Publications by authors named "Giulio Cesare Passali"

54 Publications

A systematic review of the clinical evidence and biomarkers linking allergy to adeno-tonsillar disease.

Int J Pediatr Otorhinolaryngol 2021 Jun 12;147:110799. Epub 2021 Jun 12.

Department of Neuroscience, Reproductive and Odontostomatological Sciences - ENT Section, University "Federico II", Naples, Italy.

Introduction: allergy may be an important risk factor for adenotonsillar disease in children, although conflicting results have been reported in the literature. In previous articles, authors often failed in distinguishing between adeno-tonsillar hypertrophy and recurrent tonsillitis and in not discriminating between isolated or combined adenoid and tonsillar hypertrophy.

Aim: to evaluate clinical evidence and biomarkers linking allergy to different phenotypes of adeno-tonsillar disease. Furthermore, we questioned whether anti-allergy treatment might prevent occurrence of adeno-tonsillar disease or improve its specific management.

Methods: our systematic review, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) process, yielded 1010 articles finally screened. This resulted in 21 full texts that were included in a qualitative analysis.

Results: literature data support the association between allergy and combined adeno-tonsillar hypertrophy and isolated adenoid hypertrophy, whereas describe a mainly negative correlation between allergy and isolated tonsillar hypertrophy. The results of this review suggest that local allergic inflammation may play a role in adeno-tonsillar hypertrophy. Data correlating bacterial recurrent tonsillitis and allergy are few, although evidence from the lab revealed that allergy might suppress innate immunity in tonsillar tissue by reducing levels of anti-microbial proteins.

Conclusion: basing on our qualitative analyses allergy should not be misdiagnosed in children with combined adenotonsillar hypertrophy or isolated adenoid hypertrophy, whereas evidence do not support a link between allergy and isolated tonsil hypertrophy. Finally, some data support a link between allergy and recurrent adeno-tonsillar infection although future studies are required to confirm this data. We summarized our conclusions in a practical algorithm.
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http://dx.doi.org/10.1016/j.ijporl.2021.110799DOI Listing
June 2021

Beneficial Effects of Remote Medical Care for Patients with Hereditary Hemorrhagic Telangiectasia during the COVID-19 Pandemic.

J Clin Med 2021 May 25;10(11). Epub 2021 May 25.

Multidisciplinary Gemelli Group for HHT, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

Background: Hereditary hemorrhagic telangiectasia (HHT) needs high-quality care and multidisciplinary management. During the COVID-19 pandemic, most non-urgent clinical activities for HHT outpatients were suspended. We conducted an analytical observational cohort study to evaluate whether medical and psychological support, provided through remote consultation during the COVID-19 pandemic, could reduce the complications of HHT.

Methods: A structured regimen of remote consultations, conducted by either video-calls, telephone calls, or e-mails, was provided by a multidisciplinary group of physicians to a set of patients of our HHT center. The outcomes considered were: number of emergency room visits/hospitalizations, need of blood transfusions, need of iron supplementation, worsening of epistaxis, and psychological status.

Results: The study included 45 patients who received remote assistance for a total of eight months. During this period, 9 patients required emergency room visits, 6 needed blood transfusions, and 24 needed iron supplementation. This was not different from what was registered among the same 45 patients in the same period of the previous year. Remote care also resulted in better management of epistaxis and improved quality of life, with the mean epistaxis severity score and the Euro-Quality of Life-Visual Analogue Scale that were significantly better at the end than at the beginning of the study.

Discussion: Remote medical care might be a valid support for HHT subjects during periods of suspended outpatient surveillance, like the COVID-19 pandemic.
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http://dx.doi.org/10.3390/jcm10112311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199008PMC
May 2021

Salivary Biomarkers in COVID-19 Patients: Towards a Wide-Scale Test for Monitoring Disease Activity.

J Pers Med 2021 May 8;11(5). Epub 2021 May 8.

Dipartimento di Scienze di Laboratorio e Infettivologiche, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.

The ongoing outbreak of coronavirus disease 2019 (COVID-19), which impairs the functionality of several organs, represents a major threat to human health. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients' access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for the fast and non-invasive collection of specimens and can be repeated multiple times.

Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free light chains (kFLC and λFLC) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects.

Results: We found that each biomarker differs significantly between the two groups, with -values ranging from 10 to 10. A Receiving Operator Curve analysis shows that λFLC level is the best-suited candidate to discriminate the two groups (AUC = 0.96), with an accuracy of 0.94 (0.87-1.00 95% CI), a precision of 0.91 (0.81-1.00 95% CI), a sensitivity of 1.00 (0.96-1.00 95% CI), and a specificity of 0.86 (0.70-1.00 95% CI).

Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This hypothesis is strengthened by the consideration that the λFLC half-life (approximately 6 h) is significantly shorter than the IgA one (21 days), thus confirming the potential of λFLC for effectively monitoring patients' fluctuation in real-time.
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http://dx.doi.org/10.3390/jpm11050385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151878PMC
May 2021

Smell impairment in patients with chronic rhinosinusitis: a real-life study.

Eur Arch Otorhinolaryngol 2021 May 3. Epub 2021 May 3.

Allergy Office, Casa Di Cura Villa Montallegro, Genoa, Italy.

Objective: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequently occurring condition involving type 2 inflammation. It has a global prevalence of approximately 4% and has a major effect on the quality of life of those affected by it. CRSwNP is a complex condition for otorhinolaryngologists to manage, since its precise pathogenic basis has not been established, treatment is challenging and the condition often recurs. It is common to find abnormalities in smelling in those with CRSwNP.

