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Purpose: Endotype-driven treatment has been introduced in the management of chronic rhinosinusitis with nasal polyps (CRSwNP), and an understanding of the associations between phenotypes and endotypes of CRSwNP will be beneficial in identifying responders. We aimed to determine the correlations between clinical manifestations and type 2 inflammatory mediators of sinonasal tissues. Methods: Adult patients undergoing endoscopic sinus surgery for bilateral CRSwNP were prospectively enrolled. Tissue eosinophilia and type 2 mediator expression in tissue homogenates were assessed and correlated with clinical features, including symptoms, comorbidities, blood eosinophil counts, specific allergen immunoglobulin (IgE) testing, computed tomography (CT) scan findings, and Sino-Nasal Outcome Test-22 scores. Results: A total of 93 subjects were recruited in our study. Fifty-nine (63.4%) cases were identified as the eosinophilic endotype, demonstrating with higher rates of comorbidity of asthma, blood eosinophilia and a high ethmoid-maxillary ratio on CT images. To correlate of phenotypes with the inflammatory mediator profile, multivariate analyses revealed the associations of IgE expression in nasal polyp tissues with allergen sensitization (p = 0.042), CT ethmoid-maxillary ratio (p = 0.001) and tissue eosinophil counts (p = 0.022); the association of interleukin (IL-5) expression with the blood eosinophil percentage (p = 0.020); and the association of IL-13 expression with white blood cell count (p = 0.002) and central compartment-type inflammation (p < 0.001). Conclusion: We demonstrated associations of IgE and IL-5 expression with clinical features of eosinophilic-type inflammation and a significantly elevated level of IL-13 in patients with central-compartment-type CRSwNP. These observations may be useful when considering the use of type 2 biologic treatment and require further validation studies. [ABSTRACT FROM AUTHOR]

Background: The clinical characteristics of central‐compartment‐type chronic rhinosinusitis (CRS) in East Asian individuals are not clear. We sought to investigate the clinical features and the cytokine profiles of central‐compartment‐type CRS in our patient group. Methods: Adult patients diagnosed with bilateral CRS were recruited, and patients who had previously undergone sinus surgery and pansinusitis (Lund‐Mackay scores >23) were excluded. Central‐compartment‐type CRS was defined by both endoscopic and radiological features. The symptoms, inhalant allergen sensitization status, endoscopic findings, and radiological assessments were recorded and compared between patients with central‐compartment‐type CRS and other types of CRS. We also examined the extent of tissue eosinophilia and specific cytokine protein levels (eosinophil cationic protein [ECP], myeloperoxidase [MPO], immunoglobulin E [IgE], interleukin [IL]‐4, IL‐5, and IL‐13) in the sinonasal tissues. Results: Central‐compartment‐type CRS was found in 16 (23.9%) patients, and non–central‐compartment‐type CRS was found in 51 (76.1%) patients. Hyposmia or anosmia as the major symptom was more common in the central‐compartment‐type CRS group. The numbers of eosinophils in tissue and serum were significantly higher in the central‐compartment‐type CRS patients. The presence of allergen sensitization was not significantly different between groups. The levels of IL‐5 and IL‐13 were increased in middle turbinate tissues of patients with central‐compartment‐type CRS. Conclusion: Central‐compartment‐type CRS was associated with hyposmia or anosmia, eosinophilic subtypes, and elevated levels of IL‐5 and IL‐13 in middle turbinate tissues but not necessarily correlated with allergic disease in our patients. [ABSTRACT FROM AUTHOR]

Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction. Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection. Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced. Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells. [ABSTRACT FROM AUTHOR]

