Extracellular Kir2.1C122Y Mutant Upsets Kir2.1-PIP2 Bonds and Is Arrhythmogenic in Andersen-Tawil Syndrome.

BACKGROUND: Andersen-Tawil syndrome type 1 is a rare heritable disease caused by mutations in the gene coding the strong inwardly rectifying K+ channel Kir2.1. The extracellular Cys (cysteine)122-to-Cys154 disulfide bond in the channel structure is crucial for proper folding but has not been associated with correct channel function at the membrane. We evaluated whether a human mutation at the Cys122-to-Cys154 disulfide bridge leads to Kir2.1 channel dysfunction and arrhythmias by reorganizing the overall Kir2.1 channel structure and destabilizing its open state. METHODS: We identified a Kir2.1 loss-of-function mutation (c.366 A>T; p.Cys122Tyr) in an ATS1 family. To investigate its pathophysiological implications, we generated an AAV9-mediated cardiac-specific mouse model expressing the Kir2.1C122Y variant. We employed a multidisciplinary approach, integrating patch clamping and intracardiac stimulation, molecular biology techniques, molecular dynamics, and bioluminescence resonance energy transfer experiments. RESULTS: Kir2.1C122Y mice recapitulated the ECG features of ATS1 independently of sex, including corrected QT prolongation, conduction defects, and increased arrhythmia susceptibility. Isolated Kir2.1C122Y cardiomyocytes showed significantly reduced inwardly rectifier K+ (IK1) and inward Na+ (INa) current densities independently of normal trafficking. Molecular dynamics predicted that the C122Y mutation provoked a conformational change over the 2000-ns simulation, characterized by a greater loss of hydrogen bonds between Kir2.1 and phosphatidylinositol 4,5-bisphosphate than wild type (WT). Therefore, the phosphatidylinositol 4,5-bisphosphate-binding pocket was destabilized, resulting in a lower conductance state compared with WT. Accordingly, on inside-out patch clamping, the C122Y mutation significantly blunted Kir2.1 sensitivity to increasing phosphatidylinositol 4,5-bisphosphate concentrations. In addition, the Kir2.1C122Y mutation resulted in channelosome degradation, demonstrating temporal instability of both Kir2.1 and NaV1.5 proteins. CONCLUSIONS: The extracellular Cys122-to-Cys154 disulfide bond in the tridimensional Kir2.1 channel structure is essential for the channel function. We demonstrate that breaking disulfide bonds in the extracellular domain disrupts phosphatidylinositol 4,5-bisphosphate-dependent regulation, leading to channel dysfunction and defects in Kir2.1 energetic stability. The mutation also alters functional expression of the NaV1.5 channel and ultimately leads to conduction disturbances and life-threatening arrhythmia characteristic of Andersen-Tawil syndrome type 1.

A Point-Based Risk Calculator for Mortality After Hepatectomy.

BACKGROUND: Preoperative risk stratification for hepatectomy patients can aid clinical decision making. The objective of this retrospective cohort study was to determine postoperative mortality risk factors and develop a score-based risk calculator using a limited number of preoperative predictors to estimate mortality risk in patients undergoing hepatectomy. METHODS: Data were collected from patients that underwent hepatectomy from the National Surgical Quality Improvement Program dataset from 2014 to 2020. Baseline characteristics were compared between survival and 30-day mortality cohorts using the χ 2 test. Next, the data were split into a training set to build the model and a test set to validate the model. A multivariable logistic regression model modeling 30-day postoperative mortality was trained on the training set using all available features. Next, a risk calculator using preoperative features was developed for 30-day mortality. The results of this model were converted into a score-based risk calculator. A point-based risk calculator was developed that predicted 30-day postoperative mortality in patients who underwent hepatectomy surgery. RESULTS: The final dataset included 38,561 patients who underwent hepatectomy. The data were then split into a training set from 2014 to 2018 (n = 26,397) and test set from 2019 to 2020 (n = 12,164). Nine independent variables associated with postoperative mortality were identified and included age, diabetes, sex, sodium, albumin, bilirubin, serum glutamic-oxaloacetic transaminase (SGOT), international normalized ratio, and American Society of Anesthesiologists classification score. Each of these features were then assigned points for a risk calculator based on their odds ratio. A univariate logistic regression model using total points as independent variables were trained on the training set and then validated on the test set. The area under the receiver operating characteristics curve on the test set was 0.719 (95% confidence interval, 0.681-0.757). CONCLUSIONS: Development of risk calculators may potentially allow surgical and anesthesia providers to provide a more transparent plan to support patients planned for hepatectomy.

