Silvia Baroni

Nasal lavage CCL24 levels correlate with eosinophils trafficking and symptoms in chronic sino-nasal eosinophilic inflammation.

BACKGROUND According to the Federal Institution of Health Insurance, ENT doctors perform more skin prick tests for the diagnosis of allergic rhinitis (AR) than other medical specialties in Belgium. However, immunotherapy (IT) is not practiced by all. This study aims to obtain insight into IT practice by ENT doctors, the type of IT performed and the reasons not to perform IT. METHODOLOGY A questionnaire was sent to all registered ENT doctors of Belgium (n=648), involving questions on type and duration of ENT practice, geography and gender. In addition, the questionnaire informed about diagnosis of AR, indication for IT, type of IT performed, and reasons not to perform IT and referral pattern. RESULTS The response rate among ENT doctors was 54%, with 7% of responders being excluded as they do not diagnose AR. 81% of Belgian ENT doctors make the indication for IT in AR patients, with 19% neglecting the indication for IT in AR patients. The two main reasons for not indicating IT are lack of expertise and the perception of high costs associated with IT. 70% of ENT specialists are practicing IT themselves, with sublingual IT being mostly performed. Interestingly, IT is mostly frequently performed by those ENT doctors with long-standing ENT practice, in private practice and in Wallonia. CONCLUSION Despite the high prevalence of AR in ENT practice, IT is most frequently performed by ENT doctors with longstanding practice, working in private practice and/or in the French speaking part of Belgium. Among the different types of IT, sublingual IT is the most frequently performed means of IT by ENT doctors.OBJECTIVE To investigate the role of inflammation in non-allergic rhinitis (NAR) patients in a large series to establish the prevalence of different NAR-subtypes, clinical features and the role of nasal cytology in the diagnostic algorithm. METHODOLOGY Patients were selected out of 3650 individuals who spontaneously presented at our institution. We consecutively enrolled 519 NAR-patients in an analytical cross-sectional study between November 2007 and June 2013 (level of evidence: 3b). All patients underwent rhinological evaluation including symptoms questionnaire, endoscopy, CT scan, allergy tests and nasal cytology. RESULTS The inflammatory cell infiltrate affects the severity of symptoms differently, allowing for identification of different phenotypes of NAR. We distinguished two groups: “NAR without inflammation”(NAR-) and “NAR with inflammation”(NAR+), in addition to different NAR-subtypes with inflammation. A significant difference was observed in terms of clinical symptoms and association with comorbidities (previously diagnosed asthma and aspirin intolerance) between NAR–, NAR+ and between different NAR+ subtypes. CONCLUSION Our data suggest that NAR- and NAR with neutrophils behave similarly, showing lower symptom score values and a lower risk of association with comorbidities compared to NAR with eosinophils and mast cells (singularly or mixed). In our belief it is very important to establish the presence and type of inflammation in non-allergic rhinitis patients and nasal cytology is a very useful test in correct differential diagnosis.OBJECTIVE To assess the applicability of the Peak Nasal Inspiratory Flow (PNIF) curves in follow-up of children in the treatment of allergic rhinitis. METHODS Prospective study of 40 patients with AR, grouped in corticosteroid spray versus physiological saline solution use. Follow up for 10 weeks through clinical score and PNIF percentages in relation to the reference curves, with was-out at week 8. Statistical assessment of the effect of treatment on variation of PNIF and clinical score was calculated by ANOVA model and Multiple Comparison of Means Test - Least Significant Difference. RESULTS There was a statistically significant influence of the group, time and interaction between time and group on PNIF percentages. Throughout follow up, patients from the treatment group had mean PNIF percentages significantly higher than the placebo group. Clinical score results also demonstrated a statistically significant influence between the groups, time and interaction between time and group. CONCLUSION Increase in PNIF percentage values observed in children treated with intranasal corticosteroids revealed the applicability of PNIF curves in their follow up.OBJECTIVE This study aims to examine humans ́ abilities to localize odorants within the open field. METHODOLOGY Young participants were tested on a localization task using a relatively selective olfactory stimulus (2-phenylethyl-alcohol, PEA) and cineol, an odorant with a strong trigeminal component. Participants were blindfolded and had to localize an odorant source at 2 m distance (far-field condition) and a 0.4 m distance (near-field condition) with either two nostrils open or only one open nostril. RESULTS For the odorant with trigeminal properties, the number of correct trials did not differ when one or both nostrils were used, while more PEA localization trials were correctly completed with both rather than one nostril. In the near-field condition, correct localization was possible in 72-80% of the trials, irrespective of the odorant and the number of nostrils used. Localization accuracy, measured as spatial deviation from the olfactory source, was significantly higher in the near-field compared to the far-field condition, but independent of the odorant being localized. CONCLUSION Odorant localization within the open field is difficult, but possible. In contrast to the general view, humans seem to be able to exploit the two-nostril advantage with increasing task difficulty.BACKGROUND This study was designed to assess if illness perception, mood state and coping strategies differ according to allergic rhinitis (AR) persistence and severity. METHODS Illness perception, mood profiles, coping behaviors and rhinitis symptoms were assessed by means of validated tools inpatients classified according to the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines. RESULTS Two hundred and thirty-one patients underwent data analysis. No difference in age, sex, socio-economic status, smoking habits was detected comparing patients according to AR severity, duration or 4 ARIA classes. Patients with intermittent AR reported higher scores than those with persistent AR in confusion-bewilderment of Profile of Mood States (POMS); patients with moderate/severe rhinitis had significantly higher scores than those with mild rhinitis in TSSS, Identity and Consequences. No differences were detected in all assessed outcomes in the 4 ARIA classes. CONCLUSIONS The patients perspective about AR is independent of persistence and severity of symptoms. This may explain why AR remains under-diagnosed and under-treated, even in its most severe forms. Self-management plans should consider the patients perspective.The assessment of Chronic Rhinosinusitis, like any other disease, may involve multiple possible disease manifestations, including subjective patient-reported outcomes, objective disease (e.g. endoscopy or radiographic), and physician-driven (e.g. need for systemic medications). Disease control is often used as a global metric of disease burden and represents the extent to which disease manifestations are within an acceptable range. Achieving control is an important treatment goal.The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012(1-3). The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings.BACKGROUND Endoscopic dacryocystorhinostomy (EN-DCR) is a commonly used procedure in the treatment of nasolacrimal duct obstruction (NLDO). However, there is no generally accepted disease-specific questionnaire for assessing outcomes. METHODOLOGY We conducted a prospective study to initially validate a Nasolacrimal Duct Obstruction Symptom Score questionnaire(NLDO-SS) and to evaluate the long-term success of EN-DCR procedures. Seventy-six patients (86 eyes) were evaluated in follow-up visits at 1-8 years after EN-DCR. The patients completed the NLDO-SS questionnaire twice, first, at home and, second,after receiving information from the otorhinolaryngologist, during the visit. The surgical outcome was considered successful if the irrigation succeeded and if the patient symptoms were relieved as assessed with the NLDO-SS. RESULTS The diagnostic accuracy of the NLDO-SS was 84%, sensitivity 82%, specificity 85%, positive predictive value 58%, negative predictive value 95%, odds ratio 26, risk ratio 11 and usefulness index 0.55. Cronbachs alpha was 0.85, and the test-retest reliability coefficient was 0.87. The long-term success rate after EN-DCR was 79%. CONCLUSION The NLDO-SS iss a feasible clinical tool in assessing the success of EN-DCR. The success rate was found to decrease EN-DCR at long-term follow-up.

