In Vivo Identification of H3K9me2/H3K79me3 as an Epigenetic Barrier to Carcinogenesis.

The highly dynamic nature of chromatin's structure, due to the epigenetic alterations of histones and DNA, controls cellular plasticity and allows the rewiring of the epigenetic landscape required for either cell differentiation or cell (re)programming. To dissect the epigenetic switch enabling the programming of a cancer cell, we carried out wide genome analysis of Histone 3 (H3) modifications during osteogenic differentiation of SH-SY5Y neuroblastoma cells. The most significant modifications concerned H3K27me2/3, H3K9me2, H3K79me1/2, and H3K4me1 that specify the process of healthy adult stem cell differentiation. Next, we translated these findings in vivo, assessing H3K27, H3K9, and H3K79 methylation states in biopsies derived from patients affected by basalioma, head and neck carcinoma, and bladder tumors. Interestingly, we found a drastic decrease in H3K9me2 and H3K79me3 in cancer specimens with respect to their healthy counterparts and also a positive correlation between these two epigenetic flags in all three tumors. Therefore, we suggest that elevated global levels of H3K9me2 and H3K79me3, present in normal differentiated cells but lost in malignancy, may reflect an important epigenetic barrier to tumorigenesis. This suggestion is further corroborated, at least in part, by the deranged expression of the most relevant H3 modifier enzymes, as revealed by bioinformatic analysis. Overall, our study indicates that the simultaneous occurrence of H3K9me2 and H3K79me3 is fundamental to ensure the integrity of differentiated tissues and, thus, their combined evaluation may represent a novel diagnostic marker and potential therapeutic target.

A novel tumour enhancer function of Insulin-like growth factor II mRNA-binding protein 3 in colorectal cancer.

CRC cells evolve a variety of strategies to limit or circumvent apoptosis cell death. RNA binding proteins (RBPs) regulate many of the molecular mechanisms that underlie the development of cancer. The insulin-like growth factor II mRNA-binding proteins (IMP) family are oncofoetal RBPs, consisting of IMP1, IMP2 and IMP3, which have an important role in RNA metabolism. IMP3 is highly expressed in colorectal cancer (CRC) tissue, where its expression often correlates with poor prognosis. However, the role of IMP3 in CRC is not fully understood. IMP3 expression was analysed using a public database and by Western blotting and immunohistochemistry in human colon samples derived from patients with sporadic CRC and healthy subjects. To address whether IMP3 controls cancer cell survival, we analysed cell death pathways in in vitro and in vivo experiments after IMP3 downregulation by siRNA or an antisense oligonucleotide. IMP3 was highly expressed in CRC samples compared to normal control tissues. The knockdown of IMP3 enhanced a caspase-independent cell death in CRC cell lines. Furthermore, the treatment of CRC cells with IMP3 siRNA did not alter the expression of GSDMD, GPX-4 and the activated form of RIP3, three key molecules that govern pyroptosis, ferroptosis and necroptosis, respectively. Abrogation of IMP3 in CRC significantly reduced Bcl-2 and Bcl-xL mRNA and was associated with an altered mitochondrial membrane potential that allowed the nuclear migration of the apoptosis-inducing factor (AIF). Moreover, specific immunoprecipitation experiments on CRC human cell lines indicated that IMP3 binds Bcl-2 and Bcl-xL mRNA, suggesting that IMP3 acts as a regulator of the intrinsic apoptotic pathway through the surveillance of anti-apoptotic Bcl mRNA metabolism. Finally, we showed that IMP3 block inhibited the growth of CRC cell lines in vivo after transplantation into immunodeficient mice. Altogether, these data support a novel role for IMP3 in controlling the intrinsic caspase-independent apoptotic pathway in CRC.

Mirabegron relaxes arteries from human visceral adipose tissue through antagonism of α1-adrenergic receptors.

