Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

A parabrachial hub for the prioritization of survival behavior.

Long-term sustained pain in the absence of acute physical injury is a prominent feature of chronic pain conditions. While neurons responding to noxious stimuli have been identified, understanding the signals that persist without ongoing painful stimuli remains a challenge. Using an ethological approach based on the prioritization of adaptive survival behaviors, we determined that neuropeptide Y (NPY) signaling from multiple sources converges on parabrachial neurons expressing the NPY Y1 receptor to reduce sustained pain responses. Neural activity recordings and computational modeling demonstrate that activity in Y1R parabrachial neurons is elevated following injury, predicts functional coping behavior, and is inhibited by competing survival needs. Taken together, our findings suggest that parabrachial Y1 receptor-expressing neurons are a critical hub for endogenous analgesic pathways that suppress sustained pain states.

Risk of Early Postoperative Cardiovascular and Cerebrovascular Complication in Patients with Preoperative COVID-19 Undergoing Cancer Surgery.

BACKGROUND: As the COVID-19 pandemic shifts to an endemic phase, an increasing proportion of cancer patients with a preoperative history of COVID-19 will require surgery. This study aimed to assess the influence of preoperative COVID-19 on postoperative risk for major adverse cardiovascular and cerebrovascular events (MACE) among those undergoing surgical cancer resection. Secondary objectives included determining optimal time-to-surgery guidelines based on COVID-19 severity and discerning the influence of vaccination status on MACE risk. STUDY DESIGN: National COVID Cohort Collaborative (N3C) Data Enclave, a large multi-institutional dataset, was used to identify patients that underwent surgical cancer resection between January 2020 and February 2023. Multivariate regression analysis adjusting for demographics, comorbidities, and risk of surgery was performed to evaluate risk for 30-day postoperative MACE. RESULTS: Of 204,371 included patients, 21,313 (10.4%) patients had a history of preoperative COVID-19. History of COVID-19 was associated with an increased risk for postoperative composite MACE as well as 30-day mortality. Among patients with mild disease who did not require hospitalization, MACE risk was elevated for up to 4-weeks following infection. Postoperative MACE risk remained elevated 8+ weeks following infection in those with moderate disease. Vaccination did not reduce risk for postoperative MACE. CONCLUSION: Together, these data highlight that assessment of the severity of preoperative COVID-19 infection should be a routine component of both preoperative patient screening as well as surgical risk stratification. In addition, strategies beyond vaccination that increase patients' cardiovascular fitness and prevent COVID-19 infection are needed.

Transcriptomic-Based Microenvironment Classification Reveals Precision Medicine Strategies for Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: The complex tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) has hindered the development of reliable predictive biomarkers for targeted therapy and immunomodulatory strategies. A comprehensive characterization of the TME is necessary to advance precision therapeutics in PDAC. METHODS: A transcriptomic profiling platform for TME classification based on functional gene signatures was applied to 14 publicly available PDAC datasets (n = 1657) and validated in a clinically annotated independent cohort of patients with PDAC (n = 79). Four distinct subtypes were identified using unsupervised clustering and assessed to evaluate predictive and prognostic utility. RESULTS: TME classification using transcriptomic profiling identified 4 biologically distinct subtypes based on their TME immune composition: immune enriched (IE); immune enriched, fibrotic (IE/F); fibrotic (F); and immune depleted (D). The IE and IE/F subtypes demonstrated a more favorable prognosis and potential for response to immunotherapy compared with the F and D subtypes. Most lung metastases and liver metastases were subtypes IE and D, respectively, indicating the role of clonal phenotype and immune milieu in developing personalized therapeutic strategies. In addition, distinct TMEs with potential therapeutic implications were identified in treatment-naive primary tumors compared with tumors that underwent neoadjuvant therapy. CONCLUSIONS: This novel approach defines a distinct subgroup of PADC patients that may benefit from immunotherapeutic strategies based on their TME subtype and provides a framework to select patients for prospective clinical trials investigating precision immunotherapy in PDAC. Further, the predictive utility and real-world clinical applicability espoused by this transcriptomic-based TME classification approach will accelerate the advancement of precision medicine in PDAC.