Materials And Methods: This cross-sectional study enrolled patients suffering from CRS. Three groups were compared: 1812 patients with CRS, 571 with CRSwNP, and 120 with CRSwNP treated by FESS. The Sniffin' Sticks olfactory test was used to measure olfactory function in all patients.

Results: Olfactory dysfunction was a common symptom in patients with CRS, ranging in frequency from 56 to 74%. In patients with CRSwNP, impairment of sense of smell affected 64% of subjects (42% with anosmia, 10% with hyposmia, and 12% with cacosmia). After surgery, there was a significant improvement in the ability to smell normally.

Conclusion: The present study confirms that impairment of smell is a common symptom in patients with chronic rhinosinusitis, mainly in subjects with nasal polyps. FESS reduces the prevalence of olfactory dysfunction.
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http://dx.doi.org/10.1007/s00405-021-06848-9DOI Listing
May 2021

Smell impairment in patients with allergic rhinitis.

Int Forum Allergy Rhinol 2021 Jun 16;11(6):1031-1032. Epub 2021 Mar 16.

Allergy Clinic, Casa di Cura Villa Montallegro, Genoa, Italy.

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http://dx.doi.org/10.1002/alr.22786DOI Listing
June 2021

Functional results of exclusive interventional radiotherapy (brachytherapy) in the treatment of nasal vestibule carcinomas.

Brachytherapy 2021 Jan-Feb;20(1):178-184. Epub 2020 Oct 9.

UOC di Otorinolaringoiatria, Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della testa collo. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy; Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Policlinico Agostino Gemelli, Rome, Italy.

Purpose: Surgery, external beam radiotherapy (EBRT), and interventional radiotherapy (IRT, BrachyTherapy BT) are the current therapeutic options for nose vestibule (NV) squamous cell carcinoma (SCC). In this article, we evaluate the nose functional parameters of patients affected by SCCs of the NV, primarily treated by interstitial IRT comparing them with healthy controls and with patients treated with intensity-modulated EBRT.

Methods: Ten patients treated by using IRT (group 1), 10 healthy controls and eight patients treated by EBRT (group 2) on the region of the nose were submitted to clinical evaluation (with the NOSE scale score), rhinomanometry, olfactory testing, nasal citology, and evaluation of mucociliary clearance through saccharine test.

Results: No long-term skin or cartilaginous toxicity are recorded. The olfactometry threshold discrimination identification TDI is lower in EB group. The mean NOSE scale score was significantly higher in group 2 than in group 1 and healthy controls (p < 0.05). The distribution of cytologic patterns resulted significantly different as well. Patients treated by EB have a significantly impaired mucociliary clearance, with a mean time for the transport of the stained marker, which is more than double in the patients treated by EB than in those treated with IRT (p < 0.001).

Conclusions: Nasal function and cytological findings are significantly better, substantially preserved, in patients treated by IRT than in those treated by EBRT, bringing new relevant evidence for the establishment of interstitial IRT as the new standard for the treatment of the primary lesion in cT1 and cT2 -Wang staging NV SCCs.
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http://dx.doi.org/10.1016/j.brachy.2020.08.008DOI Listing
October 2020

Traumatic benign paroxysmal positional vertigo: personal experience and comparison with idiopathic BPPV.

Int J Audiol 2021 May 22;60(5):393-397. Epub 2020 Sep 22.

Otolaryngology, Catholic University, Rome, Italy.

Objective: Benign paroxysmal positional vertigo (BPPV) is the most common cause of vestibular vertigo, with post-traumatic origin in about 15% of cases. Management and prognosis of traumatic BPPV (T-BPPV) are still debated, especially about recurrence. The aim was to compare T-BPPV to idiopathic (I-BPPV).

Design And Study Sample: We analysed data about 795 BPPV patients: 716 idiopathic (90%) and 79 post-traumatic (10%), evaluating clinical history and bedside-examination, treating all patients with repositioning manoeuvres and reassessing them until the resolution of symptoms and nystagmus.

Results: Persistence rate in T-BPPV and I-BPPV patients was significantly different ( = 0.0074, OR = 2.31), respectively 12.6% and 5%. Also the rate of bilateral disease ( = 0.0063, OR = 4.72) and multicanalar involvement ( = 0.0183; OR = 4.67) were significantly higher in T-BPPV patients . There were no significant differences in age and sex distribution, side and canal interested. In T-BPPV group, the resolution rate with one manoeuvre was lower than I-BPPV ( = 0.0132: OR: 0,56). Recurrence rate was 38% in the T-BPPV group and 30.6% in the I-BPPV group, without significant difference.

Conclusions: T-BPPV resulted different from I-BPPV in the resolution rate, bilateral or multiple canal involvement and persistence rate. T-BPPV and I-BPPV does not differ for recurrence rate, suggesting that, after resolution, the natural course of post-traumatic and idiopathic BPPV is similar.
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http://dx.doi.org/10.1080/14992027.2020.1821253DOI Listing
May 2021

The Italian Society Indication for Rhinologists during Covid-19: Italy Phase 2.

Int Arch Otorhinolaryngol 2020 Jul 19;24(3):e388-e390. Epub 2020 Jun 19.

Department of Neuroscience, Reproductive and Odontostomatological Sciences - ENT Section, Università degli Studi di Napoli Federico II, Naples, Italy.

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http://dx.doi.org/10.1055/s-0040-1713141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394651PMC
July 2020

Patients With Voice Prosthesis Rehabilitation During the COVID-19 Pandemic: Analyzing the Effectiveness of Remote Triage and Management.

Otolaryngol Head Neck Surg 2021 02 4;164(2):277-284. Epub 2020 Aug 4.