AIM: As inadequate perfusion has emerged as a key determinant of adipose tissue dysfunction in obesity, interest has grown regarding possible pharmacological interventions to prevent this process. Mirabegron has proved to improve insulin sensitivity and glucose homeostasis in obese humans via stimulation of ß3-adrenoceptors which also seem to mediate endothelium-dependent vasodilation in disparate human vascular beds. We characterized, therefore, the vasomotor function of mirabegron in human adipose tissue arteries and the underlying mechanisms. METHODS: Small arteries (116-734 µm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. After vessels had been contracted, changes in vascular tone in response to mirabegron were determined under different conditions. RESULTS: Mirabegron did not elicit vasorelaxation in vessels contracted with U46619 or high-K+ (both P > 0.05). Notably, mirabegron markedly blunted the contractile effect of the α1-adrenergic receptor agonist phenylephrine (P < 0.001) either in presence or absence of the vascular endothelium. The anti-contractile action of mirabegron on phenylephrine-induced vasoconstriction was not influenced by the presence of the selective ß3-adrenoceptor blocker L-748,337 (P < 0.05); lack of involvement of ß3-adrenoceptors was further supported by absent vascular staining for them at immunohistochemistry. CONCLUSIONS: Mirabegron induces endothelium-independent vasorelaxation in arteries from visceral adipose tissue, likely through antagonism of α1-adrenoceptors.

The prognostic value of subjective nasal symptoms and SNOT-22 score in middle ear surgery.

BACKGROUND: The relationship between nasal functions and middle ear surgery is still under debate. Nasal obstruction is considered as a negative prognostic factor in middle ear surgery. This is based on the theory that it may cause Eustachian tube dysfunction (ETD) by leading to reduced ventilation of the middle ear, as found in several patients with nasal septal deviation, chronic rhinitis and nasal polyps. OBJECTIVES: To assess how the subjective feeling of nasal function, evaluated by a preoperative questionnaire, may be predictive of surgical outcome and/or risk of failure in middle ear surgery. METHODS: We prospectively evaluated data of patients undergoing middle ear surgery for chronic otitis media with and without cholesteatoma. All patients completed the SNOT-22 and ETDQ-7 questionnaires. They underwent surgery for their pathology, as appropriate. RESULTS: The SNOT-22 score was higher in patients with retraction pocket and in patients whose retraction pockets recurred after surgery (p < 0.05). Patients with higher score at SNOT-22 questionnaire, were more likely to show recurrence of atelectasis aftersurgery. CONCLUSIONS: The SNOT-22 questionnaire, administrered before surgical procedure, can help in the identification of patients who are at risk of failure in the post-operative period, as well as ETDQ-7.

Anti-Inflammatory and Active Biological Properties of the Plant-Derived Bioactive Compounds Luteolin and Luteolin 7-Glucoside.

Flavonoids are interesting molecules synthetized by plants. They can be found abundantly in seeds and fruits, determining the color, flavor, and other organoleptic characteristics, as well as contributing to important nutritional aspects. Beyond these characteristics, due to their biochemical properties and characteristics, they can be considered bioactive compounds. Several interesting studies have demonstrated their biological activity in different cellular and physiological processes in high-order organisms including humans. The flavonoid molecular structure confers the capability of reacting with and neutralizing reactive oxygen species (ROS), behaving as scavengers in all processes generating this class of molecules, such as UV irradiation, a process widely present in plant physiology. Importantly, the recent scientific literature has demonstrated that flavonoids, in human physiology, are active compounds acting not only as scavengers but also with the important role of counteracting the inflammation process. Among the wide variety of flavonoid molecules, significant results have been shown by investigating the role of the flavones luteolin and luteolin-7-O-glucoside (LUT-7G). For these compounds, experimental results demonstrated an interesting anti-inflammatory action, both in vitro and in vivo, in the interaction with JAK/STAT3, NF-κB, and other pathways described in this review. We also describe the effects in metabolic pathways connected with inflammation, such as cellular glycolysis, diabetes, lipid peroxidation, and effects in cancer cells. Moreover, the inhibition of inflammatory pathway in endothelial tissue, as well as the NLRP3 inflammasome assembly, demonstrates a key role in the progression of such phenomena. Since these micronutrient molecules can be obtained from food, their biochemical properties open new perspectives with respect to the long-term health status of healthy individuals, as well as their use as a coadjutant treatment in specific diseases.

