Radiogenomic analysis of primary breast cancer reveals [18F]-fluorodeoxglucose dynamic flux-constants are positively associated with immune pathways and outperform static uptake measures in associating with glucose metabolism.

BACKGROUND: PET imaging of 18F-fluorodeoxygucose (FDG) is used widely for tumour staging and assessment of treatment response, but the biology associated with FDG uptake is still not fully elucidated. We therefore carried out gene set enrichment analyses (GSEA) of RNA sequencing data to find KEGG pathways associated with FDG uptake in primary breast cancers. METHODS: Pre-treatment data were analysed from a window-of-opportunity study in which 30 patients underwent static and dynamic FDG-PET and tumour biopsy. Kinetic models were fitted to dynamic images, and GSEA was performed for enrichment scores reflecting Pearson and Spearman coefficients of correlations between gene expression and imaging. RESULTS: A total of 38 pathways were associated with kinetic model flux-constants or static measures of FDG uptake, all positively. The associated pathways included glycolysis/gluconeogenesis ('GLYC-GLUC') which mediates FDG uptake and was associated with model flux-constants but not with static uptake measures, and 28 pathways related to immune-response or inflammation. More pathways, 32, were associated with the flux-constant K of the simple Patlak model than with any other imaging index. Numbers of pathways categorised as being associated with individual micro-parameters of the kinetic models were substantially fewer than numbers associated with flux-constants, and lay around levels expected by chance. CONCLUSIONS: In pre-treatment images GLYC-GLUC was associated with FDG kinetic flux-constants including Patlak K, but not with static uptake measures. Immune-related pathways were associated with flux-constants and static uptake. Patlak K was associated with more pathways than were the flux-constants of more complex kinetic models. On the basis of these results Patlak analysis of dynamic FDG-PET scans is advantageous, compared to other kinetic analyses or static imaging, in studies seeking to infer tumour-to-tumour differences in biology from differences in imaging. Trial registration NCT01266486, December 24th 2010.

Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Quality of life measurements for patients with chronic suppurative otitis media: Italian adaptation of "Chronic Ear Survey".

The chronic ear survey (CES) is a sensitive and disease specific quality of life (QoL) measurement tool in patients with chronic suppurative otitis media (CSOM). It is a 13-item survey that evaluates the frequency, duration and severity of problems associated with this disease. It is composed of three subscales that describe activity restrictions, symptoms and medical resource utilisation. Based on patient's answers, it is possible to obtain a score resulting in a scale ranging from 0 to 100; the highest indicates the best health, while the lowest denotes poor health. The questionnaire was originally created in English. The aim of this study is to validate the CES questionnaire in Italian (CES-I). Translation was made following international guidelines. The application follows the stages of translation from English to Italian and linguistic adaptation, and grammatical and idiomatic equivalence review. The CES-I and the Short Form Health Survey 36 (SF-36) questionnaires were administered to 54 patients with CSOM. A cross-sectional design was used to examine the internal consistency (Cronbach's alpha) and concurrent validity (Pearson's product moment correlation). To confirm the external validity of CES-I, Pearson correlation coefficient, considering the total score and single subscales of CES and the 8 scales of the SF-36, was calculated. Cronbach's alpha coefficient for internal consistency was 0.737. The intraclass correlation coefficient, measured through mixed effects, was 0.737 (95% CI: 0.600-0.835, p < 0.001) for average measures and 0.412 (95%CI: 0.273-0.559, p < 0.001) for individual measures. According to our results, CES-I is a reliable tool for evaluation of QoL in patients with CSOM among the Italian-speaking population.

Validity of Italian adaptation of the Dizziness Handicap Inventory (DHI) and evaluation of the quality of life in patients with acute dizziness.

The impact of dizziness on Quality of Life (QoL) can be assessed by the Dizziness Handicap Inventory (DHI), which is used as a discriminative and evaluative tool. Although the DHI is available in several languages, an equivalent version for the Italian population is not yet available. Aim of this study was to translate the DHI into the Italian language (DHI-I), assess its correlation to the Italian version of the Short Form-36 Health Survey and to investigate its reliability in evaluating the QoL of patients with acute dizziness. The study population consisted of 50 patients (76% females and 24% males), mean age 51.6 years, range 25-85 years (SD = 14.5). A cross-sectional design was used to examine the internal consistency (Cronbach's α) and concurrent validity (Pearson's product moment correlation r). The application followed the stages of translation from English to Italian and linguistic adaptation, grammatical and idiomatic equivalence review. To confirm the external validity of DHI-I, the Pearson correlation test between the total score and single subscales of DHI-I and the 8 scales of the Short Form Health Survey (SF-36) was performed. The Cronbach α coefficients for internal consistency were 0.92 for the DHI-I and 0.82, 0.84 and 0.75 for the sub-scale functional, emotional and physical, respectively. The frequency distribution of no one item showed a percentage higher than 75% in a single possible answer (0, 2, 4), excluding a ceiling or floor effect. Correlations with the total score of DHI-I were consistent and the correlation between total score of DHI-I and total score on SF-36 was -0.593. Of the single subscales, the emotional scale showed a closer correlation with almost all scales of the SF-36. The correlation between the total score of SF-36 and the single sub-scale of DHI-I (functional, emotional, physical) were respectively -0.599, -0.563, -0.398. The DHI was culturally and linguistically adapted for its application in the Italian population. The DHI-I demonstrated a good reliability and is recommended as a measure of disability in patients with dizziness and unsteadiness. According to the DHI-I, patients with acute dizziness and with a clinical diagnosis of vestibular syndrome presented a decreased QoL; the physical aspects were the most compromised.

