Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room: A Cluster Randomized Clinical Trial.

Importance: Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. Objective: To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Design, Setting, and Participants: Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Interventions: Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. Main Outcomes and Measures: The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Results: Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). Conclusion and Relevance: In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04701762.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Proteomics evaluation of five economical commercial abundant protein depletion kits for enrichment of diseases-specific biomarkers from blood serum.

Blood serum is arguably the most analyzed biofluid for disease prediction and diagnosis. Herein, we benchmarked five different serum abundant protein depletion (SAPD) kits with regard to the identification of disease-specific biomarkers in human serum using bottom-up proteomics. As expected, the IgG removal efficiency among the SAPD kits is highly variable, ranging from 70% to 93%. A pairwise comparison of database search results showed a 10%-19% variation in protein identification among the kits. Immunocapturing-based SAPD kits against IgG and albumin outperformed the others in the removal of these two abundant proteins. Conversely, non-antibody-based methods (i.e., kits using ion exchange resins) and kits leveraging a multi-antibody approach were proven to be less efficient in depleting IgG/albumin from samples but led to the highest number of identified peptides. Notably, our results indicate that different cancer biomarkers could be enriched up to 10% depending on the utilized SAPD kit compared with the undepleted sample. Additionally, functional analysis of the bottom-up proteomic results revealed that different SAPD kits enrich distinct disease- and pathway-specific protein sets. Overall, our study emphasizes that a careful selection of the appropriate commercial SAPD kit is crucial for the analysis of disease biomarkers in serum by shotgun proteomics.

Serratus anterior and pectoralis plane blocks for robotically assisted mitral valve repair: a randomised clinical trial.

BACKGROUND: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. METHODS: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1-3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. RESULTS: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1-3 with a median difference of 0.08 (95% confidence interval [CI]: -0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85-1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. CONCLUSIONS: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. CLINICAL TRIAL REGISTRATION: NCT03743194.

Engineering Analysis of Non-Braided Polycaprolactone Bioresorbable Flow Diverters for Aneurysms.

This paper reports a nonbraided, bioresorbable polycaprolactone (PCL) flow diverter (FD) for the endovascular treatment of aneurysms. Bioresorbable FDs can reduce the risk associated with the permanent metallic FDs as they are resorbed by the body after curing of aneurysms. PCL FDs were designed and fabricated using an in-house hybrid electromelt spinning-fused deposition fabrication unit. Flow diverter's properties, surface qualities, and mechanical characteristics of PCL FDs of 50%, 60%, and 70% porosities were studied using scanning electron microscope (SEM), atomic force microscopy (AFM), and high precision universal testing machine (UTM). The deployability through a clinically relevant catheter was demonstrated in a PDMS aneurysm model. The angiographic visibility of the developed PCL FDs was evaluated using BaSO4 and Bi2O3 coatings of various concentration. The average strut thicknesses were 74.12 ± 6.63 µm, 63.07 ± 1.26 µm, and 56.82 ± 2.09 µm for PCL FDs with 50%, 60%, and 70% porosities, respectively. They average pore areas for the 50%, 60% and 70% porosities FDs were 0.055 ± 0.0056 mm2, 0. 0605 ± 0.0065 mm2, and 0.0712 ± 0.012 mm2, respectively. The surface quality was great with an RMS roughness value of 14.45 nm. The tensile, radial strength, and flexibility were found to be satisfactory and comparable to the nonbraided coronary stents. The developed PCL FDs were highly flexible and demonstrated to be deployable through conventional delivery system as low as 4 Fr catheters in a PDMS aneurysm model. The visibility under X-ray increases with the increasing concentration of coating materials BaSO4 and Bi2O3. The visibility intensity was slightly higher with Bi2O3 coating of PCL FDs. The overall results of the engineering analysis of the developed nonbraided PCL FDs are promising.

Identifying commonalities in definition and governance of point-of-care ultrasound within statements from medical organizations in the United States: A scoping review for a shared understanding.

This scoping review analyzed statements from 22 medical organizations in the United States to identify commonalities in the definition and governance of point-of-care ultrasound (POCUS). A total of 41 statements were included. The review found that the most commonly used elements in defining POCUS were "focused," "bedside," and "patient care." In terms of governance, consistent requirements included specific training programs, documentation in medical records, continuous quality assurance, and standards for credentialing and privileging. These findings suggest the existence of essential commonalities that could facilitate communication and the development of standardized POCUS programs in the future.

