Molecular characteristics of Staphylococcus aureus associated with chronic rhinosinusitis

The anterior nares have been regarded as the major carriage site of Staphylococcus aureus. From here, the organism can spread to other parts of the body where it might act as harmless commensal or cause mild to severe infections. Nasal sinuses are normally sterile, but in patients with chronic rhinosinusitis (CRS), the finding of S. aureus in maxillary sinus cultures is common. Isolates were obtained from the nares and maxillary sinus of patients with CRS and the nares of healthy controls. A significantly higher frequency of S. aureus was found in nares samples from patients (24/42) compared to controls (16/57) (p = 0.004). There is no consensus regarding whether S. aureus is a relevant pathogen in CRS. A DNA microarray was used to investigate the prevalence of S. aureus virulence genes with focus on staphylococcal enterotoxins, toxic shock syndrome toxin‐1, agr types, and cell wall‐associated proteins. The genotyping of S. aureus isolates revealed only small and non‐significant differences in gene prevalence between isolates collected from patients with CRS and those collected from healthy nasal carriers. This study provides an increased knowledge of the genetic pattern of virulence genes among S. aureus collected in CRS.     

Activating KRAS mutations are characteristic of oncocytic sinonasal papilloma and associated sinonasal squamous cell carcinoma

Oncocytic sinonasal papillomas (OSPs) are benign tumours of the sinonasal tract, a subset of which are associated with synchronous or metachronous sinonasal squamous cell carcinoma (SNSCC). Activating EGFR mutations were recently identified in nearly 90% of inverted sinonasal papillomas (ISPs) – a related tumour with distinct morphology. EGFR mutations were, however, not found in OSP, suggesting that different molecular alterations drive the oncogenesis of these tumours. In this study, tissue from 51 cases of OSP and five cases of OSP‐associated SNSCC was obtained retrospectively from six institutions. Tissue was also obtained from 50 cases of ISP, 22 cases of ISP‐associated SNSCC, ten cases of exophytic sinonasal papilloma (ESP), and 19 cases of SNSCC with no known papilloma association. Using targeted next‐generation and conventional Sanger sequencing, we identified KRAS mutations in 51/51 (100%) OSPs and 5/5 (100%) OSP‐associated SNSCCs. The somatic nature of KRAS mutations was confirmed in a subset of cases with matched germline DNA, and four matched pairs of OSP and concurrent associated SNSCC had concordant KRAS genotypes. In contrast, KRAS mutations were present in only one (5%) SNSCC with no known papilloma association and none of the ISPs, ISP‐associated SNSCCs, or ESPs. This is the first report of somatic KRAS mutations in OSP and OSP‐associated SNSCC. The presence of identical mutations in OSP and concurrent associated SNSCC supports the putative role of OSP as a precursor to SNSCC, and the high frequency and specificity of KRAS mutations suggest that OSP and OSP‐associated SNSCC are biologically distinct from other similar sinonasal tumours. The identification of KRAS mutations in all studied OSP cases represents an important development in our understanding of the pathogenesis of this disease and may have implications for diagnosis and therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Expression of p16 in sinonasal malignant melanoma

The aim of this study was to investigate the expression of p16 in relation with the histopathologic features and the clinical course in patients with sinonasal melanoma. Thirty-seven sinonasal melanomas were immunostained for p16. Seventeen tumours were investigated for loss of the 9p21 region using interphase fluorescence in situ hybridization (FISH). Twenty-seven melanomas (72.9%) showed loss of p16 expression. All cases with spindle or mixed cytology showed loss of p16, whereas this was present in 50% of epithelioid tumours (p=0.01). Loss of p16 expression was more frequently seen in melanomas with alveolar architecture (87.5%) than in tumours with diffuse architecture (68.9%) (p=0.4). There was no correlation between p16 expression and presence of lymph node or distant metastases (p=0.57 and 0.24, respectively). In addition, p16 status did not influence overall survival (p=0.2). The FISH results were in good agreement with immunohistochemistry: 11 tumours out of 17 showed deletion of the 9p21 region and 10 of these showed loss of protein expression. Loss of p16 expression is a frequent event in sinonasal melanoma and it is mainly related to deletion of 9p21 region. At variance from cutaneous melanoma, loss of p16 is not correlated with the prognosis of patients affected by sinonasal melanoma.     

