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Objectives: Congenital Cytomegalovirus (cCMV) has been associated with hearing, vision, and neurodevelopmental long-term sequelae. Despite the social burden associated with the disease, a universally accepted consensus on screening, diagnostic, therapeutic and follow-up approaches has not been reached. The present observational retrospective study aims at describing long-term sequelae and radiological abnormalities associated with cCMV in children early identified by extended hearing-targeted screening and evaluated by audiological follow-up in a single III Level Audiological Referral Center for at least 2 years., Methods: Audiological neonatal and follow-up data were available for all subjects. Data collection included clinical neonatal and virological assessment at birth. Ophthalmological, neurodevelopmental and neuroradiological follow-up abnormalities compatible with cCMV sequelae were collected by clinical reports. Spearman's rank correlation coefficient (rho-ρ) was used to evaluate possible correlations among the considered parameters., Results: 61 newborns were identified by extended hearing-targeted cCMV screening and diagnosed mostly (83.6 %) by PCR viral DNA extraction in urine collected within the 15° day of life. Seventeen babies were born preterm, with a mean gestational age of 33.5 weeks. Sixteen patients (26.2 %) were admitted to an Intensive or sub-Intensive Neonatal Care Unit. At birth, 35 newborns were symptomatic (57.3 %), and 19 of them received antiviral treatment by valganciclovir or ganciclovir. Overall, 20 children (32.7 %) were diagnosed with sensorineural hearing loss (SNHL), among them 17 (85 %) were refer at the newborn hearing screening while 3 (15 %) were Pass. 5/20 children (25 %) presented isolated SNHL, while in 15/20 (75 %) children SNHL was associated to other long-term sequelae. In 5 patients (25 %) a progression of the hearing threshold was observed, with a mean age of progression of 26 months of age. Risk factors for progression were a worse final hearing threshold (Spearman's ρ = 0.434; p = 0.0001) and a worse hearing threshold at birth (Spearman's ρ = 0.298; p = 0.020). Thirteen children were fitted with hearing aids, 8 of whom subsequently underwent cochlear implantation. Concerning long term impairments, 10/61 children (17 %) presented a variety of ophthalmological sequelae, while 16/40 cCMV patients (40 %) were diagnosed with neurodevelopmental abnormalities. Language delays were significantly associated with a worse hearing threshold (ρ = 0.582; p = 0.0001) and with other neurocognitive abnormalities (ρ = 0.677, p = 0.0001). 30 children underwent radiological brain evaluation by Magnetic Resonance Imaging, and 63.3 % of them presented abnormalities compatible with cCMV. Mean viral load at birth did not show significant associations with long-term sequelae., Conclusions: The study highlights the diverse and significant long-term sequelae of cCMV infection detected through early screening. With a significant proportion of cCMV children developing sensorineural hearing loss, ophthalmological and neurodevelopmental issues, the results emphasize the importance of continuous, multidisciplinary follow-up. Early identification and tailored interventions are crucial for improving the long-term health and quality of life of children affected by cCMV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: This study proposes a revised version of the Reflux Symptom Index (R-RSI), a seventeen-item questionnaire that was revised to increase the suspicion of laryngopharyngeal reflux disease (LPRD)., Methods: Internal validation involved 213 participants, comprising 160 subjects without a previous LPRD diagnosis and 53 subjects with a self-reported previous diagnosis of LPRD with or without gastroesophageal reflux disease (GERD). Test-retest reliability and internal consistency were calculated. For the external validation, 56 patients (independent from the previous cohort) were enrolled to explore the R-RSI screening properties and determine a cutoff using 24-h MII-pH as the gold standard., Results: R-RSI test-retest reliability was high, both for the total score (ICC: 0.970) and for each item (ranging from 0.876 to 0.980). Cronbach's alpha was 0.910, indicating excellent internal consistency of the questionnaire. Participants with a previous self-reported diagnosis scored significantly higher (mean 24.94 ± 7.4; median 26, IQR 20-29) than those without a previous diagnosis (mean 4.66 ± 5.3; median 4, IQR 1-6) (p value <0.0001). Participants with both previous LPRD and GERD diagnoses had higher scores (27.20 ± 7.8) compared to those with only LPRD (21.77 ± 5.5) (p value = 0.003). Using 24-h MII-pH diagnosis as a gold standard, the optimal R-RSI cutoff point was determined to be 18, with a sensitivity of 84.5% and a specificity of 81.8%, positive predictive value of 95%, and negative predictive value of 60%., Conclusions: Our results suggest that the R-RSI may be useful to suspect LPRD, with or without GERD. The R-RSI is a self-administered patient-reported outcome questionnaire that demonstrates excellent reliability and high screening properties. Employing a cutoff of ≥18 in the R-RSI can assist in diagnosing and monitoring LPRD., (© 2024 S. Karger AG, Basel.)

Acute otitis media (AOM) is one of the most common ENT diseases in children. In the antibiotic/post-antibiotic era, facial paralysis is a very rare complication of AOM (0.004-0.005%). Despite the rarity of this complication, it should be known by all physicians for proper therapeutic management to avoid serious sequelae. The aim of this review is to provide a management guide based on the current literature., Materials and Methods: Fifteen studies published between 2000 and 2022 were selected, including 120 patients (62 M/58 F) with an average age of 4.96 years old (range = 4 months-16 years; SD: 4.2). The paralysis frequently has a sudden onset and is of a severe grade (medium House-Brackmann (HB) score at onset: 4.68; SD: 0.5); however, it tends to have an almost complete recovery in most patients (88.49% HB 1 at follow-up)., Results: Its first-line treatment must be based on the use of antibiotics (beta-lactam antibiotics as penicillins or cephalosporins). Corticosteroids should be used concomitantly for their anti-inflammatory and neuroprotective actions; however, there is no unanimity between authors about their application. Myringotomy, with or without ventilation tube insertion, is indicated in cases where the tympanic membrane is intact. Other kinds of surgery should be performed only in patients who have a worsening of their AOM symptoms or a worsening in HB score even with clinical treatment., Conclusions: The obtained data show that a conservative treatment can be sufficient for complete recovery in most patients, and it is preferred as the first-line therapy. Mastoidectomy should be performed only in patients with acute mastoiditis and without symptom improvement after a conservative approach. There are insufficient data in the current literature to provide clear selection criteria for patients who need to undergo mastoidectomy with facial nerve decompression. The choice of this treatment is based on an individual center expertise. Further studies are needed to clarify the role of corticosteroids and the role of facial nerve decompression in this clinical scenario.

