Type 2 and Non-type 2 Inflammation in the Upper Airways: Cellular and Molecular Alterations in Olfactory Neuroepithelium Cell Populations.

PURPOSE OF REVIEW: Neurogenesis occurring in the olfactory epithelium is critical to continuously replace olfactory neurons to maintain olfactory function, but is impaired during chronic type 2 and non-type 2 inflammation of the upper airways. In this review, we describe the neurobiology of olfaction and the olfactory alterations in chronic rhinosinusitis with nasal polyps (type 2 inflammation) and post-viral acute rhinosinusitis (non-type 2 inflammation), highlighting the role of immune response attenuating olfactory neurogenesis as a possibly mechanism for the loss of smell in these diseases. RECENT FINDINGS: Several studies have provided relevant insights into the role of basal stem cells as direct participants in the progression of chronic inflammation identifying a functional switch away from a neuro-regenerative phenotype to one contributing to immune defense, a process that induces a deficient replacement of olfactory neurons. The interaction between olfactory stem cells and immune system might critically underlie ongoing loss of smell in type 2 and non-type 2 inflammatory upper airway diseases. In this review, we describe the neurobiology of olfaction and the olfactory alterations in type 2 and non-type 2 inflammatory upper airway diseases, highlighting the role of immune response attenuating olfactory neurogenesis, as a possibly mechanism for the lack of loss of smell recovery.

Scuba Diving-Induced Inner-Ear Pathology: Imaging Findings of Superior Semicircular Canal and Tegmen Tympani Dehiscence.

BACKGROUND Superior semicircular canal dehiscence is an inner-ear pathology which presents with vertigo, disequilibrium, and hearing loss. Although the exact etiology of superior semicircular canal dehiscence is unknown, it is thought that an increase in middle-ear pressure disrupts a thin overlying temporal bone. Superior semicircular canal dehiscence is frequently seen in association with dehiscence of the tegmen tympani, which overlies the middle ear. Here, we present a case report of a 52-year-old Puerto Rican man with vertigo, dizziness, vomiting, and mild hearing loss associated with superior semicircular canal and tegmen tympani dehiscence after performing improper scuba diving techniques. CASE REPORT A 52-year-old Puerto Rican man presented to the emergency department with vertigo, dizziness, vomiting, and mild hearing loss in the right ear. The symptoms began shortly after scuba diving with inadequate decompression techniques on ascent. He was treated with recompression therapy with mild but incomplete improvement in symptoms. Bilateral temporal magnetic resonance imaging was suggestive of segmental dehiscence of the right superior semicircular canal and tegmen tympani. High-resolution computed tomography of the temporal bone confirmed right superior semicircular canal and tegmen tympani dehiscence with an intact left inner ear. CONCLUSIONS The increased inner-ear pressure that occurs during scuba diving can lead to dehiscence of the superior semicircular canal and tegmen tympani, causing vertigo and hearing loss. Performance of improper diving techniques can further increase the risk of dehiscence. Therefore, appropriate radiologic evaluation of the inner ear should be performed in such patients.

Olfactory Dysfunction in Mental Illness.

PURPOSE OF REVIEW: Olfactory dysfunction contributes to the psychopathology of mental illness. In this review, we describe the neurobiology of olfaction, and the most common olfactory alterations in several mental illnesses. We also highlight the role, hitherto underestimated, that the olfactory pathways play in the regulation of higher brain functions and its involvement in the pathophysiology of psychiatric disorders, as well as the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in psychiatric conditions. RECENT FINDINGS: The olfactory deficits present in anxiety, depression, schizophrenia or bipolar disorder consist of specific alterations of different components of the sense of smell, mainly the identification of odours, as well as the qualifications of their hedonic valence (pleasant or unpleasant). Epidemiological findings have shown that both environmental factors, such as air pollutants, and inflammatory disease of the upper respiratory tract, can contribute to an increased risk of mental illness, at least in part, due to peripheral inflammatory mechanisms of the olfactory system. In this review, we describe the neurobiology of olfaction, and the most common olfactory function alterations in several psychiatric conditions and its role as a useful symptom for the differential diagnosis. We also highlight the effect of inflammation on neurogenesis as a possible mechanism involved in olfactory dysfunction in these psychiatric conditions.