Sinus Microbiome Diversity Depletion and Corynebacterium tuberculostearicum Enrichment Mediates Rhinosinusitis

Persistent mucosal inflammation and microbial infection are characteristics of chronic rhinosinusitis (CRS). Mucosal microbiota dysbiosis is found in other chronic inflammatory diseases; however, the relationship between sinus microbiota composition and CRS is unknown. Using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, we demonstrate that the sinus microbiota of CRS patients exhibits significantly reduced bacterial diversity compared with that of healthy controls. In our cohort of CRS patients, multiple, phylogenetically distinct lactic acid bacteria were depleted concomitant with an increase in the relative abundance of a single species, Corynebacterium tuberculostearicum. We recapitulated the conditions observed in our human cohort in a murine model and confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, Lactobacillus sakei, which was identified from our comparative microbiome analyses as a potentially protective species, defended against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota as well as identify both a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.     

Staphylococcus epidermidis and biofilm‐associated neutrophils in chronic rhinosinusitis. A pilot study

A key role of bacterial biofilm in the pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP) is commonly accepted. However, the impact of some bacterial species isolated from inflamed sinus mucosa on biofilm formation is unclear. In particular, the role of Staphylococcus epidermidis as aetiological agents of CRS is controversial. Moreover, the effect of biofilm formation on neutrophil infiltration and activity in CRSwNP calls for explanation. In this study, biofilms were found in three of 10 patients (mean age = 46 ± 14) with CRS undergoing endoscopic sinus surgery by means of scanning electron microscopy. Unexpectedly, S. epidermidis was the primary isolated bacteria and was also found to be present in all biofilm‐positive mucosa specimens, indicating its pivotal role in the pathogenesis of severe chronic infections associated with biofilm formation. We have also measured the activity of myeloperoxidase (MPO), the most abundant neutrophil enzyme, to demonstrate the presence of neutrophils in the samples tested. Our present results show that the level of MPO in CRS associated with biofilm is lower than that without biofilm. It may suggest either a low number of neutrophils or the presence of a type of neutrophils with compromised antimicrobial activity, described as biofilm‐associated neutrophils (BAN). Finally, we conclude that further studies with a large number of CRS cases should be performed to establish the association between S. epidermidis and other frequently isolated bacterial species from paranasal sinuses, with the severity of CRS, biofilm formation and the infiltration of BAN.     

Severity of Cytokine Release Syndrome and Its Association with Infections after T Cell-Replete Haploidentical Related Donor Transplantation

An increased risk of infections has been described after T cell-replete haploidentical cell transplantation (haploHCT). Cytokine release syndrome (CRS) after haploHCT is a known phenomenon, but the impact of CRS severity on the risk of infections remains unexplored. We retrospectively evaluated 78 consecutive adult haploHCT recipients from 2012 to 2018 for the development of CRS (graded based on the criteria of Lee et al) and examined the incidence and mortality due to infections in correlation with CRS severity. In our study cohort, which was stratified into 3 groups by severity of CRS, 80% of the patients developed infections within 180 days of HCT. Significantly higher proportions of patients with CRS grade 2 (89%) and grade ≥3 (90%) than patients with CRS grade 0-1 (68%) had at least 1 infection in the first 100 days (P = .04). Bloodstream infections (BSIs) were seen more frequently in patients with CRS grade 2 and grade ≥3 in the first 6 months. Multivariable analysis for time to infection showed that CRS grade ≥3 was independently associated with an elevated risk of any infection compared with CRS grade 0-1 (hazard ratio [HR], 3.05; P = .007). CRS grade ≥3 was also associated with a higher hazard of viral (HR, 3.42; P = .04) and bacterial infections (HR, 2.83; P = .03) compared with CRS grade 0-1. After adjusting for time to neutrophil engraftment as a time-dependent covariate, CRS grade ≥3 still had a significant effect on viral infections (HR, 2.49; P = .03), but not on bacterial infections (HR, 1.32; P = .57). CRS grade was also a significant predictor for infection density (overall, bacterial, and viral). The incidence of infection-related mortality by day +100 was higher in patients with severe CRS. Severe CRS developing after post-transplantation cyclophosphamide-based haploHCT is independently associated with viral infections and an increased risk of bacterial infections, likely through delayed neutrophil engraftment.     