Introduction: Vocal tract discomfort (VTD), dysphonia, and laryngopharyngeal reflux (LPR) symptoms are complaints frequently reported by amateur singers. There are two aims of this study. The first is to evaluate the prevalence of these symptoms using validated questionnaires. The second is to correlate singing-related variables with the questionnaire responses., Methods: A total of 392 amateur choir singers (ACS) and 514 control subjects completed an online survey divided into four parts: (1) clinical and demographic characteristics, (2) training in singing and singing experience, (3) history of gastroesophageal reflux disease and LPR symptoms, (4) validated questionnaires. Specifically, the reflux symptom index (RSI), the vocal tract discomfort scale (VTDS), and the voice symptom scale (VoiSS) were included to analyze the actual burden related to LPR symptoms, VTD, and dysphonia., Results: ACS demonstrated a healthier lifestyle and a lower prevalence of gastroesophageal reflux disease symptoms in comparison with control subjects. ACS scored significantly higher in VTDS and VoiSS than control subjects, while no differences in the RSI results were found. Significant correlations among the questionnaires' results were demonstrated. Occasional professional singing was the variable influencing VTDS and VoiSS results the most., Conclusion: ACS do not evidently manifest a higher impairment connected to LPR (RSI score), while they do report higher levels of voice (VoiSS score) and vocal tract (VTDS score) impairments, in comparison with control subjects. The relevant correlations among the PRO measures suggest that LPR symptoms, VTD, and dysphonia are related to each other. Given the relevant repercussion on the severity of VTD and dysphonia, providers should specifically ask about occasional professional singing when treating amateur singers., Competing Interests: Declarations of interest None, (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to adapt and validate the Italian version of the singing Voice Handicap Index-10 (SVHI-10-IT)., Methods: 99 Italian singers were enrolled in the study. All subjects underwent videolaryngostroboscopic examination and were asked to fill out the self-reported 10-item SVHI-10-IT. Laryngostroboscopic examination was pathological in 56 subjects (study group) (56.6%), while it was normal in the remaining 43 singers (control group) (43.4%). Dimensionality, test retest and internal validity for SVHI-10-IT were performed. Videolaryngostroboscopy was used as gold-standard for external validity., Results: The items of SVHI-10-IT were uni-dimensional and Cronbach's α was 0.853 (95% CI = 0.805-0.892). High and comparable area under curve (AUC:0.93 95% CI = 0.88-0.98) values indicate a good ability of the scale to distinguish between the study and control groups. Based on balanced sensitivity (Se = 83.9%) and specificity (Sp = 86.0%), the optimal cut-off score for a singer's perceived voice handicap was 12., Conclusions: The SVHI-10-IT is a reliable and valid instrument to evaluate the self-reported singing voice handicap among singers. It can also be used as a quick screening tool since a score higher than 12 is indicative of a problematic voice as perceived by singers., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Objective: Since the recent early music (EM) revival, a subset of singers have begun to specialize in a style of singing that is perceptually different from the more "mainstream" romantic operatic (RO) singing style. The aim of this study is to characterize EM with respect to RO singing in terms of its vibrato characteristics and the singer's formant cluster., Study Design: This study presents a within-subject experimental design., Methods: Ten professional singers (5 F; 5M) versed in both EM and RO repertoire were enrolled in the study. Each singer recorded the first 10 bars of the famous Aria, "Amarilli Mia Bella" (Giulio Caccini, 1602) a cappella, in RO and EM styles, in random order. Three sustained notes were extracted from the acoustical recordings and were analyzed using the free user-friendly software Biovoice to extract five parameters: vibrato rate, vibrato extent, vibrato jitter (J vib ), vibrato shimmer, and quality ratio (QR), an estimation of the singer's formant power., Results: Vibrato in EM singing was characterized by a higher rate, a smaller extent, and less regular cycle-cycle period duration (higher J vib ) compared to RO singing. As in previous studies, RO singing presented a more prominent singer's formant, as indicated by a smaller QR., Conclusions: Acoustical analysis of some vibrato characteristics and the Singer's Formant significantly differentiated EM from RO singing styles. Given the acoustical distinctions between EM and RO styles, future scientific and musicological studies should consider distinguishing between the two styles rather than using a singular term for and description of Western Classical singing., Competing Interests: DECLARATION OF COMPETING INTEREST The authors have no conflict of interest to declare. The authors did not receive any funding., (Copyright © 2023 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background and objectives : Otoferlin is a multi-C2 domain protein implicated in neurotransmitter-containing vesicle release and replenishment of the cochlear inner hair cell (IHC) synapses. Mutations in the OTOF gene have been associated with two different clinical phenotypes: a prelingual severe-to-profound sensorineural hearing loss (ANSD-DFNB9); and the peculiar temperature-sensitive auditory neuropathy (TS-ANSD), characterized by a baseline mild-to-moderate hearing threshold that worsens to severe-to-profound when the body temperature rises that returns to a baseline a few hours after the temperature has fallen again. The latter clinical phenotype has been described only with a few OTOF variants with an autosomal recessive biallelic pattern of inheritance. Case report: A 7-year-old boy presented a picture compatible with TS-ANSD exacerbated by febrile states or physical exercise with mild-to-moderate hearing loss at low and medium frequencies and a decrease in speech discrimination that worsened with an unfavorable speech-to-noise ratio. Otoacoustic emissions (OAEs) were present whereas auditory brainstem responses (ABRs) evoked by a click or tone-burst were generally absent. No inner ear malformations were described from the CT scan or MRI. Next-generation sequencing (NGS) of the known deafness genes and multi-phasic bioinformatic analyses of the data detected in OTOF a c.2521G>A missense variant and the deletion of 7.4 Kb, which was confirmed by array-comparative genomic hybridization (array-CGH). The proband's parents, who were asymptomatic, were tested by Sanger sequencing and the father presented the c.2521G>A missense variant. Conclusions : The picture presented by the patient was compatible with OTOF-induced TS-ANSD. OTOF has been generally associated with an autosomal recessive biallelic pattern of inheritance; in this clinical report, two pathogenic variants never previously associated with TS-ANSD were described.