Idiopathic benign paroxysmal vertigo in children, a migraine precursor.

Vertigo and dizziness are common conditions in the adult population that can be rarely seen during childhood; only a few articles describing vertigo in children can be found in literature. Although many causes of vertigo in adulthood occur also in childhood, their frequency may be different. A typical example is benign paroxysmal positional vertigo, the most common peripheral vestibular disorder in adults, which occurs quite uncommonly in children. Furthermore, many common diseases causing vertigo in children may be unique for this population, such as benign paroxysmal vertigo (BPV) of childhood. At present, BPV is defined as a migraine's equivalent, a precursor of migraine or a periodic syndrome of childhood. The International Headache Society also studied this form of vertigo and included the Benign Paroxysmal Vertigo in section 1.3.3. of the International Classification of Headaches (ICHD-2). The present review analyzes recent patho-physiological and clinical evidences regarding idiopathic BPV in children.

High frequency surgery in the treatment of turbinate hypertrophy: 11 years' experience.

For over a century, surgical management of lower turbinate hypertrophy has given rise to much discussion. Aim of the present investigation was to establish, by means of the analysis of a large patient population, the efficacy and reproducibility of high frequency surgery in the treatment of this condition. A total of 1689 non-allergic patients with nasal obstruction, presenting hypertrophy of the lower turbinates, were submitted, under local anaesthesia, to turbinates decongestion using a high frequency instrumental unit with a bipolar terminal electrode. Efficacy of the procedure was evaluated on the basis of objective examination, results of questionnaires, active anterior rhinomanometry and mucociliar transport time. Results revealed a reduction of hypertrophy, an improvement in symptoms, a reduction in nasal resistances and an improvement of mucociliar transport time. The large patient population, low post-operative complication rate and the good patient compliance, due also to the fact that no haemostatic procedure is necessary, would suggest that this method is particularly valid, effective and safe for the treatment of hypertrophy of the lower turbinates.

Distortion product otoacoustic emmissions in Ménière's disease.

Distortion product otoacoustic emissions (DPOAEs) are an objective, non-invasive measure for evaluating outer hair cell (OHC) activity. In this study DPOAEs were measured in 70 patients affected by Meniere's disease (MD). In addition 58 out of 70 patients performed both an audiometric threshold evaluation pre- and postglycerol administration (i.e. glycerol test) and DPOAEs pre- and post-osmotic drug assumption. The purpose of this combined form of testing was to explore the effects of glycerol on the active non-linear mechanisms of the cochlea. More than 60% of the ears with MD emitted DPOAEs despite the presence of an average hearing threshold level above 40 dB (HTL). Changes in the DPOAE baseline measures were observed in 32.4% of cases after glycerol administration. Patients were divided in four groups according to the different pattern of DPOAEs shown after the glycerol test. In particular, three-quarters of cases showed a significant increase in DPOAE amplitude, one-quarter of patients, who initially did not express DPOAEs, eventually did after intake of the osmotic agent, while no decreased DPOAEs were observed in these series. The different expressions of DPOAEs should be associated with the evolutive phases of MD. In addiction, elucidation of the relationship between DPOAEs and the stages of MD was an outcome of this test.

DPOAE modifications induced by pure tone overstimulation in guinea pigs.

Distortion Product Otoacoustic Emissions (DPOAEs) shows a vulnerability to acoustic overstimulation that is easily detectable by changes in amplitude, frequency distribution and time course. The frequency-specific changes in DPOAE provide more information than the more general changes in click evoked otoacoustic emissions. In this work five anesthetized guinea pigs were examined for changes DPOAE after exposure to pure tones. The noise was a 110 dB SPL pure tones for 45 minutes and the fatiguing tone centered on the geometric mean (GM) of primaries or 2/3 of GM. The most measurable effects were obtained in the latter conditions. The main DP level reduction lasts about one hour after exposure, but the complete recovery is observable only after 24 hours. The frequency distribution of fatiguing effects on the DP- audiogram shows a remarkable fine tuning and a pattern like a low-pass filter. After four hours, in one guinea pig, it is observable an enhancement of the DP amplitude, compared to the pre-exposure level; in another guinea pig, a second overstimulation produced a more extensive and time-lasting effects than the first exposure.