SIRT1 gene polymorphisms are associated with nondiabetic type 1 cardiorenal syndrome

Type 1 cardiorenal syndrome (CRS1) is characterized by acute cardiac disease (e.g., acute heart failure [AHF]), leading to acute kidney injury. Sirtuin 1 (SIRT1), an NAD⁺‐dependent deacylase, has been found to be associated with CRS1. To confirm whether a correlation exists between SIRT1 variants and the risk of CRS1, the association between the prevalence of CRS1 and single‐nucleotide polymorphisms (SNPs) within the SIRT1 gene was investigated in AHF patients. A total of 316 Chinese AHF participants (158 patients with CRS1 and 158 age‐ and sex‐matched controls) were recruited for the present observational study to investigate the association between nine common SIRT1 SNPs (i.e., rs7895833 G > A, rs10509291 T > A, rs3740051 A > G, rs932658 A > C, rs33957861 C > T, rs7069102 C > G, rs2273773 T > C, rs3818292 A > G, and rs1467568 A > G) and the susceptibility to CRS1. Significant differences in genotype distribution between the control and CRS1 groups were found for rs7895833 and rs1467568. After applying a Bonferroni adjustment, the A allele of rs7895833 was still found to be protective (p = 0.001; odds ratio [OR] = 0.77) against CRS1 in this study population. The AA genotype of rs7895833 and the GA genotype of rs1467568 were associated with a significantly reduced risk of CRS1 (OR = 0.23 and 0.49, respectively). rs7895833 and rs1467568 were further analyzed as a haplotype, and the GA haplotype (rs7895833‐rs1467568) exhibited a significant association with CRS1 (p = 0.008), while the AA haplotype showed a significant protective effect (p = 0.022). Our study showed that SIRT1 rs7895833 and rs1467568 polymorphisms had a significant effect on the risk of developing CRS1 in a population in China.     

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis.MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis.ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019).ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.     

Microbiota of newborn meconium is associated with maternal anxiety experienced during pregnancy

Little is known about whether a mother's psychological state during pregnancy influences her offspring's microbiome. This study examined whether maternal anxiety, depression, and stress during pregnancy is associated with the diversity of meconium microbiome, the first internal discharge, in 75 newborns from an existing birth cohort study. The meconium microbiome was profiled using multibarcode16S rRNA sequencing at V3-V4 hypervariable region followed by taxonomic assignment to the green gene 16S references at 97% similarity and diversity analysis at the genus level. Results showed that the meconium contained diversified microbiota, and greater pregnancy-related anxiety was significantly associated with a less diverse meconium microbiota community (p = 0.001). At the specific taxa level, greater pregnancy-related anxiety was correlated with a lower level of the Enterococcaceae family (p = 2e-4, Spearman rho = −0.43). These findings support a significant role of prenatal maternal mood in the early-life bacteria colonization of their offspring.     

Olfactory cleft mucus galectin-10 predicts olfactory loss in chronic rhinosinusitis