Changes in Speech Range Profile Are Associated with Cognitive Impairment.

BACKGROUND AND PURPOSE: The aim of this study was to describe the variations in the speech range profile (SRP) of patients affected by cognitive decline. METHODS: We collected the data of patients managed for suspected voice and speech disorders, and suspected cognitive impairment. Patients underwent an Ear Nose and Throat evaluation and Mini-Mental State Examination (MMSE). To obtain SRP, we asked the patients to read 18 sentences twice, at their most comfortable pitch and loudness as they would do in daily conversation, and recorded their voice on to computer software. RESULTS: The study included 61 patients. The relationship between the MMSE score and SRP parameters was established. Increased severity of the MMSE score resulted in a statistically significant reduction in the average values of the semitones to the phonetogram, and the medium and maximum sound pressure levels (p<0.001). The maximum predictivity of MMSE was based on the highly significant values of semitones (p<0.001) and the maximum sound pressure levels (p=0.010). CONCLUSIONS: The differences in SRP between the various groups were analyzed. Specifically, the SRP value decreased with increasing severity of cognitive decline. SRP was useful in highlighting the relationship between all cognitive declines tested and speech.

Anti-Inflammatory and Proliferative Properties of Luteolin-7-O-Glucoside.

Flavonoids display a broad range of structures and are responsible for the major organoleptic characteristics of plant-derived foods and beverages. Recent data showed their activity, and in particular of luteolin-7-O-glucoside (LUT-7G), in reduction of oxidative stress and inflammatory mechanisms in different physiological systems. In this paper, we tried to elucidate how LUT-7G could exert both antioxidant and anti-inflammatory effects in endothelial cells cultured in vitro. Here, we showed that LUT-7G is able to inhibit the STAT3 pathway, to have an antiproliferative action, and an important antioxidant property in HUVEC cells. These properties are exerted by the flavone in endothelial through the transcriptional repression of a number of inflammatory cytokines and their receptors, and by the inhibition of ROS generation. ROS and STAT3 activation has been correlated with the production of oxysterols and other hydroxylated fatty acids, and they have been recognized important as players of atherogenesis and cardiocirculatory system diseases. The analysis of the general production pathway of these hydroxylated species, showed a strong decrease of cholesterol hydroxylated species such as 7-alpha-hydroxicholesterol, 7-beta-hydroxicholesterol by the treatment with LUT-7G. This confirms the anti-inflammatory properties of LUT-7G also in the endothelial district, showing for the first time the molecular pathway that verify previous postulated cardiovascular benefits of this flavone.

Mechanisms of SGLT2 (Sodium-Glucose Transporter Type 2) Inhibition-Induced Relaxation in Arteries From Human Visceral Adipose Tissue.