Venovenous extracorporeal membrane oxygenation in patients with traumatic brain injuries and severe respiratory failure: A single-center retrospective analysis.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) can support trauma patients with severe respiratory failure. Use in traumatic brain injury (TBI) may raise concerns of worsening complications from intracranial bleeding. However, VV ECMO can rapidly correct hypoxemia and hypercarbia, possibly preventing secondary brain injury. We hypothesize that adult trauma patients with TBI on VV ECMO have comparable survival with trauma patients without TBI. METHODS: A single-center, retrospective cohort study involving review of electronic medical records of trauma admissions between July 1, 2014, and August 30, 2022, with discharge diagnosis of TBI who were placed on VV ECMO during their hospital course was performed. RESULTS: Seventy-five trauma patients were treated with VV ECMO; 36 (48%) had TBI. Of those with TBI, 19 (53%) had a hemorrhagic component. Survival was similar between patients with and without a TBI (72% vs. 64%, p = 0.45). Traumatic brain injury survivors had a higher admission Glasgow Coma Scale (7 vs. 3, p < 0.001) than nonsurvivors. Evaluation of prognostic scoring systems on initial head computed tomography demonstrated that TBI VV ECMO survivors were more likely to have a Rotterdam score of 2 (62% vs. 20%, p = 0.03) and no survivors had a Marshall score of ≥4. Twenty-nine patients (81%) had a repeat head computed tomography on VV ECMO with one incidence of expanding hematoma and one new focus of bleeding. Neither patient with a new/worsening bleed received anticoagulation. Survivors demonstrated favorable neurologic outcomes at discharge and outpatient follow-up, based on their mean Rancho Los Amigos Scale (6.5; SD, 1.2), median Cerebral Performance Category (2; interquartile range, 1-2), and median Glasgow Outcome Scale-Extended (7.5; interquartile range, 7-8). CONCLUSION: In this series, the majority of TBI patients survived and had good neurologic outcomes despite a low admission Glasgow Coma Scale. Venovenous extracorporeal membrane oxygenation may minimize secondary brain injury and may be considered in select patients with TBI. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Functional recovery in a cohort of ECMO and non-ECMO acute respiratory distress syndrome survivors.

BACKGROUND: The mortality benefit of VV-ECMO in ARDS has been extensively studied, but the impact on long-term functional outcomes of survivors is poorly defined. We aimed to assess the association between ECMO and functional outcomes in a contemporaneous cohort of survivors of ARDS. METHODS: Multicenter retrospective cohort study of ARDS survivors who presented to follow-up clinic. The primary outcome was FVC% predicted. Univariate and multivariate regression models were used to evaluate the impact of ECMO on the primary outcome. RESULTS: This study enrolled 110 survivors of ARDS, 34 of whom were managed using ECMO. The ECMO cohort was younger (35 [28, 50] vs. 51 [44, 61] years old, p < 0.01), less likely to have COVID-19 (58% vs. 96%, p < 0.01), more severely ill based on the Sequential Organ Failure Assessment (SOFA) score (7 [5, 9] vs. 4 [3, 6], p < 0.01), dynamic lung compliance (15 mL/cmH20 [11, 20] vs. 27 mL/cmH20 [23, 35], p < 0.01), oxygenation index (26 [22, 33] vs. 9 [6, 11], p < 0.01), and their need for rescue modes of ventilation. ECMO patients had significantly longer lengths of hospitalization (46 [27, 62] vs. 16 [12, 31] days, p < 0.01) ICU stay (29 [19, 43] vs. 10 [5, 17] days, p < 0.01), and duration of mechanical ventilation (24 [14, 42] vs. 10 [7, 17] days, p < 0.01). Functional outcomes were similar in ECMO and non-ECMO patients. ECMO did not predict changes in lung function when adjusting for age, SOFA, COVID-19 status, or length of hospitalization. CONCLUSIONS: There were no significant differences in the FVC% predicted, or other markers of pulmonary, neurocognitive, or psychiatric functional recovery outcomes, when comparing a contemporaneous clinic-based cohort of survivors of ARDS managed with ECMO to those without ECMO.

