Mouse Model of Spinal Cord Hypoperfusion with Immediate Paralysis Caused by Endovascular Repair of Thoracic Aortic Aneurysm.

BACKGROUND: A clinically relevant mouse model of thoracic endovascular aortic repair-induced ischemic spinal cord injury has been lacking since the procedure was first employed in 1991. The hypothesis was that ligation of mouse intercostal arteries would simulate thoracic endovascular aortic repair-induced ischemic spinal cord injury and behavioral deficit. The aim was to create a mouse model of thoracic endovascular aortic repair-induced spinal cord hypoperfusion by ligating five pairs of mouse intercostal vessels. METHODS: Mice were divided into sham (n = 53) and ligation (n = 60) groups. The procedures called for double ligation of three pairs and single ligation of two pairs of thoracic intercostal arteries in adult C57BL/6 mice. A laser Doppler probe was used in vivo on the spinal cords and intercostal arteries to document the extent of arterial ligation and spinal cord hypoperfusion. The Basso Mouse Scale for Locomotion, histological studies, and electron microscopy demonstrated postligation locomotive and histopathological changes. RESULTS: Ligation induced a significant and instantaneous drop in blood flow in the intercostal arteries (% change; mean = -63.81; 95% CI, -72.28 to -55.34) and the thoracic spinal cord (% change; mean = -68.55; 95% CI, -80.23 to -56.87). Paralysis onset was immediate and of varying degree, with behavioral deficit stratified into three groups: 9.4% exhibited severe paralysis, 37.5% moderate paralysis, and 53.1% mild paralysis at day 1 (n = 32; P < 0.001). Mild and moderate paralysis was transient, gradually improving over time. Severe paralysis showed no improvement and exhibited a higher mortality rate (83%; n = 15 of 18) compared to moderately (33%; n = 6 of 18) and mildly (24%; n = 6 of 25) paralyzed mice (P < 0.001). The overall ligation group survival rate (84%; n = 46 of 55) was significantly lower than the sham group (100%; n = 48 of 48) with P = 0.003. CONCLUSIONS: The mouse model generates reproducible spinal cord hypoperfusion and accompanying histopathological ischemic spinal cord damage. The resulting anatomical changes and variable behavioral deficits mimic the variability in radiological and clinical findings in human patients.

Hypoxemia After Endobronchial Valve Deployment for Persistent Air Leak.

Endobronchial valves (EBVs) are a novel, minimally invasive bronchoscopic management technique for persistent air leaks that fail conservative therapy. Currently, 2 EBVs are available in the United States: the Spiration Valve System (Olympus, Redmond, WA) and the Zephyr Valve (Pulmonx, Redwood, CA). These valves are Food and Drug Administration-approved to reduce hyperinflation in emphysematous patients via bronchoscopic lung-volume reduction. However, more recently, the Spiration Valve has been granted a compassionate use exemption through the Food and Drug Administration for persistent postsurgical air leaks. Despite their popularity, these devices are not free from side effects. As an anesthesiologist, it is vital to be aware of the pathophysiology of this patient population so that safe and effective anesthetics may be provided during valve placement. Here, the use of EBVs is discussed in a patient who presented with a persistent air leak after a transthoracic needle aspiration that failed treatment due to persistent hypoxemia, warranting EBV removal.

Intraoperative Hypotension-Physiologic Basis and Future Directions.

Intraoperative hypotension (IOH) is a major concern to the anesthesiologist. Its appropriate identification and management require an understanding of the physiology of blood pressure regulation, prudent blood pressure monitoring, and treatment. Even short durations of low mean arterial pressure have been associated with adverse postoperative clinical outcomes. The challenge is for the clinician to respond proactively, address the specific etiology of IOH, and keep in mind any changes to the patient's physiology. Predictive technology, such as the Hypotension Prediction Index, offers the clinician new insight into IOH. It has been shown to predict hypotension up to 15 minutes before occurrence. It also calculates stroke volume variation, dynamic arterial elastance, and left ventricular contractility, which can inform the anesthesiologist of the etiology of IOH to direct management. This new technology has the potential to reduce duration or even prevent IOH. In the authors' opinion, it is an example of how human-machine interaction will contribute to future advances in medicine. Additional studies should evaluate the effects of its use on postoperative outcomes.

The histologic and molecular correlates of liver disease in fatal COVID-19 including with alcohol use disorder.

