Age-related hearing loss is not linked to cerebrospinal fluid levels of ß-amyloid or p-tau181.

INTRODUCTION: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. METHODS: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. RESULTS: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-ß and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-ß values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. DISCUSSION: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-ß levels.

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

A novel aerosolisation mitigation device for endoscopic sinus and skull base surgery in the COVID-19 era.

PURPOSE: To provide a novel solution to reduce aerosol exposure in the operating room during endoscopic sinus and skull base procedures in the COVID-19 era. METHODS: We have designed a 3D printable midfacial mask that partially seals the nose, while allowing instrumentation during endoscopic transnasal surgery. The mask when connected to a vacuum system creates a constant negative pressure inside it, sucking out aerosols and gases generated during surgical procedures. Its effectiveness was tested using vapour exhalations by a human volunteer and drilling bone in a head model. The physical barrier effect was measured using fluorescein atomization in a head model. RESULTS: The pressure and airflow measured remained negative inside it in all the different situations tested. The mask was capable of completely evacuating human adult exhalation, and was more effective than the hand suction instrument. However, it was as effective as hand suction instrument at preventing aerosol spread from bone drilling. The physical barrier effect achieved a 72% reduction in the splatter created from the fluorescein atomization. CONCLUSIONS: The mask effectively prevented the spread of aerosols and reduced droplet spread during simulated transnasal endoscopic skull base surgery in laboratory conditions. This device has potential benefits in protecting surgical personnel against airborne transmission of COVID-19 and could be useful in reducing chronic exposure to the hazard of surgical smoke.

In-office endoscopic nasal polypectomy: prospective analysis of patient tolerability and efficacy.

PURPOSE: In-office rhinologic procedures have become popularised in the last decade, especially in North America. Endoscopic nasal polypectomy under local anaesthesia offers instant relief in selected patients with obstructive chronic rhinosinusitis with nasal polyps. We aimed to analyse patient tolerability during the procedure while measuring its effectiveness. METHODS: A prospective study of patients who underwent in-office microdebrider-assisted polypectomy under local anaesthetic from September 2018 to November 2019 in a Spanish tertiary hospital was performed. The tolerability was measured by monitoring vital signs during the procedure and using a visual analogue scale posteriorly. The effectiveness was calculated through patient-reported outcomes (SNOT-22) and endoscopic evaluation 1 and 6 months follow-up. RESULTS: Forty-four patients were included, with a mean age of 60.7 years. The mean visual analogue scale score was 2.76 out of 10 points. Vital signs were steady overall, with a statistically significant reduction (p < 0.001) in systolic pressure during the procedure. Presyncope and epistaxis were among the few mild complications. However, we registered one major complication that required intensive care admission. There was a 64% reduction in the SNOT-22 score in the first month, with a maintained effect after 6 months. Patients with asthma and a higher polyp load were the subgroups that required more time to achieve significant improvement. CONCLUSIONS: In-office polypectomy is a very effective technique that alleviates obstructive symptoms in patients with nasal polyposis, and it is generally safe and well tolerated when performed by an expert. However, rhinologists must be aware of potentially severe complications.

Durability of antimicrobial activity of antibiotic-impregnated external ventricular drains: a prospective study.

BACKGROUND: Antibiotic-impregnated external ventricular drains (AI-EVDs) have a debated efficacy in clinical studies. OBJECTIVES: Our aim was to assess the durability of antimicrobial activity of AI-EVDs used in clinical settings. METHODS: From April 2017 to January 2018, all consecutive AI-EVDs (Bactiseal™) inserted in adult patients were prospectively included. After removal, each AI-EVD was cultured and assessed for antimicrobial activity on both internal and external sides of AI-EVDs. Catheters were each challenged with a single Staphylococcus strain [MSSA, MRSA or methicillin-resistant Staphylococcus epidermidis (MRSE)]. MS was used to measure residual concentrations of rifampicin and clindamycin. RESULTS: Sixty-five AI-EVDs were included (56 patients). Among these, 21 were challenged with MSSA, 23 with MRSA and 21 with MRSE. Five ventriculostomy-related colonizations (9%) and two ventriculostomy-related infections (4%) occurred. Staphylococcus was the main bacterium responsible for colonization (4/5). AI-EVD inhibition decreased significantly against MRSA and MRSE according to duration of catheterization (for external and internal sides, P < 0.02) and overall volume of CSF drained (P < 0.005 for both sides against MRSE, P < 0.005 for external side against MRSA), but not against MSSA. Clindamycin concentration was not correlated with duration of catheterization or CSF volume drained, but <20% of initial concentration was recovered even after 5 days of AI-EVD dwelling. Conversely, rifampicin concentration showed a rapid and significant decline correlated to duration and CSF volume (P < 0.001 and P = 0.03, respectively). CONCLUSIONS: Antimicrobial activity of AI-EVDs dropped quickly in vivo. Antimicrobial impregnation did not prevent AI-EVD colonization by susceptible strains in 9% of the cases.