Bile acids and total bilirubin detection in saliva of patients submitted to gastric surgery and in particular to subtotal Billroth II resection

Objective:The aim of our study was to detect bile acids and total bilirubin in saliva of gastrectomized patients, to confirm objectively presence of biliary laryngopharyngeal reflux and its relationship with laryngeal mucosa damage. Summary Background Data:Recently, it has been hypothesized that biliary-reflux may reach the upper aerodigestive tract and enhance development of laryngeal malignancies; nevertheless, the presence of duodenogastric contents in this region has never been revealed. Methods:We carried out a prospective observational case-control study on 52 patients (cases) previously submitted to gastric surgery, mainly to subtotal Billroth II resection, and on 51 healthy volunteers (controls). Patients were submitted to clinical interview, esophagogastroduodenal endoscopy, endoscopic laryngeal evaluation, and saliva collection. In all saliva samples, bile acids, total bilirubin, and pepsinogen II were assayed. Results:In cases, group bile acids levels were recorded in 17 of 52 (32.6%) patients, while in 35 of 52 (67.4%) they were undetectable. All controls were negative to bile acids. In positive cases to bile acids, we found a significant (P < 0.05) correlation between bile acids, total bilirubin, and pepsinogen II values and a significant (P < 0.05) higher prevalence of symptoms and findings of laryngeal damage and of previous laryngeal neoplastic lesions. Conclusions:We found detectable levels of bile acids and total bilirubin in saliva of patients submitted to previous gastric surgery, prospecting an intriguing diagnostic role of this dosage in the study of biliary laryngopharyngeal reflux. We finally revealed a high incidence of laryngeal disorders in patients with positive bile acids in saliva.