BackgroundEosinophils have been reported to be involved in the pathogenesis of olfactory fluctuation in chronic rhinosinusitis (CRS). Galectin-10 is more frequently associated with type 2 inflammation and potentially a sign of intense eosinophil activation.ObjectiveTo explore olfactory cleft mucus and olfactory mucosa galectin-10 level and its association with olfactory dysfunction (OD) in CRS.MethodsWe prospectively enrolled 50 patients with CRS and 15 healthy controls. Olfactory cleft mucus and superior turbinate biopsy specimens were collected to analyze galectin-10 levels and quantify tissue eosinophils. Psychophysical olfactory testing, olfactory cleft endoscopy scale, and olfactory cleft computed tomography scores were obtained. The predictability of galectin-10 levels for OD in patients with CRS was analyzed by multivariable logistic regression analysis.ResultsBoth olfactory cleft mucus and olfactory mucosa galectin-10 levels in patients with CRS with OD were significantly higher than those in patients with CRS without OD (all P < .001). Mucus galectin-10 levels were positively correlated with tissue eosinophils (r = 0.541, P = 0.002), olfactory cleft endoscopy scale (r = 0.498, P = 0.006), and olfactory cleft computed tomography scores (r = 0.432, P = 0.019) in patients with CRS. Mucus galectin-10 levels were negatively correlated threshold, discrimination, and identification (r = ?0.589,  P = 0.001), olfactory threshold (r = ?0.522, P = 0.003), olfactory discrimination (r = ?0.488, P = 0.007), and olfactory identification (r = ?0.466, P = 0.011) scores. After adjusting for patient demographics and comorbidities, mucus galectin-10 levels were significantly associated with OD in patients with CRS (odds ratio, 1.299; P = .008). Mucus galectin-10 levels greater than 8.975 ng/mL were the best predictor of OD in CRS.ConclusionOlfactory cleft mucus galectin-10 is highly associated with OD in CRS.     

Microbiology of hip and knee periprosthetic joint infections: a database study

ObjectivesKnowledge of the microbiological aetiology of periprosthetic joint infection (PJI) is essential to its management. Contemporary literature from the United States on this topic is lacking. This study aimed to identify the most common microorganisms associated with types of arthroplasty, the timing of infection, and clues to polymicrobial infection.MethodsWe performed an analytical cross-sectional study of patients 18 years of age or older with hip or knee PJI diagnosed at our institution between 2010 and 2019. PJI was defined using the criteria adapted from those of the Musculoskeletal Infection Society. Cases included PJI associated with primary or revision arthroplasty and arthroplasty performed at our institution or elsewhere.ResultsA total of 2067 episodes of PJI in 1651 patients were included. Monomicrobial infections represented 70% of episodes (n = 1448), with 25% being polymicrobial (n = 508) and the rest (5%, n = 111) culture-negative. The most common group causing PJI was coagulase-negative Staphylococcus species (other than S. ludgunensis) (37%, n = 761). The distribution of most common organisms was similar regardless of arthroplasty type. The S. aureus complex, Gram-negative bacteria, and anaerobic bacteria (other than Cutibacterium species) were more likely to be isolated than other organisms in the first year following index arthroplasty (OR 1.7, 95%CI 1.4–2.2; OR 1.5, 95%CI 1.1–2.0; and OR 1.5, 95%CI 1.0–2.2, respectively). The proportion of culture-negative PJIs was higher in primary than revision arthroplasty (6.5% versus 3%, p 0.0005). The presence of a sinus tract increased the probability of the isolation of more than one microorganism by almost three-fold (OR 2.6, 95%CI 2.0–3.3).ConclusionsJoint age, presence of a sinus tract, and revision arthroplasties influenced PJI microbiology.     

Physical fitness factors to predict male Olympic wrestling performance

To determine differences in maximal strength and muscle power output of the arm and leg extensor muscles, peak and mean power during a modified standing crank-arm Wingate test, running speed, muscle extensibility, and anthropometric markers between elite and amateurs wrestlers according to the weight classes system; 92 male wrestlers were assigned into 6 groups according to their body mass (light, middle and heavy weight) and their competitive level (elite and amateur): Light Weight (body mass ranged between 55 and 68 kg) in elite (LW_E, n = 18) and amateur (LW_A, n = 15) level; Middle Weight (body mass ranged between 68 and 84 kg) in elite (MW_E, n = 18) and amateur (MW_A, n = 19) level; and Heavy Weight (body mass ranged between 84 and 100 kg) in elite (HW_E, n = 10) and amateur (HW_A, n = 12) level. Elite wrestlers were older (8–12%), had more training experience (25–37%), fat-free mass (3–5%), maximal strength in absolute and relative terms (8–25%), muscle power (14–30%), mean and peak power during crank-arm Wingate testing in absolute and relative terms (13–22%), jumping height (8–17%) as well as grip (6–19%) and back strength (7–20%) compared to amateur wrestlers. However, no differences were observed between elite and amateur groups in height, body mass index, percentage of body fat, hamstring extensibility and running speed. The present results suggest that the higher absolute and relative values of maximal strength, muscle power, and anaerobic metabolism, explained in part by the differences in lean mass and neural activation patterns, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling.     