Unità Operativa Complessa di Otorinolaringoiatria, Area Testa-Collo, Dipartimento Scienze dell'Invecchiamento, Neurologiche, Ortopediche e della Testa-collo, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy.

Objective: To describe a remote approach used with patients with voice prosthesis after laryngectomy during the COVID-19 pandemic and the resulting clinical outcomes in terms of voice prosthesis complications management, oncological monitoring, and psychophysical well-being.

Study Design: Prospective cohort study.

Setting: Otolaryngology Clinic of the University Polyclinic A. Gemelli, IRCCS Foundation.

Subjects And Methods: All patients with voice prosthesis who underwent laryngectomy followed by our institute were offered enrollment. Patients who agreed to participate were interviewed to inquire about the nature of the need and to plan a video call with the appropriate clinician. Before and 1 week after the clinician's call, patients were tested with the Hospital Anxiety and Depression Scale. Degrees of satisfaction were investigated with a visual analog scale. A comparison between those who accepted and refused telematic support was carried out to identify factors that influence patient interest in teleservice.

Results: Video call service allowed us to reach 37 (50.68%) of 73 patients. In 23 (62.16%) of 37 cases, the video call was sufficient to manage the problem. In the remaining 14 cases (37.83%), an outpatient visit was necessary. Participants who refused telematic support had a significantly shorter time interval from the last ear, nose, and throat visit than patients who accepted (57.95 vs 96.14 days, = .03). Video-called patients showed significantly decreased levels of anxiety and depression (mean Hospital Anxiety and Depression Scale total score pre- vs post-video call: 13.97 vs. 10.23, < .0001) and reported high levels of satisfaction about the service.

Conclusion: Remote approach may be a viable support in the management of patients with voice prosthesis rehabilitation.
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http://dx.doi.org/10.1177/0194599820948043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404089PMC
February 2021

Hereditary haemorrhagic telangiectasia: A disease not to be forgotten during the COVID-19 pandemic.

J Thromb Haemost 2020 07;18(7):1799-1801

Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore School of Medicine, Rome, Italy.

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http://dx.doi.org/10.1111/jth.14885DOI Listing
July 2020

HMGB1 in nasal inflammatory diseases: a reappraisal 30 years after its discovery.

Expert Rev Clin Immunol 2020 05 12;16(5):457-463. Epub 2020 May 12.

International Federation ORL Societies (IFOS).

Introduction: High mobility group protein box 1 (HMGB1) is a protein belonging to the alarmin family. HMGB1 has a relevant role in starting the inflammatory cascade by means of receptors, such as RAGE and TLR. HMGB1 supports transcription of many genes in interactions with many transcription factors, including NF-kB. The axis HMGB1-RAGE-NF-kB has, therefore, a pivotal role in the inflammatory cascade. HMGB1 controls the production of several pro-inflammatory cytokines and the proliferation and activation of many inflammatory cells.

Areas Covered: The present report concerns the role of HMGB1 in nasal inflammatory disorders, including allergic and non-allergic rhinitis, and chronic rhinosinusitis with nasal polyps. HMGB1 modulation has been the aim of several studies. The literature search included recent papers that covered this topic.

Expert Opinion: As HMGB1 has a pivotal role in inflammatory events, its modulation could be attractive for designing new therapeutic strategies. In this regard, glycyrrhetic acid (GA), the active component of , can efficiently block HMGB1. Promising reports seem to suggest that GA could exert favorable anti-inflammatory activity in patients with nasal inflammatory disorders.
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http://dx.doi.org/10.1080/1744666X.2020.1752668DOI Listing
May 2020

Olfactory perception rehabilitation after total laryngectomy (OPRAT): proposal of a new protocol based on training of sensory perception skills.

Eur Arch Otorhinolaryngol 2020 Jul 21;277(7):2095-2105. Epub 2020 Mar 21.

Fondazione Policlinico Universitario A. Gemelli IRCSS, Clinica Di Otorinolaringoiatria, Roma, Università Cattolica del Sacro Cuore, Rome, Italy.

Purpose: We aim to propose a new protocol for olfaction rehabilitation after total laryngectomy based on training of sensory perception levels using the Nasal Airflow-Inducing Maneuver.

Methods: This is a randomized clinical trial including patients undergoing total laryngectomy between March 2010 and March 2019. Patients with nasal or oral abnormalities, prior olfaction impairment, a muco-ciliary transport time higher than 30 min, positive history for feeding, and neurological disorders were excluded. Thirty-three patients were enrolled and were randomized into two groups: an Experimental group, submitted to the new protocol (olfactory perception rehabilitation after total laryngectomy-OPRAT) and a Control group that did not receive any treatment. Subjective Olfactometry, Chemosensory Complaints Score, and University of Washington Quality of Life version 4 questionnaires were used to assess the outcomes before and after treatment, and at 3-month, 6-month, and 10-month follow-up.

Results: Among the 33 patients included (32 men and 1 woman; mean age, 67.94 ± 5.64 years), 17 were subjected to olfaction rehabilitation and 16 did not receive any treatment. At baseline evaluation, there were not significant differences between the two groups. At the end of treatment, the rehabilitated group improved their olfaction capability significantly. Such improvement remained stable over time, and after 10 months, only the Experimental group had significant improvements in all outcome measures.

Conclusions: The OPRAT may guarantee excellent results in the short- and long-term time with positive effects on the Quality of Life.
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http://dx.doi.org/10.1007/s00405-020-05918-8DOI Listing
July 2020

Turbinate hypertrophy in children with allergic rhinitis: clinical relevance.

Acta Biomed 2020 02 17;91(1-S):43-47. Epub 2020 Feb 17.

Otorhinolaryngology Unit, Casa di Cura Villa Montallegro Health, Genoa, Italy.