Background: The role of allergy in the development of chronic rhinosinusitis (CRS) in East Asians is not clear. Aims/objectives: The aim was to investigate the impact of allergies in the clinical characteristics of chronic rhinosinusitis. Material and methods: A total of 138 CRS patients who underwent endoscopic sinus surgery were included. A brief history of rhinosinusitis symptoms, blood eosinophil count, blood-specific allergen tests, computed tomography (CT) scan findings, Lund-Mackay (LM) CT scores, and Sino-Nasal Outcome Test (SNOT-22) Questionnaire scores, and sinoscopy findings at 3 and 6 months postoperatively. Results: The ImmunoCAP test was positive in 71(51%) patients and negative in 67(49%) patients. The mean age of those who received endoscopic sinus surgery was 7-years younger in the allergic group compared with the non-allergic group (p = .008). The peripheral eosinophil count in the allergic group was higher than that of the non-allergic group (p = .008). The LM scores and SNOT-22 scores were not significantly different between the two groups. The recurrence rate of nasal polyps in the allergic group was higher but without statistical significance. Conclusions and significance: Allergy may accelerate the disease progression of CRS. The presence of the serum-specific IgE was correlated with peripheral eosinophil percentage, especially in the CRSwNP patients. [ABSTRACT FROM AUTHOR]

Background: The endoscopic endonasal prelacrimal recess approach to the maxillary sinus provides wide access to the walls and recesses of the maxillary sinus, and its use has been reported in many maxillary sinus and skull base diseases. The objective of this study was to determine the indication and feasibility of endoscopic sinus surgery using the prelacrimal recess approach in unilateral maxillary sinus diseases. Methods: We reviewed 192 cases of unilateral maxillary sinus diseases; over 2 years, 15 cases underwent endoscopic surgery via the prelacrimal recess approach. Data regarding preoperative computed tomography scans, operative findings, postoperative pathological diagnoses, postoperative complications, and disease recurrences were obtained from medical records. Results: Patients who underwent surgery via the prelacrimal recess approach did so mostly because tumors were present in the maxillary sinuses (12/15; 80%), while most of the patients in this study underwent surgery because of chronic inflammation (122/177; 68.9%) and fungal infections (40/177; 22.6%). Among 15 patients undergoing surgery via the prelacrimal recess approach, 9 were cases of inverted papilloma. The mean follow‐up period was 16.5 months (range, 6 to 28 months). No postoperative complications occurred after the prelacrimal recess approach. One out of the 15 cases undergoing the prelacrimal recess approach had tumor recurrence Conclusion: Most chronic inflammation and fungal infections of the unilateral maxillary sinuses can be managed through a middle meatal antrostomy. The endoscopic prelacrimal recess approach is a reliable and effective method used to approach maxillary sinus diseases. [ABSTRACT FROM AUTHOR]

CONCLUSION Patients with CRSwNP and comorbid ETD are likely to experience improvement in ETD symptoms on dupilumab, at a similar magnitude as sinus surgery. Keywords: chronic rhinosinusitis; quality of life; therapeutics EN chronic rhinosinusitis quality of life therapeutics 1561 1563 3 07/26/23 20230801 NES 230801 INTRODUCTION Eustachian tube dysfunction (ETD) occurs in ~50% of patients with chronic rhinosinusitis with nasal polyposis (CRSwNP).[1] While treatment of CRSwNP with endoscopic sinus surgery (ESS) has been shown to improve comorbid ETD,[2] little is currently understood about the impact of biologics on ETD in CRSwNP. A baseline ETDQ-7 score of >14.5 was considered clinically significant ETD, or "ETD-positive", and a ETDQ7 value of >3.5 was considered the minimal clinically important difference (MCID).[[4]] Pre- and post-treatment ETDQ-7 were compared using I t i -tests. [Extracted from the article]

Key points: We proposed a hierarchical framework including an unsupervised candidate image selection and a weakly supervised patch image detection based on multiple instance learning (MIL) to effectively estimate eosinophil quantities in tissue samples from whole slide images.MIL is an innovative approach that can help deal with the variability in cell distribution detection and enable automated eosinophil quantification from sinonasal histopathological images with a high degree of accuracy.The study lays the foundation for further research and development in the field of automated histopathological image analysis, and validation on more extensive and diverse datasets will contribute to real‐world application. [ABSTRACT FROM AUTHOR]

