Annexin A1 is a cell-intrinsic metalloregulator of zinc in human ILC2s.

Group 2 innate lymphoid cells (ILC2s) produce large amounts of type 2 cytokines including interleukin-5 (IL-5) and IL-13 in response to various stimuli, causing allergic and eosinophilic diseases. However, the cell-intrinsic regulatory mechanisms of human ILC2s remain unclear. Here, we analyze human ILC2s derived from different tissues and pathological conditions and identify ANXA1, encoding annexin A1, as a commonly highly expressed gene in non-activated ILC2s. The expression of ANXA1 decreases when ILC2s activate, but it increases autonomously as the activation subsides. Lentiviral vector-based gene transfer experiments show that ANXA1 suppresses the activation of human ILC2s. Mechanistically, ANXA1 regulates the expression of the metallothionein family genes, including MT2A, which modulate intracellular zinc homeostasis. Furthermore, increased intracellular zinc levels play an essential role in the activation of human ILC2s by promoting the mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) pathways and GATA3 expression. Thus, the ANXA1/MT2A/zinc pathway is identified as a cell-intrinsic metalloregulatory mechanism for human ILC2s.

Anterior ethmoid and frontal sinus drainage pathways: five patterns formed and defined by their bony walls.

PURPOSE: To perform endoscopic sinus surgery safely and effectively, surgeons need to visualize the complex anatomy of the anterior ethmoid and frontal sinus region. Because this anatomy is so variable and individualized, the foundation of understanding lies in identifying, following, and visualizing the drainage pathway patterns and anticipating possible variations. METHODS: We studied 100 sides (50 cases: 22 male, 28 female, aged 12-86, average age 46.5 years, ± 19.5) using computed tomography (CT) and multiplanar reconstruction (MPR) to identify and classify the drainage pathways leading to the frontal sinus and anterior ethmoidal cells. RESULTS: Analysis revealed five patterns of drainage pathways defined by their bony walls: between the uncinate process and the lamina papyracea [UP-LP]; between the uncinate process and the middle turbinate [UP-MT]; between the uncinate process and the accessory uncinate process [UP-UPa]; between the uncinate process and the basal lamella of the ethmoidal bulla [UP-BLEB]; and between the basal lamella of the ethmoidal bulla and the basal lamella of the middle turbinate [BLEB-BLMT]. In most cases, BLEB formed the posterior wall of the drainage pathway of the frontal sinus, indicating BLEB could be one of the most important landmarks for approaching the frontal sinus. CONCLUSIONS: As endoscopic sinus surgery depends on an understanding of this anatomy, this study may help surgeons to identify and follow the drainage pathways more accurately and safely through the anterior ethmoid to the frontal sinus.

Dysregulated fatty acid metabolism in nasal polyp-derived eosinophils from patients with chronic rhinosinusitis.

BACKGROUND: Eosinophils are multifunctional granulocytes capable of releasing various cytokines, chemokines, and lipid mediators. We previously reported dysregulated fatty acid metabolism in peripheral blood-derived eosinophils from patients with severe asthma. However, functional characteristics of eosinophils present in allergic inflammatory tissues remain largely uncharacterized. METHODS: We established a method for isolating CD69hi CCR3low CXCR4- siglec-8int eosinophils from nasal polyps of patients with eosinophilic rhinosinusitis (NP-EOS). Multi-omics analysis including lipidomics, proteomics, and transcriptomics was performed to analyze NP-EOS as compared to peripheral blood-derived eosinophils from healthy subjects (PB-EOS). RESULTS: Lipidomic analysis revealed impaired synthesis of prostaglandins and 15-lipoxygenase (15-LOX)-derived mediators, and selective upregulation of leukotriene D4 production. Furthermore, proteomics and transcriptomics revealed changes in the expression of specific enzymes (GGT5, DPEP2, and 15-LOX) responsible for dysregulated lipid metabolism. Ingenuity pathway analysis indicated the importance of type 2 cytokines and pattern recognition receptor pathways. Stimulation of PB-EOS with eosinophil activators IL-5, GM-CSF, and agonists of TLR2 and NOD2 mimicked the observed changes in lipid metabolism. CONCLUSION: Inflammatory tissue-derived eosinophils possess a specific phenotype with dysregulated fatty acid metabolism that may be targeted therapeutically to control eosinophilic inflammatory diseases.

Pretreatment monocyte counts and neutrophil counts predict the risk for febrile neutropenia in patients undergoing TPF chemotherapy for head and neck squamous cell carcinoma.

