilated cardiomyopathy (DCM). Currently, no disease‐specific therapies exist to treat viral myocarditis. Here it is examined whether reconstituted, lyophilized extracellular vesicles (EVs) from platelets from healthy men and women reduce acute or chronic myocarditis in male mice. Human‐platelet‐derived EVs (PEV) do not cause toxicity, damage, or inflammation in naïve mice. PEV administered during the innate immune response significantly reduces myocarditis with fewer epidermal growth factor (EGF)‐like module‐containing mucin‐like hormone receptor‐like 1 (F4/80) macrophages, T cells (cluster of differentiation molecules 4 and 8, CD4 and CD8), and mast cells, and improved cardiac function. Innate immune mediators known to increase myocarditis are decreased by innate PEV treatment including Toll‐like receptor (TLR)4 and complement. PEV also significantly reduces perivascular fibrosis and remodeling including interleukin 1 beta (IL‐1β), transforming growth factor‐beta 1, matrix metalloproteinase, collagen genes, and mast cell degranulation. PEV given at days 7–9 after infection reduces myocarditis and improves cardiac function. MicroRNA (miR) sequencing reveals that PEV contains miRs that decrease viral replication, TLR4 signaling, and T‐cell activation. These data show that EVs from the platelets of healthy individuals can significantly reduce myocarditis and improve cardiac function.

Abstract Aims Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. Methods and results The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018–2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th–75th percentile, 1.6–2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66–86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. Conclusion In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs). Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described. Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006–2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair. Results: A total of 2603 patients (69% males; mean age 72±10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P<0.001) and rates of MAEs (34% vs 20%, P<0.001). Median follow-up was 15 months (interquartile range, 7–37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50±4% vs 70±1% and 21±3% vs 7±1%, P<0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality (hazard ratio, 1.92; 95% CI] 1.50–2.44; P<0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63–3.62; P<0.001). Conclusions: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.

Cancers originating in the esophagus or esophagogastric junction constitute a major global health problem. Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) or adenocarcinoma, which differ in their etiology, pathology, tumor location, therapeutics, and prognosis. In contrast to esophageal adenocarcinoma, which usually affects the lower esophagus, esophageal SCC is more likely to localize at or higher than the tracheal bifurcation. Systemic therapy can provide palliation, improved survival, and enhanced quality of life in patients with locally advanced or metastatic disease. The implementation of biomarker testing, especially analysis of HER2 status, microsatellite instability status, and the expression of programmed death-ligand 1, has had a significant impact on clinical practice and patient care. Targeted therapies including trastuzumab, nivolumab, ipilimumab, and pembrolizumab have produced encouraging results in clinical trials for the treatment of patients with locally advanced or metastatic disease. Palliative management, which may include systemic therapy, chemoradiation, and/or best supportive care, is recommended for all patients with unresectable or metastatic cancer. Multidisciplinary team management is essential for all patients with locally advanced esophageal or esophagogastric junction cancers. This selection from the NCCN Guidelines for Esophageal and Esophagogastric Junction Cancers focuses on the management of recurrent or metastatic disease.