Hepatic disease is common in severe COVID-19. This study compared the histologic/molecular findings in the liver in fatal COVID-19 (n = 9) and age-matched normal controls (n = 9); three of the fatal COVID-19 livers had pre-existing alcohol use disorder (AUD). Controls showed a high resident population of sinusoidal macrophages that had variable ACE2 expression. Histologic findings in the cases included periportal/lobular inflammation. SARS-CoV2 RNA and nucleocapsid protein were detected in situ in 2/9 COVID-19 livers in low amounts. In 9/9 cases, there was ample in situ SARS-CoV-2 spike protein that co-localized with viral matrix and envelope proteins. The number of cells positive for spike/100× field was significantly greater in the AUD/COVID-19 cases (mean 5.9) versus the non-AUD/COVID-19 cases (mean 0.4, p < 0.001) which was corroborated by Western blots. ACE2+ cells were 10× greater in AUD/COVID-19 livers versus the other COVID-19/control liver samples (p < 0.001). Co-expression experiments showed that the spike protein localized to the ACE2 positive macrophages and, in the AUD cases, hepatic stellate cells that were activated as evidenced by IL6 and TNFα expression. Injection of the S1, but not S2, subunit of spike in mice induced hepatic lobular inflammation in activated macrophages. It is concluded that endocytosed viral spike protein can induce hepatitis in fatal COVID-19. This spike induced hepatitis is more robust in the livers with pre-existing AUD which may relate to why patients with alcohol abuse are at higher risk of severe liver disease with SARS-CoV2 infection.

Histologic, viral, and molecular correlates of heart disease in fatal COVID-19.

Cardiac manifestations are common in severe COVID-19. This study compared the histologic, viral, and molecular findings in cardiac tissue in fatal COVID-19 (n = 11) and controls (n = 11). In situ hybridization (SARS-CoV2 RNA) and immunohistochemistry for viral proteins and the host response were quantified for the samples and compared with qRTPCR and Western blot data. Control hearts showed a high resident population of macrophages that had variable ACE2 expression. Cardiac ACE2 expression was 10× greater in the heart tissues of cases and controls with obesity or type II diabetes. Multifocal endothelial cell swelling and degeneration, perivascular edema plus microvascular thrombi were unique to the cases. SARS-CoV2 RNA and nucleocapsid protein were rarely detected in situ in any COVID-19 heart. However, in each case abundant SARS-CoV-2 spike protein was evident. Co-expression experiments showed that the spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Western blots confirmed the presence of the viral spike protein, but not the nucleocapsid protein, in the cardiac homogenates. The intercalated disc proteins connexin 43, the primary cardiac gap junction protein, and NaV1.5, the predominant cardiac sodium channel, each showed marked lateral migration in the myocytes in the cases, which would increase the risk of reentrant arrhythmias. It is concluded that the viral spike protein, endocytosed by macrophages/pericytes, can induce a myocarditis with the possibility of conduction dysfunction due to abnormal localization of key intercalated disc proteins.

A Novel Triazole Schiff Base Derivatives for Remediation of Chromium Contamination from Tannery Waste Water.

Tannery industries are one of the extensive industrial activities which are the major source of chromium contamination in the environment. Chromium contamination has been an increasing threat to the environment and human health. Therefore, the removal of chromium ions is necessary to save human society. This study is oriented toward the preparation of a new triazole Schiff base derivatives for the remediation of chromium ions. 4,4'-((1E)-1,2-bis ((1H-1,2,4-triazol-3-yl) imino)ethane-1,2-diyl) diphenol was prepared by the interaction between 3-Amino-1H-1,2,4-triazole and 4,4'-Dihydroxybenzil. Then, the produced Schiff base underwent a phosphorylation reaction to produce the adsorbent (TIHP), which confirmed its structure via the different tools FTIR, TGA, 1HNMR, 13CNMR, GC-MS, and Phosphorus-31 nuclear magnetic resonance (31P-NMR). The newly synthesized adsorbent (TIHP) was used to remove chromium oxyanions (Cr(VI)) from an aqueous solution. The batch technique was used to test many controlling factors, including the pH of the working aqueous solution, the amount of adsorbent dose, the initial concentration of Cr(VI), the interaction time, and the temperature. The desorption behaviour of Cr(VI) changes when it is exposed to the suggested foreign ions. The maximum adsorption capacity for Cr(VI) adsorption on the new adsorbent was 307.07 mg/g at room temperature. Freundlich's isotherm model fits the adsorption isotherms perfectly. The kinetic results were well-constrained by the pseudo-second-order equation. The thermodynamic studies establish that the adsorption type was exothermic and naturally spontaneous.

The Future of Cardiothoracic Surgical Critical Care Medicine as a Medical Science: A Call to Action.

Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate in the coming decades. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry. This two-part review concentrates on CT-CCM as its own subspeciality of critical care and cardiothoracic surgery and provides aspirational goals for its practitioners and scientists. In part one, a list of guiding principles and a call-to-action agenda geared towards growth and promotion of CT-CCM are offered. In part two, an evaluation of selected scientific data is performed, identifying gaps in CT-CCM knowledge, and recommending direction to future scientific endeavors.

Primary Stroke and Failure-to-Rescue Following Thoracic Endovascular Aortic Aneurysm Repair.