As novel drug treatments for diabetes have shown favorable cardiovascular effects, interest has mounted with regard to their possible vascular actions, particularly in relation to visceral adipose tissue perfusion and remodeling in obesity. The present study tested the vasorelaxing effect of the SGLT2 (sodium-glucose transporter type 2) inhibitor canagliflozin in arteries from visceral adipose tissue of either nonobese or obese humans and investigated the underlying mechanisms. Also, the vasorelaxing effect of canagliflozin and the GLP-1 (glucagon-like peptide 1) agonist liraglutide were compared in arteries from obese patients. To these purposes, small arteries (116-734 µm) isolated from visceral adipose tissue were studied ex vivo in a wire myograph. Canagliflozin elicited a higher concentration-dependent vasorelaxation in arterioles from obese than nonobese individuals (P=0.02). The vasorelaxing response to canagliflozin was not modified (P=0.93) by inhibition of nitric oxide synthase (L-NAME) or prostacyclin (indomethacin), or by H2O2 scavenging (catalase); also, canagliflozin-induced relaxation was similar (P=0.23) in endothelium-intact or -denuded arteries precontracted with high potassium concentration, thereby excluding an involvement of endothelium-derived hyperpolarizing factors. The vasorelaxing response to canagliflozin was similar to that elicited by the Na+/H+ exchanger 1 inhibitor BIX (P=0.67), but greater than that to the Na+/Ca++ exchanger inhibitor SEA 0400 (P=0.001), hinting a role of Na+/H+ exchanger inhibition in canagliflozin-induced relaxation. In arterioles from obese patients, the vasorelaxing response to canagliflozin was greater than that to liraglutide (P=0.004). These findings demonstrate that canagliflozin induces endothelium-independent vasorelaxation in arterioles from human visceral adipose tissue, thereby suggesting that SGLT2 inhibition might favorably impact the processes linking visceral adipose burden to vascular disease in obesity.

Predictive factors of severity and persistence of oropharyngeal dysphagia in sub-acute stroke.

PURPOSE: This study aims to understand the factors contributing to the severity of oropharyngeal dysphagia and its persistence in the sub-acute phase of stroke. METHODS: We retrospectively collected the data of all the patients suffering from a stroke in the last year. The severity of stroke was reported according to the NIHSS score. All the patients were evaluated with the Dysphagia Risk Score and with a FEES. We classified the Dysphagia Risk Score and FEES results using the PAS score and ASHA-NOMS levels. The data were analysed statistically with ANOVA test, Student's t test and Pearson's correlation coefficient. RESULTS: A series of 54 patients were evaluated. The ANOVA test did not find any difference in the mean score of Dysphagia Risk Score, PAS and ASHA-NOMS when compared with the brain area of stroke. An NIHSS at hospital admission (stroke unit) of more than 12 was predictive of ASHA-NOMS score 1-4 after 60 days (p < 0.05). A PAS score between 6 and 8 at first FEES evaluation was predictive of poor (1-4) ASHA-NOMS score after 60 days (p < 0.01). A moderate positive linear correlation was found between NIHSS score and both PAS (r 0.65) and Dysphagia Risk Score (r 0.50); a moderate negative linear correlation was recorded between NIHSS and ASHA-NOMS (r - 0.66) scores. CONCLUSION: In the sub-acute phase of stroke, the predictive factors of persistent dysphagia are not linked to the damaged neuroanatomical region and others factors such as NIHSS value and high PAS score seem more useful.

Oropharyngeal dysphagia in elderly population suffering from mild cognitive impairment and mild dementia: Understanding the link.

PURPOSE: To evaluate the prevalence of oropharyngeal dysphagia in elderly patients suffering from minimal or mild cognitive decline. PATIENTS AND METHODS: We retrospectively collected the data of patients suffering from mild cognitive impairment or mild dementia and were undergoing management for suspected oropharyngeal dysphagia, in our department. All our patients were subjected to Mini Mental State Examination test, MD Anderson dysphagia inventory and caregiver mealtime and dysphagia questionnaire. We performed a mealtime observation study and endoscopic evaluation of swallowing in all our patients. Following evaluation, we then analysed the data statistically. RESULTS: Out of 708 patients who visited us for cognitive decline and suspected oropharyngeal dysphagia in the last two years, 52 patients were confirming to the inclusion criteria of this study. Classification of oropharyngeal dysphagia patients according to ASHA-NOMS scale showed that 32.7% of patients presented with grade 4 of dysphagia followed by another 32.7% with grade 5 and 30.8% presented with grade 6. Only 3.8% of our patients were considered normal (grade 7 of ASHA-NOMS scale). MD Anderson dysphagia inventory could collected swallowing alterations in only 23.1% of the cases. The caregiver mealtime and dysphagia questionnaire showed acceptable caregivers patient management in 53.8% of patients. CONCLUSION: Our study underscores the fact that oropharyngeal dysphagia is present in many cases of mild cognitive decline. While patients understate their swallowing problems, the caregivers are not competent enough to manage this situation in a great percentage of cases. Only a mealtime observation by a speech-language pathologist along with FEES is able to identify the true prevalence of the condition.