Prognostic relevance of lipoprotein cholesterol levels in acute lymphocytic and nonlymphocytic leukemia.

We studied serum lipid and lipoprotein changes before and after induction treatment in 25 acute nonlymphocytic leukemia (ANLL) and in 18 acute lymphocytic leukemia (ALL) patients in order to investigate their relationship with disease activity and their prognostic relevance. ANLL at diagnosis is associated with significantly low levels of all lipid parameters, the same applies to ALL patients apart from plasma triglycerides and very-low-density-lipoprotein cholesterol (VLDL-C) which are significantly higher than in the normal population. In ANLL responders, after effective chemotherapy, a significant increase of total cholesterol, low-density-lipoprotein cholesterol (LDL-C) and apolipoprotein B levels, without changes of high-density-lipoprotein cholesterol (HDL-C) values, is observed. A further decrease of total cholesterol and LDL-C was found in nonresponders and in ANLL responders treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), known for its cholesterol-lowering action; in fact after the completion of GM-CSF therapy, these parameters returned progressively toward normal values. In ALL responders an increase of total cholesterol, HDL-C and apolipoprotein A1 with a simultaneous decrease of triglycerides and VLDL-C is evident; no variation was found in the nonresponder group. These results suggest a close correlation between serum lipids and acute leukemia: total cholesterol and LDL-C in ANLL, and HDL-C and VLDL-C in ALL may be considered reliable markers of complete remission and may be useful in the follow-up of leukemic patients.

Lipids and lipoproteins in acute lymphoblastic leukaemia (ALL)

Current studies suggest a derangement of the cholesterol homeostasis in certain types of leukaemia. The low serum cholesterol levels observed in patients with AML have been related to the tumoral mass and to the disease activity. Only a few studies have taken into consideration a possible change of the serum lipids in ALL. The aim of this study was to evaluate a possible prognostic significance of serum levels of total cholesterol (TC), triglycerides, HDL-C, LDL-C, VLDL-C, apolipoproteins A1 and B and lipoprotein (a), investigated in 10 newly diagnosed ALL patients before and after induction treatment. At diagnosis all these parameters were not significantly different in our patients vs control group except cholesterol and HDL-C levels, which were significantly lower. After the induction treatment, we found a significant increase of HDL-C and Apo A1 values only in those patients that achieved a complete remission. These results support the idea that some serum lipids, such as HDL-C and Apo A1, may have a role as early and reliable markers of the effectiveness of chemotherapy.

Synergistic modulation by chloride and organic phosphates of hemoglobin from bear (Ursus arctos)

The oxygen binding properties of hemoglobin (Hb) from brown bear (Ursus arctos) have been studied focussing on the effect of heterotropic ligands, and the behaviour has been compared with that of human HbA, taken as a prototype of mammalian Hbs. It has been observed that in bear Hb chloride ions and 2,3-diphosphoglyceric acid (Gri(2,3)P2) can modulate the oxygen affinity in a synergistic way such that their individual effect is enhanced whenever they are both present in saturating amounts. The thermodynamic analysis of such a feature indicates that in bear Hb there are two classes of chloride binding sites, one acting synergistically with Gri(2,3)P2 and another one, which likely overlaps with the organic phosphate interaction cleft, and is therefore fully operative only in the absence of Gri(2,3)P2. The behaviour of the last site is similar to that observed in human HbA, where the effect of Cl- and Gri(2,3)P2 is mutually exclusive. The interaction energy between chloride and Gri(2,3)P2 synergistic binding sites appears to be O2-linked so that the interplay may have a relevant physiological role in modulating the oxygen transport in brown bear. This behaviour is associated with a marked pH-dependence of the oxygenation enthalpy in bear Hb, such that under acidotic and hypercloruremic conditions, oxygen supply to peripheral tissues could be maintained essentially unaltered even under low temperature conditions.

Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation

The aim of the present study was to measure eotaxin‐3 (CCL26) and eotaxin‐2 (CCL24) in nasal lavage fluid of patients with different forms of chronic sinonasal eosinophilic inflammation to evaluate their role in the pathophysiology of nasal hypereosinophilia.

Soluble urokinase-type plasminogen activator receptor as a putative marker of male accessory gland inflammation.