Human papillomavirus infection and the malignant transformation of sinonasal inverted papilloma: A meta-analysis

A growing number of molecular epidemiological studies have been conducted to evaluate the association between human papillomavirus (HPV) infection and the malignancy of sinonasal inverted papilloma (SNIP). However, the results remain inconclusive. Here, a meta-analysis was conducted to quantitatively assess this association. Case-control studies investigating SNIP tissues for presence of HPV DNA were identified. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by the Mantel-Haenszel method. An assessment of publication bias and sensitivity analysis were also performed. We calculated a pooled OR of 2.16 (95% CI = 1.46–3.21, P < 0.001) without statistically significant heterogeneity or publication bias. Stratification by HPV type showed a stronger association for patients with high-risk HPV (hrHPV) types, HPV-16, HPV-18, and HPV-16/18 infection (OR = 8.8 [95% CI: 4.73–16.38], 8.04 [95% CI: 3.34–19.39], 18.57 [95% CI: 4.56–75.70], and 26.24 [4.35–158.47], respectively). When only using PCR studies, pooled ORs for patients with hrHPV, HPV-16, and HPV18 infection still reached statistical significance. However, Egger’s test reflected significant publication bias in the HPV-16 sub-analysis (P = 0.06), and the adjusted OR was no longer statistically significant (OR = 1.65, 95%CI: 0.58–4.63). These results suggest that HPV infection, especially hrHPV (HPV-18), is significantly associated with malignant SNIP.     

Investigating the relationship between infraorbital canal morphology and maxillary sinus size

The purpose of the current study was to investigate relationships between maxillary sinus (MS) dimensions and the bony structures associated with the infraorbital nerve (ION). Computed tomographic scans of 87 adult crania (174 sides) from four morphologically diverse groups (West Africans, East Africans, North Asians, Europeans) were utilized. Seven primary variables were collected: infraorbital canal (IOC) type; infraorbital foramen (IOF) shape; distance from the foramen rotundum to IOF (FR-IOF); distance from the posterior wall of the infraorbital groove to IOF (IOG-IOF); and MS length, breadth, and height. Chi-square analyses indicated a significant association between IOC-type and IOF-shape (Pearson chi-square = 12.710; p-value = .013), with the most common pattern being oval IOFs and Type-I IOCs (45.68% of the sample; 74/162 sides). Analysis of covariance indicated a significant effect of ancestry (F = 8.333; p < .001) and MS length (F = 15.406; p < .001) on IOG-IOF distance. Ordinal regression analyses indicated that MS length (Wald chi-square = 7.103; p = .008) also maintained a significant effect on IOC-type, while multinominal regression analyses indicated that none of the measured parameters had a significant effect on IOF-shape. These results have clinical implications: recognizing IOC-type and IOF-shape relative to the MS is important to avoid ION damage during medical procedures. Overall, this study found most individuals possess Type-I IOCs (housed in the maxillary sinus roof) and oval-shaped IOFs. Most aspects of the ION pathway, including IOC-type and IOF-shape, were not influenced by ancestry or sex. However, antero-posteriorly longer MSs tend to possess Type-III IOCs protruding into the sinus, which could lead to surgical complications.     

Dendritic cells in inflammatory sinonasal diseases

Dendritic cells (DCs) are critical in linking the innate and adaptive immune responses, which have been implicated in the pathogenesis of many immune and inflammatory diseases as well as the development of tumours. The role of DCs in the pathophysiology of lung diseases has been widely studied. However, the phenotype, subset and function of DCs in upper airways under physiological or pathological conditions remain largely undefined. Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) are two important upper airway diseases with a high worldwide prevalence. Aberrant innate and adaptive immune responses have been considered to play an important role in the pathogenesis of AR and CRS. To this end, understanding the function of DCs in shaping the immune responses in sinonasal mucosa is critical in exploring the pathogenic mechanisms underlying AR and CRS as well as in developing novel therapeutic strategies. This review summarizes the phenotype, subset, function and regulation of DCs in sinonasal mucosa, particularly in the setting of AR and CRS. Furthermore, this review discusses the perspectives for future research and potential clinical utility focusing on DC pathways in the context of AR and CRS.     