[The contralateral ear in acquired cholesteatoma in children and adults]. / L'orecchio controlaterale nel colesteatoma acquisito del bambino e dell'adulto.

Contralateral ear pathologies are frequently found in patients suffering from acquired cholesteatoma. A retrospective study was performed on 85 pediatric patients and 105 adults surgically treated for acquired middle ear cholesteatoma. All the patients were checked and the otomicroscopic picture photographed and compared in an attempt to gain insight into the pathogenesis and clinical indications by comparing two samplings from different age groups. In both groups the frequency of pathological contralateral ear manifestations was higher than found in the normal population. Similar results were obtained in the two groups and indicate that the same mechanisms come into play in both ears, starting at infancy. The finding of a particularly common association between cholesteatoma and contralateral retraction pockets with sinus cholesteatoma or pars tensa in the pediatric group appears to confirm that tubal dysfunction plays a pathogenic role in the genesis of cholesteatoma. From the practical point of view, systematic preventative measurement of the contralateral ear can lead to a reduction in major surgery and can affect the choice between open or closed tympanoplasty. Moreover, it may also condition the precision and length of the follow-up.

[Analysis of otoacoustic distortion products in a group of otosclerotic patients]. / Analisi dei prodotti di distorsione otoacustici in un gruppo di pazienti affetti da otosclerosi.

There is indication that middle ear pathologies can affect otoacoustic emissions (OAE) to varying degrees. In fact, since acoustic emissions are recorded in the outer ear duct, the energy transfer mechanisms both up and downstream of the middle ear must be intact. OAE distortion products (DP) enable one to analyze cochlear response by frequency and to verify the retrograde response as a function of frequency. In the present work this method was used to test otosclerosis patients. A group of 45 patients with otosclerosis was tested to determine whether the OAE-DP could be identified and measured. Subsequently the characteristics of these DPs were analyzed in a group of 18 subjects who had previously undergone stapedectomy. All the results obtained were compared with those from a control group of normal hearing subjects with normal emissions and free of any E.N.T. pathology. In approximately half of the cases (53%) in the otosclerosis patient group it was possible to detect clearly evident DPs. Obviously, the DP-Gram differed greatly and average amplitude was lower than those found in normal subjects. Indeed, there was no signal at all at the lower and middle frequencies reflecting a hearing loss typical of cases of otosclerosis. Most (58%) of the otosclerosis patients who had successfully undergone stapedectomy recorded valid DPs. The DP-Gram frequency range was much broader (750-4000 Hz) than in those who had not undergone surgery. Moreover the lower and mid frequency amplitudes were significantly better. The data obtained are quite encouraging and suggest that DP should be studied in depth in patients with otosclerosis.

[Initial symptoms in Meniere's disease]. / I sintomi precoci della malattia di Menire.

Menière's disease appears with the classic triad of symptoms in about 1/3 of cases so that, on the whole, diagnosis is delayed until full symptomatology develops. Spontaneous reversibility and effective control, if any, of the disease mechanism are limited to the beginning phases and thus it seems appropriate focus attention on the earliest symptoms. Unfortunately, the pre-diagnosis period is poorly known and, for this reason, we decided to investigate it in our series. The purposes of this research were: 1) to estimate the prevalence of isolated symptoms in subjects successively found to be menieric; 2) to make a clinical outline of the pre-diagnosis period; 3) to investigate the relationship between the pre-diagnosis period and the post-diagnosis disease course. From a group of 216 Menière's patients (diagnosed according to the 1985 AAOO criteria), 170 were selected on the basis of availability of audiometric and clinical data pertaining to the pre- and post-diagnosis disease course. Isolated symptoms in the pre-diagnosis period were found in 107/170 subjects (63%). The nature of the symptoms was cochlear (71.9%), vestibular (22.4%) and mixed (5.6%). In the largest group of patients (41 cases), the pre-diagnosis period lasted from 2 to 5 years. This period was shorter in the cases with mixed symptoms in comparison with patients suffering from either cochlear or vestibular symptoms. Between the 2nd and 5th year following diagnosis, hearing was seen to deteriorate more significantly in patients with a history of isolated cochlear symptoms. Furthermore, patients whose first disturbances were of cochlear origin suffer significantly shorter vertigo attacks.(ABSTRACT TRUNCATED AT 250 WORDS)

[Distortion products in Menière's disease]. / I prodotti di distorsione nella malattia di Menière.