Allergic rhinitis (AR) is the most common immune-mediated disorder in childhood as it may affect up to 40% of children. Turbinate hypertrophy (TH) is an important sign as reliably predicts AR both in children and adults. Consistently, nasal obstruction is a very common symptom in AR patients and is closely linked with turbinate hypertrophy. This study investigated 544 (304 males) children with AR to define factors associated with TH. TH was diagnosed in 438 (80.81%) AR children. The multivariate analysis demonstrated a significant association between age, male gender, and recurrent acute otitis media (RAOM), and TH (p-values: 0.0219, <0.0001, and 0.0003, respectively; OR 0.87, 3.97, and 0.22 respectively). In conclusion, this real-life study showed that TH was very frequent in children with AR and age, male gender, and RAOM were significantly associated with TH.
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http://dx.doi.org/10.23750/abm.v91i1-S.9254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947744PMC
February 2020

A new therapeutic approach for the Dry Eye Syndrome in patients with laryngopharyngeal reflux: first data.

Acta Biomed 2020 02 17;91(1-S):36-42. Epub 2020 Feb 17.

Studio Oculistico "Balestrazzi", Rome, Italy.

Laryngopharyngeal reflux (LPR) is a common disorder. Pepsin has been detected also at eye level, this was a starting point for newest theories about LPR impact on Dry Eye Syndrome. The current preliminary study compared two treatments in patients with Dry Eye Syndrome and LPR. Patients were treated with Gastroftal eye drops and Gastroftal tablets or hyaluronic acid eye drops for 3 months. The following parameters were evaluated: Ocular Surface Disease Index (OSDI), OSDI categories, Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Fluorescein Tear Breakup Time (B-TUT), and Schirmer test before and after treatment. On the whole, 21 patients were enrolled: 10 were treated with hyaluronic acid Atlantis (Group A) and 11 with Gastroftal eye drops and tablets (Group B). After treatment, in Group A only OSDI significantly diminished (p=0.029); in Group B there were significant reductions concerning OSDI (p=0.0277), OSDI categories (p=0.0211), RSI (p=0.0172), Schirmer test (p=0.0172), T-BUT (p=0.0265), and RFS (p=0.0205). The current preliminary demonstrated that the combined ocular and systemic therapy with hyaluronic acid, Magnesium alginate, Simethicone, and Camelia sinensis may be considered a promising treatment in patients with Dry Eye Syndrome due to LPR.
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http://dx.doi.org/10.23750/abm.v91i1-S.9250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947740PMC
February 2020

The impact of rhinosinusitis in clinical practice: an Italian Survey.

Acta Biomed 2020 02 17;91(1-S):28-35. Epub 2020 Feb 17.

Allergy Clinic, Casa di Cura Villa Montallegro, Genoa, Italy.

Rhinosinusitis is a common disease that is classified in acute (ARS) and chronic (CRS). The current Survey was conducted on a sample of about 5,000 adult subjects in 5 Italian cities. A questionnaire, containing 15 questions, was administered on the road. RS affects about 20% of the general population. The most common diagnostic test was the skull x-ray. Antibiotics were the most frequently prescribed therapy. In conclusion, the current Survey demonstrated that RS is a common disorder in Italy, the diagnostic work-up is still incorrect, and the therapeutic approach does not adhere to the guidelines. Therefore, there is a need to implement adequate information on this topic in Italy.
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http://dx.doi.org/10.23750/abm.v91i1-S.9247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947734PMC
February 2020

Nasal Muco-ciliary transport time alteration: efficacy of 18 B Glycyrrhetinic acid.

Multidiscip Respir Med 2017 29;12:29. Epub 2017 Nov 29.

ENT Clinic, Policlinico S. M. alle Scotte, Siena, Italy.

Background: Mucociliary clearance is the main self-clearing system of the nasal cavity and paranasal sinuses.This is a very important means of non specific defence against continuous organic and inorganic contamination conveyed by air. It works by trapping particles and microorganisms in the mucus and then by transporting the mucous film to the pharynx where it is eliminated with a cough or swallowed. Its congenital or acquired abnormalities are involved in the occurrence of widespread infectious and often severe nose and paranasal sinuses diseases; generally concerning the rhinopharyngealtubal district.Restoring mucociliary clearance of the nasal epithelium when altered thus represents a key therapeutic tool against rhinosinus chronic diseases.This study evaluates the clinical efficacy of the inhalation of a natural compound (Narivent® nasal spray) in chronic vasomotor rhinitis.

Methods: The study involved 79 patients suffering from chronic vasomotor rhinitis presenting an increased mucociliary clearance time. Patients were randomized into 2 groups: a first group of 49 subjects and a second group of 30 subjects.The first group was treated with a nasal spray (Narivent® nasal spray) (2 sprays per nostril twice a day) for 30 days.The second group was treated with a nasal spray containing isotonic solution in the same way and for the same period of the first group.Nasal Mucociliary transport time was measured in the patients of both groups before treatment, after 15 days of treatment, and at the end of the 30 days treatment.

Results: The study shows how one of the treatments carried out determines a major objective reduction of the mucociliary clearance time in the patients under examination, using the method which involves the use of an insoluble coloured tracer (vegetable carbon), bringing the values back within normal range. At the end of the study we objectivated an increase in the rate of mucociliary transport in 97.9% percentage of patients we enrolled.

Conclusions: This study shows the effectiveness of treatment with natural extracts with nasal mucosa restoring function in the treatment of chronic vasomotor rhinitis, a nasal inflammatory disease characterized by morphological and functional alteration of the normal nasal mucosa.
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http://dx.doi.org/10.1186/s40248-017-0110-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5706351PMC
November 2017

Radon-enriched hot spring water therapy for upper and lower respiratory tract inflammation.