Introduction: The present study aimed to develop a new tool for the evaluation of singers with self-reported symptoms suggestive of laryngopharyngeal reflux (LPR) (the SVHI-12-LPR), by correlating RSI with SVHI in a population sample of 163 subjects (both professional and amateur singers), evaluated also by videolaryngostroboscopy. This study was a cross-sectional, double-observational study., Methods: RSI and SVHI were administered to 159 singers (amateurs, singing students, and professional singers). All subjects underwent videolaryngostroboscopy to objectively identify four subgroups: normal subjects (41.5%), subjects with organic lesions occupying the glottic space (17.6%), subjects with functional dysphonia (18.2%), and subjects presenting solely signs suggestive of LPR (22.6%). Using the validated RSI threshold, 33.9% of participants presented an RSI total score >13, suggestive of LPR., Results: Subjects with a suspected diagnosis of LPR at videolaryngostroboscopy presented a mean RSI significantly higher than other subgroups (p < 0.001). Moreover, the SVHI-36 score did not statistically differ between pathological subgroups. A significant positive relationship was observed between RSI and SVHI total score (Spearman's rank correlation coefficient [ρ] = 0.474, p < 0.001). 12 SVHI items (items 1, 2, 4, 5, 6, 7, 12, 20, 24, 25, 26, 30) showed a significant association with RSI pathology classification. Statistical analysis demonstrated for the 12 selected items (SVHI-12-LPR) acceptable specificity (0.691) and sensibility (0.833) for the suspected diagnosis of LPR with a cut-off of 15., Conclusions: From the SVHI-36, 12 items were extracted that correlated with the specific impact that LPR has on the singer's voice (SVHI-12-LPR), as evaluated by RSI and videolaryngostroboscopy. Such questionnaire represents a new tool that could be applied to singers with symptoms suggestive of LPR to select which patients would benefit from a further phoniatric and videolaryngostroboscopic evaluation., (© 2023 S. Karger AG, Basel.)

Otorhinolaryngology (Ear, Nose and Throat-ENT) focuses on inflammatory, immunological, infectious, and neoplastic disorders of the head and neck and on their medical and surgical therapy. The fields of interest of this discipline are the ear, the nose and its paranasal sinuses, the oral cavity, the pharynx, the larynx, and the neck. Besides surgery, there are many other diagnostic aspects of ENT such as audiology and Vestibology, laryngology, phoniatrics, and rhinology. A new advanced technology, named metabolomics, is significantly impacting the field of ENT. All the "omics" sciences, such as genomics, transcriptomics, and proteomics, converge at the level of metabolomics, which is considered the integration of all "omics." Its application will change the way several of ENT disorders are diagnosed and treated. This review highlights the power of metabolomics, including its pitfalls and promise, and several of its most relevant applications in ENT to provide a basic understanding of the metabolites associated with these districts. In particular, the attention has been focused on different heterogeneous diseases, from head and neck cancer to allergic rhinitis, hearing loss, obstructive sleep apnea, noise trauma, sinusitis, and Meniere's disease. In conclusion, metabolomics study indicates a " fil rouge " that links these pathologies to improve three aspects of patient care: diagnostics, prognostics, and therapeutics, which in one word is defined as precision medicine., Competing Interests: The reviewer AC declared a shared affiliation with the authors AA and RA to the handling editor at the time of review. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Noto, Piras, Atzori, Mussap, Albera, Albera, Casani, Capobianco and Fanos.)

Background: When learning and improving singing, the quantitative characterization of artists' performances based only on vocal parameters does not provide enough information to identify strategies for improvement. Simultaneous monitoring of sound production and breathing patterns in professional singers can allow the exploration of the mechanisms that promote effective singing modalities through association with respiratory efforts., Methods: We developed and tested a novel portable device that simultaneously monitors vocal activity and breathing patterns without interfering with natural singing. The device utilizes a combination of a miniature accelerometer to measure vocal doses from skin vibrations on the neck and two respiratory inductive plethysmography (RIP) bands to estimate the breathing pattern by measuring changes in the thoracoabdominal cross-sectional area., Results: The device was tested on 13 professional baroque-style singers and 14 untrained individuals during the execution of singing tasks. It was accurate compared with reference systems (R 2  = 0.99 and R 2  = 0.91 for the accelerometer and RIP, respectively) and showed differences between the two groups (p ≤ 0.001)., Conclusions: By allowing a quantitative characterization of the effectiveness of singing technique, this novel device can help provide a better understanding of the physiology of singing and may be a tool for support learning and training optimization for professional singers., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aortic stenosis is the most common primary valve lesion requiring surgery or, especially for older patients, transcatheter intervention (TAVI). We showcase a successful transfemoral TAVI procedure in a very high-risk patient and an extremely tortuous S-shaped descending aorta, characterized by heavy calcifications and multiple strong resistance points. We demonstrated that transfemoral TAVI using the "buddy stiff guidewire" technique could be a feasible, simple, quick, and easy procedure able to straighten an extremely abdominal aorta tortuosity. With all techniques available and careful pre-procedural planning, and thanks to the flexibility of new generation TAVI delivery systems, it is possible to safely perform the procedure even in the most challenging patients.

Objective: To evaluate retrospectively the incidence of complications during fiberoptic endoscopic evaluation of swallowing (FEES) in 5,680 examinations., Patients and Methods: 5,680 patients were evaluated at the Department of Otorhinolaryngology, Audiology and Phoniatrics of Pisa University Hospital between January 2014 and December 2018, involving both inpatients and outpatients. Most common comorbidities included neurological pathologies such as stroke (11.8%), neurodegenerative diseases (28.9%) and a history of previous head and neck surgery (24.6%). The evaluation was conducted by clinicians with experience in swallowing for a minimum of 10 years with the assistance of one or more speech-language pathologists., Results: In all patients studied the endoscope insertion was tolerated, and it was possible to visualize the pharyngolaryngeal structures. Three subjects refused to undergo the procedure after being informed regarding the protocol and were therefore not included in this study. Most patients reported discomfort (70.1%) and gagging (20.8%). In a minority of patients complications were recorded, such as anterior epistaxis (0.1%), posterior epistaxis (0.02%), vasovagal crises (0.08%) and laryngospasm (0.04%). Especially laryngospasm was recorded in patients affected by amyotrophic lateral sclerosis. Multivariate binary logistic regression showed that discomfort (OR 9.944; CI 7.643-12.937), chronic gastrointestinal diseases (OR 2.003; CI 1.518-2.644), neurodegenerative diseases (OR 1.550; CI 1.302-1.846) and brain tumors (OR 1.577; CI 1.179-2.111) were risk factors associated with minor complications., Conclusions: FEES proved to be easy to perform, well tolerated by the patients and cost-effective. It can be performed at the patient's bedside, and it is characterized by a low rate of complications. As a matter of fact, normally only discomfort, gagging and/or vomiting are reported. Complications occurred only rarely, such as anterior or posterior epistaxis episodes or vasovagal crises, but these are still easily managed. Exceptionally, more severe complications are reported: adverse drug reactions to substances such as blue dye (methylene blue) and local anesthetics (not used in our protocol), and laryngospasm., (© 2022 S. Karger AG, Basel.)

