Contrast-Induced Encephalopathy and the Blood-Brain Barrier.

BACKGROUND: Contrast-induced encephalopathy (CIE) is an adverse event associated with diagnostic and therapeutic endovascular procedures. Decades of animal and human research support a mechanistic role for pathological blood-brain barrier dysfunction (BBBd). Here, we describe an institutional case series and review the literature supporting a mechanistic role for BBBd in CIE. METHODS: A literature review was conducted by searching MEDLINE, Web of Science, Embase, CINAHL and Cochrane databases from inception to January 31, 2022. We searched our institutional neurovascular database for cases of CIE following endovascular treatment of cerebrovascular disease during a 6-month period. Informed consent was obtained in all cases. RESULTS: Review of the literature revealed risk factors for BBBd and CIE, including microvascular disease, pathological neuroinflammation, severe procedural hypertension, iodinated contrast load and altered cerebral blood flow dynamics. In our institutional series, 6 of 52 (11.5%) of patients undergoing therapeutic neuroendovascular procedures developed CIE during the study period. Four patients were treated for ischemic stroke and two patients for recurrent cerebral aneurysms. Mechanical stenting or thrombectomy were utilized in all cases. CONCLUSION: In this institutional case series and literature review of animal and human data, we identified numerous shared risk factors for CIE and BBBd, including microvascular disease, increased procedure length, large contrast volumes, severe intraoperative hypertension and use of mechanical devices that may induce iatrogenic endothelial injury.

Prolonged Elevations of Factor VIII and von Willebrand Factor Antigen After Multisystem Inflammatory Syndrome in Children.

Multisystem Inflammatory Syndrome in Children (MIS-C) is a late systemic inflammatory response to a recent mild or asymptomatic coronavirus disease of 2019 infection. The pathophysiology is incompletely understood but it often features significant coagulopathy along with cardiac and endothelial dysfunction. Endothelial inflammation has been primarily described in acute coronavirus disease of 2019 infection, with less characterization in MIS-C. Here we describe novel findings of nearly universal severe and prolonged factor VIII (FVIII) and von Willebrand factor antigen elevations in an institutional cohort of patients with MIS-C ages younger than or 21 years old (N=31). All patients had elevated acute phase reactants and D-dimer at presentation and met published criteria for MIS-C. FVIII was high at presentation in 97% of patients but continued to rise during the ensuing weeks of treatment to a mean 429%, peaking on median day 17 of illness as an outpatient. FVIII levels were >600% in multiple patients. von Willebrand factor antigen was measured less frequently but showed similar trends. These escalations occurred amidst resolving cardiac dysfunction and acute phase reactant normalization and despite patients receiving multimodal anti-inflammatory treatments and aspirin and enoxaparin thromboprophylaxis. No thrombotic events occurred. Endothelial dysfunction represented by very elevated FVIII levels may persist longer than other acute phase reactants may reflect.

The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.

Postoperative delirium and its relationship with biomarkers for dementia: a meta-analysis.

OBJECTIVES: This study seeks to identify Alzheimer's and related dementias (ADRD) biomarkers associated with postoperative delirium (POD) via meta-analysis. DESIGN: A comprehensive search was conducted. Studies met the following inclusion criteria: >18 years of age, identified POD with standardized assessment, and biomarker measured in the AT(N)-X (A = amyloid, T = tau, (N)=neurodegeneration, X-Other) framework. Exclusion criteria: focus on prediction of delirium, delirium superimposed on dementia, other neurologic or psychiatric disorders, or terminal delirium. Reviewers extracted and synthesized data for the meta-analysis. SETTING: Meta-analysis. PARTICIPANTS: Patients with POD. MEASUREMENTS: Primary outcome: association between POD and ATN-X biomarkers. Secondary outcomes involved sample heterogeneity. RESULTS: 28 studies were included in this meta-analysis. Studies focused on inflammatory and neuronal injury biomarkers; there were an insufficient number of studies for amyloid and tau biomarker analysis. Two inflammatory biomarkers (IL-6, and CRP) showed a significant relationship with POD (IL-6 n = 10, standardized mean difference (SMD): 0.53, 95% CI: 0.36-0.70; CRP n = 14, SMD: 0.53, 95% CI: 0.33-0.74). Two neuronal injury biomarkers (blood-based S100B and NfL) were positively associated with POD (S100B n = 5, SMD: 0.40, 95% CI: 0.11-0.69; NFL n = 2, SMD: 0.93, 95% CI: 0.28-1.57). Of note, many analyses were impacted by significant study heterogeneity. CONCLUSIONS: This meta-analysis identified an association between certain inflammatory and neuronal injury biomarkers and POD. Future studies will need to corroborate these relationships and include amyloid and tau biomarkers in order to better understand the relationship between POD and ADRD.