Does aggressive management of solitary pulmonary nodules pay off?

Indeterminate solitary pulmonary nodules (SPNs), measuring up to 3 cm in diameter, are incidental radiological findings. The ever-growing use of modern imaging has increased their detection. The majority of those nodules are benign; however, the possibility of diagnosing early-stage lung cancer still stands. Guidelines for the management of SPNs have never been validated in prospective comparative studies. Positron emission tomography (PET) is a useful tool to provide functional information on SPNs. However, overall sensitivity and specificity of PET in detecting malignant SPNs of at least 10 mm in diameter are about 90% and false-negative results are reported. The development of video-assisted thoracic surgery has provided minimally invasive diagnosis and treatment of SPNs. In our series, 105 patients underwent surgery based on combined increased 18F-labelled 2-fluoro-2-deoxy-d-glucose (FDG) uptake on PET computed tomography and radiological features (morphology and density) without prior histological confirmation. We detected 26 false negatives (24.8%) and only nine false positives (8.57%). Therefore, our minimally invasive surgical approach prevented 25% of patients with lung cancer from a delayed treatment versus only 9% undergoing "overtreatment". In our monocentric cohort, patients with SPNs with large diameter, irregular outline, no calcifications, central location, increased FDG uptake and/or subsolid aspect benefited from a primary surgical resection.

Lp-PLA2, a new biomarker of vascular disorders in metabolic diseases.

Metabolic diseases are chronic disorders correlated to a greater risk of cardiovascular event and death. Recently, many data have sustained the biological link between microvascular dysfunction, oxidative stress, vascular inflammation, and metabolic diseases. The determination of new and specific blood biomarkers of vascular inflammation associated with obesity-related metabolic syndrome (MetS) and diabetes such as lipoprotein-associated phospholipase A2 (Lp-PLA2) could be useful to identify subject with high risk of cardiovascular events. Lp-PLA2 participates by a crucial role in microvascular dysfunction and oxidative stress showing positive association with metabolic disorders. In this review, we will argue the evolving role of Lp-PLA2 in predicting cardiovascular events in metabolic disease patients.

Performance characteristics of lipoprotein-associated phospholipase A2 activity assay on the Dimension Vista analyser and preliminary study of a healthy Italian population.

INTRODUCTION: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a marker of vascular inflammation associated with coronary heart disease and stroke. We evaluated analytical performance of the PLAC® Activity Test on Siemens Dimension Vista® 1500 analyzer and measured Lp-PLA2 activity in Italian adults to establish reference intervals (RIs) and evaluate correlation with circulating lipids and age. MATERIALS AND METHODS: The evaluation protocol consisted of precision, linearity, sensitivity, method comparison, substrate depletion ("hook") effect and interference assessment. Inhibitor (Darapladib) effect was also evaluated. Lp-PLA2 activity was measured in 250 healthy donors (123 males, 127 females, aged 18-70 years). Central 95% RIs were established using nonparametric statistics. RESULTS: Intra-assay and inter-assay precision showed CVs of 0.6% - 1.4% and 0.9% - 2.0%, respectively. Linearity replicates showed R2 > 0.98. Limit of quantitation was 5.8 U/L (CV = 9.4%). Bland Altman plot showed bias - 0.9, 95% limits of agreement -6.5 - 4.72. Passing-Bablok regression showed excellent correlation (Slope = 1.02, 95% CI: 1.01 to 1.03; Intercept = - 1.86, 95% CI: - 3.08 to - 1.26; R2 = 0.999). No "hook effect" was observed at Lp-PLA2 activities ≤ 1000 U/L. Average Lp-PLA2 activity in 250 healthy donors was 182 ± 44 U/L (mean ± SD). Males showed statistically significant higher activities than females (P < 0.001). RIs were 107 - 265 U/L for males and 84 - 225 U/L for females. Moderate significant correlation (r = 0.29, P < 0.001) was found between Lp-PLA2 activity and total cholesterol. CONCLUSIONS: The PLAC® Activity Test shows very good performance characteristics on Dimension Vista® 1500.

