Role of serum eosinophil cationic protein in distinct endotypes of chronic rhinosinusitis.

BACKGROUND: Serum eosinophil cationic protein (ECP) levels affect the surgical outcome of chronic rhinosinusitis (CRS) with nasal polyps. Primary CRS can be classified into type 2 (T2) and non-T2. We aimed to differentiate the role of serum ECP levels in surgical outcomes between the distinct endotypes of primary CRS. METHODS: We prospectively enrolled patients with bilateral primary CRS who underwent surgical treatment with postoperative follow-up for at least 12 months. Endotyping and serum parameter measurements were completed within 1 week before surgery. RESULTS: In total, 113 patients were enrolled, including 65 with T2 CRS and 48 with non-T2 CRS. Patients in the T2 CRS group with uncontrolled CRS had significantly higher serum ECP levels than those in patients in the non-T2 CRS group. An optimal cut-off value was obtained at 17.0 λg/L using the receiver operating characteristic curve, attaining a sensitivity of 91.7% and specificity of 56.6%. Multivariate logistic regression analysis showed that a higher serum ECP level was an independent factor for postoperative uncontrolled disease. The hazard ratio was 11.3 for the T2 group, with serum ECP levels over 17.0 λg/L. In the non-T2 group, no parameters were significantly correlated with postoperative uncontrolled CRS. CONCLUSIONS: Serum ECP levels appear to be a feasible predictor of postoperative uncontrolled disease in patients with T2 CRS as preoperative serum ECP levels >17.0 λg/L in these patients have an approximately 16.7-fold increased risk of postoperative uncontrolled disease and should be closely monitored.

Tissue eosinophilia and computed tomography features in paediatric chronic rhinosinusitis with nasal polyps requiring revision surgery.

BACKGROUND: Endoscopic sinus surgery (ESS) is an effective and safe treatment modality for medically recalcitrant chronic rhinosinusitis (CRS) in the paediatric population, especially in older children or those with nasal polyposis (CRSwNP). We aimed to elucidate the inflammatory pattern and clinical characteristics of CRSwNP related to revision surgery after ESS in a paediatric population. METHODS: We retrospectively enrolled 146 patients with bilateral CRSwNP. Twenty-two patients had recurrent nasal polyps that required revision surgery. The clinical characteristics, computed tomography (CT) features, tissue eosinophil count, and immunoactivity of signature cytokines in the two groups were analysed. RESULTS: Tissue eosinophil infiltration and immunoreactivity of eosinophilic cationic protein and IL-5 in the sinus mucosa were higher in patients that required revision surgery. The revision surgery group was significantly younger and had positive aeroallergen test results, higher total Lund-Mackay scores, and ethmoid/maxillary sinus ratio on CT images than those without revision surgery. A nomogram was developed to predict the probability of the requirement of revision surgery according to the logistic regression analysis results. CONCLUSIONS: We developed a nomogram model using clinical characteristics, tissue eosinophilia, and CT features for the preoperative identification of patients vulnerable to revision surgery in paediatric CRSwNP. This could help clinicians predict the probability of recurrence and perform intensive postoperative adjunct therapy and follow-up.

Sleep impairment in patients with empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) is characterized by paradoxical nasal obstruction that usually occurs after turbinate surgery. Patients with ENS may also experience significant psychiatric symptoms and sleep dysfunction, which negatively affect the quality of life of affected subjects. This study aimed to evaluate sleep impairment and sleepiness in patients with ENS. METHODS: Patients with ENS and control participants were recruited prospectively. The Sino-Nasal Outcome Test-25 (SNOT-25), Empty Nose Syndrome 6-item Questionnaire (ENS6Q), Epworth Sleepiness Scale (EpSS), and modified sleep quality index (MSQI) were used to evaluate the participants before and after nasal surgery. RESULTS: Forty-eight patients with ENS and forty-eight age- and sex-matched control subjects were enrolled. The SNOT-25, ENS6Q, EpSS, and MSQI scores in the ENS group were all significantly higher than those in the control group before and after surgery. After surgery, ENS patients all exhibited significant improvements in SNOT-25, ENS6Q, EpSS, and MSQI scores. Regression analysis revealed that SNOT-25 score was a significant predictor of EpSS and MSQI in preoperative evaluations. ENS patients experiencing daytime sleepiness suffered from significantly more "dryness of nose" and "suffocation" than those not experiencing daytime sleepiness. CONCLUSIONS: Patients with ENS experienced significantly impaired sleep quality and sleepiness. Nasal reconstruction surgery improved the sleep quality of ENS patients. The severity of sleep dysfunction is associated with the severity of ENS symptoms. Recognizing individuals with significant sleep impairment and sleepiness and providing appropriate management are critical issues for ENS patients.