Patients with severe aortic valve stenosis who are candidates for transcatheter aortic valve replacement represent a high-risk population for the presence of frequent comorbidities (reduced left ventricular ejection fraction, associated valve insufficiency, right ventricular dysfunction and/or pulmonary hypertension). Aortic valve stenosis can be associated with any other valve defects but among these mitral regurgitation is the most commonly associated valve disease. The simultaneous presence of severe mitral regurgitation in patients with aortic stenosis is a negative prognostic factor, resulting in increased mortality and a high diagnostic complexity, in particular in the accuracy of the evaluation of the two valve defects and therapeutic management which, at present, are not supported by strong scientific evidence.

The number of older people has been increasing over recent decades in Western populations. Dizziness, imbalance, and vertigo constitute some of the most common complaints in older patients, and risk of falling is the most frequent and worrying consequence. It has been reported that 15-20% of the adult population experiences these debilitating symptoms. Among the diseases that may be associated with vertigo, the three classes of otological, central, and functional (psychological) dizziness may be distinguished. Overall, vestibular disorders account for 48% of vertiginous complaints in the older population. The main focus of this article is to review the forms of pharmacotherapy for vertigo, especially with regard to older patients, who may be treated simultaneously with other drugs for different comorbidities. Interactions with other drugs should be considered in the choice of a particular course of treatment. Moreover, overuse of pharmacotherapy for the management of vertigo in the elderly may prevent the development of the central compensatory mechanism that sustains both static and dynamic imbalance after a vertiginous crisis. In the majority of patients, vestibular and physical rehabilitation are strongly advised and rarely contraindicated., (© 2021. The Author(s).)

Background: Malposition of intraosseous needles in pediatric patients is frequently reported. Incorrect needle length and penetration depth related to the puncture site and level are possible causes., Aims: Aim of this study was to analyze anatomic dimensions of the proximal tibia in the pediatric population with respect to intraosseous needle placement and needle tip position., Methods: Plain lower leg radiographs of children aged from birth to 16 years of age were analyzed. Pretibial tissue layer, cortical bone thickness, and the diameter of the medullary cavity were measured at two different puncture levels. Data were analyzed as descriptive statistics and by polynomial regression plots and set in context to commonly used EZ-IO ® needle lengths of 15 and 25 mm., Results: Radiographs from 190 patients (104 boys/86 girls) were included. When fully inserted to skin level, up to 10.5% of needles do not reach medullary cavity at one and 18.5% at two patient's fingerbreadths distal to tibial tuberosity. The opposite cortical wall is touched or penetrated in 16% and 25%, respectively. Up to 96% of too deep needle tip positions occur in children younger than 24 months, as do too superficial tip positions in 59%., Conclusions: Puncture level and needle length have a great influence on potential needle tip positions. Infants and toddlers are at highest risk for malpositioning. Due to relevant growth-related differences in tibial anatomy, an age-related and well-reflected approach is crucial to successfully establish intraosseous access., (© 2020 John Wiley & Sons Ltd.)

Ambulatory voice monitoring is a promising tool for investigating phonotraumatic vocal hyperfunction (PVH), associated with the development of vocal fold lesions. Since many patients with PVH are professional vocalists, a classifier was developed to better understand phonatory mechanisms during speech and singing. Twenty singers with PVH and 20 matched healthy controls were monitored with a neck-surface accelerometer-based ambulatory voice monitor. An expert-labeled ground truth data set was used to train a logistic regression on 15 subject-pairs with fundamental frequency and autocorrelation peak amplitude as input features. Overall classification accuracy of 94.2% was achieved on the held-out test set.

Stroke has significant physical, psychological and social consequences. Recent rehabilitation approaches suggest that cognitive exercises with dual-task (sensory-motor) exercises positively influence the recovery and function of the hemiplegic hand grip. The purpose of this study was to describe a rehabilitation protocol involving the use of a new neurocognitive tool called "UOVO" for hand grip recovery after stroke. A 58-year-old right-handed male patient in the chronic stage of stroke, presenting with left-sided hemiparesis and marked motor deficits at the level of the left hand and forearm, was treated with the UOVO, a new rehabilitation instrument based on the neurocognitive rehabilitation theory of Perfetti. The patient was evaluated at T0 (before treatment), T1 (after treatment) and T2 (2 months of follow-up). At T2, the patient showed improvements of motor functions, shoulder, elbow and wrist spasticity, motility and performance. This case report explores the possibility of improving traditional rehabilitation through a neurocognitive approach with a dual-task paradigm (including motor and somato-sensory stimulation), specifically one involving the use of an original rehabilitation aid named UOVO, which lends itself very well to exercises proposed through the use of motor imagery. The results were encouraging and showed improvements in hemiplegic hand grip function and recovery. However, further studies, in the form of randomized controlled trials, will be needed to further explore and confirm our results.

Background: Mohs micrographic surgery (MMS) is used for treatment of primary and recurrent tumors. Compared with primary tumors, recurrent tumors are often more aggressive., Objective: To understand differing characteristics between primary versus recurrent tumors treated by MMS., Materials and Methods: The authors conducted a retrospective review of a 12-year period at 1 academic center. Recurrent tumors were defined as recurrent if previously treated with cryotherapy, topical chemotherapeutics, electrodesiccation and curettage, or excision. Statistical analysis was conducted with p ≤ .05 considered significant., Results: A total of 17,971 cases were reviewed, of which 10.5% represented recurrent tumors. Recurrent tumors occurred more commonly in men (ratio 2.2:1). They presented in older individuals (p < .01) and occurred more commonly on the scalp (p < .0001), neck (p < .0001), and trunk (p < .0001). Primary tumors were more commonly located on the periocular (p < .0001), nose (p < .0001), and perioral areas (p < .0001). Squamous cell carcinoma more commonly presented as primary tumors (p = .02) while squamous cell carcinoma in situ more commonly presented as recurrent tumors (p < .001)., Conclusion: Distinct characteristics separate primary and recurrent tumors treated by MMS. Primary tumors were more commonly located in Area H, compared with recurrent tumors, which were more commonly located in Area M. This suggests appropriate usage of MMS based on appropriate use criteria.

Introduction: Concurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non-small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established., Patients and Methods: In the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m(2) intravenously on days 1 and 22, 20 mg/m(2) intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg(2)) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1-year OS rate was ≥ 70%., Results: A total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively., Conclusion: Full-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: This study aims to investigate the incidence and the relative risk factors of retinopathy of prematurity (ROP) and posterior-ROP (P-ROP): ROP in Zone I and posterior Zone II, as well as to analyze the occurrence of surgical treatment of ROP and to evaluate the short term outcome of the disease in Italy., Methods: It is a prospective multicenter observational study; all infants with a birth weight (BW) ≤ 750 g and/or a gestational age (GA) ≤27 weeks born between January 1st 2008 and December 31st 2009 in 25 III level Italian neonatal intensive care units were eligible for the study., Results: 421 infants were examined: 265 (62.9%) developed ROP and 102 (24.2%) P-ROP., Conclusions: P-ROP is the most aggressive type of ROP. It associates with lower GA and sepsis. Obstetricians and Neonatologists must focus on the reduction of severe preterm births and on the prevention of neonatal early and late onset sepsis in order to reduce the incidence of P-ROP.