The association between male accessory gland infection/inflammation (MAGI) and infertility is well‐known in clinical practice. Standard semen analysis, leukocytospermia, and microbiological tests are often not enough accurate for a diagnosis. A large amount of biochemical parameters in seminal plasma have been suggested as inflammation markers, however, there is not yet a sensitive and specific biomarker that accurately identifies MAGI. We investigated the presence of soluble urokinase‐type plasminogen activator receptor (suPAR), known marker of systemic inflammation, in the seminal plasma to evaluate its possible involvement in urogenital tract inflammation. On the basis of andrological evaluation, including spermiogram and ultrasound findings, we selected 76 patients with MAGI and 30 healthy men as control group. Patients were classified according to the results of the semen culture in group A (n = 28) presenting a bacterial MAGI and group B (n = 48) with abacterial MAGI. C‐reactive protein (CRP), total protein (TP), procalcitonin (PCT), leukocytes peroxidase (LP), and suPAR concentrations were assayed on seminal plasma. Spermiogram parameters were significantly lower in the patients with MAGI than in controls. CRP, TP, PCT, and LP did not differ in MAGI vs. controls. suPAR was detectable in all semen samples; it was significantly increased in A and B groups (86.6 ± 30.7 ng/mL vs. 39.7 ± 17.2 ng/mL) with an inverse correlation with sperm parameters. We selected by receiver operating characteristic curve a suPAR cut‐off value of 55.3 ng/mL as a diagnostic threshold for the diagnosis of MAGI. We report in this study the first evidence of suPAR presence in seminal plasma, focusing on its interesting role as reliable and sensitive marker of inflammation for the differential diagnosis of MAGI.

Effects of prednisone on biomarkers of tubular damage induced by radiocontrast in interventional cardiology

BACKGROUND Contrast-induced nephropathy (CI-AKI) is a complication of diagnostic/therapeutic hemodynamic procedures in cardiology, which may also cause renal cholesterolinic atheroembolism. Despite the 
severe clinical impact of these complications, there is no optimal therapy for preventing and treating them. We suggest a short course of high-dose steroids as an effective preventive measure. METHODS Patients at risk of CI-AKI (n = 38) undergoing cardiovascular procedures were assigned 1:1 to 1 of 2 experimental arms (prednisone+hydration vs. hydration alone). Oral prednisone 1 mg/kg was administered 12 hours before, at 6 am on the same day, and 24 hours following the procedure. Serum creatinine was tested immediately before and again 24-48 hours after the procedure; neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), protein and albumin were assayed in spot urine before and 6 hours after the procedure.
 RESULTS NGAL and KIM-1 tended to rise after the procedure, but to a lesser degree in the prednisone group (delta NGAL: hydration = +128%, prednisone = +46%; 
p = 0.26; delta KIM-1: hydration = +99%, prednisone = +11%; p = 0.02). Proteinuria and albuminuria decreased significantly in the prednisone group. In 5 patients developing CI-AKI, their delta NGAL and delta KIM-1 did not differ from the values seen in patients without 
CI-AKI. Hypertension, peripheral arteriopathy and use of low-dose aspirin or diuretics were positive predictors of baseline NGAL, while treatment with calcium channel blockers and statins were negative predictors. Statins were negative predictors of baseline KIM-1. CONCLUSIONS A short course of prednisone reduces the procedure-induced changes in biomarkers of renal tubular damage. This study suggests that steroids had a tubule-protecting effect.

Human growth hormone (GH) immunoassay: standardization and clinical implications

Abstract Background: The poor comparability of growth hormone (GH) results obtained using commercially available methods, is partly due to standard preparations used in calibration. The system relies on the use of the International Reference Preparation (IRP) international standard (IS) 80/505, of human pituitary origin, containing all GH isoforms. Recently, a 22K recombinant GH isoform IRP IS 98/574 was commercialized. Our aim was to evaluate the influence of both calibrators on GH results. Methods: GH concentration in 97 serum samples from children undergoing a growth hormone releasing hormone+arginine stimulation test was measured using Siemens IMMULITE electro-chemiluminescence method, calibrated with both IS 80/505 and IS 98/574 (GRH Growth hormone-Recombinant 98/574-kit). Results: Comparison of our results obtained with the two sets of calibrators showed good correlation, although we found higher percentage variation (var%) than that stated by Siemens. The mean var% value was confirmed when all results were sub-divided into subgroups based on both high and low GH concentrations. Conclusions: Since the GH assay is influenced by a variety of binding proteins, isoforms and conversion factors, standardization of the assay is strongly required. In Italy, the Agenzia Italiana del Farmaco 39 note provides GH laboratory values which are useful for therapy. On the basis of our results, we therefore propose to adjourn these GH values in order to ensure better management of patients with GH-related disorders.

Nasal lavage levels of granulocyte‐macrophage colony‐stimulating factor and chronic nasal hypereosinophilia

The aim of the present study was to measure levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in nasal lavage of patients affected by chronic eosinophilic sinonasal inflammation to clarify the relationship with eosinophilic tissue infiltration and clinical features.