Visualization of the tentorial innervation of human dura mater

Posterior projections of the ophthalmic division of the trigeminal nerve (the ophthalmic nerve) are distributed in the tentorium cerebelli as recurrent meningeal branches. We investigated the morphological tentorial distribution of the ophthalmic nerve. Fifty‐two sides of the tentorium cerebelli and adjacent dura mater obtained from 29 human specimens were stained using Sihler's method to examine the nerve fibres in the dural sheets. The innervation patterns of the tentorium cerebelli were classified into the following four types according to their distributions: Type 1, where nerve fibres projected to both the straight and transverse sinuses; Type 2, where nerve fibres projected only to the transverse sinus and lateral convexity; Type 3, where nerve fibres projected medially only to the straight sinus and the posterior part of the falx cerebri; and Type 4, where the nerve fibres terminated within the tentorium cerebelli. Images of the tentorium cerebelli were superimposed to identify areas of dense innervation. The incidence rates of Types 1–4 were 71.2% (n = 37), 21.2% (n = 11), 3.8% (n = 2) and 3.8% (n = 2), respectively. More branches of nerve fibres traversed towards the transverse sinus posterolaterally than towards the straight sinus medially. The space between the anterior half of the straight sinus and the medial tentorial notch can be considered a safe surgical area where innervation is scarce. The posterior part of the falx cerebri was innervated by the ophthalmic nerve that traversed to the straight sinus. The parietal branches of the middle meningeal artery in the lateral convexity that were projected orthogonally by the ophthalmic nerve traversed the transverse sinus, implicating their vulnerability and possible sensitivity under physiological or neurosurgical conditions. This study has revealed the macroscopic tentorial innervation of the dura mater in humans, which could be useful information for both neurosurgeons and neurologists.     

Imidazoline use in sinonasal surgery

The nasal mucosa is very vascular, receiving more blood flow per cubic centimeter of tissue than does muscle, brain or liver (Drettner and Aust, 1974; [1]). This vascularity can present a major problem during sinus surgery. Surgeons routinely use topical vasoconstrictors in endoscopic sinus surgery however, the optimal regimen is not clear. Imidazoline nasal sprays are often used up to 1 hour before sinonasal surgery to aid in intraoperative vasoconstriction. After the induction of anaesthesia, epinephrine-based topical and submucosal preparations are subsequently administered to further enhance vasoconstriction. Imidazolines are non-selective, partial alpha adrenoceptor agonists with a higher affinity, yet lower potency, for alpha adrenoceptors when compared to epinephrine. It is hypothesized that imidazolines block the action of epinephrine on the alpha adrenoceptors of the nasal mucosa resulting in less vasoconstriction, and a poorer intra-operative field, when compared to the use of epinephrine alone. This paper hypothesizes that preoperative imidazoline administration may adversely affect optimal intra-operative vasoconstriction.     

Sinonasal papillomas: A single centre experience on 137 cases with emphasis on malignant transformation and EGFR/KRAS status in “carcinoma ex papilloma”