Endothelial progenitor cells (EPCs) are a heterogeneous population of cells that are provided by the bone marrow and other adult tissue in both animals and humans. They express both hematopoietic and endothelial surface markers, which challenge the classic dogma that the presumed differentiation of cells into angioblasts and subsequent endothelial and vascular differentiation occurred exclusively in embryonic development. This breakthrough stimulated research to understand the mechanism(s) underlying their physiologic function to allow development of new therapeutic options. One focus has been on their ability to form new vessels in injured tissues, and another has been on their ability to repair endothelial damage and restore both monolayer integrity and endothelial function in denuded vessels. Moreover, measures of their density have been shown to be a better predictor of cardiovascular events, both in healthy and coronary artery disease populations than the classical tools used in the clinic to evaluate the risk stratification. In the present paper we review the effects of EPCs on revascularization and endothelial repair in animal models and human studies, in an attempt to better understand their function, which may lead to potential advancement in clinical management.

The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years. Cardiac function is compromised in diabetes. Diabetic patients manifest accelerated atherosclerosis in coronary arteries. These data are confirmed in diabetic animal models, where lesions of small coronary arteries have been described. These concepts are epitomized in the classic microvascular complications of diabetes, i.e. blindness, kidney failure and distal dry gangrene. Most importantly, accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility. This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes, and assesses the current state of knowledge regarding the triggers for inflammation in this disease. We evaluate the roles of hyperglycemia, oxidative stress, polyol pathway, protein kinase C, advanced glycation end products, insulin resistance, peroxisome proliferator-activated receptor-γ, inflammation, and diabetic cardiomyopathy as a "stem cell disease". Furthermore, we discuss the mechanisms responsible for impaired coronary arteriole function. Finally, we consider how new insights in diabetes may provide innovative therapeutic strategies.

Socioemotional selectivity theory (SST) has been used successfully to explain age differences in interpersonal conflict behavior: older adults are generally less likely to engage in destructive responses, and more likely to employ nonconfrontational ones. However, this research has focused almost exclusively on conflict with intimates (spouses, family, friends), and has typically not examined conflict in the workplace. The present investigation uses behavior ratings made by bosses, peers, and subordinates of 2513 working adults to examine the association between age and workplace conflict behavior; more specifically, it tests three hypotheses generated from socioemotional selectivity theory. Consistent with predictions, raters generally agreed that older working adults were more likely to engage in nonconfrontational responses (yielding, delaying responding); also as expected, older and younger respondents did not consistently differ in their efforts to constructively solve conflict. Unexpectedly, little evidence was found that older adults engage in less active destructive behavior.

Endothelium-derived hyperpolarizing factor (EDHF) plays a crucial role in modulating vasomotor tone, especially in microvessels when nitric oxide-dependent control is compromised such as in diabetes. Epoxyeicosatrienoic acids (EETs), potassium ions (K+), and hydrogen peroxide (H2O2) are proposed as EDHFs. However, the identity (or identities) of EDHF-dependent endothelial dilators has not been clearly elucidated in diabetes. We assessed the mechanisms of EDHF-induced vasodilation in wild-type (WT, normal), db/db (advanced type 2 diabetic) mice, and db/db mice null for TNF (dbTNF-/dbTNF-). In db/db mice, EDHF-induced vasodilation [ACh-induced vasodilation in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME, 10 micromol/l) and prostaglandin synthase inhibitor indomethacin (Indo, 10 mumol/l)] was diminished after the administration of catalase (an enzyme that selectively dismutates H2O2 to water and oxygen, 1,000 U/ml); administration of the combination of charybdotoxin (a nonselective blocker of intermediate-conductance Ca2+-activated K+ channels, 10 micromol/l) and apamin (a selective blocker of small-conductance Ca2+-activated K+ channels, 50 micromol/l) also attenuated EDHF-induced vasodilation, but the inhibition of EETs synthesis [14,15-epoxyeicosa-5(Z)-enoic acid; 10 mumol/l] did not alter EDHF-induced vasodilation. In WT controls, EDHF-dependent vasodilation was significantly diminished after an inhibition of K+ channel, EETs synthesis, or H2O2 production. Our molecular results indicate that mRNA and protein expression of interleukin-6 (IL-6) were greater in db/db versus WT and dbTNF-/dbTNF- mice, but neutralizing antibody to IL-6 (anti-IL-6; 0.28 mg.ml(-1).kg(-1) ip for 3 days) attenuated IL-6 expression in db/db mice. The incubation of the microvessels with IL-6 (5 ng/ml) induced endothelial dysfunction in the presence of l-NAME and Indo in WT mice, but anti-IL-6 restored ACh-induced vasodilation in the presence of L-NAME and Indo in db/db mice. In db(TNF-)/db(TNF-) mice, EDHF-induced vasodilation was greater and comparable with controls, but IL-6 decreased EDHF-mediated vasodilation. Our results indicate that EDHF compensates for diminished NO-dependent dilation in IL-6-induced endothelial dysfunction by the activation of H2O2 or a K+ channel in type 2 diabetes.

Objective: Deferoxamine therapy in lifelong transfusion-dependent anaemias, as beta-thalassemia major, is associated with an increased risk of ototoxic changes. With increasing survival rates, prevention and/or early detection of ototoxicity are important for providing management options. The predictive value of pure-tone audiometry in early detection of ototoxicity has been questioned, particularly in the higher frequencies. Otoacoustic emissions appear to be more sensitive to cochlear insult than the conventional pure-tone audiometry. The aim of our study was to compare the efficacy of otoacoustic emissions (distortion-product otoacoustic emissions) with that of pure-tone audiometry as method of audiological monitoring., Methods: Baseline audiometric (0.25-8kHz) and otoacoustic emission testing (distortion-product otoacoustic emissions) was conducted in a group of patients with beta-thalassemia major, 60 of whom met the criteria for inclusion in the study. Comparisons were performed between baseline measurements and those recorded after 20 months. Distortion-product otoacoustic emissions were obtained as DP-grams. The DP-gram amplitude was determined for each child., Results: Threshold changes from baseline were found to be statistically significant from 4 to 8kHz in 68.4% of the subjects (P<0.01). Distortion-product otoacoustic emissions demonstrated a significant threshold shift and a decreased amplitude in the frequencies >3kHz (P<0.05). Furthermore, DP-gram amplitude also reduced significantly at 3kHz (P<0.05) without any similar change in pure-tone audiometry., Conclusions: As ototoxicity screening tool DP-gram was extremely sensitive and superior to pure-tone audiometry. Their use is recommended for regular monitoring of cochlear function, aiming in prevention of permanent damage.