Update on intrathecal management of cerebral vasospasm: a systematic review and meta-analysis.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm with delayed ischemic neurological deficit is thought to be responsible for much of the morbidity associated with aSAH. This has illuminated some treatment options that have the potential to target specific components of the vasospasm cascade. Intrathecal management via lumbar drain (LD) or external ventricular drain (EVD) offers unique advantages in this patient population. The aim of this review was to provide an update on intrathecal vasospasm treatments, emphasizing the need for larger-scale trials and updated protocols using data-driven evidence. METHODS: A search of PubMed, Ovid MEDLINE, and Cochrane databases included the search terms (subarachnoid hemorrhage) AND (vasospasm OR delayed cerebral ischemia) AND (intrathecal OR intraventricular OR lumbar drain OR lumbar catheter) for 2010 to the present. Next, a meta-analysis was performed of select therapeutic regimens. The primary endpoints of analysis were vasospasm, delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome. RESULTS: Twenty-nine studies were included in the analysis. There were 10 studies in which CSF drainage was the primary experimental group. Calcium channel antagonists were the focus of 7 studies. Fibrinolytics and other vasodilators were each examined in 6 studies. The meta-analysis included studies examining CSF drainage via LD (n = 4), tissue plasminogen activator in addition to EVD (n = 3), intraventricular nimodipine (n = 2), and cisternal magnesium (n = 2). Results showed that intraventricular nimodipine decreased vasospasm (OR 0.59, 95% CI 0.37-0.94; p = 0.03). Therapies that significantly reduced DCI were CSF drainage via LD (OR 0.47, 95% CI 0.25-0.88; p = 0.02) and cisternal magnesium (OR 0.27, 95% CI 0.07-1.02; p = 0.05). CSF drainage via LD was also found to significantly reduce the incidence of cerebral infarction (OR 0.35, 95% 0.24-0.51; p < 0.001). Lastly, functional outcome was significantly better in patients who received CSF drainage via LD (OR 2.42, 95% CI 1.39-4.21; p = 0.002). CONCLUSIONS: The authors' results showed that intrathecal therapy is a safe and feasible option following aSAH. It has been shown to attenuate cerebral vasospasm, reduce the incidence of DCI, and improve clinical outcome. The authors support the use of intrathecal management in the prevention and rescue management of cerebral vasospasm. More randomized controlled trials are warranted to determine the best combination of pharmaceutical agents and administration route in order to formulate a standardized treatment approach.

The effects of amiodarone on thyroid function in pediatric and adolescent patients.

PURPOSE OF REVIEW: Amiodarone-induced thyroid dysfunction is well established. The present review discusses recent literature related to the effects of amiodarone on the thyroid gland and thyroid function in pediatrics. RECENT FINDINGS: Current guidelines in adults treated with amiodarone recommend baseline thyroid function testing followed by initiation of thyroid hormone monitoring after 3 months on therapy. Two retrospective studies to evaluate amiodarone-induced thyroid dysfunction in children and young adults reveal thyroid dysfunction as soon as 2 weeks after amiodarone initiation with a greater percentage of pediatric patients developing amiodarone-induced hypothyroidism rather than thyrotoxicosis. Although additional studies are needed to determine if AIH is associated with negative impact on growth and neurocognitive development, what is clear is that in both adults and pediatrics, there is low compliance with recommended side effect-monitoring guidelines. SUMMARY: Pediatric patients are at similarly high risk to develop amiodarone-induced thyroid dysfunction as are adults. It is hoped that through improved education of providers and patients further research into the incidence, the potential risks of amiodarone therapy and the potential benefits of thyroid hormone replacement therapy in patients with AIH will be investigated and reported.

miRNA expression can classify pediatric thyroid lesions and increases the diagnostic yield of mutation testing.

BACKGROUND: Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. In this study, we evaluated the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions. PROCEDURE: Double-blind case-control study with 113 resected pediatric lesions: 66 malignant and 47 benign. Quantitative and qualitative molecular data generated with a 10-miRNA expression panel (ThyraMIR) and a next-generation sequencing oncogene panel (ThyGeNEXT) were compared with clinicopathological parameters. RESULTS: miRNAs were differentially expressed in benign versus malignant tumors with distinct expression patterns in different histopathology categories. The 10-miRNA classifier identified 39 (59%) malignant lesions with 100% specificity. A positive classifier score was associated with lymph node metastasis, extrathyroidal extension and intrathyroidal spread. Genetic alterations associated with increased risk for malignancy were detected in 35 (53%) malignant cases, 20 positive for point mutations in BRAF, HRAS, KRAS, NRAS, PIK3CA, or TERT and 15 positive for gene rearrangements involving ALK, NTRK3, PPARG, or RET. The 10-miRNA classifier correctly identified 11 mutation-negative malignant cases. The performance of the combined molecular test was 70% sensitivity and 96% specificity with an area under the curve of 0.924. CONCLUSIONS: These data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children. miRNA expression can identify malignant lesions with high specificity, augment the diagnostic yield of mutation testing, and improve the molecular classification of pediatric thyroid nodules.

Brain reading and behavioral methods provide complementary perspectives on the representation of concepts.