Emergency and Compassionate Use of a Novel Ascending Endograft for Ascending and Arch Aortic Pathology.

PURPOSE: Patients with complicated ascending aortic pathology, including patients with acute type A aortic dissection may be at extreme risk for open repair. Thoracic endovascular aortic repair (TEVAR), infrequently used for the ascending aorta, may be considered an alternative in this setting. We describe early results for emergency and compassionate (E&C) use of a novel endograft, specifically designed for use to treat pathology of the ascending aorta. MATERIALS AND METHODS: This case series evaluated 19 patients (mean age, 68.84±13.12 years; 57.9% female) treated with ascending TEVAR for acute and chronic acute (4), subacute (1), or chronic (1) aortic dissection or pseudoaneurysm (13). Six of the 19 patients (31.5%) were treated under compassionate use and 13 patients (68.4%) were treated under the emergency use exemption. Ten patients (52.6%) received additional devices to extend treatment into the arch and descending aorta. RESULTS: Device delivery was achieved in all patients (100%). Thirty-day mortality and stroke occurred in 3 patients (15.8%) and in 1 patient (5.3%), respectively. In 1 patient (5.3%), with an Unanticipated Adverse Device Event, the aorta ruptured when the endograft eroded into the adventitial portion of dissection site at the posterior aspect of the ascending wall. Devices were explanted in 2 patients (10.5%), 353 and 610 days after the index procedure, respectively. Six patients had endoleaks (31.6%), including type I (n=2, 10.5%), type II endoleaks (n=3, 15.8%), and indeterminate endoleak (n=1, 5.3%). CONCLUSIONS: Delivery and deployment of a novel ascending thoracic stent graft with or without an additional branched arch extension is feasible in patients with complex anatomy and pathology, including acute aortic dissection and pseudoaneurysm. Additional experience with this novel device will further refine the patient population most suitable for endovascular ascending aortic repair for these pathologies. CLINICAL IMPACT: This study describes a novel stent graft specifically designed for treatment of ascending aortic pathology, including acute type A dissection. The patients described in this series constituted a group outside the formal US FDA sponsored clinical trial, and were those accepted as part of an emergency and compassionate use basis.

Thoracic Dorsal Root Ganglion Application of Resiniferatoxin Reduces Myocardial Ischemia-Induced Ventricular Arrhythmias.