Otolaryngol Pol 2017 Aug;71(4):8-13

Department of Otolaryngology, University of Siena, Italy.

Background Radon-222-enriched hot spring therapy, which is characterized by a safe level of radioactivity, is used for the treatment of rheumatic disorders, and its efficacy has already been studied in several clinical trials. Radon-water inhalation therapy for the treatment of upper and lower airway inflammatory diseases is used in many hot springs centers. However, its application has not been reviewed to date. Methods We systematically searched the PubMed and Scopus databases for clinical trials published in the last 20 years in which objective parameters of upper and lower airway function had been tested before and after radon-enriched inhalation treatment. Results Four prospective studies were found: 1 asthma trial, 1 placebo-controlled chronic rhinosinusitis trial, 1 upper respiratory tract inflammation with nasal obstruction trial, and 1 case-control allergic rhinitis trial. Patients were treated with nasal inhalations of radon-enriched water for 12 to 28 days and were assessed at baseline and after therapy. After 2 weeks of treatment, nasal resistance decreased, flow increased, mucociliary clearance was enhanced, ciliated-to-muciparous cell ratio increased, and %FEV1 increased in asthmatic patients. Conclusion Radon-enriched inhalation therapy improves objective indicators of nasal function in allergic rhinitis and chronic rhinosinusitis, and causes relief of pulmonary obstruction in asthma.
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http://dx.doi.org/10.5604/01.3001.0010.2242DOI Listing
August 2017

HMGB1 in the Pathogenesis of Nasal Inflammatory Diseases and its Inhibition as New Therapeutic Approach: A Review from the Literature.

Int Arch Otorhinolaryngol 2017 Oct 4;21(4):390-398. Epub 2017 Jan 4.

ENT Department, University of Siena, Siena, Italy.

 This study is a systematic review on recent developments about the importance of HMGB1 protein in the pathogenesis of rhino-sinusal inflammatory diseases. We also report data on the use of 18-β-glycyrrhetic acid (GA), which has been shown able to inhibit the pro-inflammatory activities of HMGB1, in young patients affected by allergic rhinitis and complaining of nasal obstruction as main symptom.  The objective of this study was to review the literature to demonstrate the importance of HMGB1 in the pathogenesis of nasal inflammatory disorders and understand whether the inhibition of this protein may be an efficacious and innovative therapeutic strategy for patients with rhino-sinusal inflammation.  Authors searched for pertinent articles indexed in PubMed, Scopus, and other health journals between 2004 and 2015. In total, the authors gathered 258 articles: 219 articles through Pubmed and 39 articles from other search engines. The search terms used were as follows: HMGB1 AND "respiratory epithelium," "airway inflammation," "rhinitis," "allergic rhinitis," "rhinosinusitis," "nasal polyposis," "glycyrrhetic acid," "children."  Patients with severe symptoms have the highest serum levels and the highest extracellular expression of HMGB1. GA inhibits HMGB1 chemotactic and mitogenic function by a scavenger mechanism on extracellular HMGB1 accumulation stimulated by lipopolysaccharides in vitro. Treatment of allergic rhinitis with GA is not associated with local or systemic side effects in children and adults.
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http://dx.doi.org/10.1055/s-0036-1597665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5629088PMC
October 2017

Radioactive Merano SPA Treatment for Allergic Rhinitis Therapy.

Int J Otolaryngol 2016 8;2016:2801913. Epub 2016 Sep 8.

ENT Department, University of Siena, Siena, Italy.

Allergic rhinitis is a common nasal disorder with a high impact on quality of life, high social costs in therapies, and a natural development towards asthma. Pharmacological therapy is based on several genres of medications, of which intranasal corticosteroids are currently the most widespread. Thermal water treatment has traditionally been used as adjunctive treatment for chronic rhinitis and sinusitis. The present study was carried out to assess the clinical efficacy of nasal inhalation of radioactive oligomineral water vapours from the Merano hot spring and to compare it with the clinical efficacy of mometasone furoate nasal spray. A comparative prospective study was performed in 90 allergic patients treated at Merano hot springs: a group of 54 subjects treated with radioactive thermal oligomineral water and a control group of 36 subjects treated with mometasone nasal spray. Patients of both groups were assessed before and after treatment by Sino-Nasal Outcome Test questionnaire, active anterior rhinomanometry with flow and resistance monitoring, measurement of mucociliary transport time, and cytological examination of nasal brushing/scraping. The study showed that inhalation treatment with radioactive hydrofluoric thermal water for two weeks produces an objective clinical and cytological improvement in allergic patients, similar to that obtained with mometasone furoate nasal spray.
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http://dx.doi.org/10.1155/2016/2801913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031909PMC
September 2016

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

Int Forum Allergy Rhinol 2015 Jun 26;5(6):557-62. Epub 2015 Mar 26.

Department of Head and Neck Surgery-Institute of Otorhinolaryngology, Catholic University School of Medicine and Surgery, Rome, Italy.

Background: 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.

Methods: Between November 2012 and June 2013, we selected 70 patients with chronic eosinophilic inflammation (average age 41.8 years) who were classified into the following groups: persistent allergic rhinitis (group 1), noninfectious non-allergic rhinitis with eosinophilia syndrome (group 2) and chronic rhinosinusitis with polyps (group 3). Finally, we enrolled 20 healthy subjects as controls (group 4). All patients underwent symptoms score questionnaire based on a visual analogue scale, nasal endoscopy and/or computed tomography (CT) scan, and allergy testing. Nasal cytology by scraping of the mucosa and GM-CSF assays in nasal lavage were performed in all subjects.