Identifying a sphenoid sinus fungus ball using a nomogram model.

BACKGROUND: Sphenoid sinus fungus ball (SSFB) is a rare entity and usually presents with non-specific symptoms. SSFB could potentially lead to serious orbital and intracranial complications. Computed tomography (CT) scan is usually the first imaging test of the diagnostic workup in patients with specific clinical symptoms. This study aimed to compare the clinical characteristics and CT features between SSFB and unilateral (non-fungus ball) chronic sphenoid rhinosinusitis (USRS) and help differentiate between these two most common inflammatory diseases of the sphenoid sinus. METHODS: By retrospective database review, 66 patients with a histopathologic diagnosis of isolated SSFB were recruited for analysis. Fifty-four patients who underwent endoscopic sinus surgery with clinical and histopathological diagnoses of USRS were enrolled as the control group. Clinical characteristics and CT features were evaluated. RESULTS: Headache, rhinorrhoea, nasal obstruction, postnasal dripping, and hyposmia were the most common symptoms in both groups. In the univariate analysis, older age, lower white blood cell counts, irregular surface, bony dehiscence, lateral wall sclerosis, and intralesional hyperdensity (IH) were significant predictors for SSFB. Older age, irregular surface, and IH remained statistically significant in the multivariate analysis. Based on the results of the regression analysis, a nomogram for predicting the probability of SSFB was plotted. CONCLUSIONS: We developed a nomogram model as a novel preoperative diagnostic tool for identifying SSFB according to the predictors both in clinical characteristics and on CT features. This could help the clinicians in predicting the probability of SSFB, to reduce ineffective or delayed treatment and occurrence of complications.

Risk factors and mortality associated with multi-drug-resistant Gram-negative bacterial infection in adult patients following abdominal surgery.

BACKGROUND: Multi-drug-resistant (MDR) Gram-negative bacterial (GNB) infection remains a significant cause of morbidity and mortality among surgical patients. The objective of this study was to recognize the risk factors for MDR GNB infection in patients following abdominal surgery, and determine the predictors independently associated with death. METHODS: From 2010 to 2017, a retrospective cohort study was conducted among patients with abdominal surgery admitted to the surgical intensive care unit (ICU). Patients with GNB infection were included for analyses. RESULTS: In total, 364 patients experienced GNB infection following abdominal surgery. Of these, 117 (32.1%) were MDR GNB infection. Of 133 MDR GNB isolates, the most common isolate was Escherichia coli (45.1%). Patients with MDR GNB infection had significantly longer ventilator-days and hospital stay, as well as higher 30-day and in-hospital mortality compared with non-MDR GNB patients. Multi-variable analysis showed that longer length of pre-ICU stay, surgical re-exploration, receipt of group 2 carbapenems (e.g. imipenem, meropenem and doripenem) and fluoroquinolones, and higher total bilirubin were independent risk factors for the acquisition of MDR GNB infection. Predictors for 30-day mortality among patients with MDR GNB infection were chronic kidney disease, receipt of group 2 carbapenems and inappropriate empirical antimicrobial therapy. CONCLUSIONS: This study provides important information about the risk factors for MDR GNB infection and 30-day mortality among patients following abdominal surgery.

What drives depression in empty nose syndrome? A Sinonasal Outcome Test-25 subdomain analysis.

BACKGROUND: Empty nose syndrome (ENS) is a debilitating disorder characterised by paradoxical nasal obstruction after excessive surgical excision of nasal tissues. ENS negatively impacts the quality of life (QOL) and psychological status of patients. This study aimed to determine the associations among disease-specific QOL impairments and the severity of anxiety and depression before and after surgery in ENS patients. METHODS: A total of 68 ENS patients were prospectively recruited and underwent submucosal Medpor implantation. QOL impairments and the severity of anxiety and depression were evaluated using the Sinonasal Outcome Test-25 (SNOT-25), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI) 1 day before and 6 months after surgery. RESULTS: The BDI-II and BAI scores were significantly associated with the total score and ear/facial symptoms, psychological dysfunction, sleep dysfunction, and empty nose symptoms domains of the SNOT-25. Surgery improved disease-specific and psychological symptoms. Post-operative changes in the BDI-II score were correlated with changes in the total score and sleep dysfunction and empty nose symptoms domains of the SNOT-25. A SNOT-25 total score of greater than 60, sleep dysfunction domain score of greater than 18, and empty nose symptoms domain score of greater than 14 were good predictors of moderate-to-severe depression. CONCLUSIONS: ENS symptoms are associated with psychological burden and could be good predictors of moderate-to-severe depression. Targeted symptom improvement could reduce the psychological burden.

