Surgery for severe rhinosinusitis

Sinusitis is one of the most common reasons patients visit their primary care physician. The etiology of sinusitis is multifactorial in most cases. However, the final common pathway of disruption is usually made with a thorough history. The physical examination is often unremarkable. Complaints of nasal obstruction, mucopuluent nasal drainage, and facial pain/pressure are most diagnostic chronic sinusitis. Isolated headache is an uncommon presenting symptom. Computed tomography scans are the gold standard for diagnostic imaging. They can be used both for diagnosis and surgical treatment. All chronic sinusitis patients, being considered for endoscopic sinus surgery, should have failed a trial of maximal medical therapy. This includes a 4–6 wk course of oral antibiotics, nasal steroids, topical nasal decongestants, and oral prednisone if possible. Patients who fail maximal medical therapy have persistent symptoms that significantly effect their daily activities, have chronic abnormalities on computet tomography scan, and are candidates for endoscopic sinus surgery. Appropriate patient selection and preoperative counseling are key factors in patient satisfaction. Most patients with symptoms that significantly impact their daily activities will receive marked improvement in symptoms after sinus surgery. Endoscopic sinus surgery has undergone radical changes in the last 15 yr. Minimally invasive techniques, combined with advances in instrumentation and computers have reduced postoperative discomfort and improved patient satisfaction.     

Failure mode and effects analysis: a novel approach to avoiding dangerous medication errors and accidents

It is time that hospitals realize that human error is inevitable and must be anticipated. A technique developed in the aerospace industry and known as "failure mode and effects analysis" involves identifying mistakes that will happen before they happen, and determining whether the consequences of those mistakes would be tolerable or intolerable. This article shows how this practice can be adapted to a hospital environment by using a continuous quality improvement approach. Examples show how actual fatal errors can be prevented.     

Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.Improving the design of nanomedicines is key for their success and ultimate clinical application (1). The accumulation of such therapeutic or diagnostic nanomaterials primarily relies on enhanced endothelial permeability of the microvasculature in diseased tissue (2). This holds true for a wide range of pathological conditions, including inflammation, atherosclerosis, and most notably, oncological disease (3–6). Although attributed to the enhanced permeability and retention (EPR) effect, the exact mechanism by which nanoparticles accumulate in tumors continues to be a topic of research (7, 8). The “leaky” vasculature of tumors, which facilitates the extravasation of nanoparticles from microvessels (9), is a heterogeneous phenomenon that varies between different tumor models and even more so in patients. Moreover, the exploitation of nanomedicines in other conditions with enhanced microvessel permeability has only recently begun to be studied in detail. For example, in the last 5 y, a small but increasing number of preclinical studies that apply nanoparticle therapy in atherosclerosis models has surfaced (10). Although several targeting mechanisms have been proposed (4), the exact mechanism by which nanoparticles accumulate in atherosclerotic plaques remains to be investigated, but is likely facilitated by highly permeable neovessels that penetrate into the plaque from the vasa vasorum (Fig. 1A), a network of microvessels that supplies the wall of larger vessels (11).Open in a separate windowFig. 1.Development of an endothelialized microfluidic device to probe nanoparticle translocation over a permeable microvessel. (A) Schematics of continuous normal capillaries surrounding the vessel wall as well as permeable capillaries that penetrate into the atherosclerotic plaque from the vasa vasorum. (B) Schematic of an endothelialized microfluidic device that consists of two-layer microfluidic channels that are separated by a porous membrane (3 μm pore) on which ECs are grown. (C) TEER was dynamically measured across the endothelial layer on the membrane between the upper and lower channels. (D) A well-established monolayer of the microvascular endothelium is formed at TEER ∼400 (Ω·cm²). (E) The monolayer becomes highly permeable when stimulated with the inflammatory mediator, TNF-α, as well as with shear stress, with disruption of intercellular junctional structures (i.e., adherens junctions) between ECs, as evidenced by patchy expression of VE–cadherin (green) in the image on the right versus the left. Blue depicts nuclei stained with DAPI. (Scale bar, 20 μm.) (F) FITC–albumin translocation through the endothelial monolayer increases when the chip is treated with TNF-α. (G) The chip with endothelium cultured in different culture media [base, +FBS, +growth factors (GFs)] for 6 h shows a decrease in TEER with increased FITC–albumin translocation. No cell indicates the membrane only. TEER was normalized to the level with no cells (membrane only). (H) Schematic and TEM image of PEGylated lipid-coated nanoparticles encapsulating PLGA-conjugated AuNCs and Cy5.5. The average size was 69.7 ± 14 nm, which was measured from TEM images. (Scale bar, 100 nm.) Details on labeling, synthesis, characterization, and large-scale production procedures can be found in Materials and Methods and Fig. S2.Advances in biomedical imaging allow the study of plaque-targeting nanoparticles in a dynamic fashion with exceptional detail (12, 13). Microchip technology has the potential to monitor nanoparticle behavior at the (sub)cellular level. Microfluidic chips in which endothelial cells (ECs) are grown in the channels can serve as unique in vitro test systems to study microvascular function and associated disorders (14–18). They allow the isolation of specific biological hallmarks relevant to nanoparticle accumulation, such as the leaky endothelium. In the current study, we validate the potential utility of our microchip technology to study nanoparticle translocation over the endothelium and combine this with in vivo and ex vivo multimodality imaging studies on a rabbit model to better understand nanoparticle targeting of atherosclerotic plaques.     

