Biomechanical Evaluation of Tracheal Needle Puncture Forces: Comparative Analysis of Annular Ligaments and Tracheal Cartilage.

Percutaneous tracheotomies (PCT) are commonly performed minimally invasive procedures involving the creation of an airway opening through an incision or puncture of the tracheal wall. While the medical intervention is crucial for critical care and the management of acute respiratory failure, tracheostomy complications can lead to severe clinical symptoms due to the alterations of the airways biomechanical properties/structures. The causes and mechanisms underlaying the development of these post-tracheotomy complications remain largely unknown. In this study, we aimed to investigate the needle puncture process and its biomechanical characteristics by using a well establish porcine ex vivo trachea to simulate the forces involved in accessing airways during PCT at varying angular approaches. Given that many procedures involve inserting a needle into the trachea without direct visualization of the tracheal wall, concerns have been raised over the needle punctures through the cartilaginous rings as compared to the space between them may result in fractured cartilage and post-tracheostomy airway complications. We report a difference in puncture force between piercing the cartilage and the annular ligaments and observe that the angle of puncture does not significantly alter the puncture forces. The data collected in this study can guide the design of relevant biomechanical feedback system during airway access procedures and ultimately help refine and optimize PCT.

A Novel Instrument Holder to Improve Operative Efficiency in Endoscopic Laryngeal and Airway Surgery.

OBJECTIVE: Receiving instruments from surgical technicians during endoscopic laryngeal and airway microsurgery (ELAM) has challenges including repeated, expeditious handling of delicate instruments and passing them to the surgeon's hand opposite of where the surgical assistant is standing. Optimizing this interaction may reduce surgical errors and improve operative efficiency. METHODS: A proprietary ELAM instrument holder was attached to both sides of the operating room bed. The device consisted of an articulating arm with custom silicone inserts mounted on a tray (storing up to three endoscopic instruments). ELAM cases were randomized to be performed either with (device) or without the holder (control). Using custom software, instrument pass time (IPT), instrument drop rate (IDR), and communication errors (eg handing incorrect instruments) were manually recorded. Qualitative use metrics relating to overall device satisfaction were also obtained. RESULTS: Data were collected from 25 device and 23 control cases among three different laryngologists. Average IPT was nearly three times quicker for the device (0.80 s, n = 1175 passes) compared with controls (2.09 s, n = 1208 passes) [p < 0.001]. IPT interquartile range was five times higher for control (1.65 s) versus device cases (0.42 s). IDR was not significantly different [p = 0.48]; however, device cases had significantly lower communication errors compared to control cases [p = 0.01]. Surgeons and surgical assistants were similarly satisfied with the device on a 5-point Likert scale (mean: 4.2/5, standard deviation: 0.92). CONCLUSION: The proposed endoscopic instrument holder can improve ELAM operative workflow by reducing instrument passing time and variability without increasing IDR. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3492-3498, 2023.

COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis.

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect. Mechanisms underlying these brain symptoms remain understudied. Here we report that SARS-CoV-2-infected hamsters exhibit a lack of viral neuroinvasion despite aberrant blood-brain barrier permeability. Hamsters and patients deceased from coronavirus disease 2019 (COVID-19) also exhibit microglial activation and expression of interleukin (IL)-1ß and IL-6, especially within the hippocampus and the medulla oblongata, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uraemia or trauma. In the hippocampal dentate gyrus of both COVID-19 hamsters and humans, we observed fewer neuroblasts and immature neurons. Protracted inflammation, blood-brain barrier disruption and microglia activation may result in altered neurotransmission, neurogenesis and neuronal damage, explaining neuropsychiatric presentations of COVID-19. The involvement of the hippocampus may explain learning, memory and executive dysfunctions in COVID-19 patients.

Genome-wide association study and functional validation implicates JADE1 in tauopathy.

Primary age-related tauopathy (PART) is a neurodegenerative pathology with features distinct from but also overlapping with Alzheimer disease (AD). While both exhibit Alzheimer-type temporal lobe neurofibrillary degeneration alongside amnestic cognitive impairment, PART develops independently of amyloid-ß (Aß) plaques. The pathogenesis of PART is not known, but evidence suggests an association with genes that promote tau pathology and others that protect from Aß toxicity. Here, we performed a genetic association study in an autopsy cohort of individuals with PART (n = 647) using Braak neurofibrillary tangle stage as a quantitative trait. We found some significant associations with candidate loci associated with AD (SLC24A4, MS4A6A, HS3ST1) and progressive supranuclear palsy (MAPT and EIF2AK3). Genome-wide association analysis revealed a novel significant association with a single nucleotide polymorphism on chromosome 4 (rs56405341) in a locus containing three genes, including JADE1 which was significantly upregulated in tangle-bearing neurons by single-soma RNA-seq. Immunohistochemical studies using antisera targeting JADE1 protein revealed localization within tau aggregates in autopsy brains with four microtubule-binding domain repeats (4R) isoforms and mixed 3R/4R, but not with 3R exclusively. Co-immunoprecipitation in post-mortem human PART brain tissue revealed a specific binding of JADE1 protein to four repeat tau lacking N-terminal inserts (0N4R). Finally, knockdown of the Drosophila JADE1 homolog rhinoceros (rno) enhanced tau-induced toxicity and apoptosis in vivo in a humanized 0N4R mutant tau knock-in model, as quantified by rough eye phenotype and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) in the fly brain. Together, these findings indicate that PART has a genetic architecture that partially overlaps with AD and other tauopathies and suggests a novel role for JADE1 as a modifier of neurofibrillary degeneration.

COVID-19 induces neuroinflammation and loss of hippocampal neurogenesis.

Infection with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is associated with onset of neurological and psychiatric symptoms during and after the acute phase of illness 1-4 . Acute SARS-CoV-2 disease (COVID-19) presents with deficits of memory, attention, movement coordination, and mood. The mechanisms of these central nervous system symptoms remain largely unknown.In an established hamster model of intranasal infection with SARS-CoV-2 5 , and patients deceased from COVID-19, we report a lack of viral neuroinvasion despite aberrant BBB permeability, microglial activation, and brain expression of interleukin (IL)-1ß and IL-6, especially within the hippocampus and the inferior olivary nucleus of the medulla, when compared with non-COVID control hamsters and humans who died from other infections, cardiovascular disease, uremia or trauma. In the hippocampus dentate gyrus of both COVID-19 hamsters and humans, fewer cells expressed doublecortin, a marker of neuroblasts and immature neurons.Despite absence of viral neurotropism, we find SARS-CoV-2-induced inflammation, and hypoxia in humans, affect brain regions essential for fine motor function, learning, memory, and emotional responses, and result in loss of adult hippocampal neurogenesis. Neuroinflammation could affect cognition and behaviour via disruption of brain vasculature integrity, neurotransmission, and neurogenesis, acute effects that may persist in COVID-19 survivors with long-COVID symptoms.