Sound is a natural stimulus for both cochlear and saccular receptors. At high intensities it evokes in active masseter muscles of healthy subjects two overlapping reflexes: p11/n15 and p16/n21 waves, whose origin has not yet been demonstrated. Our purpose was to test which receptor in the inner ear is responsible for these reflexes. We compared masseter EMG responses induced in normal subjects (n = 9) by loud clicks (70-100 dB normal hearing level (NHL), 0.1 ms, 3 Hz) to those evoked in subjects with a selective lesion of the cochlea (n = 5), of the vestibule (n = 1) or with mixed cochlear-vestibular failure (n = 5). In controls, 100 dB clicks induced bilaterally, in the unrectified mean EMG (unrEMG), a clear p11 wave followed by a less clear n15 wave and a subsequent n21 wave. Lowering the intensity to 70 dB clicks abolished the p11/n15 wave, while a p16 wave appeared. Rectified mean EMG (rectEMG) showed, at all intensities, an inhibitory deflection corresponding to the p16/n21 wave in the unrEMG. Compared to controls, all deaf subjects had a normal p11 wave, together with more prominent n15 wave; however, the p16/n21 waves, and their corresponding inhibition in the rectEMG, were absent. The vestibular patient had bilaterally clear p11 waves only when 100 dB clicks were delivered bilaterally or to the unaffected ear. Stimulation of the affected ear induced only p16/n21 waves. Data from mixed patients were consistent with those of deaf and vestibular patients. We conclude that click-induced masseter p11/n15 waves are vestibular dependent, while p16/n21 waves depend on cochlear integrity.

Background: We hypothesized that the inflammatory cytokine tumor necrosis factor-alpha (TNF) produces endothelial dysfunction in type 2 diabetes., Methods and Results: In m Lepr(db) control mice, sodium nitroprusside and acetylcholine induced dose-dependent vasodilation, and dilation to acetylcholine was blocked by the NO synthase inhibitor N(G)-monomethyl-L-arginine. In type 2 diabetic (Lepr(db)) mice, acetylcholine- or flow-induced dilation was blunted compared with m Lepr(db), but sodium nitroprusside produced comparable dilation. In Lepr(db) mice null for TNF (db(TNF-)/db(TNF-)), dilation to acetylcholine or flow was greater than in diabetic Lepr(db) mice and comparable to that in controls. Plasma concentration of TNF was significantly increased in Lepr(db) versus m Lepr(db) mice. Real-time polymerase chain reaction and Western blotting showed that mRNA and protein expression of TNF and nuclear factor-kappaB were higher in Lepr(db) mice than in controls. Administration of anti-TNF or soluble receptor of advanced glycation end products attenuated nuclear factor-kappaB and TNF expression in the Lepr(db) mice. Immunostaining results show that TNF in mouse heart is localized predominantly in vascular smooth muscle cells rather than in endothelial cells and macrophages. Superoxide generation was elevated in vessels from Lepr(db) mice versus controls. Administration of the superoxide scavenger TEMPOL, NAD(P)H oxidase inhibitor (apocynin), or anti-TNF restored endothelium-dependent dilation in Lepr(db) mice. NAD(P)H oxidase activity, protein expression of nitrotyrosine, and hydrogen peroxide production were increased in Lepr(db) mice (compared with controls), but these variables were restored to control levels by anti-TNF., Conclusions: Advanced glycation end products/receptor of advanced glycation end products and nuclear factor-kappaB signaling play pivotal roles in TNF expression through an increase in circulating and/or local vascular TNF production in the Lepr(db) mouse with type 2 diabetes. Increases in TNF expression induce activation of NAD(P)H oxidase and production of reactive oxidative species, leading to endothelial dysfunction in type 2 diabetes.

Background: Anemia is now recognized as being a common finding in CHF and is associated with increased mortality and morbidity. However, it is uncertain whether the anemia is actually causing the worse prognosis or is merely a marker of more severe cardiac disease. Previous intervention studies with subcutaneous (s.c.) beta-EPO in combination with iron have either been uncontrolled or case-controlled studies. We report a randomized, double-blind, placebo-controlled study of the combination of s.c. EPO and oral iron versus oral iron alone in patients with anemia and resistant CHF., Objectives: The present study examines, in patients with advanced congestive heart failure (CHF) and anemia, the effects of beta-erythropoietin (EPO) and oral iron on the anemia and on cardiac and renal functional parameters., Methods: Forty consecutive subjects with moderate to severe CHF and anemia (hemoglobin [Hb] <11 g/dL) were studied. They were randomized to receive, in a double-blind fashion, either (a) (group A, the treatment group, 20 patients) s.c. beta-EPO for 3 months twice weekly, in addition to daily oral iron, or (b) (group B, the placebo group, 20 patients) normal saline in s.c. injections and daily oral iron. Two patients in group B were eventually excluded because of a fall of Hb <8 g/dL requiring transfusion, leaving 18 patients in group B. After the 3-months study, the group A patients were maintained on the same treatment for an additional 9 months, whereas in Group B, the placebo and oral iron were stopped., Results: In group A, after a mean of 3.5 +/- 0.8 months of treatment, there was a significant increase in Hb from 10.4 +/- 0.6 to 12.4 +/- 0.8 g/dL (P < .01); a significant improvement in New York Heart Association functional class from 3.5 +/- 0.6 to 2.8 +/- 0.5 (P < .05); a longer endurance time on exercise testing, from 5.8 +/- 2.2 to 7.8 +/- 2.5 minutes (P < .01); a greater distance walked on exercise testing, from 278 +/- 55 to 356 +/- 88 meters (P < .01); a significant increase in the peak oxygen consumption (VO2) from 12.8 +/- 2.8 to 15.1 +/- 2.8 mL/kg per minute (<.05); and the VO2 at the anaerobic threshold, from 9.2 +/- 2.0 to 13.2 +/- 3.6 mL/kg minute (P < .01). There was also a significant fall in plasma B-type natriuretic peptide levels from 568 +/- 320 to 271 +/- 120 pg/mL (P < .01), a significant reduction in serum creatinine (P < .01), and an increase in estimated creatinine clearance (P < .05). In group B, there were no significant changes in any of the above parameters over the study period. At the end of the 1-year study, the Hb was still higher in group A than group B, and the rate of hospital admissions/patients over the year averaged 0.8 +/- 0.2 in group A and 1.7 +/- 0.8 in group B (P < .01)., Conclusions: In anemic CHF patients, correction of anemia with EPO and oral iron leads to improvement in New York Heart Association status, measured exercise endurance, oxygen use during exercise, renal function and plasma B-type natriuretic peptide levels and reduces the need for hospitalization.