The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery.

BACKGROUND: Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability of XT to be used for the more crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation. METHODS: Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration. RESULTS: Forty-one patients underwent DBS surgery-25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XT was not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518). CONCLUSION: XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.

Topographical Analysis of the Hamate for Proximal Pole Scaphoid Nonunion Reconstruction.

PURPOSE: To quantify the similarity of the surface topography of the proximal hamate and proximal pole of the scaphoid for nonunion reconstruction. METHODS: Using previously acquired computed tomographic scans of the wrist of 10 patients, the 2 bones were segmented and subsequently aligned using both a manual and automated technique. Surface error between corresponding articular surfaces was computed to determine the similarity of the shape of the 2 bones. RESULTS: The median distance between the 2 articulating surfaces for each patient was 1 mm or less for all cases. Maximum distance varied from 2.7 to 9.7 mm. The automated method improved alignment such that the maximum distance was 4.1 mm. Visual review of the alignment revealed that the maximum error occurred on or around the margin of the articulating surfaces. CONCLUSIONS: In most cases, the proximal hamate appears to be a suitable donor match to reconstruct proximal pole scaphoid nonunions. CLINICAL RELEVANCE: This study serves as a guide to practitioners when considering the suitability of the proximal hamate autograft for unsalvageable proximal pole scaphoid nonunions.

Comparing the Use of Injectable Fillers for the Youthful Lip and the More Mature Lip.

Enhancement of the lips with facial fillers is currently one of the most popular nonsurgical cosmetic treatments worldwide. Patients from all age ranges have interest in these treatments, but there is wide variance of their esthetic goals. Practitioners must be aware of the challenges posed by both the youthful and mature lip, which usually requires different approaches and techniques. This article reviews the lip anatomy, aging changes in the lips and perioral region, techniques to produce consistent results, and ways to manage and avoid potential complications.

Transient perceived back pain induced by prolonged sitting in a backless office chair: are biomechanical factors involved?

It is not currently known if biomechanical factors contribute to low back pain (LBP) during prolonged sitting. Thus, this study recruited 90 participants (61 with no history of LBP, and 29 with) to sit for 1 hour where back electromyography, spine posture, and perceived pain ratings (PPR) were collected. Participants were classified as Pain Developers (PD) or Non-Pain Developers (NPD) based on their maximum PPR. PDs had significantly higher PPR (p = 0.000) and lower number of spine fidgets (p = 0.004) than NPDs. There was a significant interaction between clinical health history and pain group (p = 0.037) for PPR. Besides fidget frequency, there were no biomechanical differences between pain groups. Therefore, sitting-induced back pain does not appear to be due to posture or muscle activity; however, it may be related to micro-movement strategies. Future work should explore fidgeting further and whether healthy PDs are at risk for clinical LBP in the future. Practitioner summary: We have replicated the differential transient sitting-induced pain response observed in previous studies. Pain developers do not sit differently than non-pain developers, although they do appear to move less. More research is warranted to better understand these groups and the relationship between pain developers and future cases of back pain. Abbreviations: LBP: low back pain; PG: pain group; PD: pain developer; NPD: non-pain developer; +veHx: positive clinical history for low back pain; -veHx: negative clinical history for low back pain; RTS: right thoracic erector spinae; LTS: left thoracic erector spine; RLM: right lumbar multifidus; LLM: left lumbar multifidus; MVC: maximum voluntary contraction; Pelvic N: normalized pelvic angle; ANOVA: analysis of variance; SD: standard deviation.

Carpal Realignment Using a Strip of Extensor Carpi Radialis Longus Tendon.