OBJECTIVE: To characterize the impact, on failure to rescue, of cerebrovascular accident as a first postoperative complication after thoracic endovascular aortic aneurysm repair (TEVAR). DESIGN: A retrospective cohort study using of National Surgical Quality Improvement Program Participants User File. SETTING: United States hospitals taking part in the National Surgical Quality Improvement Program. PARTICIPANTS: Patients >18 years, who underwent TEVAR for nonruptured thoracic aortic aneurysm between 2005 and 2018, and developed one or more major postoperative complications within 30 days after surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out of 3,937 patients who underwent TEVAR for nonruptured thoracic aneurysm, 1,256 (31.9%) developed major postoperative complications (stroke incidence: 11.4% [143/1256]). In adults <65 years old, the occurrence of stroke as the primary complication, relative to the occurrence of other complications, was associated with ten times greater risk of failure to rescue (29.4% v 4.6%; odds ratio [OR]: 10.10; 95% confidence interval [CI] 2.45-41.56; p < 0.001). The effect size was relatively lower when stroke occurred but was not the primary complication (20.0% v 4.6%; OR: 7.55; 95% CI 1.37-41.71; p = 0.020). In patients ≥65 years, the occurrence of stroke as the primary complication did not carry the similar prognostic value. CONCLUSION: Younger patients who developed stroke were up to ten times more likely to die, relative to patients who developed other major complications. Survival was substantially reduced when stroke was the primary complication. The authors' findings imply that to maximize the survival of patients undergoing TEVAR, efforts may be needed to predict and prevent stroke occurrence as a primary postoperative morbidity event.

Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein.

Neurologic complications of symptomatic COVID-19 are common. Brain tissues from 13 autopsies of people who died of COVID-19 were examined. Cultured endothelial and neuronal cells were incubated with and wild type mice were injected IV with different spike subunits. In situ analyses were used to detect SARS-CoV-2 proteins and the host response. In 13/13 brains from fatal COVID-19, pseudovirions (spike, envelope, and membrane proteins without viral RNA) were present in the endothelia of microvessels ranging from 0 to 14 positive cells/200× field (mean 4.3). The pseudovirions strongly co-localized with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons demonstrated increased NMDAR2 and neuronal NOS plus decreased MFSD2a and SHIP1 proteins. Tail vein injection of the full length S1 spike subunit in mice led to neurologic signs (increased thirst, stressed behavior) not evident in those injected with the S2 subunit. The S1 subunit localized to the endothelia of microvessels in the mice brain and showed co-localization with caspase-3, ACE2, IL6, TNFα, and C5b-9. The surrounding neurons showed increased neuronal NOS and decreased MFSD2a. It is concluded that ACE2+ endothelial damage is a central part of SARS-CoV2 pathology and may be induced by the spike protein alone. Thus, the diagnostic pathologist can use either hematoxylin and eosin stain or immunohistochemistry for caspase 3 and ACE2 to document the endothelial cell damage of COVID-19.

The Effect of Increased Intraocular Pressure During Steep Trendelenburg Positioning in Robotic Prostatectomy and Hysterectomy on Structural and Functional Ocular Parameters.

BACKGROUND: Robotic prostatectomy and robotic hysterectomy require steep Trendelenburg positioning. Many authors documented significant increases in intraocular pressure (IOP) during steep Trendelenburg. However, the long-term biological effect of a significant increase in IOP on the structural and functional ocular system is unknown. This study examines the effect of a significant increase in IOP on the visual acuity, retinal nerve fiber layer thickness (RNFLT), and ganglion cell complex (GCC) thickness in 52 patients without preexisting ocular disease of both genders before and 3 months after their procedures. METHODS: This was a prospective cohort study. The total number of patients included was 56, then 3 females and 1 male case were excluded, totaling 28 robotic hysterectomies and 24 robotic prostatectomies were performed. Patients underwent complete eye examination before the procedure and 3 months after, measuring the main outcome of RNFLT and the secondary outcomes of GCC thickness, foveal threshold (FT), mean deviation (MD), and pattern standard deviation (PSD). These outcomes were analyzed using linear mixed-effects models. On the day of surgery, we examined the IOP after induction of anesthesia, at the end of steep Trendelenburg, and in the recovery room. RESULTS: There were significant differences in IOP values at the end of steep Trendelenburg versus after induction and 45-60 minutes post-awakening (P < .001 for both groups). No difference between IOP 45 and 60 minutes post-awakening and IOP after induction was observed in either group. The highest IOPs occurred at the end of the steep Trendelenburg time point for both groups. The mean duration of steep Trendelenburg in robotic prostatectomy was 184.6 minutes (standard deviation [SD] = 30.8), while the mean duration in robotic hysterectomy was 123.0 minutes (SD = 29.8). All ophthalmologic examinations were normal preoperatively and 3 months postoperatively. The ocular parameters in the retina and optic disk did not differ significantly before surgery and 3 months after. CONCLUSIONS: There is a significant increase in IOP during steep Trendelenburg positioning. There was no significant difference in the ocular parameters examined 3 months after the procedure in this cohort.

miR-155 expression in antitumor immunity: The higher the better?