Treatment-associated severe thrombocytopenia affects survival rate in esophageal cancer patients undergoing concurrent chemoradiotherapy.

BACKGROUND: Esophageal cancer is commonly treated with surgery, concurrent chemoradiotherapy (CCRT), or a combination of both. The correlation between the hematological parameters during CCRT and early survival of esophageal cancer has not been fully evaluated. MATERIALS AND METHODS: We analyzed the records of 65 esophageal cancer patients treated by CCRT between 2007 and 2010 retrospectively. The association between CCRT-associated myelosuppression, demographic variables, and survival rates were analyzed by univariate and multivariate analysis. RESULTS: The univariate analysis showed that tumor extent of T3-4, a higher stage of tumor, a lower albumin level, grade 3 or higher anemia and thrombocytopenia, and interruptions in treatment affected survival rates. Further, the multivariate analysis revealed that stage IV (P = 0.030) is an independently negative prognostic factor for a one-year survival rate. Stage IV (P = 0.035), tumor extent of T3-4 (P = 0.002), and grade 3-4 thrombocytopenia (P = 0.015) are independently negative prognostic factors for a two-year survival rate. CONCLUSIONS: Severe decrease in platelet count during CCRT independently affects survival of esophageal cancer patients in addition to stage of the tumor.

Clinical analysis of submucosal Medpor implantation for empty nose syndrome.

BACKGROUND: Empty nose syndrome (ENS) describes symptomatology and radiographic findings after surgeries on turbinates.The treatment of ENS is still debatable. PURPOSE: To analyse clinical outcomes of submucosal Medpor® implantation for ENS. METHODS: A total of 18 patients underwent submucosal Medpor® implantation from 2006 to 2011. We applied SNOT-22 (SinoNasalOutcome Test) for statistical survey of the patients' symptoms before and after surgery. RESULTS: Two patients were lost to follow up after the surgery. Most of the patients developed ENS-related symptoms gradually within 2 years to 16 years after the previous nasal surgery or treatment. The sites of submucosal implantation are mainly septum and nasal floor, unilaterally or bilaterally. There is a significant improvement of SNOT-22 pre-operatively to one year post-operatively. CONCLUSIONS: The symptomatolgy remains the most important point when dealing with patients with ENS. Submucosal implantation of Medpor® is a feasible surgical treatment to ENS. A positive cotton test is suggested for the surgical indication and planning.

miR-495 is upregulated by E12/E47 in breast cancer stem cells, and promotes oncogenesis and hypoxia resistance via downregulation of E-cadherin and REDD1.

MicroRNAs (miRNAs) are involved in tumorigenecity by regulating specific oncogenes and tumor suppressor genes, and their roles in breast cancer stem cells (BCSCs) are becoming apparent. Distinct from the CD44(+)/CD24(-/low) sub-population, we have isolated a novel PROCR(+)/ESA(+) BCSC sub-population. To explore miRNA-regulatory mechanisms in this sub-population, we performed miRNA expression profiling and found miR-495 as the most highly upegulated miRNA in PROCR(+)/ESA(+) cells. Coincidently, high upregulation of miR-495 was also found in CD44(+)/CD24(-/low) BCSCs, reflecting its potential importance in maintaining common BCSC properties. Ectopic expression of miR-495 in breast cancer cells promoted their colony formation in vitro and tumorigenesis in mice. miR-495 directly suppressed E-cadherin expression to promote cell invasion and inhibited REDD1 expression to enhance cell proliferation in hypoxia through post-transcriptional mechanism. miR-495 expression was directly modulated by transcription factor E12/E47, which itself is highly expressed in BCSCs. These findings reveal a novel regulatory pathway centered on miR-495 that contributes to BCSC properties and hypoxia resistance.

Expression of cathepsin S and its inhibitor stefin A in sinonasal inverted papilloma.