Objectives: Endoscopic endonasal transsphenoidal adenomectomy (TSA) is the most frequently performed skull base surgery, and researchers have recently focused on preserving nasal function. The endoscopic transseptal approach is a promising procedure due to its reduced injury to the nasal mucosa; however, there are no studies comparing rhinological and neurosurgical outcomes concurrently with the standard endoscopic transnasal approach. Therefore, we conducted this study to investigate whether the transseptal approach could reduce nasal morbidities with comparable neurosurgical outcomes. Methods: We retrospectively reviewed 25 patients who underwent endoscopic endonasal transseptal TSA for pituitary adenoma without encasement of internal carotid artery from January 2019 to December 2020. Another 25 patients who received transnasal approach from January 2017 to December 2018 were selected as controls. Patients with diseases affecting the nasal cavity/olfaction or usage of a nasoseptal flap were excluded for a better comparison of the two procedures. We collected data from radiological studies, endocrine studies, endoscopic evaluations, 22‐item sinonasal outcome tests (SNOT‐22) and Top International Biotech Smell Identification Test (TIBSIT) for comparison. Results: Lower postoperative SNOT‐22 and Lund‐Kennedy endoscopic scores were observed in the transseptal group. The effect size of differences were classified as large effect (The absolute value of Cohen's d > 0.8). Nevertheless, the TIBSIT scores were not significantly different. The rates of gross total resection, recovery of hormonal abnormalities, and complications were not significantly different. After controlling possible confounding factors using multivariate analysis, the endoscopic transseptal approach remained an independent factor for lower SNOT‐22 scores and Lund‐Kennedy endoscopic scores. Conclusions: The endoscopic transseptal approach provides improved recovery of nasal mucosa and intact olfaction without compromising neurosurgical outcomes. Level of Evidence: 2b. [ABSTRACT FROM AUTHOR]

This study was divided into two parts: (i) an optimal hydrolysing procedure of chicken liver hydrolysates ( CLHs) and (ii) the in vivo antioxidant properties of CLHs via a D-galactose-induced mouse model. A pepsin-to-raw chicken liver mass ratio (1:400, w:w) and 2-h hydrolysing period were chosen to manufacture CLHs based on yield, peptide level and antioxidant effect. Molecular masses of CLHs were lower than 10 kDa. CLH was rich in aspartic acid and glutamic acid, and also contained both manganese and selenium, which are essential cofactors of superoxide dismutase and glutathione peroxidase, respectively. The contents of cadmium, mercury, tin, and arsenic in CLHs were very low and even no detectible. Regarding the in vivo antioxidant activity of CLHs, a dosage of 1.2 g D-galactose kg−1 body weight increased ( P < 0.05) 2-thiobarbituric acid reactive substances values and decreased ( P < 0.05) glutathione and Trolox equivalent antioxidant capacity values, as well as superoxide dismutase, catalase, and glutathione peroxidase activities in serum and organs of mice. However, the in vivo antioxidant capacities were improved ( P < 0.05) by supplementing CLHs. [ABSTRACT FROM AUTHOR]