Homocysteine, cysteine, folate and vitamin B12 status in type 2 diabetic patients with chronic kidney disease.

BACKGROUND: Hyperhomocysteinemia (hHcy) is a risk factor in the progression of chronic kidney disease (CKD). In type 2 diabetes (T2D), hHcy is strongly associated with increased risk of cardiovascular disease. Vitamin B12 and folic acid supplementation have been reported to lower homocysteine (tHcy) levels, but no data on plasma tHcy, cysteine (Cys), folate and vitamin B12 levels in T2D-CKD patients are reported. PROCEDURES: tHcy and Cys levels were analyzed in 178 T2D-CKD patients by high performance liquid chromatography (HPLC) with fluorescence detection. In addition, we determined folate and vitamin B12 levels using a chemiluminescence method. RESULTS: tHcy and Cys levels were increased in T2D patients, and this rise positively correlated with the CKD stage (P < 0.001). Folate levels were comparable to controls at various CKD stages, whereas vitamin B12 levels were lower, except at stage IV. We did not find any correlation between B-vitamins and levels of tHcy and Cys, regardless of the CKD stage. CONCLUSIONS: This is the first study reporting tHcy, Cys and B-vitamins status in T2D-CKD patients. Although limited to our cohort of 178 patients, our findings could be helpful in clarifying the conflicting literature regarding B-vitamins supplementation. Further studies are necessary before any Hcy-lowering therapy can be safely established in T2D-CKD subjects.

Ectopic thyroid tissue in the head and neck: a case series.

BACKGROUND: Through a review of three cases, the etiopathogenetic, clinical-diagnostic, and therapeutic aspects of ectopic thyroid tissue are herein discussed to highlight the main presentations of this polymorphous disease. CASE PRESENTATIONS: The first case involved an ectopic thyroid gland in the lingual area in a 45-year-old Caucasian woman who presented with dysphagia and midline swelling at the base of the tongue. The second case involved a 22-year-old Caucasian woman with a submandibular mass comprising ectopic thyroid tissue. The third case involved a 33-year-old Caucasian man with a typical thyroglossal duct cyst characterized by the presence of thyroid tissue upon histological analysis. CONCLUSION: Surgery seems to be the most appropriate treatment for patients with ectopic thyroid tissue showing clinical signs of upper airway obstruction or when the lesion shows signs of infection or malignant degeneration. When a site of ectopic thyroid tissue is the only such site in the body, removal of this tissue will usually lead to hypothyroidism that requires medical thyroid hormone replacement.

Plasma and erythrocyte membrane phospholipids and fatty acids in Italian general population and hemodialysis patients.

BACKGROUND: Dyslipidemia and abnormal phospholipid metabolism are frequent in uremic patients and increase their risk of cardiovascular disease (CVD): ω-3 polyunsaturated fatty acids (PUFAs) may reduce this risk in the general population. In this study we compared the plasma and erythrocyte cell membrane composition of PUFAs in a group of Caucasian hemodialysis (HD) patients and in a control group of healthy subjects and evaluated the erythrocyte/cell membrane fatty acid ratio as a marker of the dietary intake of phospholipids. The relationship between ω-3 and ω-6 fatty acids and the possible differences in PUFAs concentrations were also investigated. METHODS AND RESULTS: After obtaining a fully informed consent, a total of ninety-nine HD patients and 160 non uremic control subjects from "Tor Vergata" University Hospital were enrolled into the study. None of them took antioxidant drugs or dietary supplements for at least 90 days prior to the observation. Blood samples were analysed by gas-chromatographic coupled to a mass spectrometric detector.The daily intake of total calories, proteins, lipids and carbohydrates is significantly lower in HD patients than in controls (p < 0.001). Most plasma and erythrocyte PUFA were also reduced significantly in HD patients (p < 0.001). CONCLUSIONS: Our results suggest that many classes of PUFAs are lacking in HD patients, due to the removal of nutrients during the dialysis and to persistent malnutrition. A dietary treatment addressed to increase plasma ω-3 PUFAs and to optimize ω-6/ω-3 ratio may exert a protective action and reduce the risk of CVD in HD patient.