Racial and Ethnic Differences in the Receipt of Regional Anesthesia Among Patients Undergoing Thoracic Surgery.

OBJECTIVES: The objective of this study was to assess differences in the use of perioperative regional anesthesia for thoracic surgery based on race and ethnicity. DESIGN: This retrospective cohort study used data from the American College of Surgeons National Surgical Quality Improvement Program from 2015 to 2020. The study authors applied a multivariate logistic regression in which the dependent variable was the primary endpoint (regional versus no regional anesthesia). The primary independent variables were race and ethnicity. SETTING: Multiple healthcare systems in the United States. PARTICIPANTS: Participants were ≥18 years of age and undergoing thoracic surgery. INTERVENTIONS: Regional anesthesia. MEASUREMENTS AND MAIN RESULTS: On adjusted multivariate analysis, Hispanic patients had lower odds (odds ratio [OR] 0.61, 95% CI 0.46-0.80, p = 0.0003) of receiving regional anesthesia for postoperative pain control compared to non-Hispanic patients. There was no significant difference in the odds of regional anesthesia when comparing racial cohorts (ie, White, Black, Asian, or other). CONCLUSIONS: There were differences observed in the provision of regional anesthesia for thoracic surgery among ethnic groups. Although the results of this study should not be taken as evidence for healthcare disparities, it could be used to support hypotheses for future studies that aim to investigate causes of disparities and corresponding patient outcomes.

Racial and Ethnic Differences in the Use of Regional Anesthesia for Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: There is an increasing body of evidence that suggests racial and ethnic disparities exist in medical care. In the field of anesthesiology, few studies have investigated the association of race and ethnicity with the provision of regional anesthesia for patients undergoing total knee arthroplasty. This analysis queried a large national surgical database to determine whether there were racial or ethnic differences in the administration of peripheral nerve blocks for patients undergoing total knee arthroplasty. METHODS: In this retrospective cohort study, data were collected from a large national database during the years 2017-2019. Multivariable logistic regressions were used to measure the association of race and ethnicity with utilization of regional anesthesia. The participants for the study were patients 18 years or older undergoing total knee arthroplasty. RESULTS: Our primary finding was that among patients undergoing total knee arthroplasty, Black patients had lower odds (adjusted odds ratio [aOR]: 0.93, 99% confidence interval [CI]: 0.89-0.98) of receiving regional anesthesia than White patients. Also, Hispanic patients had lower odds (aOR: 0.88, 99% CI: 0.83-0.94) of receiving regional anesthesia than non-Hispanic patients. Native Hawaiian/Pacific Islander patients had increased odds (aOR: 2.04, 99% CI: 1.66-2.51) of receiving regional anesthesia. CONCLUSION: This study demonstrated that there might be racial and ethnic differences in the provision of regional anesthesia for patients undergoing total knee arthroplasty. These differences underscore the need for more studies aimed at equitable access to high quality and culturally competent health care.

A Retrospective Analysis Investigating Whether Case Volume Experience of the Anesthesiologist Correlates with Intraoperative Efficiency for Joint Arthroplasty.

The objective of this retrospective study was to determine if there was an association between anesthesiology experience (e.g. historic case volume) and operating room (OR) efficiency times for lower extremity joint arthroplasty cases. The primary outcome was time from patient in the OR to anesthesia ready (i.e. after spinal or general anesthesia induction was complete). The secondary outcomes included time from anesthesia ready to surgical incision, and time from incision to closing completed. Mixed effects linear regression was performed, in which the random effect was the anesthesiology attending provider. There were 4,575 patients undergoing hip or knee arthroplasty included. There were 82 unique anesthesiology providers, in which the median [quartile] frequency of cases performed was 79 [45, 165]. On multivariable mixed effects linear regression - in which the primary independent variable (anesthesiologist case volume history for joint arthroplasty anesthesia) was log-transformed - the estimate for log-transformed case volume was - 0.91 (95% confidence interval [CI] -1.62, -0.20, P = 0.01). When modeling time from incision to closure complete, the estimate for log-transformed case volume was - 2.07 (95% -3.54, -0.06, P = 0.01). Thus, when comparing anesthesiologists with median case volume (79 cases) versus those with the lowest case volume (10 cases), the predicted difference in times added up to only approximately 6 min. If the purpose of faster anesthesia workflows was to open up more OR time to increase surgical volume in a given day, this study does not support the supposition that anesthesiologists with higher joint arthroplasty case volume would improve throughput.