Distortion Product Otoacoustic Emissions (DPOAEs) are elicited by simultaneous application of two tones to the ear canal. These emissions are a result of nonlinear mechanical characteristics of the cochlea at a specific point and have a precise mathematical relation with the frequencies of the two eliciting primary tones f1 and f2. This frequency-selective property of DPOAEs suggests that they should be regarded as useful monitor of localized cochlear function at any predetermined frequency. The present study was designed to investigate DPOAEs in patients with Menière's disease. DPOAEs were recorded before and after glycerol administration to verify if the fluctuation of the hearing threshold induced by this hyperosmotic agent causes selective changes in the activity of the outer hair cells. DPOAEs were present in patients in which the mean duration of the disease was shorter compared to those patients without measurable DPOAEs. An improvement of DPOAEs after glycerol intatte was observed in a half of our cases. The improvement of DPOAEs does not appear to be brought about by modifications of the auditory threshold induced by glycerol.

[Recovery from Meniere's disease]. / La guarigione della malattia di Ménière.

When vertigo attacks and balance disorders stop, menieric patients are generally considered recovered although they complain of more or less severe sensorineural hearing loss. As far as a true clinical recovery is concerned, the Authors think that it should correspond not only to absence of vertiginous spells but even to a long lasting normal and stable hearing level. On the basics of this presumption, they select the files of 7/207 patients showing complete recovery since not less than 8 years. Age at the onset of the disease, associated disease, isolated symptoms before the appearance of the classic triade, age at the first attack, total number of crises, length of active period of the disease, maximum hearing loss, shape of audiometric tracing are all analyzed. Healed patients are characterized by a smooth evolution, which reverses in the very first phases of the disease, as well as by the following: 1) absence of head injury and viral labyrinthitis in clinical history; 2) onset of disease with complete symptomatology; 3) slight hearing loss and up-sloping audiometric configuration; 4) few attacks of vertigo (less than 30) lasting no longer than 12 hours; 5) active period of disease not exceeding 18 months. Recovery from Ménière's disease seems possible as long as labyrinth lesions are not stabilized.

Incidence of Menière's disease in Italy.

Numerous epidemiologic investigations have been conducted regarding the incidence of Menière's disease, but the values obtained for different countries vary greatly. This can be attributed to the fact that different criteria have been applied in defining Menière's disease. The objective of this study was to evaluate the incidence and prevalence of Menière's disease in Italy following the American Academy of Ophthalmology and Otolaryngology guidelines. A total of 111 cases with Menière's disease were diagnosed in a district of southeastern Latium over a 13-year period, with an incidence of 82 per 10(6). A figure 3.4 times greater was found in hospital personnel, thus showing that a greater availability of medical facilities increases the number of diagnoses. Sex was found not to be a determining factor. The authors suggest that the incidence reported in this paper is an underestimate and that the actual one remains undetermined, but probably higher than generally believed.

[Effect of acetazolamide on Menière's disease]. / Effetto dell'acetazolamide sulla malattia di Menière.

The effect of acetazolamide was assessed in 25 patients with Menière's disease. During the test session hearing threshold and plasmatic osmolality were monitored along with fluctuations in hearing loss, fullness, tinnitus and balance. A single, 250 mg dose of acetazolamide was administered to all patients via os early in the morning on an empty stomach. Hearing was tested prior to administration and every hour for five hours thereafter. Plasmatic osmolality was also assessed during the same session. In 52% of this group an improvement in the threshold was seen. The greatest shift was observed two hours after administration of acetazolamide at 250 Hz, whereas the smallest threshold shift corresponded to 2000 Hz. In all cases, plasmatic osmolality remained constant throughout. Of the patients 44% presented an improvement of all or one of the symptoms: hearing loss, tinnitus, fullness, balance. The data were compared with data obtained for a control group (9 patients) which received a placebo while following the same testing criteria. The results of this study suggest that acetazolamide can have a positive effect on endolymphatic hydrops. It should be stressed, therefore, that acetazolamide could be introduced in the diagnostic and therapeutic strategies applied in Menière's disease.

[Diseases associated with Ménière's disease]. / Associazioni morbose della malattia di Ménière.

The object of the present paper was to investigate the presence of other diseases in patients suffering from Menière's disease and to identify any common etiopathogenetic factors. In a group of 100 patients there was a high incidence of three pathological associations: 1) anxiety and depression; 2) dyspepsia; and 3) vasomotor headache. The percentages were then compared with the data found in the literature and with the non menieric population. The association of dyspepsia proved statistically significant. The relationship between anxiety and vasomotor headache remains suspect while awaiting more precise definition of these diseases and findings more comparable with the total population.