Secondary Insults and Adverse Events During Intrahospital Transport of Severe Traumatic Brain-Injured Patients.

BACKGROUND: Our aim was to assess the occurrence of secondary insults (SIs) or adverse events (AEs) during intrahospital transport (IHT) of severe traumatic brain injury (TBI) patients for head computed tomography (CT) scanning. METHODS: A prospective study based on severe TBI patients admitted from June 2011 through June 2013 in a level I trauma center. Patients received an IHT to perform a control CT scan in the first 3 days following trauma. The occurrence of SIs and AEs was assessed during the IHT for a control CT scan. The frequency of SIs was compared to the periods "before," "during," and "after" IHT. SI was defined by an intracranial pressure (ICP) >30 mmHg, a cerebral perfusion pressure (CPP) <50 mmHg, systolic blood pressure (SBP) <90 mmHg, or saturation pulse O2 (SpO2) <90 % for more than five consecutive minutes. An AE was defined as failures of hardware or ventilator asynchrony requiring therapeutic intervention during transport. In addition, we assessed the therapeutic benefit of a CT scan control. RESULTS: The final analysis included 31 patients and 31 IHTs. The median duration of IHT was 29 min [25;37]. SIs occurred in 16 patients (52 %) during transport, whereas it was observed in 4 patients (13 %) before (p = 0.002) and 4 patients (13 %) after IHT (p = 0.001). Twenty-four AEs occurred during transport of 19 patients (61 %). One patient benefited from hematoma evacuation after implementation of control CT. CONCLUSION: IHT carries significant SIs and AEs in severe TBI patients. To improve a risk/benefit ratio favorable for patients, a program focusing on IHT complications regarding therapeutic impact of control CT scan is needed.

Biofilm-associated infection: the hidden face of cerebrospinal fluid shunt malfunction.

Diagnosis of cerebrospinal fluid (CSF) shunt infection is difficult. Growing evidence links this pattern to biofilm-associated infections (BAI). Biofilm may explain the indolent development of the infection, and the poor efficiency of traditional microbiologic methods. We report the case of a patient admitted for hydrocephalus associated to CSF shunt malfunction. None of the clinical, serum, or CSF laboratory findings were in favor of an infectious process. Only scanning electron microscopy (SEM) revealed the presence of biofilm. Hence, despite a broad CSF shunt infection definition, some infections could remain undiagnosed by the traditional approach. This study is the first to provide some direct evidence for bacterial biofilm-associated CSF shunt infection.

Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study.

BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis.

Feasibility of an Exoskeleton Armrest to Improve Ergonomics during Endoscopic Sinus and Skull Base Surgery.

OBJECTIVE: The main objective of this study was to develop and evaluate the feasibility and effectiveness of a novel exoskeleton system designed to provide ergonomic assistance to surgeons while preserving or improving the quality of endoscopic sinus and skull base surgical procedures. METHODS: To evaluate the functionality and ergonomic characteristics of the device, five experiments were conducted in different and increasingly realistic scenarios: silicone model of the nasal cavity, freshly frozen cadavers and finally in a real surgery. Each volunteer's task was recorded and timed. The National Aeronautics and Space Administration Task Load Index (NASA-TLX) rating scale was used to estimate the surgeons' workload while performing the tasks. RESULTS: Twenty-five volunteers took part in the experiments. Volunteers perceived more comfort and less fatigue and pain when using the armrest than when not using the device (3.3, SD 1.75 vs. 5.9 SD 1.49; p = 0.02). Participants found the device intuitive, comfortable, and improving accuracy and stability with endoscope use. CONCLUSION: A new system that provides ergonomic assistance to surgeons was tested in simulation surgery with acceptable usability. Initial results in terms of pain and fatigue reduction and efficiency were excellent, justifying further research into this technology. LEVEL OF EVIDENCE: NA Laryngoscope, 134:79-86, 2024.

Effect of turbinate surgery on mucociliary clearance. A systematic review and metanalysis.