Machine Learning Prediction Models to Reduce Length of Stay at Ambulatory Surgery Centers Through Case Resequencing.

The post-anesthesia care unit (PACU) length of stay is an important perioperative efficiency metric. The aim of this study was to develop machine learning models to predict ambulatory surgery patients at risk for prolonged PACU length of stay - using only pre-operatively identified factors - and then to simulate the effectiveness in reducing the need for after-hours PACU staffing. Several machine learning classifier models were built to predict prolonged PACU length of stay (defined as PACU stay ≥ 3 hours) on a training set. A case resequencing exercise was then performed on the test set, in which historic cases were re-sequenced based on the predicted risk for prolonged PACU length of stay. The frequency of patients remaining in the PACU after-hours (≥ 7:00 pm) were compared between the simulated operating days versus actual operating room days. There were 10,928 ambulatory surgical patients included in the analysis, of which 580 (5.31%) had a PACU length of stay ≥ 3 hours. XGBoost with SMOTE performed the best (AUC = 0.712). The case resequencing exercise utilizing the XGBoost model resulted in an over three-fold improvement in the number of days in which patients would be in the PACU past 7pm as compared with historic performance (41% versus 12%, P<0.0001). Predictive models using preoperative patient characteristics may allow for optimized case sequencing, which may mitigate the effects of prolonged PACU lengths of stay on after-hours staffing utilization.

Cardiovascular Progerin Suppression and Lamin A Restoration Rescue Hutchinson-Gilford Progeria Syndrome.

BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a rare disorder characterized by premature aging and death mainly because of myocardial infarction, stroke, or heart failure. The disease is provoked by progerin, a variant of lamin A expressed in most differentiated cells. Patients look healthy at birth, and symptoms typically emerge in the first or second year of life. Assessing the reversibility of progerin-induced damage and the relative contribution of specific cell types is critical to determining the potential benefits of late treatment and to developing new therapies. METHODS: We used CRISPR-Cas9 technology to generate LmnaHGPSrev/HGPSrev (HGPSrev) mice engineered to ubiquitously express progerin while lacking lamin A and allowing progerin suppression and lamin A restoration in a time- and cell type-specific manner on Cre recombinase activation. We characterized the phenotype of HGPSrev mice and crossed them with Cre transgenic lines to assess the effects of suppressing progerin and restoring lamin A ubiquitously at different disease stages as well as specifically in vascular smooth muscle cells and cardiomyocytes. RESULTS: Like patients with HGPS, HGPSrev mice appear healthy at birth and progressively develop HGPS symptoms, including failure to thrive, lipodystrophy, vascular smooth muscle cell loss, vascular fibrosis, electrocardiographic anomalies, and precocious death (median lifespan of 15 months versus 26 months in wild-type controls, P<0.0001). Ubiquitous progerin suppression and lamin A restoration significantly extended lifespan when induced in 6-month-old mildly symptomatic mice and even in severely ill animals aged 13 months, although the benefit was much more pronounced on early intervention (84.5% lifespan extension in mildly symptomatic mice, P<0.0001, and 6.7% in severely ill mice, P<0.01). It is remarkable that major vascular alterations were prevented and lifespan normalized in HGPSrev mice when progerin suppression and lamin A restoration were restricted to vascular smooth muscle cells and cardiomyocytes. CONCLUSIONS: HGPSrev mice constitute a new experimental model for advancing knowledge of HGPS. Our findings suggest that it is never too late to treat HGPS, although benefit is much more pronounced when progerin is targeted in mice with mild symptoms. Despite the broad expression pattern of progerin and its deleterious effects in many organs, restricting its suppression to vascular smooth muscle cells and cardiomyocytes is sufficient to prevent vascular disease and normalize lifespan.

Regional Anesthesia Techniques for Pain Management for Laparoscopic Surgery: a Review of the Current Literature.