BACKGROUND: A myocardial ischemia/reperfusion (IR) injury activates the transient receptor potential vanilloid 1 (TRPV1) dorsal root ganglion (DRG) neurons. The activation of TRPV1 DRG neurons triggers the spinal dorsal horn and the sympathetic preganglionic neurons in the spinal intermediolateral column, which results in sympathoexcitation. In this study, we hypothesize that the selective epidural administration of resiniferatoxin (RTX) to DRGs may provide cardioprotection against ventricular arrhythmias by inhibiting afferent neurotransmission during IR injury. METHODS: Yorkshire pigs (n = 21) were assigned to either the sham, IR, or IR + RTX group. A laminectomy and sternotomy were performed on the anesthetized animals to expose the left T2-T4 spinal dorsal root and the heart for IR intervention, respectively. RTX (50 µg) was administered to the DRGs in the IR + RTX group. The activation recovery interval (ARI) was measured as a surrogate for the action potential duration (APD). Arrhythmia risk was investigated by assessing the dispersion of repolarization (DOR), a marker of arrhythmogenicity, and measuring the arrhythmia score and the number of non-sustained ventricular tachycardias (VTs). TRPV1 and calcitonin gene-related peptide (CGRP) expressions in DRGs and CGRP expression in the spinal cord were assessed using immunohistochemistry. RESULTS: The RTX mitigated IR-induced ARI shortening (-105 ms ± 13 ms in IR vs. -65 ms ± 11 ms in IR + RTX, p = 0.028) and DOR augmentation (7093 ms2 ± 701 ms2 in IR vs. 3788 ms2 ± 1161 ms2 in IR + RTX, p = 0.020). The arrhythmia score and VT episodes during an IR were decreased by RTX (arrhythmia score: 8.01 ± 1.44 in IR vs. 3.70 ± 0.81 in IR + RTX, p = 0.037. number of VT episodes: 12.00 ± 3.29 in IR vs. 0.57 ± 0.3 in IR + RTX, p = 0.002). The CGRP expression in the DRGs and spinal cord was decreased by RTX (DRGs: 6.8% ± 1.3% in IR vs. 0.6% ± 0.2% in IR + RTX, p < 0.001. Spinal cord: 12.0% ± 2.6% in IR vs. 4.5% ± 0.8% in IR + RTX, p = 0.047). CONCLUSIONS: The administration of RTX locally to thoracic DRGs reduces ventricular arrhythmia in a porcine model of IR, likely by inhibiting spinal afferent hyperactivity in the cardio-spinal sympathetic pathways.

Alleviation of neuropathic pain with neuropeptide Y requires spinal Npy1r interneurons that coexpress Grp.

Neuropeptide Y targets the Y1 receptor (Y1) in the spinal dorsal horn (DH) to produce endogenous and exogenous analgesia. DH interneurons that express Y1 (Y1-INs; encoded by Npy1r) are necessary and sufficient for neuropathic hypersensitivity after peripheral nerve injury. However, as Y1-INs are heterogenous in composition in terms of morphology, neurophysiological characteristics, and gene expression, we hypothesized that a more precisely defined subpopulation mediates neuropathic hypersensitivity. Using fluorescence in situ hybridization, we found that Y1-INs segregate into 3 largely nonoverlapping subpopulations defined by the coexpression of Npy1r with gastrin-releasing peptide (Grp/Npy1r), neuropeptide FF (Npff/Npy1r), and cholecystokinin (Cck/Npy1r) in the superficial DH of mice, nonhuman primates, and humans. Next, we analyzed the functional significance of Grp/Npy1r, Npff/Npy1r, and Cck/Npy1r INs to neuropathic pain using a mouse model of peripheral nerve injury. We found that chemogenetic inhibition of Npff/Npy1r-INs did not change the behavioral signs of neuropathic pain. Further, inhibition of Y1-INs with an intrathecal Y1 agonist, [Leu31, Pro34]-NPY, reduced neuropathic hypersensitivity in mice with conditional deletion of Npy1r from CCK-INs and NPFF-INs but not from GRP-INs. We conclude that Grp/Npy1r-INs are conserved in higher order mammalian species and represent a promising and precise pharmacotherapeutic target for the treatment of neuropathic pain.

Contribution of µ Opioid Receptor-expressing Dorsal Horn Interneurons to Neuropathic Pain-like Behavior in Mice.