Background: Recently, it was shown that B-type natriuretic peptide levels are increased in patients with acute coronary syndromes., Aims: To assess the relation between B-type natriuretic peptide and ischemia in patients with stable and unstable angina pectoris with normal left ventricular function in relation to the extent of ischemia and response to revascularization., Methods: Fifty-nine consecutive patients were enrolled in the study, patients were divided into two groups: stable angina patients (group I, n=18), and unstable coronary patients (group II, n=41). Baseline characteristics were compared with 15 age-matched and sex-matched participants. B-type natriuretic peptide levels were measured at baseline and 3, 7 and 90 days after coronary revascularization in group I and II., Results: Patients with unstable angina pectoris had increased B-type natriuretic peptide levels compared with stable angina pectoris patients (B-type natriuretic peptide levels: controls 15.5+/-13 pg/ml, stable angina pectoris group 28.4+/-19 pg/ml, unstable angina pectoris group 104+/-81 pg/ml; P<0.01). A relationship between the number of affected coronary vessels and B-type natriuretic peptide was assessed (one-vessel 29.9+/-21 pg/ml, two-vessel 93.8+/-87 pg/ml, three-vessel 119+/-88 pg/ml; P<0.01). After revascularization, B-type natriuretic peptide levels decreased in groups I and II (25+/-20 vs. 39+/-28 pg/ml) and were similar after 90 days in percutaneous transluminal coronary angiograghy and in coronary artery bypass grafting groups (percutaneous transluminal coronary angiography 26+/-22 pg/ml, coronary artery bypass grafting 36+/-26 pg/ml; NS)., Conclusions: B-type natriuretic peptide levels increase in unstable angina pectoris patients and are linked to the extent of coronary disease in patients with normal left ventricular systolic function, and returned to baseline level after surgical or catheter revascularization.

Patients with multiple sclerosis (MS) frequently report symptoms related to vestibular disorders in the course of their disease. At present, the fundamental tests assessing vestibulospinal involvement are posturography and vestibular evoked myogenic potentials (VEMPs). While posturography cannot be performed in every subject requiring minimal stance control, VEMPs do not require any specific skill on the part of the subjects and they may be investigated in all patients able to sit. VEMPs were recorded for 40 patients (17 men, 23 women; mean age 38 years, range 17-71 years) fulfilling diagnostic criteria of clinically defined MS, by means of rarefaction clicks, recording modulation of sterno-cleido-mastoideus tonic contraction saccule-mediated modulation. VEMPs were found to be abnormal in 28 of 40 patients. In 18 of the cases the VEMPs were asymmetric, i.e., had a prolonged latency on one side. In six cases latency was increased on both sides (mean delay 4.1 ms). In four subjects VEMPs were absent on one side. Concordance with clinical findings of presence/absence of brainstem involvement was found in 55% and with MRI findings in 65% of the cases. Abnormal VEMPs indicated brainstem dysfunction in four patients (10%) with normal MRI and no specific clinical signs.

Balance disorders are frequent with aging. They are particularly important because they decrease social autonomy of the aged subjects and they often provoke falls. The cause is always multifactorial. There is evidence that aging affects multiple sensory inputs, as well as the muscoloskeletal system and central nervous system ability to perform sensorimotor integration. For the evaluation of decreased balance skills in elderly, a specific questionnaire has been prepared, in order to identify high risk of falling called falling risk inventory (FRI) questionnaire, and a complex psycho-sensory-motor test has been studied by means of posturography, in order to detect specific vestibular impairment. Regarding ethiopathogenesis of balance disorders in aged subjects, because the decline of behavioral and cognitive performances are due also to decline of biological rhythm control, the role of melatonin (the hormone regulating circadian rhythms, being strictly connected with cerebellar function, and it is well known that cerebellum acts in elderly both at motor and cognitive regulation. The goals of the present paper are: (i) To present a self-administered FRI questionnaire aimed at identifying possible causes of falls and quantifying falling risk in aged. (ii) To validate posturography as a specific test to investigate vestibular involvement in elderly in correlation with FRI. (iii) To present a complex behavioral test (NT) aimed at evaluating both spatial orientation and spatial memory in elderly, factors involved into the genesis of complex dizziness and unsteadiness. (iv) To evaluate the role of melatonin in cognitive involvement in dizzy, old subjects due to the functional correlations between circadian rhythms, cerebellum balance disturbances and cognitive disorders. General conclusions are: FRI correlates with falling risk. Posturography identifies specific vestibular impairments correlated to balance disorders and elderly falls. Spatial orientation is altered in about 40% of dizzy patients but no significant differences are revealed in melatonin rhythm. Spatial memory is highly altered only in subjects with inversion of circadian melatonin rhythm it is possible to hypothesize that the alteration of the normal circadian melatonin rhythm plays some role in the genesis of dizziness in a subpopulation of patients.

The difficulty of accurately localizing the source of subjective tinnitus is well-known. Anamnesis and traditional audiological tests can often suggest a source if its origin as peripheral or merely central (or both). Therefore, several authors, such as Risey, Denk, and Shulman, recently proposed identifying the source of subjective tinnitus through the evaluation of the responses reported by patients to adequate pharmacological treatments. Our study presents a useful plan to perform tinnitus topodiagnosis, which consists of specific audiological tests evaluating the characteristics of symptoms (annoyance, pitch, loudness, hyperacusis) and of several pharmacological tests carried out through the administration of particular drugs, the pharmacodynamic mechanisms and meaningful side effects of which are described. On the basis of pharmacological effects on tinnitometry, some drugs will be combined.

Non-syndromic hearing loss is the most common sensory disorder in humans; 15%-20% of cases are transmitted as a dominant trait (NSDA) with 40 loci having been mapped and 16 genes having been identified. Here, we report the mapping of a novel NSDA locus, DFNA48, to chromosome 12q13-q14 in a large multigenerational Italian family. A maximum lod score of 3.31 was obtained with marker D12S83, whereas markers D12S347 and D12S1703 defined a region of approximately 18 cM. Positional candidate genes are being screened for deafness-causing mutations.