BACKGROUND: Dysregulation of cysteinyl cathepsins and their inhibitors, cystatins (stefins), were implied in progression of tumorgenesis; nevertheless, their role in sinonasal inverted papilloma (IP) is still unrecognized. METHODS: The differential expression of cathepsins and stefins in IP and normal tissues were revealed by data of human Affymetrix U133A gene chips, real-time polymerase chain reaction (PCR) and immunohistochemistry. RESULTS: Among the cathepsins and stefins family, expression of cathepsin S and stefin A were most differentially expressed (down- and up-regulated, respectively) in IP tissue as compared with normal tissues. Their expression levels were validated by real-time PCR, which showed the expression level of cathepsin S was significantly down-regulated, whereas the expression of stefin A was significantly up-regulated in IP tissue compared to normal sinus mucosa. Using immunohistochemistry, expression of cathepsin S was observed in stromal and epithelial area macrophages of normal sinus mucosa, but no obvious expression of cathepsin S was found in IP tissue. In contrast, over-expression of stefin A was present in nearly all layers of the proliferative squamous cells of IP, but expression of stefin A was only detected in a scattered area of normal sinus mucosa. CONCLUSION: Down-regulation of cathepsin S and up-regulation of its endogenous inhibitor, stefin A, were found in IP tissues as compared with their expression level in normal sinus mucosa tissues. The biological significance of inverse expression of both stefin A and cathepsin S in sinonasal IP need further investigation in the future.

An insidious preauricular sinus presenting as an infected postauricular cyst.

Preauricular sinuses are common congenital malformations that usually occur at the anterior margin of the ascending limb of the helix. We present three paediatric patients with postauricular infected cysts and coincidentally discovered auricular pits. Single-stage operations were performed to remove the cysts, pits and involved cartilage. Histopathology revealed a preauricular sinus with inflammation. Although uncommon, a postauricular infected cyst may indicate the presence of a preauricular sinus. Detailed physical examination of preauricular pits should be performed, and the operating microscope may aid during surgery to remove remnants and prevent recurrence. An infected preauricular sinus can be effectively treated with single-stage excision.

Hydatidosis in a Chapman's zebra (Equus burchelli antiquorum).

A 14-year-old male Chapman's zebra had been treated for a cervical granulomatous cellulitis for 3 months prior to sudden death associated with myocardial fibrosis. Incidental findings at necropsy included multiple 3-8-cm unilocular cysts in the liver and lungs. Cysts contained either a clear fluid with or without hydatid sand or a gelatinous substance with foci of mineralization. Light and scanning electron microscopic examination of the hydatid sand revealed free protoscolices as well as intact and ruptured brood capsules with protoscolices attached to the germinal membrane. The protoscolices had 2 rows of 36-38 rostellar hooks with a length of 25-30 microm. The cyst wall consisted of inner germinal, intermediate laminated, and outer adventitial layers. Hydatidosis caused by Echinococcus granulosus was diagnosed based on the unilocular cysts, multiple protoscolices formed in a brood capsule, typical trilayered cyst wall, and herbivorous intermediate host. This is the first reported case of animal hydatidosis in Taiwan. The infection is thought to have been established 12 years ago in South Africa prior to importation.

A peritoneal mesothelioma in a captive aardwolf (Proteles cristatus).

A 10-year-old male aardwolf (Proteles cristatus) was presented abdominal distention and emaciation for 3 months. Physical examination revealed firm abdominal masses with effusions. Cytologic assessment of the effusion showed uniform round tumor cells with a surface brush border. Necropsy showed white velvety masses covering the peritoneal surface of the liver, gall bladder, stomach, omentum, mesentery, spleen, intestine, abdominal wall and diaphragm. Histologic examination demonstrated papillary projections, lined with cuboidal tumor cells supported by fibrous connective tissue cores, arising from the serosa of visceral organs. Cytoplasmic vacuolation and a surface brush border were evident on some cells under light microscopy. Tumor cells stained positive for both cytokeratin (AE1/AE3) and vimentin. Electron microscopy showed prominent surface microvilli, rough endoplasmic reticulum, mitochondria and desmosomes in tumor cells. This may be the first reported case of peritoneal mesothelioma in a captive wild aardwolf.

Insulin, but not estrogen, correlated with indexes of desaturase function in obese women.