PURPOSE OF REVIEW: The field of regional anesthesia has evolved tremendously in the last 15 years. New anesthesia protocols for ambulatory surgery and enhanced recovery after surgery have been developed as well. The focus of these techniques and protocols has centered on patient satisfaction and pain control while minimizing the use of opioids. The field of ambulatory surgery and anesthesia continues to evolve, and regional anesthesia and its plane techniques are at the center of these changes. RECENT FINDINGS: Recent research has shown that regional techniques contribute to better pain control and patient experience and may decrease patient readmission rates. The safety of these techniques has been validated when performed by experienced practitioners. New techniques such as the erector spinae block (ESP) have been studied in the setting of laparoscopic surgery with promising results. Regional anesthesia techniques for patients presenting for laparoscopic surgery are safe and seem to provide benefits. Those are related to patient experience, pain control, and readmission rates. Different techniques can be applied to a specific type of intervention. Application of these techniques depend on the clinical picture and patient. Future research may help us clarify how these techniques may improve patient satisfaction and operating room efficiency. New regional blocks may also develop based on what we know today.

Similarities and Differences between the Orai1 Variants: Orai1α and Orai1ß.

Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP3 generation, which results in intracellular Ca2+ store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders. Orai1 is, together with STIM1, the key element of SOCE, conducting the Ca2+ release-activated Ca2+ (CRAC) current and, in association with TRPC1, the store-operated Ca2+ (SOC) current. Additionally, Orai1 is involved in non-capacitative pathways, as the arachidonate-regulated or LTC4-regulated Ca2+ channel (ARC/LRC), store-independent Ca2+ influx activated by the secretory pathway Ca2+-ATPase (SPCA2) and the small conductance Ca2+-activated K+ channel 3 (SK3). Furthermore, Orai1 possesses two variants, Orai1α and Orai1ß, the latter lacking 63 amino acids in the N-terminus as compared to the full-length Orai1α form, which confers distinct features to each variant. Here, we review the current knowledge about the differences between Orai1α and Orai1ß, the implications of the Ca2+ signals triggered by each variant, and their downstream modulatory effect within the cell.

Synthesis and screening of 6-alkoxy purine analogs as cell type-selective apoptotic inducers in Jurkat cells.

Purines are ubiquitous structures in cell biology involved in a multitude of cellular processes, because of which substituted purines and analogs are considered excellent scaffolds in drug design. In this study, we explored the key structural features of a purine-based proapoptotic hit, 8-tert-butyl-9-phenyl-6-benzyloxy-9H-purine (1), by setting up a library of 6-alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based on cell cycle analysis of a panel of six human cancer cell lines, including T cell leukemia Jurkat cells. From this study, two derivatives (12 and 13) were identified as Jurkat-selective proapoptotic compounds, displaying superior potency and cell selectivity than hit 1.

KV1.5-KVß1.3 Recycling Is PKC-Dependent.

KV1.5 channel function is modified by different regulatory subunits. KVß1.3 subunits assemble with KV1.5 channels and induce a fast and incomplete inactivation. Inhibition of PKC abolishes the KVß1.3-induced fast inactivation, decreases the amplitude of the current KV1.5-KVß1.3 and modifies their pharmacology likely due to changes in the traffic of KV1.5-KVß1.3 channels in a PKC-dependent manner. In order to analyze this hypothesis, HEK293 cells were transfected with KV1.5-KVß1.3 channels, and currents were recorded by whole-cell configuration of the patch-clamp technique. The presence of KV1.5 in the membrane was analyzed by biotinylation techniques, live cell imaging and confocal microscopy approaches. PKC inhibition resulted in a decrease of 33 ± 7% of channels in the cell surface due to reduced recycling to the plasma membrane, as was confirmed by confocal microscopy. Live cell imaging indicated that PKC inhibition almost abolished the recycling of the KV1.5-KVß1.3 channels, generating an accumulation of channels into the cytoplasm. All these results suggest that the trafficking regulation of KV1.5-KVß1.3 channels is dependent on phosphorylation by PKC and, therefore, they could represent a clinically relevant issue, mainly in those diseases that exhibit modifications in PKC activity.

Incidence of airway complications associated with deep extubation in adults.