BACKGROUND: Intersectional genetics have yielded tremendous advances in our understanding of molecularly identified subpopulations and circuits within the dorsal horn in neuropathic pain. The authors tested the hypothesis that spinal µ opioid receptor-expressing neurons (Oprm1-expressing neurons) contribute to behavioral hypersensitivity and neuronal sensitization in the spared nerve injury model in mice. METHODS: The authors coupled the use of Oprm1Cre transgenic reporter mice with whole cell patch clamp electrophysiology in lumbar spinal cord slices to evaluate the neuronal activity of Oprm1-expressing neurons in the spared nerve injury model of neuropathic pain. The authors used a chemogenetic approach to activate or inhibit Oprm1-expressing neurons, followed by the assessment of behavioral signs of neuropathic pain. RESULTS: The authors reveal that spared nerve injury yielded a robust neuroplasticity of Oprm1-expressing neurons. Spared nerve injury reduced Oprm1 gene expression in the dorsal horn as well as the responsiveness of Oprm1-expressing neurons to the selective µ agonist (D-Ala2, N-MePhe4, Gly-ol)-enkephalin (DAMGO). Spared nerve injury sensitized Oprm1-expressing neurons, as reflected by an increase in their intrinsic excitability (rheobase, sham 38.62 ± 25.87 pA [n = 29]; spared nerve injury, 18.33 ± 10.29 pA [n = 29], P = 0.0026) and spontaneous synaptic activity (spontaneous excitatory postsynaptic current frequency in delayed firing neurons: sham, 0.81 ± 0.67 Hz [n = 14]; spared nerve injury, 1.74 ± 1.68 Hz [n = 10], P = 0.0466), and light brush-induced coexpression of the immediate early gene product, Fos in laminae I to II (%Fos/tdTomato+: sham, 0.42 ± 0.57% [n = 3]; spared nerve injury, 28.26 ± 1.92% [n = 3], P = 0.0001). Chemogenetic activation of Oprm1-expressing neurons produced mechanical hypersensitivity in uninjured mice (saline, 2.91 ± 1.08 g [n = 6]; clozapine N-oxide, 0.65 ± 0.34 g [n = 6], P = 0.0006), while chemogenetic inhibition reduced behavioral signs of mechanical hypersensitivity (saline, 0.38 ± 0.37 g [n = 6]; clozapine N-oxide, 1.05 ± 0.42 g [n = 6], P = 0.0052) and cold hypersensitivity (saline, 6.89 ± 0.88 s [n = 5] vs. clozapine N-oxide, 2.31 ± 0.52 s [n = 5], P = 0.0017). CONCLUSIONS: The authors conclude that nerve injury sensitizes pronociceptive µ opioid receptor-expressing neurons in mouse dorsal horn. Nonopioid strategies to inhibit these interneurons might yield new treatments for neuropathic pain.

Endogenous µ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice.

Tissue injury creates a delicate balance between latent pain sensitization (LS) and compensatory endogenous analgesia. Inhibitory G-protein-coupled receptor (GPCR) interactions that oppose LS, including µ-opioid receptor (MOR) or neuropeptide Y Y1 receptor (Y1R) activity, persist in the spinal cord dorsal horn (DH) for months, even after the resolution of normal pain thresholds. Here, we demonstrate that following recovery from surgical incision, a potent endogenous analgesic synergy between MOR and Y1R activity persists within DH interneurons to reduce the intensity and duration of latent postoperative hypersensitivity and ongoing pain. Failure of such endogenous GPCR signaling to maintain LS in remission may underlie the transition from acute to chronic pain states.

Severity of Prior Coronavirus Disease 2019 is Associated With Postoperative Outcomes After Major Inpatient Surgery.

OBJECTIVE: To determine how the severity of prior history (Hx) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection influences postoperative outcomes after major elective inpatient surgery. BACKGROUND: Surgical guidelines instituted early in the coronavirus disease 2019 (COVID-19) pandemic recommended a delay in surgery of up to 8 weeks after an acute SARS-CoV-2 infection. This was based on the observation of elevated surgical risk after recovery from COVID-19 early in the pandemic. As the pandemic shifts to an endemic phase, it is unclear whether this association remains, especially for those recovering from asymptomatic or mildly symptomatic COVID-19. METHODS: Utilizing the National COVID Cohort Collaborative, we assessed postoperative outcomes for adults with and without a Hx of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from infection to surgery were each used as independent variables in multivariable logistic regression models. RESULTS: This study included 387,030 patients, of whom 37,354 (9.7%) were diagnosed with preoperative COVID-19. Hx of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of respiratory failure. CONCLUSIONS: Impact of COVID-19 on postoperative outcomes is dependent on the severity of illness, with only moderate and severe disease leading to a higher risk of adverse outcomes. Existing perioperative policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Severity of Prior COVID-19 Infection is Associated with Postoperative Outcomes Following Major Inpatient Surgery.