This study determined the associations of serum insulin and estrogen with fatty acid composition, fatty acid product/substrate ratios used as indexes of desaturase enzyme function, and platelet aggregation in obese and lean women. Thirty women were classified as obese (n = 8) or lean (n = 21) based on body mass index. Obese women were characterized by higher insulin levels (p < 0.05) but fasting glucose levels did not differ (p > 0.05) from lean women. Insulin positively correlated with increased C20:4n6/C18:3n6 (index of delta 5-desaturase) (p < 0.05) and C20:4n6/C18:2n6 (index of overall n6 pathway activity) (p < 0.01) in serum, and the n5 pathway in platelets (p < 0.01), but there was no correlation for insulin with platelet C18:3n6/C18:2n6 (index of delta 6-desaturase activity). Insulin was also positively related (p < 0.01) to aggregation as measured by impedance and negatively related to lag time (p < 0.05). Platelets of obese women aggregated more (p < 0.05) compared to lean women and began aggregating faster (p < 0.05), suggesting the possibility that the obese women were at greater risk for enhanced blood clotting. Plasma estrogen was correlated with age (p < 0.05) but not for other variables studied (p > 0.05). Insulin, but not estrogen, appears to influence desaturase activity, as demonstrated by increased desaturase function associated with hyperinsulinemia in obese women.

Synergy between preactivated photofrin-II and tamoxifen in killing retrofibroma, pseudomyxoma and breast cancer cells.

Exposure of photoactive compounds to light prior to their use in biological systems (preactivation) results in the generation of tumour cell specific metastable cytotoxic species that are no longer dependent on the light energy. Thus, preactivation renders the photoactive compounds suitable for systemic use. We have examined the in vitro effect of preactivated photofrin-II and tamoxifen in retroperitoneal fibroma, pseudomyxoma and male breast carcinoma cell lines. These cells were found to be non-responsive to tamoxifen and were negative for oestrogen receptors. Incubation of these cells with 0.5 microgram/ml preactivated photofrin-II and tamoxifen (less than 10(-6) mol/l) resulted in a significantly enhanced (P less than 0.001) inhibition of DNA synthesis compared with either agent alone. This synergistic effect between tamoxifen and preactivated photofrin-II was determined by multiple drug effect analysis. Treatment of cells with preactivated photofrin-II did not cause the increased expression of oestrogen receptors. These observations suggest that a combination of antihormonal drugs with preactivated compounds may be of clinical value.

Morphometric analysis of epithelial cells of frog urinary bladder, II. Effect of ADH, calcium ionophore (A23187) and verapamil on isolated dissociated cells.

Isolated frog urinary bladder epithelial cells, upon dissociation lose their polarity and develop microridges and occasional microvilli in a global fashion. These cells, when exposed only to isotonic Ringer's solution manifest a membrane conformation with smooth discontinuous microridges, a cytoplasm with numerous free ribosomes, rough ER, thin Golgi cisternae, mitochondria, small vacuoles, electron-dense granules, few microtubules, and numerous microfilaments and intermediate filaments with an apparent random distribution, the dissociated cells, when treated with ADH or calcium ionophore (A23187), have the appearance of numerous elongated microvilli over the entire cell surface. The cytoplasm, under these conditions, is occupied by large vacuoles with a distribution of long profiles of aggrephores and associated vesicles. The peripheral cytoplasm as well as the cavities of the elongated microvilli of these cells contain large concentrations of microfilaments often showing a strong axial orientation to the long axis of the microvilli. Many of these filamentous elements appear in contact with the apical membrane of these microvilli with an alignment with the external glycocalyx. There is an indication that these morphocytological changes as revealed by SEM and TEM studies, correlated with a redistribution and realignment of microfilaments and possibly microtubules as detected by fluorescent microscopy using immunofluorescent antibody labeling for actin and tubulin. Cells treated with verapamil, a calcium antagonist, presented dwarf and stout microvilli with little detectable alterations in the cytoplasmic compositions from that of non-hormonal treated cells. Verapamil prevented ADH induction of microvilli, with the membrane, under these conditions, appearing as compact microridges. The results indicate that calcium ionophore, like ADH, produces intense formation of microvilli in dissociated cells, mobilization and realignment of microfilaments, microtubules, increase in the density of vesicles, aggrephores and possibly secretory granules, whereas the calcium antagonist, verapamil, opposes these actions. The results suggests a prominent role of calcium in the morphological changes induced by ADH.