BACKGROUND: Endotracheal extubation is the most crucial step during emergence from general anesthesia and is usually carried out when patients are awake with return of airway reflexes. Alternatively, extubations can also be accomplished while patients are deeply anesthetized, a technique known as "deep extubation", in order to provide a "smooth" emergence from anesthesia. Deep extubation is seldomly performed in adults, even in appropriate circumstances, likely due to concerns for potential respiratory complications and limited research supporting its safety. It is in this context that we designed our prospective study to understand the factors that contribute to the success or failure of deep extubation in adults. METHODS: In this prospective observational study, 300 patients, age ≥ 18, American Society of Anesthesiologists Physical Status (ASA PS) Classification I - III, who underwent head-and-neck and ocular surgeries. Patients' demographic, comorbidity, airway assessment, O2 saturation, end tidal CO2 levels, time to exit OR, time to eye opening, and respiratory complications after deep extubation in the OR were analyzed. RESULTS: Forty (13%) out of 300 patients had at least one complication in the OR, as defined by persistent coughing, desaturation SpO2 < 90% for longer than 10s, laryngospasm, stridor, bronchospasm and reintubation. When comparing the complication group to the no complication group, the patients in the complication group had significantly higher BMI (30 vs 26), lower O2 saturation pre and post extubation, and longer time from end of surgery to out of OR (p < 0.05). CONCLUSIONS: The complication rate during deep extubation in adults was relatively low compared to published reports in the literature and all easily reversible. BMI is possibly an important determinant in the success of deep extubation.

A prospective, randomized comparison of ultrasonographic visualization of proximal intercostal block vs paravertebral block.

BACKGROUND: Thoracic paravertebral blockade is an accepted anesthetic and analgesic technique for breast surgery. However, real-time ultrasound visualization of landmarks in the paravertebral space remains challenging. We aimed to compare ultrasound-image quality, performance times, and clinical outcomes between the traditional parasagittal ultrasound-guided paravertebral block and a modified approach, the ultrasound-guided proximal intercostal block. METHODS: Women with breast cancer undergoing mastectomy (n = 20) were randomized to receive either paravertebral (n = 26) or proximal intercostal blocks (n = 32) under ultrasound-guidance with 2.5 mg/kg ropivacaine prior to surgery. Block ultrasound images before and after needle placement, and anesthetic injection videoclips were saved, and these images and vidoes independently rated by separate novice and expert reviewers for quality of visualization of bony elements, pleura, relevant ligament/membrane, needle, and injectate spread. Block performance times, postoperative pain scores, and opioid consumption were also recorded. RESULTS: Composite visualization scores were superior for proximal intercostal compared to paravertebral nerve block, as rated by both expert (p = 0.008) and novice (p = 0.01) reviewers. Notably, both expert and novice rated pleural visualization superior for proximal intercostal nerve block, and expert additionally rated bony landmark and injectate spread visualization as superior for proximal intercostal block. Block performance times, needle depth, opioid consumption and postoperative pain scores were similar between groups. CONCLUSIONS: Proximal intercostal block yielded superior visualization of key anatomical landmarks, possibly offering technical advantages over traditional paravertebral nerve block. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02911168. Registred on the 22nd of September 2016.

Macro Fat Embolism After Gluteal Augmentation With Fat: First Survival Case Report.

Gluteal augmentation with fat has become one of the most common cosmetic procedures worldwide. Gluteal augmentation is designed to increase the volume and contour of the gluteal region. Intramuscular lipoinjection has been linked to multiple reports of severe complications, including death due to macro fat embolism (MAFE). The authors present the first reported case of survival and successful recovery after MAFE secondary to gluteal augmentation with fat. A 41-year-old woman, ASA II, was scheduled for augmentation mammaplasty, liposuction, and gluteal augmentation with fat. The patient was operated under general anesthesia with a total intravenous anesthesia technique. A total of 3.5 liters of fat was liposuctioned with no complications. The patient was then positioned in a lateral decubitus position for gluteal augmentation with fat. Right after the last injection, the anesthesiologist noticed a sudden change in capnography followed by hypotension, bradycardia, and hypoxemia. The first reaction in the operating room was to consider that the patient was experiencing a severe episode of fat embolism. She was then resuscitated and transferred to a tertiary facility for intensive care management. To our knowledge, this is the first case report of successful resuscitation in a patient experiencing severe MAFE after gluteal augmentation with fat. We believe that this patient survived the event due to early detection, aggressive management, and proper transfer to an intensive care unit. Level of Evidence: 5.

