NMR Untargeted and HPLC-MS/MS Targeted Metabolomic Approaches for Evaluating Styrene Exposure in the Urine of Shipyard Workers.

Due to its chemical properties, styrene is largely employed in the manufacturing of several products including rubber, polymers and resins, and it is particularly suitable for shipbuilding industry purposes. In this context, the main exposure to styrene occurs in occupational settings. Despite its widespread use, its long-term effects on human health at the occupational level are still unclear. The aim of this pilot study was to evaluate changes in styrene exposure biomarkers related to the metabolic and oxidative stress profiles in the urine of seventeen shipyard workers and seventeen non-exposed subjects. Urinary metabolites were assessed by means of NMR spectroscopy, including mandelic and phenylglyoxylic acids; four oxidative stress biomarkers, namely 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine and 3-nitrotyrosine, were evaluated via HPLC-MS/MS. The metabolic profiles of exposed workers showed both long- and short-term metabolic responses to styrene exposure compared to non-exposed subjects. From the comparison between non-exposed and before-shift workers, only 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine levels were significantly different (long term exposure response). At the same time, comparing the non-exposed group with after-shift workers, we observed lower levels of pseudouridine and 1-methylnicotinamide and higher glutamine levels in after-shift workers. The comparison between before-shift and after-shift workers showed that 8-oxo-7,8-dihydroguanine significantly increased after the shift, suggesting its involvement in the exposure to styrene (short-term exposure response). The obtained results, although preliminary, allow us to lay the basis for further human studies aimed at establishing a global understanding of styrene metabolism.

Oxidative stress in occupational exposure to styrene vapors and dangerous chemicals in the shipbuilding industry.

Introduction: In the shipbuilding industry, workers are exposed to a variety of dangerous chemicals, styrene being one of them. The International Agency for Research on Cancer classified styrene as a chemical belonging to group 2A, which means it is probably carcinogenic to humans. This study aimed at evaluating the oxidative stress effects due to occupational exposure to styrene and other chemicals. Materials and methods: Styrene urinary metabolites, such as mandelic acid and phenylglyoxylic acid, and the urinary biomarkers of oxidative stress, i.e., oxidation products of DNA and RNA and of proteins, were measured in a group of 17 workers and compared to the concentrations found in a group of 17 healthy volunteers who had not been exposed to chemicals. Results and discussion: Statistically significant differences were found for 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxiguanosine (8-oxodGuo) concentrations that are higher in workers than in the control group. The workers performing the tasks of painting are the most exposed to styrene and show higher concentrations of 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Workers performing the tasks of wood refining and welding are less exposed to styrene but have higher concentrations of 8-oxoGua and 8-oxodGuo. Conclusion: The exposure scenario in shipbuilding is a complex one, in which different xenobiotics are simultaneously present. The oxidative stress effect biomarkers, obtained from the oxidation product of RNA and DNA, are promising, sensitive, but not specific.

Vascular Factors in Patients with Midlife Sensorineural Hearing Loss and the Progression to Mild Cognitive Impairment.

Background and Objectives: Midlife hearing loss (HL) has been considered as a major modifiable risk factor for a later-life progression to dementia. Our aim was to detect a link between precocious sensorineural hearing loss (SNHL) and mild cognitive impairment (MCI) and their association to putative risk factors for a common pathology. Materials and methods: In this study, a retrospective case-control study was carried out. A total of 112 patients were enrolled as following: 81 patients with bilateral SNHL and 31 subjects with normal hearing, whose ages ranged from 50 to 65 years. Both groups performed pure tone audiometry, a tinnitus handicap inventory (THI), Mini-Mental State examination (MMSE), and the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS-A and HADS-D). Results: The mean age was 58 ± 5.2 in SNHL patients and 53.2 ± 4.8 in the control group. The mean pure tone average in the SNHL group was 40.2 ± 18.7 dB HL on the right side and 41.2 ± 17.2 dB HL on the left side, while in the control group it was 12.5 ± 2.8 dB HL on right side and 12.4 ± 3.1 dB HL on left side. About 64% of patients with SNHL exhibited comorbidities, and the most common condition was hypertension. Altered MoCA test scores were significantly related to the pure tone averages in patients with SNHL compared to the control group (p = 0.0004), while the differences in the HADS-A and HADS-D were not significant. Furthermore, a significant correlation was observed in SNHL patients between an altered MoCA test and hypercholesterolemia (p = 0.043). Conclusions: Hearing impairment and screening tests to detect MCI should be considered in the midlife in order to carry out strategies to prevent the progression to dementia. Hypertension and hypercholesterolemia are two risk factors in the development of endothelial dysfunction, oxidative stress, and vascular inflammation, and may represent the common pathology linking the inner ear and brain damage.

Mometasone Furoate in Non-Allergic Rhinitis: A Real-Life Italian Study.