Objective: To determine the association between severity of prior history of SARS-CoV-2 infection and postoperative outcomes following major elective inpatient surgery. Summary Background Data: Surgical guidelines instituted early in the COVID-19 pandemic recommended delay in surgery up to 8 weeks following an acute SARS-CoV-2 infection. Given that surgical delay can lead to worse medical outcomes, it is unclear if continuation of such stringent policies is necessary and beneficial for all patients, especially those recovering from asymptomatic or mildly symptomatic COVID-19. Methods: Utilizing the National Covid Cohort Collaborative (N3C), we assessed postoperative outcomes for adults with and without a history of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from SARS-CoV-2 infection to surgery were each used as independent variables in multivariable logistic regression models. Results: This study included 387,030 patients, of which 37,354 (9.7%) had a diagnosis of preoperative COVID-19. History of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of mortality and other complications. Conclusions: Impact of COVID-19 on postoperative outcomes is dependent on severity of illness, with only moderate and severe disease leading to higher risk of adverse outcomes. Existing wait time policies should be updated to include consideration of COVID-19 disease severity and vaccination status.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Early veno-venous extracorporeal membrane oxygenation is an effective strategy for traumatically injured patients presenting with refractory respiratory failure.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for respiratory failure when standard therapy fails. Optimal trauma care requires patients be stable enough to undergo procedures. Early VV ECMO (EVV) to stabilize trauma patients with respiratory failure as part of resuscitation could facilitate additional care. As VV ECMO technology is portable and prehospital cannulation possible, it could also be used in austere environments. We hypothesize that EVV facilitates injury care without worsening survival. METHODS: Our single center, retrospective cohort study included all trauma patients between January 1, 2014, and August 1, 2022, who were placed on VV ECMO. Early VV was defined as cannulation ≤48 hours from arrival with subsequent operation for injuries. Data were analyzed with descriptive statistics. Parametric or nonparametric statistics were used based on the nature of the data. After testing for normality, significance was defined as a p < 0.05. Logistic regression diagnostics were performed. RESULTS: Seventy-five patients were identified and 57 (76%) underwent EVV. There was no difference in survival between the EVV and non-EVV groups (70% vs. 61%, p = 0.47). Age, race, and gender did not differ between EVV survivors and nonsurvivors. Time to cannulation (4.5 hours vs. 8 hours, p = 0.39) and injury severity scores (34 vs. 29, p = 0.74) were similar. Early VV survivors had lower lactic acid levels precannulation (3.9 mmol/L vs. 11.9 mmol/L, p < 0.001). A multivariable logistic regression analysis examining admission and precannulation laboratory and hemodynamic values demonstrated that lower precannulation lactic acid levels predicted survival (odds ratio, 1.2; 95% confidence interval, 1.02-1.5; p = 0.03), with a significant inflection point of 7.4 mmol/L corresponding to decreased survival at hospital discharge. CONCLUSION: Patients undergoing EVV did not have increased mortality compared with the overall trauma VV ECMO population. Early VV resulted in ventilatory stabilization that allowed subsequent procedural treatment of injuries. LEVEL OF EVIDENCE: Therapeutic Care/Management; Level III.

Emergent Total Endovascular Arch Repair for Contained Aortic Arch Rupture: Another Tool in the Box.