Patients in the intensive care unit (ICU) are at high risk of mortality which is not well predicted. Previous studies noted that leucine has prognostic value in a variety of diseases. This study investigated whether leucine concentration was a useful biomarker of metabolic and nutritional status and 6-month mortality in ICU. We recruited 454 subjects admitted to ICU (348 and 106 in the initiation and validation cohorts, respectively) with an acute physiology and chronic health evaluation (APACHE II) score ≥ 15. We measured plasma leucine concentrations, traditional biomarkers, and calculated APACHE II and sequential organ failure assessment (SOFA) scores. Leucine levels were weakly correlated with albumin, prealbumin, and transferrin levels (r = 0.30 , 0.12, and 0.15, p = 0.001 , 0.029, and 0.007, respectively). During follow-up, 116 (33.3%) patients died. Compared to patients with leucine levels between 109 and 174 μM, patients with leucine > 174 μ M or <109 μM had a lower cumulative survival rate. Death was also associated with age, higher APACHE II and SOFA scores, C-reactive protein, and longer stays in the ICU, but with lower albumin, prealbumin, and transferrin. Patients with leucine levels > 174 μ M had higher alanine aminotransferase levels, but no significant differences in other variables; patients with leucine levels < 109 μ M had higher APACHE II and SOFA scores, higher incidence of using inotropic agents, longer ICU and hospital stays, but lower albumin and transferrin levels. Multivariable analysis demonstrated that leucine > 174 μ M was an independent predictor of mortality, especially early mortality. However, among patients who stayed in ICU longer than two weeks, leucine < 109 μ M was an independent predictor of mortality. In addition, leucine < 109 μ M was associated with worse ventilator weaning profiles. These findings were similar in the validation cohort. Our study demonstrated a U-shape relationship between leucine levels and mortality rate in ICU. [ABSTRACT FROM AUTHOR]

We assessed the capability of paclitaxel, one of the taxanes, to induce death in two prostate cancer lines, LNCaP and PC3. Paclitaxel drove an apoptotic pathway in LNCaP, but not in PC3 cells, in response to G2/M arrest. An examination of the levels of anti-apoptotic proteins revealed that Bcl-xl was much higher in PC3 cells than in LNCaP cells and Bcl2 could be detected only in PC3 cells, not in LNCaP cells. Knocking down Bcl-xl enhanced paclitaxel-induced apoptosis in LNCaP cells, while we were unable to knock down Bcl-xl efficiently in PC3 cells. Significantly, a comparison of ABT-263, a specific inhibitor of Bcl2 and Bcl-xl, with ABT-199, a Bcl2 selective inhibitor, disclosed that only ABT-263, not ABT-199, could induce apoptosis in LNCaP and PC3 cells. The results indicate that Bcl-xl has a protective role against paclitaxel-induced apoptosis in LNCaP and PC3 cells, and its overexpression causes the paclitaxel resistance seen in PC3 cells. Interestingly, combined paclitaxel with ABT-263 to treat LNCaP and PC3 cells demonstrated synergistic apoptosis activation, indicating that ABT-263 could enhance paclitaxel-induced apoptosis in LNCaP cells and overcome Bcl-xl overexpression to trigger paclitaxel-induced apoptosis in PC3 cells. We also observed that the activation of apoptosis in LNCaP cells was more efficient than in PC3 cells in response to paclitaxel plus ABT-263 or to ABT-263 alone, suggesting that the apoptosis pathway in PC3 cells might have further differences from that in LNCaP cells even after Bcl-xl overexpression is accounted for. [ABSTRACT FROM AUTHOR]

Gradenigo syndrome is a rare but devastating complication of otitis media that involves the petrous apex. Clinically, it is characterized by the triad of suppurative otitis media, deep facial pain, and abducens palsy. Most of the Gradenigo syndrome cases that have been reported in the literature were caused by pyogenic bacteria. In this report, we describe the clinical courses of 4 adults with Gradenigo syndrome who were encountered consecutively at a tertiary referral hospital between 2008 and 2012. Mycobacterium abscessus was confirmed in all 4 cases by culturing the pathological tissues obtained during surgical debridement. To the best of our knowledge, this is the first report documenting infections of nontuberculous mycobacteria (NTM) in Gradenigo syndrome. An NTM infection must be considered in chronic otomastoiditis complicated by Gradenigo syndrome. The definite treatment of Gradenigo syndrome with an NTM infection requires adequate surgical debridement combined with antibiotic treatment for at least 4-6 months. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]