BACKGROUND: In order to evaluate the efficacy of intranasal mometasone furoate in patients with non-allergic rhinitis (NAR), a real-life, observational, prospective study is performed. METHODS: Thirty-one patients (age 18-64 years) receive intranasal (mometasone furoate, 200 µg b.i.d. for 15 consecutive days per month for 6 consecutive months), plus isotonic nasal saline. The cytologic pattern of local inflammation, nasal airflow, through peak nasal inspiratory flow (PNIF), quality of life (QoL), through the rhinitis quality of life questionnaire (RQLQ), the sinonasal outcome test (SNOT-22), the short-form 36-item health survey (SF-36v2), and the combined symptom medication score (CSMS), and, finally, olfactory function, through Sniffin' sticks-16 identification test (SSIT-16), are evaluated at baseline and after treatment. RESULTS: NARNE is the most frequent cytological pattern (48% of the total sample). The therapeutic response shows improvement in olfactory function and QoL. CONCLUSIONS: The results of this study confirm that intranasal mometasone furoate is an effective treatment for patients with NAR.

Calprotectin in nasal secretion: a new biomarker of non-type 2 inflammation in CRSwNP.

Objective: We analysed calprotectin in sinonasal secretions of different chronic rhinosinusitis with nasal polyps (CRSwNP) endotypes to assess its role as a biomarker of non-type 2 inflammation. Methods: We included primary diffuse CRSwNP patients (n = 41) and three different control groups [non-allergic rhinitis (NAR) (n = 13), non-allergic eosinophilic syndrome (NARES) (n = 10) and healthy subjects (n = 12)]. Calprotectin levels were detected in nasal secretions using a chemiluminescent immunoassay (CLIA). Results: Calprotectin levels in nasal secretions were significantly higher in all non-type 2 endotypes of CRSwNP compared to healthy controls (p < 0.05). In contrast, in type-2 CRSwNP calprotectin was significantly lower compared to controls (p < 0.05). A significant correlation between calprotectin levels and neutrophilic count/HPF was found in CRSwNP (p < 0.01). Clinically, mean levels of calprotectin and neutrophilia were significantly higher in patients who previously underwent 3 or more endoscopic sinus surgeries (p < 0.05). Conclusions: Calprotectin in nasal secretions may be a biomarker of non-type 2 inflammation. Low levels of calprotectin are indicative of a type-2 immune response in both CRSwNP and non-allergic rhinitis. We observed that calprotectin levels significantly increased based on the number of previous surgeries.

Benign paroxysmal positional vertigo: is hypothyroidism a risk factor for recurrence?

Objective: To investigate the relationship between risk of Benign Paroxysmal Positional Vertigo (BPPV) recurrence and hypothyroidism treated with hormone replacement therapy (HRT). Methods: 797 patients with idiopathic BPPV were divided into two groups: 250 patients with recurrence of BPPV (R-BPPV) and 547 patients without recurrence (NR-BPPV). Regarding patients with thyroid disease on HRT, we collected serum test results of thyroid-stimulating hormone (TSH), free triiodothyronine f-T3, free thyroxine f-T4, thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab). Results: Hypothyroidism in long-term HRT was found in 61/250 (24.4%) patients of the R-BPPV group vs 79/547 (14.4%) of the NR-BPPV-group (p = 0.0006). Hashimoto thyroiditis (HT) was associated with recurrence (p < 0.0001). A significant correlation was found between recurrence and level of serum TPO-Ab (p = 0.0117) and TG-Ab (p = 0.0025), but not with mean serum TSH, f-T3 and f-T4. Conclusions: We assume that patients with hypothyroidism in HRT have an increased risk of BPPV recurrence, which is particularly strong for patients with HT and positive thyroid antibodies, suggesting an association between autoimmunity and recurrent vertigo.

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

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 (p = 0.0074, OR = 2.31), respectively 12.6% and 5%. Also the rate of bilateral disease (p = 0.0063, OR = 4.72) and multicanalar involvement (p = 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 (p = 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.

Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP.

BACKGROUND: in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies. OBJECTIVE: determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP). METHODS: Eighty patients treated with ESS plus mometasone-furoate 200 µg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017-December 2018) in this prospective observational study. Type and grade of inflammation were evaluated preoperatively by nasal cytology. Based on cellular pattern, patients were grouped as neutrophilic (n = 20), eosinophilic (n = 38), or mixed eosinophil-neutrophilic (n = 22). SNOT-22 and Lund-Kennedy Endoscopic Score were evaluated at baseline and at 3, 6, 9, and 12 months after surgery and used to define disease control. RESULTS: The cumulative probability of remaining free of significant modification of endoscopic score (Lund-Kennedy Endoscopic Score >2) at 3, 6, 9, and 12 months was 0.84, 0.76, 0.71, and 0.68, respectively. At 12-month postoperative evaluation good disease control was observed in 54 of 80 patients (67.5%). Compared to those with good post-operative disease control, those with poor control had a significantly higher pre-operative mean count of eosinophils and neutrophils (p < 0.05). The preoperative inflammatory pattern was associated with relative risk of poor control: neutrophilia (RR: 3.10; CI:1.24-7.71), eosinophilia (RR:8.42; CI:2.72-15.12), and mixed eosinophilic and neutrophilic (RR:25.11; CI:19.41-30.01). We also confirmed that asthma, allergy, blood eosinophilia, and ASA triad could predict poor control. CONCLUSIONS: The type and load of inflammation evaluated preoperatively and selected clinical factors can predict poor control of CRSwNP treated with ESS and local corticosteroids.