Scapholunate instability can lead to posttraumatic dysfunction of the wrist. If unrecognized, it commonly leads to degenerative osteoarthritis. Numerous reparative techniques have been proposed with mixed long-term success. We present a technique that uses a distally based strip of the extensor carpi radialis longus to better maintain reduction of the scaphoid and reconstruct the volar and dorsal scapholunate ligament and the scaphotrapezium-trapezoid ligament. To illustrate the technique, we describe a clinical case with 17 months of follow-up.

Skin tightening technologies.

Radiofrequency (RF) and intense focused ultrasound (IFUS) are increasingly used to address skin laxity of the face and neck. Both nonablative RF and ultrasound create a heat-induced tissue response that leads to collagen remodeling and other ultrastructural changes. Although these treatments are not meant to replace surgical procedures, patient satisfaction in the majority of studies has been consistently high. This article discusses the various RF and IFUS technologies currently in use and reviews pertinent clinical studies evaluating their efficacy and safety.

Histologic effects of resurfacing lasers.

By utilizing resurfacing lasers, physicians can significantly improve the appearance of sun-damaged skin, scars, and more. The carbon dioxide and erbium:yttrium-aluminum-garnet lasers were the first ablative resurfacing lasers to offer impressive results although these earlier treatments were associated with significant downtime. Later, nonablative resurfacing lasers such as the neodymium:yttrium-aluminum-garnet laser proved effective, after a series of treatments with less downtime, but with more modest results. The theory of fractional photothermolysis has revolutionized resurfacing laser technology by increasing the safety profile of the devices while delivering clinical efficacy. A review of the histologic and molecular consequences of the resurfacing laser-tissue interaction allows for a better understanding of the devices and their clinical effects.

Massive open online courses in nursing education.

MOOCs are changing the face of higher education. Online programs provide nurses with access to technologies, networking with other professionals, and opportunities reflect on their practice. The changing climate of online, higher education provides access and flexibility to students balancing work, family, and financial responsibilities. Offering free courses may provide nursing students ambivalent about online learning the chance to experience otherwise unavailable educational opportunities including the chance to earn a BSN degree.

Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].

Effects of voluntary wheel running on LPS-induced sickness behavior in aged mice.

Peripheral stimulation of the innate immune system with LPS causes exaggerated neuroinflammation and prolonged sickness behavior in aged mice. Regular moderate intensity exercise has been shown to exert anti-inflammatory effects that may protect against inappropriate neuroinflammation and sickness in aged mice. The purpose of this study was to test the hypothesis that voluntary wheel running would attenuate LPS-induced sickness behavior and proinflammatory cytokine gene expression in ~22-month-old C57BL/6J mice. Mice were housed with a running wheel (VWR), locked-wheel (Locked), or no wheel (Standard) for 10 weeks, after which they were intraperitoneally injected with LPS across a range of doses (0.02, 0.08, 0.16, 0.33 mg/kg). VWR mice ran on average 3.5 km/day and lost significantly more body weight and body fat, and increased their forced exercise tolerance compared to Locked and Shoebox mice. VWR had no effect on LPS-induced anorexia, adipsia, weight-loss, or reductions in locomotor activity at any LPS dose when compared to Locked and Shoebox groups. LPS induced sickness behavior in a dose-dependent fashion (0.33>0.02 mg/kg). Twenty-four hours post-injection (0.33 mg/kg LPS or Saline) we found a LPS-induced upregulation of whole brain TNFα, IL-1ß, and IL-10 mRNA, and increased IL-1ß and IL-6 in the spleen and liver; these effects were not attenuated by VWR. We conclude that VWR does not reduce LPS-induced exaggerated or prolonged sickness behavior in aged animals, or 24h post-injection (0.33 mg/kg LPS or Saline) brain and peripheral proinflammatory cytokine gene expression. The necessity of the sickness response is critical for survival and may outweigh the subtle benefits of exercise training in aged animals.

Memantine inhibits cortical spreading depolarization and improves neurovascular function following repetitive traumatic brain injury.

Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor antagonism on electrically triggered CSDs in healthy and brain-injured animals. Rats received either one moderate or four daily repetitive mild closed head impacts (rmTBI). Ninety-three animals underwent craniectomy with electrocorticographic (ECoG) and local blood flow monitoring. In brain-injured animals, ketamine or memantine inhibited CSDs in 44 to 88% and 50 to 67% of cases, respectively. Near-DC/AC-ECoG amplitude was reduced by 44 to 75% and 52 to 67%, and duration by 39 to 87% and 61 to 78%, respectively. Daily memantine significantly reduced spreading depression and oligemia following CSD. Animals (N = 31) were randomized to either memantine (10 mg/kg) or saline with daily neurobehavioral testing. Memantine-treated animals had higher neurological scores. We demonstrate that memantine improved neurovascular function following CSD in sham and brain-injured animals. Memantine also prevented neurological decline in a blinded, preclinical randomized rmTBI trial.

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies.

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.

Motor evoked potentials versus Macrostimulation in predicting the postoperative motor threshold in STN Deep brain stimulation.

INTRODUCTION: Accuracy is crucial in Deep Brain Stimulation (DBS). Electrophysiological and image-based techniques are used to avoid suboptimal positioning. Macrostimulation is the gold standard to delineate the therapeutic window intraoperatively. Despite this, electrode revision rates due to malpositioning are as high as 17%. The goal was to compare motor evoked potentials (MEPs) with the gold standard of Macrostimulation. We assessed accuracy and precision as well as the correlation in predicting motor side effects at the initial mapping 4 weeks postoperatively. METHODS: In this prospective study intraoperative MEPs from 94 contacts in 16 patients undergoing STN DBS under local anesthesia were correlated to the postoperative threshold for stimulation-induced motor side effects and compared to intraoperative Macrostimulation. Analysis of accuracy, precision and correlation (Pearson) was performed. RESULTS: MEPs of the upper extremity had a mean percentage error of 25% (SD 38.8%) and correlated significantly with the motor threshold at postoperative mapping (R=0.235). Macrostimulation was less accurate and precise with a mean percentage error of - 68% (SD 78.8%) but had a higher correlation (R=0.388). MEPs rarely (3%) overestimated the threshold by maximally 1 mA. In contrast, Macrostimulation overestimated the threshold by over 1 mA in 69% leading to a false sense of security. CONCLUSION: MEPs are feasible in an awake setting during Deep Brain Stimulation in the STN for PD patients. MEPs of the upper extremity are more accurate and precise predicting the motor threshold and avoid a false sense of security in comparison to the gold standard of Macrostimulation.

Evaluating Instability in Degenerative Lumbar Spondylolisthesis: Objective Variables Versus Surgeon Impressions.

The subjective degenerative spondylolisthesis instability classification (S-DSIC) system attempts to define preoperative instability associated with degenerative lumbar spondylolisthesis (DLS). The system guides surgical decision-making based on numerous indicators of instability that surgeons subjectively assess and incorporate. A more objective classification is warranted in order to decrease variation among surgeons. In this study, our objectives included (1) proposing an objective version of the DSIC system (O-DSIC) based on the best available clinical and biomechanical data and (2) comparing subjective surgeon perceptions (S-DSIC) with an objective measure (O-DSIC) of instability related to DLS. Methods: In this multicenter cohort study, we prospectively enrolled 408 consecutive adult patients who received surgery for symptomatic DLS. Surgeons prospectively categorized preoperative instability using the existing S-DSIC system. Subsequently, an O-DSIC system was created. Variables selected for inclusion were assigned point values based on previously determined evidence quality. DSIC types were derived by point summation: 0 to 2 points was considered stable, Type I); 3 points, potentially unstable, Type II; and 4 to 5 points, unstable, Type III. Surgeons' subjective perceptions of instability (S-DSIC) were retrospectively compared with O-DSIC types. Results: The O-DSIC system includes 5 variables: presence of facet effusion, disc height preservation (≥6.5 mm), translation (≥4 mm), a kyphotic or neutral disc angle in flexion, and low back pain (≥5 of 10 intensity). Type I (n = 176, 57.0%) and Type II (n = 164, 53.0%) were the most common DSIC types according to the O-DSIC and S-DSIC systems, respectively. Surgeons categorized higher degrees of instability with the S-DSIC than the O-DSIC system in 130 patients (42%) (p < 0.001). The assignment of DSIC types was not influenced by demographic variables with either system. Conclusions: The O-DSIC system facilitates objective assessment of preoperative instability related to DLS. Surgeons assigned higher degrees of instability with the S-DSIC than the O-DSIC system in 42% of cases. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.