To date, emergent total endovascular aortic arch repair has not been described in the literature. We present a 67-year-old female with a poorly differentiated posterior mediastinal sarcoma. Imaging obtained was concerning for intravascular extension of the tumor into the thoracic aorta. While awaiting radiation therapy, the patient complained of worsening chest and arm pain, vital signs demonstrating tachypnea and hypoxia. Subsequent imaging revealed an increase in vascular erosion, concerning for a contained rupture, with complete obliteration of the left mainstem bronchus. The patient was emergently taken for percutaneous endovascular repair of her aortic arch. A three-vessel physician modified fenestrated graft was created and deployed with concurrent stenting of the innominate, left carotid, and left subclavian arteries. Interval computed tomography angiography revealed patency in all stented vessels, with no endoleak and no evidence of pseudoaneurysm. The patient was able to undergo chemotherapy with favorable decrease in tumor burden. Total endovascular aortic arch repair, when planned carefully, is an attractive option in high-risk patients who are otherwise not ideally suited for open total arch replacement.

Mechanical and Heat Hyperalgesia upon Withdrawal From Chronic Intermittent Ethanol Vapor Depends on Sex, Exposure Duration, and Blood Alcohol Concentration in Mice.

Approximately half of patients with alcohol use disorder report pain and this can be severe during withdrawal. Many questions remain regarding the importance of biological sex, alcohol exposure paradigm, and stimulus modality to the severity of alcohol withdrawal-induced hyperalgesia. To examine the impact of sex and blood alcohol concentration on the time course of the development of mechanical and heat hyperalgesia, we characterized a mouse model of chronic alcohol withdrawal-induced pain in the presence or absence the alcohol dehydrogenase inhibitor, pyrazole. Male and female C57BL/6J mice underwent chronic intermittent ethanol vapor ± pyrazole exposure for 4 weeks, 4 d/wk to induce ethanol dependence. Hind paw sensitivity to the plantar application of mechanical (von Frey filaments) and radiant heat stimuli were measured during weekly observations at 1, 3, 5, 7, 24, and 48 hours after cessation of ethanol exposure. In the presence of pyrazole, males developed mechanical hyperalgesia after the first week of chronic intermittent ethanol vapor exposure, peaking at 48 hours after cessation of ethanol. By contrast, females did not develop mechanical hyperalgesia until the fourth week; this also required pyrazole and did not peak until 48 hours. Heat hyperalgesia was consistently observed only in females exposed to ethanol and pyrazole; this developed after the first weekly session and peaked at 1 hour. We conclude that Chronic alcohol withdrawal-induced pain develops in a sex-, time-, and blood alcohol concentration-dependent manner in C57BL/6J mice. PERSPECTIVE: Alcohol withdrawal-induced pain is a debilitating condition in individuals with AUD. Our study found mice experience alcohol withdrawal-induced pain in a sex and time course specific manor. These findings will aid in elucidating mechanisms of chronic pain and AUD and will help individuals remain abstinent from alcohol.

Effect of process parameters on vitamins and sensory acceptability in micronutrient-fortified soymilk prepared by small-scale batch processing.

Effects of holding time before cooling, cooling method, and light or dark refrigerated storage on the stability of vitamin A, vitamin C, thiamine, riboflavin, and folate were investigated in fortified and unfortified soymilk. Vitamin C loss (6%) and mild vitamin A isomerization occurred when soymilk was held hot after fortification. Cooling bottled soymilk at ambient temperature or in an ice-water bath did not affect any vitamins. Loss of riboflavin (18%) and vitamin A isomerization occurred during 12 days of light-exposed refrigerated storage, in contrast to no vitamin degradation during dark refrigerated storage. A sensory panel of youth and children indicated no significant preferences between fortified and unfortified soymilk except for color, where the lighter-colored unfortified soymilk was preferred. Acceptable vitamin stability and sensory characteristics can be achieved in fortified soymilk produced in small-scale batch processes with appropriate management of production and storage conditions.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.