BACKGROUND: Febrile neutropenia (FN) is the most serious hematologic toxicity of systemic chemotherapy. However, accurate prediction of FN development has been difficult because the risk varies largely depending on the chemotherapy regimen and various individual factors. METHODS: We retrospectively analyzed diverse clinical factors including pretreatment hematological parameters to clarify the reliable predictors of FN development during chemotherapy with a docetaxel, cisplatin, and fluorouracil (TPF) regimen in patients with head and neck squamous cell carcinoma. RESULTS: Among the 50 patients, grade ≥3 neutropenia, grade 4 neutropenia, and FN developed in 36 (72%), 21 (42%), and 12 (24%) patients, respectively. Multivariate logistic regression revealed that a pretreatment absolute monocyte count (AMC) <370/mm3 is an independent predictor of TPF chemotherapy-induced FN (odds ratio=6.000, p=0.017). The predictive performance of the model combining AMC and absolute neutrophil count (ANC), in which the high-risk group was defined as having an AMC <370/mm3 and/or ANC <3500/mm3, was superior (area under the curve [AUC]=0.745) to that of the model with a cutoff for AMC alone (AUC=0.679). CONCLUSIONS: On the basis of our results, we recommend primary prophylactic use of granulocyte colony-stimulating factor and/or antibiotics selectively for patients predicted to be at high risk for TPF chemotherapy-induced FN.

Minimally invasive endoscopic middle meatal antrostomy for the prevention of maxillary sinusitis in association with dental implantation in the posterior maxilla--a proposal.

Penetration of the maxillary sinus floor membrane during sinus lift occasionally induces maxillary sinusitis. However, maxillary sinusitis may still develop even when its floor membrane has been kept intact during such procedures. The decisive factor for the occurrence of maxillary sinusitis is not the integrity of the membrane; more important is the patency of the maxillary sinus natural ostium. The occlusion of the natural ostium presumably results from the expansive edema of the sinus membrane induced by surgical manipulations to the maxillary sinus floor. We propose a minimally invasive endoscopic sinus surgery which conceivably is useful to prevent potential occlusion of the natural ostium associated with maxillary sinus floor augmentation procedures. Although our technique is not a new concept, this is the first report to propose this kind of procedure as an adjunct to dental implantation. Our method is cost-effective and can be performed under topical anesthesia as a same-day surgery. In addition, it brings about no serious complications, such as orbital injuries or cerebrospinal fluid leakage. It aims to correct anatomical deviations, such as septal deviation, concha bullosa, hypertrophied uncinate process, and excessively pneumatized ethmoid bulla, all of which precipitate the occlusion of the natural ostium. Our method consists of a combination of resection of the uncinate process, widening of the natural ostium, and excision of the anterior and inferior edge of the middle turbinate. First, the anterior and inferoposterior segments of the uncinate process are resected with a curved rongeur, leaving the agger nasi cell intact (caution must be exercised to avoid injury to the nasolacrimal duct). This enables visualization of the maxillary natural ostium. The ostium is widened in all directions, using a forceps and/or a scalpel. The resultant widened ostium is bordered anteriorly by the nasolacrimal duct, inferiorly by the base of the inferior turbinate, posteriorly by the anterior surface of the ethmoid bulla, and superiorly by the medio-inferior angle of the orbit. Then the anterior and inferior edge of the middle turbinate is trimmed to prevent its adhesion to the lateral nasal wall or narrowing of the middle meatus. This surgery does not cause cerebrospinal fluid leakage and, at the same time, minimizes the risk for olfactory dysfunction. The antrostomy window thus formed is large enough to secure drainage and ventilation of the maxillary sinus. Moreover, the middle meatus, now deprived of the antero-inferior aspect of the middle turbinate, enables the patient to irrigate the maxillary sinus with a saline solution at home. Septal deviation can also be corrected simultaneously, if postoperative packing of bilateral nasal cavities is tolerable to the patient. Our experiences in treating over 100 patients are encouraging; although postoperative care such as irrigation of the maxillary sinus at home was mandatory and the start of dental implantation was delayed for 2-6 months, no patient who underwent surgery at our clinic developed maxillary sinusitis during the following course of dental implantation. We believe that collaboration between the otorhinolaryngologist and the dentist/oral surgeon is required to minimize the risk of maxillary sinusitis associated with dental implantation in the maxilla.

Cholesterol granuloma surrounding the endolymphatic sac.