Among the three major histological subtypes of sinonasal papillomas, inverted (ISP) and oncocytic (OSP) sinonasal papillomas tend to undergo malignant transformation to carcinoma. However, criteria determining risk of recurrence and malignant progression have not been established. Recently, EGFR and KRAS mutations were detected to be characteristic for ISP and OSP, respectively. In this study, we analyzed 137 sinonasal papilloma cases (132 ISP and 5 OSP) for clinicopathological characteristics, frequency of recurrences/malignant transformation, and histological types and genetic features of carcinoma ex Schneiderian papilloma. OSP presented at a higher age than ISP (median, 75 vs. 57 years) and affected predominantly females. Overall frequency of recurrences and malignant transformation was 23.1% and 9.5%, respectively. Rates of recurrence (33.3% vs. 22.0%) and malignant transformation (33.3% vs. 8.8%) were higher in OSP compared to ISP, respectively. Carcinomas (n = 10) occurred mostly synchronously, more frequently in females and mainly associated with ISP (n = 9). Squamous cell carcinoma (SCC) was the most frequently associated malignancy. Concordant EGFR (in ISP/associated carcinoma) and KRAS (in the OSP/associated carcinoma) mutations were detected in all successfully analyzed matching papilloma/carcinoma pairs, confirming their shared clonal origin. Results of this large study are in line with recent studies showing frequent EGFR and KRAS mutations in sinonasal carcinoma ex Schneiderian papilloma. As the papilloma component might on occasion be missed on biopsy of synchronous carcinoma ex papilloma, EGFR and KRAS mutation testing represents a promising molecular surrogate for sinonasal “carcinoma ex papilloma”, at the same time offering an opportunity for targeting mutant EGFR in this rare cancer type.     

Evaluation of TLR2, TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Previous studies indicated that single‐nucleotide polymorphisms (SNPs) of genes coding for toll‐like receptors (TLRs) and toll‐interacting protein (TOLLIP) may be involved in the pathogenesis of pulmonary tuberculosis (PTB). This study was designed to investigate potential associations between the polymorphisms in TLR2, TLR4, and TOLLIP and susceptibility to latent tuberculosis infection (LTBI) or subsequent PTB in a Chinese Han population. A total of 209 PTB and 201 LTBI patients and 204 healthy control subjects (HCS) were enrolled in our study. We performed a logistic regression including sex and age as covariates to test the effect of genotype. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR). Eleven markers in TLR2, TLR4, and TOLLIP were assessed. No significant association between polymorphisms of TLR2 and TLR4 with PTB or LTBI was detected. For TOLLIP, rs5743899 (p = 0.005, OR = 1.83, 95% CI: 1.20–2.80) CC genotype were risk factors for PTB progression. Moreover, rs5743867 under addictive (p = 0.005, OR = 1.54, 95% CI: 1.14–2.07) and recessive model (p = 0.004, OR = 1.86, 95% CI: 1.22–2.83) were also risk factors for PTB susceptibility. Our results indicate that polymorphisms in TOLLIP affected the risk of PTB disease.     

Comparison of Austrian, Hungarian and Macedonian methicillin-resistant and methicillin-sensitive Staphylococcus aureus strains in relation to prevalence of cytotoxin genes

Cytotoxin genes in 128 Austrian (AT) MSSA, 48 MRSA, 94 Hungarian (HU) MSSA, 110 MRSA and 67 Macedonian (MK) MSSA, 81 MRSA strains were examined. The presence of alfa-haemolysin gene (hla) was more common in HU MSSA strains compared to AT and MK (99%, 86%, 72%: p < 0.001). AT and MK MRSA harboured hlb genes more frequently compared to HU (60%, 62%, 33%: p < 0.001). HU and MK MRSA strains carried gamma-haemolysin gene (hlg) in higher percentage in contrast to AT (88%, 83%, 69%: p = 0.01). Haemolysin gamma-variant gene (hlgv) was more prevalent in HU MSSA compared to AT and MK (84%, 56%, 69%: p < 0.001). Panton–Valentine leukocidin genes were found only in AT, HU, MK MSSA and MK MRSA in 2.3%, 4%, 1.5% (p = 0.53) and 1% (p = 0.38), respectively. The 3-gene combination pattern comprising of hla, hlg and hld genes showed increased prevalence among AT MSSA compared to HU (27%, 11%: p < 0.001). The 4-gene pattern composed of hla, hlg, hlgv and hld genes was significantly characteristic for HU MRSA in contrast to AT and MK MRSA (56%, 12.5%, 27%: p < 0.001). Frequency of certain cytotoxin genes and combinations differed significantly in Staphylococcus aureus strains according to geographical origin and methicillin-resistance.