Survival prediction of glioblastoma patients—are we there yet? A systematic review of prognostic modeling for glioblastoma and its clinical potential

Glioblastoma is associated with a poor prognosis. Even though survival statistics are well-described at the population level, it remains challenging to predict the prognosis of an individual patient despite the increasing number of prognostic models. The aim of this study is to systematically review the literature on prognostic modeling in glioblastoma patients. A systematic literature search was performed to identify all relevant studies that developed a prognostic model for predicting overall survival in glioblastoma patients following the PRISMA guidelines. Participants, type of input, algorithm type, validation, and testing procedures were reviewed per prognostic model. Among 595 citations, 27 studies were included for qualitative review. The included studies developed and evaluated a total of 59 models, of which only seven were externally validated in a different patient cohort. The predictive performance among these studies varied widely according to the AUC (0.58–0.98), accuracy (0.69–0.98), and C-index (0.66–0.70). Three studies deployed their model as an online prediction tool, all of which were based on a statistical algorithm. The increasing performance of survival prediction models will aid personalized clinical decision-making in glioblastoma patients. The scientific realm is gravitating towards the use of machine learning models developed on high-dimensional data, often with promising results. However, none of these models has been implemented into clinical care. To facilitate the clinical implementation of high-performing survival prediction models, future efforts should focus on harmonizing data acquisition methods, improving model interpretability, and externally validating these models in multicentered, prospective fashion.

     

Congenital hairy polyp of the nasopharynx associated with cleft palate: report of two cases

Congenital hairy polyp of the nasopharynx is an unusual but well-recognized entity. These benign lesions have not been reported in the modern literature in association with cleft palate. We report two cases of hairy polyp in association with cleft palate, and discuss the pathology of the tumor with emphasis on embryology and pathogenesis.     

Airway management in the obese child

Airway management in severely obese children requires familiarity with the equipment and techniques used for establishing a patent airway. Normal anatomic landmarks are obscured in these patients, making assessment a challenge. Therapy should be individualized, and because the airway is marginal in many of these patients, small insults, such as respiratory tract infection or loss of muscle tone during sleep, can result in a perilous airway. Pediatric airway charts should be maintained and reviewed frequently in emergency departments and clinics caring for these patients. Currently, the body of literature devoted to airway management in obese children is small. Inconsistencies in parameters make comparison of studies difficult. Continued, consistent reporting of airway-management issues in these patients is needed.     

Independent effects of denervating the cricothyroid muscle and stenting on the anterior cricoid split: canine model

The anterior cricoid split (ACS) has gained in popularity since its introduction in 1980, for the treatment of the difficult to extubate child. The procedure allows a successful extubation and avoids a tracheotomy about 75% of the time. How the ACS allows extubation remains poorly understood. Animal research has shown that in the canine model the ACS results in a gap in the cricoid cartilage with a subjective increase in the subglottic space (Senders and Eisele, 1978). This gap in the cricoid cartilage develops whether or not an endotracheal tube stent is used. This experiment was designed to quantitatively evaluate the effect of the ACS on the subglottic space with or without the use of the stent, and to evaluate the effect of the cricothyroid muscle on the ACS procedure. The results show that the ACS does result in an increase in the subcricoid space, and that the use of an endotracheal tube stent does result in a larger increase. The cricothyroid muscle has a strong immediate effect on the gap in the cricoid cartilage, which is eliminated by sectioning the external laryngeal nerve. The long-term effects of sectioning the external laryngeal nerve on the gap in the cricoid cartilage were not conclusive.