Despite the fact that turbinate surgery provides satisfactory results regarding nasal obstruction, most of these procedures are destructive, to some extent, for the respiratory epithelium. There are valid hypotheses suggesting either that turbinate surgery may improve mucociliary clearance (MCC) by improving rhinitis, as well hypotheses suggesting that these surgeries may impair it by damaging the nasal ciliated epithelia. This systematic review is designed with the objective of exploring the effect of turbinate surgery on MCC. Pubmed (Medline), the Cochrane Library, EMBASE, SciELO were analyzed. Four authors members of the YO-IFOS rhinology study group independently analyzed the articles. Extracted variables encompassed: sample size, age, indication for surgery, surgical technique, method used to measure mucociliary clearance, mucociliary transport time before and after surgery, and main outcome. 15 studies with a total population of 1936 participants (1618 patients excluding healthy controls) met the inclusion criteria. 9 studies could be combined in a metanalysis, wich revealed a non-statistically significant decrease of 3.86 min in MCTT after turbinate surgery (p = 0.06). The subgroup analysis of the 5 cohorts who underwent microdebrider turbinoplasty reached statistical significance under a random effect model, revealing a 7.02 min decrease in MCTT (p < 0.001). The laser turbinoplasty subgroup, composed of 4 cohorts, also reached significance, although the difference was lower than that for microdebrider turbinoplasty, 1.01 min (p < 0.001). This systematic review and meta-analysis suggests that turbinate surgery does not compromise mucociliary clearance. The available evidence also suggests that turbinate surgery with mucosa sparing techniques improves MCC, while with aggressive techniques it increases or remains the same. This beneficial effect is evident since the first to third month after surgery. However, for solid conclusions, a standard way to measure MCTT should be stablished, as well as a method to appropriately describe the extension of the surgery.

Expression of toll-like receptors 2 and 3 on esophageal epithelial cell lines and on eosinophils during esophagitis.

BACKGROUND: The chronic disease eosinophilic esophagitis may be mediated by the innate immune system. Activation of toll-like receptors (TLRs) in other tissues is known to initiate eosinophil infiltration, thus TLRs may be a potential mediator of esophageal eosinophilia. Little is known about TLRs in the esophagus. AIMS: The purpose of this study was to identify the presence and activation of TLR2 and TLR3 on esophageal epithelial cell lines, primary epithelial cells and mucosal esophageal biopsies. METHODS: TLR2 and TLR3 were identified by immunocytochemistry and immunoblot. PCR assessed alterations to gene expression by activation of TLR2 and TLR3. Immunohistochemistry co-localized eosinophils and TLR2/TLR3 on esophageal biopsies. RESULTS: TLR2 and TLR3 were expressed on the esophageal adenocarcinoma cell lines TE-1 and TE-7, but only TLR3 was present on the esophageal epithelial cell line HET-1A. Thymic stromal lymphopoietin gene expression was altered in response to ligands zymosan and polyI:C, demonstrating activation. Primary esophageal epithelial cells did not express TLR2 or TLR3. In esophageal biopsies, TLR2 and TLR3 expression was limited to eosinophils and other immune cells during esophagitis. CONCLUSIONS: TLR2 and TLR3 expression on cultured esophageal epithelial cells differs from TLR2 and TLR3 expression in esophageal biopsies, which is limited to immune cells during esophagitis.

Gb3/cd77 Is a Predictive Marker and Promising Therapeutic Target for Head and Neck Cancer.

Head and neck squamous cell carcinoma is the sixth leading cancer in the world. This cancer is difficult to treat and is characterized by recurrences that are often fatal. This cancer is generally removed surgically, but it often regrows from the edges of the lesion from where most recurrences reappear. In this study, we have investigated if the expression of GB3 in human cell lines, tissues from patient biopsies, and a murine animal model could be used as an early and determinant marker of HNC. We found that in all the investigated systems, this marker appears in neoplastic cells from the very early stages of their malignant transformation. Our conclusions support the hypothesis that GB3 is a reliable and independent target for HNC identification and selective delivery of treatments. Furthermore, we show that the level of expression of this marker correlates with the degree of malignancy of the tumor. These studies suggest that GB3 may provide the basis for the early identification and new targeted therapies for head and neck cancer.

Frequency and risk factors of severe postoperative bleeding after proctological surgery: a retrospective case-control study.