We report a unique case of cholesterol granuloma (CG) surrounding the endolymphatic sac (ES). A 49-year-old man presented with the left side of sensorineural hearing loss, tinnitus, and vertigo. Magnetic resonance and computed tomography imaging revealed a CG surrounding the left ES. The patient initially underwent left transmastoid surgical resection of the tumor. At the time of surgery, brown fluid was aspirated from the tumor, but no other tumors were found. Histopathological examination revealed that the tumor contained cholesterol crystals, confirming the diagnosis of CG. At his 12-month postoperative follow-up, there was no evidence of recurrence. We discuss the radiology, pathology, and surgical removal of CGs surrounding ES.

[Two cases of Meniere's disease with drop attacks].

Drop attacks are sudden falls without concurrent vertigo whose etiology may be unknown. Drop attacks are also associated with cardiac, cerebrovascular, psychogenic, and vestibular disorders, in addition to seizures. Vestibular-based drop attacks without loss of consciousness can occur in patients with Meniere's disease. We present 2 cases of drop attack in patients with Meniere's disease. Case 1, a 65-year-old man, experienced 4 such attacks and case 2, a 55-year-old woman, experienced 20 within 2 years of Meniere's disease onset. Case 1 enjoyed spontaneous remission. In case 2, selective serotonin reuptake inhibitor (SSRI) administration suppressed attack frequency. Anxiety may predispose individuals to drop attack. Etiologically, inadequate stimulation of otolith organs may induce a sudden vestibulo spinal reflex that, in turn, causes sudden falls. To correctly diagnose drop attacks, the patient must exhibit sudden falls, and transient ischemic attack should be carefully ruled out.

Synchronous oncocytoma and Warthin's tumor in the ipsilateral parotid gland.

We encountered an 81-year-old Japanese man with oncocytoma of the parotid gland occurring simultaneously with a Warthin's tumor in the ipsilateral parotid gland. The patient complained of swelling in the right infra-auricular region. Computed tomographic images, magnetic resonance images, and ultrasonography showed two masses in the right parotid gland. Technetium 99m pertechnetate scintigraphy revealed a high accumulation in both tumors. We performed a superficial lobectomy of the parotid gland. Preoperative diagnosis was multiple Warthin's tumor, but upon histopathological examination Warthin's tumor proved to coexist with oncocytoma. In general, the presence of synchronous, major, salivary gland tumors with different histopathology in the ipsilateral parotid gland appears to be unique. This is especially true for the combination of oncocytomas and Warthin's tumors, which is extremely rare. Only eight cases of this kind coincidence were found in our review of the literature. The similarity of oncocytomas and Warthin's tumors based on epidemiology, image diagnostics, and histopathology is discussed.

Intramucosal PCO2 measurement as a new monitoring method of free jejunal transfer following pharyngo-laryngo-esophagectomy.

The choices for practical monitoring of free jejunal transfer have been quite limited because of its own characteristics, such as buried form, lack of skin surface, and the structure of a hollow viscous tract. Physiologically, it is known that tissue hypoxia caused by compromised perfusion leads to an increase of partial pressure of carbon dioxide (PCO2). Because of its physiological properties, the diffusion of carbon dioxide is always equilibrated between the mucosa of a hollow viscous organ and its lumen. The intramucosal PCO2 (PiCO2) of the gastrointestinal tract can therefore be determined indirectly from the intraluminal PCO2, which is measured with the aid of the tonometer catheter. To develop an optimal monitoring method for free jejunal transfer, the authors proposed the application of PiCO2 measurement by a modified use of a tonometer catheter. Since May of 1999, the authors performed postoperative PiCO2 monitoring on 20 cases of reconstructed pharyngoesophageal tracts in 18 patients who underwent radical tumor resection and one-stage reconstruction at the Shizuoka Red Cross Hospital. All 20 cases were safely monitored by PiCO2 measurement without any complications associated with the use of the tonometer catheter. In the 17 cases that succeeded uneventfully, the mean values of PiCO2 were kept lower than 40 mmHg throughout the monitoring period. On the other hand, the other three cases (15 percent) needed reexploration due to development of vascular complications, which was alerted by an abrupt increase of PiCO2 in each case (229, 130, and 99.6 mmHg). Two of the patients were fortunately successfully treated by immediate reexploration, leading to a 95 percent overall success rate. No false-negative or false-positive cases were observed. The authors' experience suggests that PiCO2 measurement using a tonometer catheter can provide the surgeon with reliable information for evaluating the perfusion and viability of a free jejunal transfer. Simplified manipulation and the objectivity of the numerical data allow stable measurement of PiCO2 and prompt judgment of the adequacy of the perfusion, which could minimize the burden and anxiety of the surgeon, particularly in the early postoperative period.