The advent of brain reading techniques has enabled new approaches to the study of concept representation, based on the analysis of multivoxel activation patterns evoked by the contemplation of individual concepts such as animal concepts. The present fMRI study characterized the representation of 30 animal concepts. Dimensionality reduction of the multivoxel activation patterns underlying the individual animal concepts indicated that the semantic building blocks of the brain's representations of the animals corresponded to intrinsic animal properties (e.g. fierceness, intelligence, size). These findings were compared to behavioral studies of concept representation, which have typically collected pairwise similarity ratings between two concepts (e.g. Henley, 1969). Behavioral similarity judgments, by contrast, indicated that the animals were organized into taxonomically defined groups (e.g. canine, feline, equine). The difference in the results between the brain reading and behavioral approaches might derive from differences in cognitive processing during judging similarities versus contemplating one animal at a time. Brain reading approaches may have an advantage in describing thoughts about an individual concept, owing to the ability to decode brain activation patterns elicited by the brief consideration of a single concept (e.g. word reading) without a complex cognitive or behavioral task (e.g. similarity judgments). On the other hand, some behavioral tasks may tend to evoke a concept from numerous perspectives, yielding a representation of the breadth and sophistication of the concept knowledge. These results suggest that neural and behavioral measures offer complementary perspectives that together characterize the content and structure of concept representations.

Newborn Screening in the US May Miss Mild Persistent Hypothyroidism.

OBJECTIVE: To determine if newborn screening (NBS) programs for congenital hypothyroidism in the US use thyroid-stimulating hormone (TSH) cutoffs that are age adjusted to account for the physiologic 4-fold reduction in TSH concentrations over the first few days of life. STUDY DESIGN: All NBS programs in the US were contacted and asked to provide information on their NBS protocols, TSH cutoffs, and whether these cutoffs were age adjusted. RESULTS: Of 51 NBS programs, 28 request a repeat specimen if the initial eluted serum TSH concentration is mildly increased (between the cutoff and a median upper limit of 50 mU/L), whereas 14 programs perform a routine second screen in all infants. Although these specimens are typically collected between 1 week and 1 month of life, 16 of the 28 programs with a discretionary second test and 8 of 14 programs with a routine second test do not have age-adjusted TSH cutoffs after the first 48 hours of life. CONCLUSIONS: There is variation in NBS practices for screening for congenital hypothyroidism across the US, and many programs do not adjust the TSH cutoff beyond the first 2 days of life. Samples are processed when received from older infants, often to retest borderline initial results. This approach will miss congenital hypothyroidism in infants with persistent mild TSH elevations. We recommend that all NBS programs provide age-adjusted TSH cutoffs, and suggest developing a standard approach to screening for congenital hypothyroidism in the US.

A brain-based account of "basic-level" concepts.

This study provides a brain-based account of how object concepts at an intermediate (basic) level of specificity are represented, offering an enriched view of what it means for a concept to be a basic-level concept, a research topic pioneered by Rosch and others (Rosch et al., 1976). Applying machine learning techniques to fMRI data, it was possible to determine the semantic content encoded in the neural representations of object concepts at basic and subordinate levels of abstraction. The representation of basic-level concepts (e.g. bird) was spatially broad, encompassing sensorimotor brain areas that encode concrete object properties, and also language and heteromodal integrative areas that encode abstract semantic content. The representation of subordinate-level concepts (robin) was less widely distributed, concentrated in perceptual areas that underlie concrete content. Furthermore, basic-level concepts were representative of their subordinates in that they were neurally similar to their typical but not atypical subordinates (bird was neurally similar to robin but not woodpecker). The findings provide a brain-based account of the advantages that basic-level concepts enjoy in everyday life over subordinate-level concepts: the basic level is a broad topographical representation that encompasses both concrete and abstract semantic content, reflecting the multifaceted yet intuitive meaning of basic-level concepts.

Macrocephaly associated with the DICER1 syndrome.

PURPOSE: Germ-line mutations in DICER1 increase the risk of various tumors, including pleuropulmonary blastoma. Macrocephaly and symmetric overgrowth have been reported in some, but not all, patients with mosaic DICER1 RNase IIIb mutations. The prevalence of these features in individuals with constitutional germ-line DICER1 mutations is unknown. METHODS: We analyzed prospectively collected auxology data from 67 DICER1 mutation carriers and 43 family controls. We assessed differences between groups using an exact test for proportions and generalized estimating equations for continuous dependent variables. RESULTS: Twenty-eight DICER1 mutation carriers (42%) were macrocephalic, and none had an occipitofrontal circumference (OFC) below the third centile, which significantly differed from family controls, of whom five were macrocephalic (12%) and two had OFC below the third centile (5%) (P < 0.001). DICER1 mutation carriers were taller than familial controls after controlling for gender (P = 0.048), but similar proportions of both groups were above the 97th centile of population norms. Head circumference remained increased after adjusting for differences in height. CONCLUSION: For the first time, we establish macrocephaly as a common finding in the DICER1 syndrome. Like some other tumor-predisposition disorders, macrocephaly may be a useful, albeit a subtle, clinical clue to the DICER1 syndrome diagnosis.Genet Med 19 2, 244-248.