A multicenter observational study on the role of comorbidities in the recurrent episodes of benign paroxysmal positional vertigo.

OBJECTIVE: Primary objective of this study was to find a statistical link between the most worldwide comorbidities affecting the elderly population (hypertension, diabetes, osteoarthrosis, osteoporosis and depression) and recurrent episodes of BPPV. Secondary objective was defining possible "groups of risk" for people suffering recurrent positional vertigo related to the presence of a well documented comorbidity. METHODS: This was an observational, cross-sectional, multicenter, spontaneous, non-pharmacological study. The data of 1092 patients suffering BPPV evaluated in 11 different Departments of Otolaryngology, Otoneurology and Neurology, referring Centers for positional vertigo evaluation, were retrospectively collected. RESULTS: Regarding evaluated comorbidities (hypertension, diabetes, osteoarthrosis, osteoporosis and depression), data analysis showed the presence of at least one comorbid disorder in 216 subjects (19.8%) and 2 or more in 408 subjects (37.4%). Moreover there was a statistical significant difference between the number of comorbidities and the number of recurrences, otherwise said as comorbidity disorders increased the number of relapses increased too. CONCLUSION: The presence of a systemic disease may worsen the status of the posterior labyrinth causing a more frequent otolith detachment. This condition increases the risk for patients suffering BPPV to have recurrent episodes, even if correctly managed by repositioning maneuvers. The combination of two or more of aforementioned comorbidities further increases the risk of relapsing BPPV, worsened by the presence of osteoporosis. On the basis of this results it was possible to define "groups of risk" useful for predicting BPPV recurrence in patients with one or more comorbidity.

Sudden sensorineural hearing loss: results of intratympanic steroids as salvage treatment.

OBJECTIVE: The aim of the present study was to verify the efficacy and the safety of intratympanic dexamethasone to treat sudden sensorineural hearing loss as salvage therapy. MATERIALS AND METHODS: A prospective study was conducted on patients affected by idiopathic sudden hearing loss who were treated before with some systemic therapy, but without recovery of the hearing The patients able to undergo the study, but who refused salvage treatment were considered as control group. A solution of Dexamethasone 4 mg/ml was then injected through the posterior-inferior quadrant filling completely the middle ear. The follow-up in the following 6 months included an audiogram every month. RESULTS: The number of patients treated with salvage therapy was 36. The patients who refused treatment were further 10. The salvage treatment was done with a mean delay of 24.3 days from the onset of symptoms. Mean hearing threshold after the onset of sudden hearing loss at PTA was 66.5 dB. After the failed treatment the mean PTA was 59.6 dB. The mean PTA after the intratympanic steroid administration was 46.8 dB, with a mean improvement of 12.8 dB. No hearing change was noted in the 10 patients who refused salvage therapy. The patients that assumed systemic steroid as first therapy showed a better PTA threshold after the salvage intratympanic treatment (p<0.01). A significant difference (p<0.05) of hearing recovery was evidenced between non-smoker patients and those with smoking habit. CONCLUSIONS: Our data showed that a salvage treatment with intratympanic dexamethasone should be suggested to all patients who failed the first systemic treatment. The systemic steroid therapy done before the salvage treatment seems to exert a protective role for the inner ear, as shown by our series. On the contrary the smoke habit is a negative prognostic factor in the hearing recovery.