Endoscopic maxillectomy: anatomo-radiological description of the "double" maxillary sinus window.

OBJECTIVES/HYPOTHESIS: To present a modified endoscopic medial maxillectomy (MEMM) approach to control maxillary sinus pathologies. METHODS: MEMM was completed in 13 fresh-frozen specimens. An MEMM includes cutting the nasolacrimal duct, inferior meatus flap, and repositioning the inferior turbinate (IT). The following measurements were obtained: length of IT, height from the nasal floor to valve of Hasner, height of the IT at the level of valve of Hasner, height of the IT at the insertion of the middle turbinate, and distance from the piriform aperture to the posterior wall of maxillary sinus and to the posterior border of palatine bone. Similar measurements were also performed on craniofacial computed tomography (CT) scans (n = 50). The surgical technique was performed in a case series (n = 8). RESULTS: The mean of the specimens was 82 (range 70-95) years old. The average area of the harvested inferior meatus flap area was 9.6 ± 1.0 cm2. In the radiologic study, the mean maximum antrostomy area was 8.8 ± 1.7 cm2 and the IT area overlapping the antral window was 5.8 ± 1.1 cm2, the area allowing a double window control was 3.1 ± 1.9 cm2, the posterior IT insertion length was 0.7 ± 0.4 cm, and the inferior meatus flap covering the inferior meatotomy had an area measuring 6.7 ± 1.7 cm2. Eight patients underwent MEMM for various benign conditions showing no recurrence after 26 month follow-up. CONCLUSION: The proposed modifications of MEMM provide a "double" window maxillary sinus control with access to all maxillary walls and preservation of the IT.

Timing, Complications, and Safety of Tracheotomy in Critically Ill Patients With COVID-19.

IMPORTANCE: The current coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented needs for invasive ventilation, with 10% to 15% of intubated patients subsequently requiring tracheotomy. OBJECTIVE: To assess the complications, safety, and timing of tracheotomy performed for critically ill patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study assessed consecutive patients admitted to the intensive care unit (ICU) who had COVID-19 that required tracheotomy. Patients were recruited from March 16 to April 10, 2020, at a tertiary referral center. EXPOSURES: A surgical tracheotomy was performed for all patients following recommended criteria for use of personal protective equipment (PPE). MAIN OUTCOMES AND MEASURES: The number of subthyroid operations, the tracheal entrance protocol, and use of PPE. Infections among the surgeons were monitored weekly by reverse-transcriptase polymerase chain reaction of nasopharyngeal swab samples. Short-term complications, weaning, and the association of timing of tracheotomy (early [≤10 days] vs late [>10 days]) with total required days of invasive ventilation were assessed. RESULTS: A total of 50 patients (mean [SD] age, 63.8 [9.2] years; 33 [66%] male) participated in the study. All tracheotomies were performed at the bedside. The median time from intubation to tracheotomy was 9 days (interquartile range, 2-24 days). A subthyroid approach was completed for 46 patients (92%), and the tracheal protocol was adequately achieved for 40 patients (80%). Adequate PPE was used, with no infection among surgeons identified 4 weeks after the last tracheotomy. Postoperative complications were rare, with minor bleeding (in 6 patients [12%]) being the most common complication. The successful weaning rate was higher in the early tracheotomy group than in the late tracheotomy group (adjusted hazard ratio, 2.55; 95% CI, 0.96-6.75), but the difference was not statistically significant. There was less time of invasive mechanical ventilatory support with early tracheotomy compared with late tracheotomy (mean [SD], 18 [5.4] vs 22.3 [5.7] days). The reduction of invasive ventilatory support was achieved at the expense of the pretracheotomy period. CONCLUSIONS AND RELEVANCE: In this cohort study, with the use of a standardized protocol aimed at minimizing COVID-19 risks, bedside open tracheotomy was a safe procedure for patients and surgeons, with minimal complications. Timing of tracheotomy may be important in reducing time of invasive mechanical ventilation, with potential implications to intensive care unit availability during the COVID-19 pandemic.