Results: Detectable levels of GM-CSF were found in 34 of 70 (48.57%) patients, with an average concentration of 2.67 ± 0.8 pg/mL, whereas in controls only 1 of 20 individuals showed detectable GM-CSF levels. Eosinophil infiltration was significantly higher in patients with detectable GM-CSF compared to those with undetectable levels (49.4% vs 39.2%, respectively; p < 0.05). Furthermore, significant weakly-moderate correlation was found between GM-CSF levels and percentage of eosinophil infiltration in tissue (p < 0.05). Correlation between symptom scores and GM-CSF levels was significant only in group 2, which showed higher average concentrations of GM-CSF compared to groups 1 and 3 (2.9 pg/mL vs 1.6 pg/mL and 1.8 pg/mL, respectively; p < 0.05).

Conclusion: Our data confirm that GM-CSF is more frequently detectable in nasal lavages of patients affected by chronic sinonasal eosinophilic inflammation than in controls. Statistical analyses revealed a significant weakly-moderate correlation between GM-CSF levels in nasal lavage of all patients and percentage of eosinophil infiltration of nasal mucosa.
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http://dx.doi.org/10.1002/alr.21519DOI Listing
June 2015

Chrono-proteomics of human saliva: variations of the salivary proteome during human development.

J Proteome Res 2015 Apr 19;14(4):1666-77. Epub 2015 Mar 19.

§Dipartimento di Scienze Chirurgiche, Università di Cagliari, Cittadella Universitaria di Monserrato, S. P. Monserrato Sestu Km 0.700, Monserrato (CA) 09042, Italy.

An important contribution to the variability of any proteome is given by the time dimension that should be carefully considered to define physiological modifications. To this purpose, whole saliva proteome was investigated in a wide age range. Whole saliva was collected from 17 preterm newborns with a postconceptional age at birth of 178-217 days. In these subjects sample collection was performed serially starting immediately after birth and within about 1 year follow-up, gathering a total of 111 specimens. Furthermore, whole saliva was collected from 182 subjects aged between 0 and 17 years and from 23 adults aged between 27 and 57 years. The naturally occurring intact salivary proteome of the 316 samples was analyzed by low- and high-resolution HPLC-ESI-MS platforms. Proteins peculiar of the adults appeared in saliva with different time courses during human development. Acidic proline-rich proteins encoded by PRH2 locus and glycosylated basic proline-rich proteins encoded by PRB3 locus appeared following 180 days of postconceptional age, followed at 7 months (±2 weeks) by histatin 1, statherin, and P-B peptide. The other histatins and acidic proline-rich proteins encoded by PRH1 locus appeared in whole saliva of babies from 1 to 3 weeks after the normal term of delivery, S-type cystatins appeared at 1 year (±3 months), and basic proline-rich proteins appeared at 4 years (±1 year) of age. All of the proteinases involved in the maturation of salivary proteins were more active in preterm than in at-term newborns, on the basis of the truncated forms detected. The activity of the Fam20C kinase, involved in the phosphorylation of various proteins, started around 180 days of postconceptional age, slowly increased reaching values comparable to adults at about 2 years (±6 months) of age. Instead, MAPK14 involved in the phosphorylation of S100A9 was fully active since birth also in preterm newborns.
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http://dx.doi.org/10.1021/pr501270xDOI Listing
April 2015

A prospective open-label study to assess the efficacy and safety of a herbal medicinal product (Sinupret) in patients with acute rhinosinusitis.

ORL J Otorhinolaryngol Relat Spec 2015 30;77(1):27-32. Epub 2015 Jan 30.

ENT Department, University of Medicine and Surgery, Siena, Italy.

Aims: We present a multicenter, prospective, open-label study to assess the efficacy and safety of a phytomedicine. The aim of the research was to evaluate the efficacy and safety of 14 days of treatment with Sinupret for acute rhinosinusitis. Sinupret is a herbal preparation used to restore and maintain the physiological function of the membranes in the sinus cavity.

Methods: Sixty patients with acute rhinosinusitis based on the EPOS guidelines were enrolled in the study. Thirty patients were treated with Sinupret Forte, while 30 patients were treated with intranasal fluticasone furoate. The criteria for the evaluation of efficacy were the major symptom scores according to the investigator and the Health-Related Quality of Life score. The criteria used to evaluate safety were the number of patients with adverse events, the patients' vital signs, and laboratory safety.

Results: All patients considered showed significant improvements in symptoms. Among the patients treated with Sinupret, none had an adverse event, while 3 patients treated with fluticasone furoate had minor adverse events. The patients' vital signs and laboratory values were normal.

Conclusions: The results of this study suggest that this phytomedicinal preparation has a significant level of efficacy in acute rhinosinusitis and that treatment is safe.
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http://dx.doi.org/10.1159/000370123DOI Listing
November 2015

An old drug for a new application: carbazochrome-sodium-sulfonate in HHT.

J Clin Pharmacol 2015 May 16;55(5):601-2. Epub 2015 Jan 16.

Department of Head and Neck Surgery, Catholic University of Sacred Heart School of Medicine, Rome, Italy.

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http://dx.doi.org/10.1002/jcph.452DOI Listing
May 2015

International study of the incidence of particular types of septal deformities in chronic rhinosinusitis patients: the outcomes from five countries.

Am J Rhinol Allergy 2014 Sep-Oct;28(5):404-13

Department of Otolaryngology-Head and Neck Surgery, Osmangazi University, Faculty of Medicine, Eskisehir, Turkey.

Background: Chronic rhinosinusitis (CRS) may be more frequent in patients with particular types of septal deformities. The aim of this article was to investigate the incidence of particular types of septal deformities in adult CRS patients and healthy volunteers in various countries to determine whether some of them are more frequent in those groups.