Impact of Tracheal Tube on Swallowing in Post-Operative Head and Neck Cancer Patients: Scintigraphic Analysis.

Dysphagia is common in tracheostomized patients who underwent head and neck surgery for cancer treatment. The objective of this study was to evaluate, by means of oropharyngoesophageal scintigraphy (OPES), the impact of an occluded tracheal tube (TT) on swallowing in patients treated for head and neck cancer before hospital discharge, to provide further information to the benefit of out-patient care management. From October 2018 to November 2019, we enrolled 19 tracheostomized patients (6 females and 13 males; mean age 61 years) who underwent primary surgical resection of head and neck tumor and swallowing rehabilitation during hospitalization. All subjects underwent a double-standard OPES, one with occluded tracheal tube and the other without TT, with their tracheal stoma being closed directly by a plaster. For each study, we assessed and compared the following quantitative parameters: oral transit time (OTTsec), pharyngeal transit time (PTTsec), esophageal transit time (ETTsec), oral retention index (ORI%), pharyngeal retention index (PRI%), esophageal retention index (ERI%), and aspiration percentage (AP%). The mean values of OTT, PTT, ORI%, PRI%, and ERI% were abnormal during OPES both with TT and without TT and did not statistically differ between the two tests (p > 0.05). Aspiration was detected in 4 cases out of 19 (21.05%) cases during OPES with TT and in 4/19 (21.05%) cases without TT who showed a mean AP% of 11.4% and 11.5% respectively (p > 0.05). Patients with abnormal AP% (> 0%) during OPES with TT showed aspiration signs without TT. Our study showed that the mere presence of a closed tracheal tube does not impact significantly the oropharyngeal transit of bolus during swallowing. This result suggests the possibility to maintain a small-diameter occluded tracheal tube in place for the postsurgical management of head and neck cancer patients.

Clinical and surgical management of patients with head and neck cancer in a COVID-19 dedicated center in Italy.

INTRODUCTION: For the EARs NOSE AND THROAT (ENT) surgeon, there are many challenges that show-up in the clinical management of a patient affected by a head and neck cancer during COVID-19 pandemic, especially in the postoperative period. METHODS: During the acute COVID-19 emergency phase in Italy, we analyzed the management of a patient affected by a head and neck cancer. We reported several clinical data about the hospitalization period, pointing out the difficulties encountered both from clinical and management point of view. RESULTS: During pandemic, we admitted 27 oncological patients at our ENT Department. Delays in surgical procedures, complications of hospitalizations, need for radiological studies, and possible transfer to other hospital ward, due to suspect SARS-CoV-2 infection, were registered. CONCLUSIONS: The changes in the whole health care system during the COVID-19 pandemic have impacted the management of patients with head and neck cancer, generating several clinical challenges for the ENT surgeon.

Is drug consumption correlated with benign paroxysmal positional vertigo (BPPV) recurrence?

BACKGROUND: Benign paroxysmal positional vertigo (BPPV) is the most common cause of peripheral vertigo and its recurrence is fairly common. Several studies correlated the pathophysiological role of different comorbidities-such as diabetes, osteoporosis, vascular, psychiatric and autoimmune diseases-in the development and recurrence of BPPV. The aim of this study is to analyse the pharmacological history of patients with idiopathic BPPV in relation to the risk of developing recurrence. METHODS: Data regarding 715 patients aged 12 to 87 years (62.7 ± 14) with non-traumatic BPPV were retrospectively evaluated. These refer to the Vestibular Service, day clinic, and were collected over a 4-year period, between 2014 and 2018. RESULTS: Recurrence of BPPV was observed in 220/715 patients (30.76%). A statistically significant correlation (p < 0.006) between recurrence and drug consumption was observed for SNC agents (p = 0.0001), vitamin D (p = 0.0005), PPI (p = 0.0007), thyroid hormones (p = 0.0011), and antihypertensives in single use (p = 0.0031). On the contrary, cholesterol-lowering statin drugs, hypoglycaemic agents, antiplatelet medication, estroprogestins and combination of two or more antihypertensives did not show significant correlation. CONCLUSION: Specific classes of drugs are significantly associated with recurrence: antihypertensive therapy with a singular agent, central nervous system agents, PPIs, vitamin D and thyroid hormones. On the other hand, the lack of correlation between some drugs and recurrence could be linked to the effectiveness of therapy in controlling hypertension, dyslipidaemia and diabetes. Pharmacological history is an essential tool to identify patients at risk of BPPV recurrence.