Olfactory Dysfunction in Neurodegenerative Diseases.

PURPOSE OF REVIEW: The sense of smell is today one of the focuses of interest in aging and neurodegenerative disease research. In several neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, the olfactory dysfunction is one of the initial symptoms appearing years before motor symptoms and cognitive decline, being considered a clinical marker of these diseases' early stages and a marker of disease progression and cognitive decline. Overall and under the umbrella of precision medicine, attention to olfactory function may help to improve chances of success for neuroprotective and disease-modifying therapeutic strategies. RECENT FINDINGS: The use of olfaction, as clinical marker for neurodegenerative diseases is helpful in the characterization of prodromal stages of these diseases, early diagnostic strategies, differential diagnosis, and potentially prediction of treatment success. Understanding the mechanisms underlying olfactory dysfunction is central to determine its association with neurodegenerative disorders. Several anatomical systems and environmental factors may underlie or contribute to olfactory loss associated with neurological diseases, although the direct biological link to each disorder remains unclear and, thus, requires further investigation. In this review, we describe the neurobiology of olfaction, and the most common olfactory function measurements in neurodegenerative diseases. We also highlight the evidence for the presence of olfactory dysfunction in several neurodegenerative diseases, its value as a clinical marker for early stages of the diseases when combined with other clinical, biological, and neuroimage markers, and its role as a useful symptom for the differential diagnosis and follow-up of disease. The neuropathological correlations and the changes in neurotransmitter systems related with olfactory dysfunction in the neurodegenerative diseases are also described.

Nasoseptal Perforation: from Etiology to Treatment.

PURPOSE OF REVIEW: Nasal septum perforation (NSP) is a communication between the two nasal cavities. This review contributes to the better knowledge of NSP causes, diagnosis, and treatment. RECENT FINDINGS: NSP prevalence is about 1%. Clinical presentation may range from absence of symptoms to the presence of bothersome sinonasal symptoms. NSP is more frequently caused by trauma or post-surgery, inflammatory diseases, and abuse substances. Conservative management (nasal irrigation, topical use of antibiotic or lubricant ointments, or placement of prosthesis) is considered the first-line treatment. Symptomatic NSP not improving with local therapies usually requires surgical approach. Selection of the technique for the endoscopic septal repair depends on perforation characteristics and surgeon experience. When NSP is diagnosed, its cause has to be promptly determined. Most of them can be controlled with conservative measures. Surgical/endoscopic approaches are usually needed in refractory cases, and new repair techniques have to be considered.

Total septal perforation repair with a pericranial flap: Radio-anatomical and clinical findings.

OBJECTIVES/HYPOTHESIS: Endonasal surgeries are the primary cause of septal perforation (SP). However, trauma, inflammation, infections, neoplasms, or abuse of inhaled drugs can also cause SP. Septal repair is indicated in patients who experience nasal obstruction, crusting, intermittent epistaxis, purulent discharge, or nasal whistling and in those who fail conservative treatment. Multiple approaches have been suggested to repair the SP; however, none has been universally adopted. This study explores the feasibility of repairing a total SP using the pericranial flap (PCF). STUDY DESIGN: Anatomical cadaver and radiological study plus case study. METHODS: Total nasal septectomy and endoscopic reconstruction with a PCF was performed in 12 injected cadaveric specimens. Maximum length and area of the nasal septum and the PCF were measured in 75 computed tomography scans. Based on the anatomical study and the radiological measurements of the cadavers, one patient underwent total nasal septum repair. RESULTS: Anatomic measurements showed that the nasal septum has a mean length of 5.8 ± 0.7 cm, whereas the PCF was on average 18.4 ± 1.3 cm long (mean surface area 121.6 ± 17.7 cm2 ). Radiological measurements revealed that the PCF should provide a surface area of 40.9 ± 4.2 cm2 to account for the total septal area and an additional 30% to account range for potential scar retraction. For total septum repair, the distal edge of the PCF had to be placed 0.8 ± 2.0 cm (3.4 ± 8.7°) from the adopted reference point (vertical projection of the external ear canal). Total septal reconstruction was performed successfully in one patient without complications. CONCLUSIONS: Radio-anatomical data and a case study demonstrate that a PCF allows complete endoscopic repair of the nasal septum. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1320-1327, 2018.