Methods: This international multicentric study involved 505 subjects from five countries: Croatia, Romania, Italy, Russia, and Turkey. The types of septal deformities were observed and grouped according to the Mladina classification. Subjects were examined by means of native anterior rhinoscopy, anterior rhinoscopy after decongestion, and fiber endoscopy with topical anesthesia. CRS patients have been diagnostically proved by computed tomography scanning of the paranasal sinuses.

Results: Considering the CRS patients, the prevalence of so-called vertical deformities (types 2, 3, and 4) was seen. Among them, type 3 deformity was found most frequently in Turkey, Croatia, Italy, and Romania.

Conclusion: Type 3 deformity has been found frequently in CRS patients in all five of the countries. Russian subjects exhibited a high frequency of type 4 deformity. Because this type consists of types 2 and 3, the later, again, has been proven to be prevalent in CRS patients also in this group of patients.
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http://dx.doi.org/10.2500/ajra.2014.28.4099DOI Listing
June 2015

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

Int Forum Allergy Rhinol 2014 Aug 2;4(8):617-24. Epub 2014 Jul 2.

Department Head and Neck Surgery-Institute of Otorhinolaryngology, Catholic University School of Medicine and Surgery, Rome, Italy.

Background: 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.

Methods: The study was an analytic cross-section study, level of evidence 3b. Patients (n = 80) with nasal hypereosinophilia were randomly recruited and grouped in the following categories: persistent allergic rhinitis (AR) (n = 25), nonallergic rhinitis with eosinophilia syndrome (NARES) (n = 30), and chronic rhinosinusitis with polyps (CRSwNP) (n = 25). Non-rhinitic volunteers (n = 20) were recruited as controls. CCL24 and CCL26 concentrations were measured by enzyme-linked immunosorbent assay (ELISA) Quantikine Human Immunoassays (R&D Systems, Minneapolis, MN) in nasal lavage fluids. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped from the inferior turbinate.

Results: Mean CCL26 levels were significantly higher (p < 0.05) in AR and in NARES (132.0 pg/mL and 187.63 pg/mL, respectively) than in the control group (13.5 pg/mL); in patients with CRSwNP, CCL26 values were increased compared to controls even though the difference was not statistically significant (58.9 pg/mL vs 16.5 pg/mL). Mean CCL24 levels measured in AR, NARES, and CRSwNP were significantly increased (p < 0.05) compared to controls (96.7 pg/mL, 135.4 pg/mL, and 107.0 pg/mL, respectively, vs 32.2 pg/mL). Moreover, we observed a significant correlation between CCL24 and CCL26 levels, evaluating them intraindividually by Spearman's rank correlation test. Finally, a significant correlation was found between CCL24 and CCL26 levels and the percentage of eosinophilic infiltration of nasal mucosa.

Conclusion: Our data suggest that CCL26 and CCL24 are likely involved in the pathogenesis of chronic nasal hypereosinophilia, with a complex cooperation and different involvement of the various members of eotaxin family. Further studies are necessary to better understand the actual physiopathologic mechanism, possible clinical relevance, and therapeutic implications.
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http://dx.doi.org/10.1002/alr.21348DOI Listing
August 2014

The natural course of allergic rhinitis: a 32-year follow-up study.

Acta Otolaryngol 2013 Nov;133(11):1188-95

ENT Department, Catholic University of the Sacred Heart, Medical School , Rome.

Conclusion: Early intervention may change the natural course of allergic rhinitis, preventing the progression to asthma. In particular, immunotherapy guarantees remission of local symptoms and valid protection against local and bronchial complications. Symptomatic treatment represents a valid alternative; it is always to be preferred to abstention from any treatment.

Objectives: Data emerging from various studies on the increase of the prevalence of allergic rhinitis in recent decades appear to be widely dishomogeneous. Another point that needs clarification is the relationship between allergic rhinitis and lower airways pathologies such as asthma or bronchitis.

Methods: We followed the evolution of allergic rhinitis in a group of patients for the last 30 years to highlight the efficacy of different treatments in the prevention of complications, specifically asthma. After 32 years (1980-2012), 46/73 (63%) patients completed the follow-up.

Results: Symptomatic drugs exhibited maximum efficacy from the third to the eighth year, with 13 of 15 patients reporting an improvement of symptoms; immunotherapy achieved the best efficacy starting from the sixth to the tenth year (8 of 10 patients recovered). Subsequently, improvements decreased in the two groups, to a steady level of 11 of 15 and 6 of 10 recovered patients. Asthma developed in 3 of 46 patients and only among patients that were not treated.
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http://dx.doi.org/10.3109/00016489.2013.815362DOI Listing
November 2013

Nasal obstruction as a key symptom in allergic rhinitis: efficacy and safety of a medical device in children.

Otolaryngol Pol 2012 Jul-Aug;66(4):249-53. Epub 2012 May 24.

Department of Otolaryngology, University of Siena, Italy.

Background: Allergic rhinitis (AR) is a global health problem that has increased rapidly in prevalence over the past few decades. Nasal congestion, which represents a cardinal symptom of AR, appears to be difficult to treat and, especially for pediatric population, therapies that are both well tolerated and effective in relieving nasal congestion are needed. The aim of the present study was to evaluate the safety and clinical effectiveness of the medical device (lactoferrin, carboximetil β-glucan, D-panthenol, dipotassium glycyrrhizinate) in reducing the allergic rhinitis symptoms.