Effects of Thermal Protection in Patients Undergoing Body Contouring Procedures: A Controlled Clinical Trial.

BACKGROUND: Hypothermia is common in many plastic surgery procedures, but few measures to prevent its occurrence are taken. OBJECTIVES: This study evaluated the effect of hypothermia in patients undergoing plastic surgery procedures and the effect of utilizing simple and inexpensive measures to prevent patient hypothermia during surgery. METHODS: A randomized controlled clinical trial was performed among 3 groups of patients who underwent body contouring surgery for longer than 3.5 hours. In group 1, no protective measures were taken to prevent hypothermia; in group 2, maneuvers were applied intraoperatively for the duration of the entire surgical procedure; and in group 3, measures were taken preoperatively and intraoperatively. The results were quantified and analyzed through a bivariate analysis, including degree of hypothermia, anesthesia recovery time, time spent in the recovery area, intensity of pain, cold perception, response to opioids, and nausea. RESULTS: There were 122 patients included in the study: 43 in group 1, 39 in group 2, and 40 in group 3. All patients in group 1 had a higher degree of hypothermia, longer recovery time from anesthesia, longer overall recovery time, increased pain, increased feeling of cold, and more nausea. These patients also required a greater amount of opioids compared with the patients in groups 2 and 3. Many of the results were statistically significant. CONCLUSIONS: The adoption of simple and inexpensive measures before and during plastic surgery can prevent patient hypothermia during the procedures, leading to a shorter anesthesia recovery time and avoiding the undesirable effects associated with hypothermia. In addition, these measures may have significant economic savings.

Isoflurane Ameliorates Acute Lung Injury by Preserving Epithelial Tight Junction Integrity.

BACKGROUND: Isoflurane may be protective in preclinical models of lung injury, but its use in patients with lung injury remains controversial and the mechanism of its protective effects remains unclear. The authors hypothesized that this protection is mediated at the level of alveolar tight junctions and investigated the possibility in a two-hit model of lung injury that mirrors human acute respiratory distress syndrome. METHODS: Wild-type mice were treated with isoflurane 1 h after exposure to nebulized endotoxin (n = 8) or saline control (n = 9) and then allowed to recover for 24 h before mechanical ventilation (MV; tidal volume, 15 ml/kg, 2 h) producing ventilator-induced lung injury. Mouse lung epithelial cells were similarly treated with isoflurane 1 h after exposure to lipopolysaccharide. Cells were cyclically stretched the following day to mirror the MV protocol used in vivo. RESULTS: Mice treated with isoflurane following exposure to inhaled endotoxin and before MV exhibited significantly less physiologic lung dysfunction. These effects appeared to be mediated by decreased vascular leak, but not altered inflammatory indices. Mouse lung epithelial cells treated with lipopolysaccharide and cyclic stretch and lungs harvested from mice after treatment with lipopolysaccharide and MV had decreased levels of a key tight junction protein (i.e., zona occludens 1) that was rescued by isoflurane treatment. CONCLUSIONS: Isoflurane rescued lung injury induced by a two-hit model of endotoxin exposure followed by MV by maintaining the integrity of the alveolar-capillary barrier possibly by modulating the expression of a key tight junction protein.

Modulation of voltage-dependent and inward rectifier potassium channels by 15-epi-lipoxin-A4 in activated murine macrophages: implications in innate immunity.

Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium channels (Kv) by specific antagonists decreases macrophage cytokine production and inhibits proliferation. In the presence of aspirin, acetylated cyclooxygenase-2 loses the activity required to synthesize PGs but maintains the oxygenase activity to produce 15R-HETE from arachidonate. This intermediate product is transformed via 5-LOX into epimeric lipoxins, termed 15-epi-lipoxins (15-epi-lipoxin A4 [e-LXA4]). Kv have been proposed as anti-inflammatory targets. Therefore, we studied the effects of e-LXA4 on signaling and on Kv and inward rectifier potassium channels (Kir) in mice bone marrow-derived macrophages (BMDM). Electrophysiological recordings were performed in these cells by the whole-cell patch-clamp technique. Treatment of BMDM with e-LXA4 inhibited LPS-dependent activation of NF-κB and IκB kinase ß activity, protected against LPS activation-dependent apoptosis, and enhanced the accumulation of the Nrf-2 transcription factor. Moreover, treatment of LPS-stimulated BMDM with e-LXA4 resulted in a rapid decrease of Kv currents, compatible with attenuation of the inflammatory response. Long-term treatment of LPS-stimulated BMDM with e-LXA4 significantly reverted LPS effects on Kv and Kir currents. Under these conditions, e-LXA4 decreased the calcium influx versus that observed in LPS-stimulated BMDM. These effects were partially mediated via the lipoxin receptor (ALX), because they were significantly reverted by a selective ALX receptor antagonist. We provide evidence for a new mechanism by which e-LXA4 contributes to inflammation resolution, consisting of the reversion of LPS effects on Kv and Kir currents in macrophages.

To breathe or not to breathe: a review of artificial airway placement and related complications.

Artificial airway devices are commonly used to provide adequate ventilation and/or oxygenation in multiple clinical settings, both emergent and nonemergent. These frequently used devices include laryngeal mask airway, esophageal-tracheal combitube, endotracheal tube, and tracheostomy tube and are associated with various acute and late complications. Clinically, this may vary from mild discomfort to a potentially life-threatening situation. Radiologically, these devices and their acute and late complications have characteristic imaging findings which can be detected primarily on radiographs and computed tomography. We review appropriate positioning of these artificial airway devices and illustrate associated complications including inadequate positioning of the endotracheal tube, pulmonary aspiration, tracheal laceration or perforation, paranasal sinusitis, vocal cord paralysis, post-intubation tracheal stenosis, cuff overinflation with vascular compression, and others. Radiologists must recognize and understand the potential complications of intubation to promptly guide management and avoid long-term or even deadly consequences.

Preoperative Evaluation of Patients Undergoing Eye Surgery.

Ophthalmic surgery encompasses a wide range of procedures addressing various ocular conditions. Although generally considered low risk, a thorough preoperative evaluation is still crucial in optimizing patient outcomes and ensuring safe surgical interventions. This review provides a comprehensive overview of the preoperative assessment and management of patients presenting for ophthalmic surgery, specifically focusing on cataract surgery. We discuss the role of routine preoperative testing, the assessment of intraocular factors, and the evaluation of systemic comorbidities and medications. The review emphasizes the importance of individualized decision-making based on patient-specific factors and collaborative efforts between ophthalmologists and the health-care team.

Retrospective Analysis of Perioperative Dexmedetomidine Use in Retina Surgeries: Impact on Postanesthesia Care.

BACKGROUND AND OBJECTIVE: Dexmedetomidine (Precedex®) has been linked to depressive hemodynamic effects and increased length of stay in the post-anesthesia care unit (PACU) when used in ambulatory phacoemulsification procedures. We aimed to determine the prevalence and impact of dexmedetomidine use during ambulatory vitreoretinal procedures. PATIENTS AND METHODS: This retrospective cohort study involved 9,666 adult vitrectomies. Cases were divided into groups by anesthesia type: general anesthesia (GA) and monitored anesthesia care (MAC). For each group, various factors were compared between those who did and did not receive dexmedetomidine. Chi-squared and t tests were used for comparisons. RESULTS: Changes in mean arterial pressure in the MAC group were -1.69 ± 0.23 mmHg for no dexmedetomidine patients and -6.31 ± 0.39 mmHg for dexmedetomidine patients (P < 0.01). In the GA group, mean arterial pressure was -6.1 ± 0.35 mmHg for no dexmedetomidine patients and -11.18 ± 0.88 mmHg for dexmedetomidine patients (P < 0.01). PACU Phase II time in the MAC group was 36.93 ± 0.37 minutes and 40.67 ± 0.86 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). In the GA group, PACU Phase II time was 58.63 ± 0.95 minutes and 65.19 ± 2.38 minutes for no dexmedetomidine and dexmedetomidine patients, respectively (P < 0.01). CONCLUSIONS: Dexmedetomidine use in vitrectomies was associated with significant PACU delays. These delays may stem from adverse hemodynamic effects. [Ophthalmic Surg Lasers Imaging Retina 2024;55:86-91.].