PURPOSE: The aim of this study was to assess frequency and risk factors of severe bleeding after proctological surgery requiring hemostatic surgery observed after publication of the French guidelines for anticoagulant and platelet-inhibitor treatment. METHODS: All patients who underwent proctological surgery between January 2012 and March 2017 in a referral center were included. Delay, severity of bleeding, and need for blood transfusion were recorded. Patients with severe postoperative bleeding were matched to controls at a 2:1 ratio adjusted on the operator, and the type of surgery. RESULTS: Among the 8,890 operated patients, 65 (0.7%) needed a postoperative hemostatic procedure in an operating room. The risk of a hemostatic surgery was significantly increased after hemorrhoidal surgery compared with other procedures (1.9% vs. 0.5%, P<10-4) and was most frequent after Milligan-Morgan hemorrhoidectomy (2.5%). Mean bleeding time was 6.2 days and no bleeding occurred after day 15. Blood transfusion rate was 0.1%. Treatment with anticoagulants and platelet inhibitors were managed according to recommendations and did not increase the severity of bleeding. The risk of severe bleeding was significantly lower in active smokers vs. non-smokers in univariate (16.9% vs. 36.2%, P=0.007) and multivariate (odds ratio, 0.31; 95% confidence interval, 0.14-0.65) analysis whereas sex, age, and body mass were not significantly associated with bleeding. CONCLUSION: Severe postoperative bleeding occurs in 0.7% of patients, but varies with type of procedure and is not affected by anticoagulant or antiplatelet treatment. These treatments given in accordance with the new guidelines do not increase the severity of postoperative bleeding.

Krebs von den Lungen-6 glycoprotein circulating levels are not useful as prognostic marker in COVID-19 pneumonia: A large prospective cohort study.

Coronavirus disease 2019 (COVID-19) has rapidly expanded worldwide. Currently, there are no biomarkers to predict respiratory worsening in patients with mild to moderate COVID-19 pneumonia. Small studies explored the use of Krebs von de Lungen-6 circulating serum levels (sKL-6) as a prognostic biomarker of the worsening of COVID-19 pneumonia. We aimed at a large study to determine the prognostic value of sKL-6 in predicting evolving trends in COVID-19. We prospectively analyzed the characteristics of 836 patients with COVID-19 with mild lung disease on admission. sKL-6 was obtained in all patients at least at baseline and compared among patients with or without respiratory worsening. The receiver operating characteristic curve was used to find the optimal cutoff level. A total of 159 (19%) patients developed respiratory worsening during hospitalization. Baseline sKL-6 levels were not higher in patients who had respiratory worsening (median {IQR} 315.5 {209-469} vs. 306 {214-423} U/ml p = 0.38). The last sKL-6 and the change between baseline and last sKL-6 were higher in the respiratory worsening group (p = 0.02 and p < 0.0001, respectively). The best sKL-6 cutoff point for respiratory worsening was 497 U/ml (area under the curve 0.52; 23% sensitivity and 85% specificity). sKL-6 was not found to be an independent predictor of respiratory worsening. A conditional inference tree (CTREE) was not useful to discriminate patients at risk of worsening. We found that sKL-6 had a low sensibility to predict respiratory worsening in patients with mild-moderate COVID-19 pneumonia and may not be of use to assess the risk of present respiratory worsening in inpatients with COVID-19 pneumonia.

Cancer Cell Direct Bioprinting: A Focused Review.

Three-dimensional printing technologies allow for the fabrication of complex parts with accurate geometry and less production time. When applied to biomedical applications, two different approaches, known as direct or indirect bioprinting, may be performed. The classical way is to print a support structure, the scaffold, and then culture the cells. Due to the low efficiency of this method, direct bioprinting has been proposed, with or without the use of scaffolds. Scaffolds are the most common technology to culture cells, but bioassembly of cells may be an interesting methodology to mimic the native microenvironment, the extracellular matrix, where the cells interact between themselves. The purpose of this review is to give an updated report about the materials, the bioprinting technologies, and the cells used in cancer research for breast, brain, lung, liver, reproductive, gastric, skin, and bladder associated cancers, to help the development of possible treatments to lower the mortality rates, increasing the effectiveness of guided therapies. This work introduces direct bioprinting to be considered as a key factor above the main tissue engineering technologies.

Cell Bioprinting: The 3D-Bioplotter™ Case.

The classic cell culture involves the use of support in two dimensions, such as a well plate or a Petri dish, that allows the culture of different types of cells. However, this technique does not mimic the natural microenvironment where the cells are exposed to. To solve that, three-dimensional bioprinting techniques were implemented, which involves the use of biopolymers and/or synthetic materials and cells. Because of a lack of information between data sources, the objective of this review paper is, to sum up, all the available information on the topic of bioprinting and to help researchers with the problematics with 3D bioprinters, such as the 3D-Bioplotter™. The 3D-Bioplotter™ has been used in the pre-clinical field since 2000 and could allow the printing of more than one material at the same time, and therefore to increase the complexity of the 3D structure manufactured. It is also very precise with maximum flexibility and a user-friendly and stable software that allows the optimization of the bioprinting process on the technological point of view. Different applications have resulted from the research on this field, mainly focused on regenerative medicine, but the lack of information and/or the possible misunderstandings between papers makes the reproducibility of the tests difficult. Nowadays, the 3D Bioprinting is evolving into another technology called 4D Bioprinting, which promises to be the next step in the bioprinting field and might promote great applications in the future.