Usefulness of office examination with narrow band imaging for the diagnosis of head and neck squamous cell carcinoma and follow-up of premalignant lesions.

BACKGROUND: The purpose of this study was to evaluate the value of narrow band imaging (NBI) examination in the office for the diagnosis and follow-up of upper airway premalignant and malignant lesions. METHODS: Four hundred eighty lesions were evaluated with white light endoscopy (WLE) and NBI before a biopsy/excision. Additionally, 151 premalignant lesions were followed up without proven biopsy. Carcinoma-free survival was calculated. The learning curve was analyzed. RESULTS: Overall, the accuracy improved from 74.1% with WLE to 88.9% with NBI, being relevant in all anatomic subsites. The accuracy of NBI increased significantly with increasing experience (area under the curve [AUC] >0.9). After a follow-up of 25 months, 14 of 151 lesions (9.3%) converted into carcinoma. The 4-year carcinoma-free survival rate was 86.4%. The 4-year carcinoma-free survival rate differed significantly between lesions classified as benign/mild dysplasia versus those presenting as moderate/severe dysplasia (88.9% vs 73.5%; P = .018). CONCLUSION: The NBI provided a greater accuracy than WLE and showed promising usefulness for the follow-up of premalignant lesions.

Radio-anatomical analysis of the pericranial flap "money box approach" for ventral skull base reconstruction.

OBJECTIVES/HYPOTHESIS: To evaluate the versatility of the pericranial flap (PCF) to reconstruct the ventral skull base, using the frontal sinus as a gate for its passage into the sinonasal corridor "money box approach." STUDY DESIGN: Anatomic-radiological study and case series. METHODS: Various approaches and their respective defects (cribriform, transtuberculum, clival, and craniovertebral junction) were completed in 10 injected specimens. The PCF was introduced into the nose through the uppermost portion of the frontal sinus (money box approach). Computed tomography (CT) scans (n = 50) were used to measure the dimensions of the PCF and the skull base defects. The vertical projection of the external ear canal was used as the reference point to standardize the incisions for the PCF. RESULTS: The surface area and maximum length of the PCF were 121.5 ± 19.4 cm2 and 18.3 ± 1.3 cm, respectively. Using CT scans, we determined that to reconstruct defects secondary to transcribriform, transtuberculum, clival, and craniovertebral approaches, the PCF distal incision must be placed respectively at -3.7 ± 2.0 cm (angle -17.4 ± 8.5°), -0.2 ± 2.0 cm (angle -1.0 ± 9.3°), +5.5 ± 2.3 cm (angle +24.4 ± 9.7°), +8.4 ± 2.4 cm (angle +36.6 ± 11.5°), as related to the reference point. Skull base defects in our clinical cohort (n = 6) were completely reconstructed uneventfully with the PCF. CONCLUSIONS: The PCF renders enough surface area to reconstruct all possible defects in the ventral and median skull base. Using the uppermost frontal sinus as a gateway into the nose (money box approach) is feasible and simple. LEVEL OF EVIDENCE: NA. Laryngoscope, 127:2482-2489, 2017.

Pediatric intranasal lobular capillary hemangioma: Report of two new cases and review of the literature.