The objective of this study was verification, through suitable hematochemical tests, of the supposition that central-systemic microtoxicosis plays a role either in the etiopathogenesis of Ménière's syndrome or in labyrinthine pathological processes or hypoacusis. We did not, therefore, exclude other well-known hypotheses in the causality of these pathologies. Nonetheless, one finds, particularly in the Ménière's cases, a constant homogeneous distribution of the metabolic products of this microtoxicosis, such as a high concentration of free radicals and low natural defenses (e.g., antioxidant plasmatic capacity). Therefore, there exists a kind of dangerous central and systemic presence of reactive molecules, aimed toward the polyunsaturated fatty acids and homeostatic complex enzymes, that is not compensated for by the natural antioxidant defense. The presence of this lack of balance, verified by suitable tests, has shown the rationality of use of a product made from reduced glutathione, thioctic acid, cysteine, and other antioxidants as a multipurpose antidote to this element of etiopathogenesis. Patients were divided into three groups (control, conventional therapy, and antioxidant treatment), and those in the antioxidant treatment group, especially those with Ménière's syndrome, demonstrated a net and more significant improvement. Also, parallel clinical and instrument evaluations of this new therapeutic solution, the efficacy of which has already been positively demonstrated, are expected to provide further evidence to support the primary hypothesis.

Tinnitus is a pathological event caused by abnormal stimulation of any point along the acoustic pathway. Generally, it produces a sharp tone accompanied by hearing impairment. Currently, no widely used standard protocol for treatment of this condition exists, and vascular microthrombotic factors are considered as the main determinants. Prompted by such observations, we implemented a protocol using an anticoagulant, sodium enoxaparin. It is a kind of heparin with a low molecular weight and is endowed with antithrombotic activity. We studied 40 patients (ages 20-65 years) who had been experiencing tinnitus for at least 2 months. We divided patients into two groups: To the first group, enoxaparin was administered for 10 days; the patients in the second group were treated with traditional therapy (corticosteroids, vasoactive agents, multivitamins, and anticoagulants). At the beginning and at the end of the therapy period, the patients were evaluated by instrumental examinations. All patients treated with anticoagulant therapy have shown an evident abatement of their tinnitus symptom. No patient experienced side effects from this treatment. The results indicate that administration of sodium enoxaparin is an excellent mode of therapy for patients with tinnitus.

Background: Cranio-cervico-mandibular disorders can cause disturbances in posture. Stabilimetry measures spatio-temporal variations in the center of body pressure and evaluates the mechanisms of maintenance of balance. The study used a stabilimetric platform to evaluate posture changes in patients with cranio-cervico-mandibular disorders before and after treatment for malocclusion., Methods: Between February 1998 and December 2000, 60 patients with cranio-cervico-mandibular disorders were recruited from the Dentistry Clinic of the University of Sassari. Each patient underwent two stabilimetric examinations (closed mouth with cotton wads inserted between the dental arches). The tests were conducted on a stabilimetric platform. Measurement of body posture load and sway were analyzed with a specific software program that correlated the vestibular, somatosensory and visual systems, and determined the role of each in postural control., Results: The stabilimetric analysis showed that the adoption of the plaque allowed rebalance of the postural system, without affecting the visual system. After treatment, 64% of patients experienced remission of pain symptoms with orthotic therapy., Conclusions: The relationship between malocclusion and posture should be seen from a holistic standpoint in other to gain a global therapeutic outcome.

In this report, we summarize our clinical experience with intratympanic dexamethasone treatment (IDT) for control of tinnitus. From March 2000 through February 2001, we observed 54 patients (23 women, 31 men; mean age, 49.6 +/- 7.2 years; range, 24-71 years) suffering from subjective idiopathic tinnitus (SIT). After common audiological tests had been performed; all patients underwent specific topodiagnostic tests to verify the cochlear SIT genesis. The 50 subjects with positive results from a furosemide test and negative results from caraverine and carbamazepine tests were selected for the IDT, consisting of transtympanic perfusion of 4 mg dexamethasone to the round window via the middle ear. The treatment was repeated three times daily for 3 consecutive months. Its short-term effects were evaluated 2 weeks after the last perfusion. In 17 of 50 of these patients (34%), the SIT disappeared; 20 of the 50 (40%) reported a significant decrease of the symptom; and the remaining 13 of the 50 (26%) did not experience any improvement. Therefore, we believe that IDT represents an effective drug delivery system for SIT control, as long as the condition arises from inner ear disorders only and treatment occurs within 3 months of symptom onset.

Arterial vascular anomalies rarely cause extrinsic ureteral obstruction and only 11 cases have been reported so far. This paper deals with an unusual extrinsic obstruction of the left ureter caused by a residue of the umbilical artery in a 37 years old man. The patient had left flank pain due to serious hydronephrosis on the same side. At operation a fibrous cord, a residue of the left umbilical artery, partially obstructed the distal left ureter. Partial left terminal ureterectomy with ureteroneocystostomy was performed. In the differential diagnosis of low extrinsic ureteral obstructions also the uncommon vascular anomalies of the umbilical artery should be taken into consideration.

Thirty three children aged 2 to 42 months (mean 9 months) with gastro-oesophageal reflux and peptic oesophagitis took part in a treatment trial comparing cimetidine (20 mg/kg/day) with an intensive regimen of antacids (Maalox, 700 mmol (mEq)/1 X 73 m2/day). All children were evaluated clinically and by radiology, acid reflux test, and endoscopy. After 12 weeks of treatment all were again evaluated clinically, by pH measurement, and endoscopy. Twenty nine children, 15 on antacid and 14 on cimetidine, completed the trial. Eight patients on antacid and seven on cimetidine were cured; five on antacid and six on cimetidine improved; and two patients on antacid and one on cimetidine underwent surgery. Both groups of children showed a statistically significant reduction in the score of clinical, pH, and endoscopic variables after treatment. Lower oesophageal sphincter pressure before treatment did not correlate significantly with the final total score. Antacids in large quantities are as effective as cimetidine in medical treatment of gastro-oesophageal reflux and peptic oesophagitis.

A patient with a juxtapapillary hamartoma is described, in consideration not only for the scarcity of such cases described in the literature, but also for the clinical and echographic characteristics that were observed for the involvement of the right eye, and because the patient was female. Echography and especially standardized A-scan echography, showing a lesion at high reflectivity without acoustic shadowing, allowed us to exclude the presence of a malignant melanoma and retinoblastoma, and directing us to the diagnosis of a malformation of angiomatous type.

A large kindred (64 members in four generations), affected by a form of apparently congenital pulverulent cataract, was studied for linkage of its gene locus with that of the Fy blood group. No indication of linkage was found. The involvement of the cortex distinguishes this form from the zonular pulverulent cataract (total nuclear) of Nettleship and Ogilvie, the locus of which is probably linked with Fy. A correlation between morphological and genetic heterogeneity, based on the linkage with Fy, cannot be established because of the scarcity of published data.

A case of a 4-year-old child with retraction syndrome and an associated posterior lenticonus is presented. The lack of specific morphological chromosome abnormalities and of any disturbance of amino acid metabolism, in our case, suggests that the retraction syndrome, in nonhereditary types, is the result of dysgenesis during the middle of the third trimester of pregnancy.