Methods: A multicenter prospective study with a pre-post design was performed consecutively enrolling 100 pediatric patients of both genders affected by persistent AR. Patients received 2 puffs into each nostril 2 times a day over the course of 4 weeks. The severity of AR symptoms, as measured by VAS score, was assessed before and after treatment. The main outcomes were improvement in each symptom score and in overall symptom burden (as measured by average symptom scores). Differences in symptoms scores measured before and after treatment were compared using paired-sample Wilcoxon signed rank test. The proportion of participants with adverse effects attributed to the treatment was also computed.

Results: All considered symptoms, including nasal congestion, significantly improve after treatment (p<0.001), while only 9 patients suffered adverse effects (itch, burning sensation, dryness).

Conclusion: These results confirm the efficacy and safety of this medical device in pediatric population.
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http://dx.doi.org/10.1016/j.otpol.2012.05.019DOI Listing
January 2014

Exhaled nitric oxide measurement in patients affected by nasal polyposis.

Otolaryngol Head Neck Surg 2012 Aug 2;147(2):351-6. Epub 2012 Apr 2.

ENT Institute, Catholic University of Sacred Heart Rome, Rome, Italy.

Objectives: Nitric oxide (NO) is produced in the respiratory tract with a major contribution coming from paranasal sinuses and the nose. The pathophysiological role of NO in the airways has been debated. The aims of this study were to measure fraction of exhaled NO (FENO), a validated marker of airway inflammation, in patients affected by nasal polyposis with and without asthma; to assess the importance of FENO measurement in detecting subclinical involvement of lower airways in patients with clinical rhinosinusal symptoms; and to clarify the impact of endoscopic surgical removal of polyps on airway inflammation.

Setting: The study was conducted at the O.R.L. Clinic and Clinical Pharmacology Unit, University Hospital Agostino Gemelli, Rome, Italy.

Study Design: Prospective study.

Subjects And Methods: Concentrations of FENO were measured with the NIOX system (Aerocrine, Stockholm, Sweden) by using a single-breath online method, according to the American Thoracic Society guidelines.

Results: Compared with those in healthy subjects (15 [11-19] ppb, n = 15; P < .0001), FENO values were elevated in patients with nasal polyposis (41 [21-77] ppb, n = 43). There was no significant difference in FENO concentrations between asthmatic and nonasthmatic patients with nasal polyposis (P = .73). Concentrations of FENO in patients with nasal polyposis were decreased after surgery (64.2 [30.0-132.7] ppb vs 56.0 [26.4-73.8] ppb, respectively; P = .03).

Conclusion: The fraction of exhaled NO is elevated in the inflammatory process involving both the rhinosinusal district and lower airways, supporting the one-airway disease hypothesis.
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http://dx.doi.org/10.1177/0194599812442322DOI Listing
August 2012

Management of foreign bodies in the airway and oesophagus.

Int J Pediatr Otorhinolaryngol 2012 May 24;76 Suppl 1:S84-91. Epub 2012 Feb 24.

Hospital de Pediatría Juan P Garrahan, Buenos Aires, Argentina.

Background: Ingestion and/or aspiration of foreign bodies (FB) are avoidable incidents. Children between 1 and 3 years are common victims for many reasons: exploration of the environment through the mouth, lack of molars which decreases their ability to properly chew food, lack of cognitive capacity to distinguish between edible and inedible objects, and tendency to distraction and to perform other activities, like playing, whilst eating. Most FBs are expelled spontaneously, but a significant percentage impacts the upper aerodigestive tract. Approximately 80% of children's choking episodes are evaluated by pediatricians. The symptoms of aspiration or ingestion of FBs can simulate different paediatric diseases such as asthma, croup or pneumonia, delaying the correct diagnosis.

Symptoms: There are three clinical phases both in aspiration and in ingestion of FBs: initial stage (first stage or impaction or FB) shows choking, gagging and paroxysms of coughing, obstruction of the airway (AW), occurring at the time of aspiration or ingestion. These signs calm down when the FB lodges and the reflexes grow weary (second stage or asymptomatic phase). Complications occur in the third stage (also defined as complications' phase), when the obstruction, erosion or infection cause pneumonia, atelectasis, abscess or fever (FB in AW), or dysphagia, mediastinum abscess, perforation or erosion and oesophagus (FB in the oesophagus). The first symptoms to receive medical care may actually represent a complication of impaction of FB. LOCATIONS AND MANAGEMENT: Determining the site of obstruction is important in managing the problem. The location of the FB depends on its characteristics and also on the position of the person at the time of aspiration. Determining the site of obstruction is important in managing the problem. Larynx and trachea have the lowest prevalence, except in children under 1year. They are linked with the most dangerous outcomes, complete obstruction or rupture. Bronchus is the preferred location in 80-90% of AW's cases. Esophageal FBs are twice more common than bronchial FBs, although most of these migrate to the stomach and do not require endoscopic removal. Diagnosis of FB proceeds following the traditional steps, with a particular stress on history and radiological findings as goal standards for the FB retrieval. The treatment of choice for AW's and esophageal FBs is endoscopic removal. Endoscopy should be carried out whenever the trained personnel are available, the instruments are checked, and when the techniques have been tested. The delay in the removal of FBs is potentially harmful. The communication between the endoscopist and the anaesthesiologist is essential before the procedure to establish the plan of action; full cooperation is important and improves the outcome of endoscopy.

Conclusions: Ingestion and or aspiration of FB in children are multifactorial in their aetiology, in their broad spectrum of different resolutions for the same FB and in the response of each patient to the treatment. Prevention remains the best treatment, implying an increased education of parents on age-appropriate foods and household items, and strict industry standards regarding the dimensions of toy parts and their secure containers.
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http://dx.doi.org/10.1016/j.ijporl.2012.02.010DOI Listing
May 2012