BACKGROUND: Lobular capillary hemangioma (LCH) is an acquired benign vascular tumor of unknown origin. It usually affects skin and mucous membranes of the oropharynx. It rarely involves the nasal cavity which most commonly manifests as epistaxis. To our knowledge, only fifteen pediatric intranasal LCH cases have been reported in the literature. None of these occurred in the inferior turbinate. We report two new pediatric cases of LCH, one of them on the inferior turbinate and the other one on the anterior nasal septum. Our principal aim was to highlight the importance of considering this lesion as a differential diagnosis for pediatric unilateral nasal obstruction and epistaxis. METHODS: Retrospective case series and review of current literature regarding the possible causes, diagnosis, and treatment of nasal LCH. DESCRIPTION OF CASES: Two adolescents presented with symptoms of unilateral nasal obstruction and epistaxis. Plain and contrast enhanced computed tomography revealed a well-defined intensely enhancing lesion in both cases. Patients underwent transnasal endoscopic excision and bipolar electrocautery at the base of the tumor for hemostasis. Histopathological examination confirmed the diagnosis of LCH. DISCUSSION: Current epidemiological and pathophysiological data suggests that the development of LCH may be associated to previous nasal trauma or endocrine disorders. LCH should be considered in the differential diagnosis of all pediatric endonasal masses associated with unilateral epistaxis and nasal obstruction. Endoscopic total excision with bipolar electrocautery for hemostasis is an appropriate treatment.

Clinical and biological markers of difficult-to-treat severe chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the upper airways of which two major phenotypes exist, CRS without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP). Some patients with CRS have suboptimal response to current guideline treatments. These patients remain severe and uncontrolled by treatment and have a poor quality of life. It is highly important to identify both clinical and biological markers, so-called biomarkers, in this subset of patients. The presence of nasal polyps and comorbidity with asthma and with aspirin-exacerbated respiratory disease (AERD) are the most common clinical traits that have been associated to difficult-to-treat severe CRS. In addition to clinical traits, numerous biological markers, with known etiopathogenic roles in CRS, have been associated to difficult-to-treat or recalcitrant CRS. This review summarizes the existing knowledge of the clinical and biological markers associated to difficult-to-treat or uncontrolled severe CRS.

Effect of Echinacea purpurea (Asteraceae) aqueous extract on antibody response to Bothrops asper venom and immune cell response

The effect of aqueous extract of Echinacea purpurea roots on the murine antibody response to Bothrops asper snake venom in vivo was studied. Three groups were used. Group #1, baseline control, was treated with snake venom plus PBS. Group #2 was treated with snake venom plus sodium alginate as adjuvant (routine method used at Instituto Clodomiro Picado), and group #3 or experimental group, was treated with snake venom plus aqueous extract ofE. purpurea root as adjuvant. In all groups, the first inoculation was done with Freund's complete adjuvant (FCA). By the time of the second bleeding, mice in group #3 showed a remarkable increment in the level of anti-venom antibodies compared with those in groups #1 or #2. In vitro immune cell proliferation as a response to aqueous extract of E. purpurea root was studied using human lymphocytes activated with different lectins (Con A, PHA and PWM). In all cases, increase in percentage of lymphoproliferation was greater when E. purpurea root extract was used in addition to individual lectins.

Effect of Echinacea purpurea (Asteraceae) aqueous extract on antibody response to Bothrops asper venom and immune cell response.

The effect of aqueous extract of Echinacea purpurea roots on the murine antibody response to Bothrops asper snake venom in vivo was studied. Three groups were used. Group #1, baseline control, was treated with snake venom plus PBS. Group #2 was treated with snake venom plus sodium alginate as adjuvant (routine method used at Instituto Clodomiro Picado), and group #3 or experimental group, was treated with snake venom plus aqueous extract ofE. purpurea root as adjuvant. In all groups, the first inoculation was done with Freund's complete adjuvant (FCA). By the time of the second bleeding, mice in group #3 showed a remarkable increment in the level of anti-venom antibodies compared with those in groups #1 or #2. In vitro immune cell proliferation as a response to aqueous extract of E. purpurea root was studied using human lymphocytes activated with different lectins (Con A, PHA and PWM). In all cases, increase in percentage of lymphoproliferation was greater when E. purpurea root extract was used in addition to individual lectins.