MicroRNAs are small noncoding RNAs that modulate gene expression either directly, by impairing the stability and/or translation of transcripts that contain their specific target sequence, or indirectly through the targeting of transcripts that encode transcription factors, factors implicated in signal transduction pathways, or epigenetic regulators. Abnormal expression of micro-RNAs has been found in nearly all types of pathologies, including cancers. MiR-155 has been the first microRNA to be implicated in the regulation of the innate and adaptative immune responses, and its expression is either increased or decreased in a variety of liquid and solid malignancies. In this review, we examine the oncogenic and antitumor potentials of miR-155, with special emphasize on its dose-dependent effects. We describe the impact of miR-155 levels on antitumor activity of lymphocytes and myeloid cells. We discuss miR-155 dose-dependent effects in leukemias and analyze results showing that miR-155 intermediate levels tend to be detrimental, whereas high levels of miR-155 expression usually prove beneficial. We also examine the beneficial effects of high levels of miR-155 expression in solid tumors. We discuss the possible causal involvement of miR-155 in leukemias and dementia in individuals with Down's syndrome. We finally propose that increasing miR-155 levels in immune cells might increase the efficiency of newly developed cancer immunotherapies, due to miR-155 ability to target transcripts encoding immune checkpoints such as cytotoxic T lymphocyte antigen-4 or programmed death-ligand 1.

Implantation of subcutaneous defibrillator is feasible and safe with monitored anesthesia care.

BACKGROUND: The perioperative anesthesia care during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is still evolving. OBJECTIVE: To assess the feasibility and safety of S-ICD implantation with monitored anesthesia care (MAC) versus general anesthesia (GA) in a tertiary care center. METHODS: This is a single-center retrospective study of patients undergoing S-ICD implantation between October 2012 and May 2019. Patients were categorized into MAC and GA group based on the mode of anesthesia. Procedural success without escalation to GA was the primary endpoint of the study, whereas intraprocedural hemodynamics, need of pharmacological support for hypotension and bradycardia, length of the procedure, stay in the post-anesthesia care unit, and postoperative pain were assessed as secondary endpoints. RESULTS: The study comprises 287 patients with MAC in 111 and GA in 176 patients. Compared to MAC, patients in GA group were younger and had a higher body mass index. All patients had successful S-ICD implantation. Only one patient (0.9%) in the MAC group was converted to GA. Despite a similar baseline heart rate (HR) and mean arterial blood pressure (MAP) in both groups, patients with GA had significantly lower HR and MAP during the procedure and more frequently required pharmacological hemodynamic support. Length of the procedure, stay in the postanesthesia care unit, and postoperative pain was similar in both groups. CONCLUSION: This retrospective experience suggests that implantation of S-ICD is feasible and safe with MAC. Use of GA is associated with more frequent administration of hemodynamic drugs during S-ICD implantation.

Enhanced Recovery for Breast Reconstruction Surgery.

PURPOSE OF REVIEW: Enhanced recovery pathways are a well-described perioperative healthcare program involving evidence-based interventions. Enhanced recovery is designed to standardize techniques such as drug selection and nerve blocks in order to speed recovery and reduce overall hospital costs. RECENT FINDINGS: A PubMed literature search was performed for articles that included the terms enhanced recovery and breast reconstruction surgery. The present investigation summarizes enhanced recovery literature related to breast surgery with a focus on breast reconstruction. Enhanced recovery considerations discussed in this review include patient education, preadmission optimization, perforator flap planning, anesthetic techniques, optimized fasting, venous thrombosis prophylaxis, early mobilization, and antimicrobial prophylaxis.

The Evolution of Surgical Enhanced Recovery Pathways: a Review.

PURPOSE OF REVIEW: Enhanced recovery pathways are a well-defined perioperative health care program utilizing evidence-based interventions in a protocol-like manner designed to standardize techniques including drug selection and dosing to improve results and to reduce overall costs including facilitating earlier discharge from hospitals after surgery. RECENT FINDINGS: A PubMed and World Wide Web search was performed with the following key words: enhanced recovery, surgical enhanced recovery, recovery pathways, and enhanced recovery pathways surgery. This introduction to enhanced recovery pathways reflects its 20-year history, worldwide appeal, and ever growing presence in our practices. Many clinical teams have not, as of yet, incorporated enhanced recovery pathway principles to their practices and therefore, continued evolution should include increasing outreach and formalized guidelines in the future.