Evaluation and management of thyroid nodules in children.

PURPOSE OF REVIEW: The review is focused on new information about the presentation and management of thyroid nodules in children and adolescents. RECENT FINDINGS: Palpable thyroid nodules are uncommon in children but many children have nodules detected by radiologic imaging. How to evaluate them, when to suspect thyroid cancer, and how best to follow apparently benign nodules has become an area of great interest. The American Thyroid Association recently published treatment guidelines for children with thyroid nodules and cancers but much has been learned since that publication. SUMMARY: Personal and family history, ultrasound features, and fine needle aspiration cytology are used to determine the risk of cancer in thyroid nodules, which are then managed according to cancer risk.

Monitoring the growth of the neural representations of new animal concepts.

Although enormous progress has recently been made in identifying the neural representations of individual object concepts, relatively little is known about the growth of a neural knowledge representation as a novel object concept is being learned. In this fMRI study, the growth of the neural representations of eight individual extinct animal concepts was monitored as participants learned two features of each animal, namely its habitat (i.e., a natural dwelling or scene) and its diet or eating habits. Dwelling/scene information and diet/eating-related information have each been shown to activate their own characteristic brain regions. Several converging methods were used here to capture the emergence of the neural representation of a new animal feature within these characteristic, a priori-specified brain regions. These methods include statistically reliable identification (classification) of the eight newly acquired multivoxel patterns, analysis of the neural representational similarity among the newly learned animal concepts, and conventional GLM assessments of the activation in the critical regions. Moreover, the representation of a recently learned feature showed some durability, remaining intact after another feature had been learned. This study provides a foundation for brain research to trace how a new concept makes its way from the words and graphics used to teach it, to a neural representation of that concept in a learner's brain.

Cerebral vasospasm in patients with traumatic subarachnoid hemorrhage, a possible point of intervention?

OBJECTIVE: To determine the incidence of vasospasm in traumatic brain injury patients with traumatic subarachnoid hemorrhage. METHODS: IRB approval was obtained for this retrospective chart review. An institutional trauma database was queried for adult patients with traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) seen on CT head obtained within 20 days. The presence of vasospasm on CTA was determined by radiology report. Association between categorical background characteristics and intracranial vasospasm was assessed by the chi-square test and association between a continuous variables and intracranial vasospasm was assessed by a paired t-test. RESULTS: 1142 patients with traumatic SAH were identified from the trauma database. 792 patients were excluded: 142 for age <18, 632 did not have CT angiography, and 18 had non-traumatic SAH. 350 patients were analyzed, of which 28 (8 %) had vasospasm. Traumatic vasospasm was associated with higher-grade TBI based on Cochran-Armitage trend test (p < 0.05). Vasospasm patients had longer length of stay in the ICU (mean days 13.64 vs 7.24, P < 0.001), and had a higher incidence of death (39.29 % vs 20.81 %), although this did not reach statistical significance. CONCLUSION: Intracranial vasospasm, specifically in patients with tSAH, is associated with more severe TBI and longer stays in the ICU. Our incidence is smaller compared to other studies likely due to the retrospective nature and the infrequency of obtaining CT angiography after initial presentation. Prospective studies are warranted as the incidence is significant and may represent a point of intervention for TBI.

Clinical Research Primer for Medical Students: Overview and Illustrative Experiences.

Background The ability to participate in clinical scholarship is a foundational component of modern evidence-based medical practice, empowering improvement across essentially every aspect of clinical care. In tandem, the need for comprehensive exposure to clinical research has been identified as a critical component of medical student training and preparation for residency that is underserved by traditional undergraduate medical education models. The goal of the current work was to provide guidelines and recommendations to assist novice medical students in taking ownership of their research education. Methods The Clinical Research Primer was composed from pooled research documents compiled by the study authors and our institutional neurosurgery student research group. The Primer was then structured as the natural evolution of a research project from its inception through the submission process. Results We divided the foundational components of the Clinical Research Primer into seven domains, each representing a landmark in the development of a peer-reviewed study, and a set of skills critical for junior scholars to develop. These vital components included the following: pitching and designing clinical studies, developing a research workflow, navigating the Institutional Review Board, data collection and analysis, manuscript writing and editing, submission mechanics, and tracking research projects for career development. Conclusion We anticipate that the tools included in the Clinical Research Primer will increase student research productivity and preparedness for residency. Although our recommendations are informed by our experiences within neurosurgery, they have been written in a manner that should generalize to almost any field of clinical study.